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1. Efficacy of an internet-based guided trauma-focused intervention in reducing ICD-11 posttraumatic stress disorder symptoms: study protocol of a randomized controlled trial

Author

Odeta Gelezelyte, Greta Guogaite, Auguste Nomeikaite, Jonathan I. Bisson, Catrin Lewis, and Evaldas Kazlauskas

Subjects
Posttraumatic stress disorder, PTSD, Internet-based intervention, Treatment, Guided self-help, Trauma-focused CBT, Psychiatry, RC435-571
Abstract

Abstract Background Posttraumatic stress disorder (PTSD) is a common mental disorder. However, many cases of PTSD remain untreated because of limited healthcare resources and other treatment-seeking barriers. Effective internet-based interventions could help to improve access to PTSD treatments. Therefore, the main objective of the planned randomized controlled trial is to evaluate the efficacy of the Lithuanian version of the guided internet-based self-help programme (Spring) in reducing ICD-11 PTSD symptoms. Methods The planned sample size is 50 participants exposed to different traumatic experiences. Participants eligible for the study will be randomized into two study groups: the immediate treatment group and the delayed treatment control group. Both groups will receive guided trauma-focused ICBT intervention, but the delayed treatment group will receive access to the programme five months after randomization. The International Trauma Interview (ITI) will be used for the assessment of ICD-11 PTSD symptoms at pre-treatment, post-treatment, and at a 3-month follow-up. Changes in disturbances in self-organization, depression and anxiety levels, as well as posttraumatic cognitions and trauma-related shame, will also be evaluated. In addition, associations between changes in symptoms of PTSD and readiness for treatment, treatment expectations and working alliance will be explored. Changes in treatment outcomes will be evaluated using multiple Latent Change Models. Discussion This study is expected to contribute to valuable knowledge on the efficacy of internet-based interventions for posttraumatic stress disorder. Trial registration ClinicalTrials.gov NCT06475716. Registered on 25 June 2024.

Published
2024
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2. Pragmatic randomised controlled trial of guided self-help versus individual cognitive behavioural therapy with a trauma focus for post-traumatic stress disorder (RAPID)

Author

Jonathan I Bisson, Cono Ariti, Katherine Cullen, Neil Kitchiner, Catrin Lewis, Neil P Roberts, Natalie Simon, Kim Smallman, Katy Addison, Vicky Bell, Lucy Brookes-Howell, Sarah Cosgrove, Anke Ehlers, Deborah Fitzsimmons, Paula Foscarini-Craggs, Shaun R S Harris, Mark Kelson, Karina Lovell, Maureen McKenna, Rachel McNamara, Claire Nollett, Tim Pickles, and Rhys Williams-Thomas

Subjects
post-traumatic stress disorder, randomised controlled trial, guided self-help, cbt, intervention, internet-based, web-assisted, Medical technology, R855-855.5
Abstract

Background Guided self-help has been shown to be effective for other mental conditions and, if effective for post-traumatic stress disorder, would offer a time-efficient and accessible treatment option, with the potential to reduce waiting times and costs. Objective To determine if trauma-focused guided self-help is non-inferior to individual, face-to-face cognitive-behavioural therapy with a trauma focus for mild to moderate post-traumatic stress disorder to a single traumatic event. Design Multicentre pragmatic randomised controlled non-inferiority trial with economic evaluation to determine cost-effectiveness and nested process evaluation to assess fidelity and adherence, dose and factors that influence outcome (including context, acceptability, facilitators and barriers, measured qualitatively). Participants were randomised in a 1 : 1 ratio. The primary analysis was intention to treat using multilevel analysis of covariance. Setting Primary and secondary mental health settings across the United Kingdom’s National Health Service. Participants One hundred and ninety-six adults with a primary diagnosis of mild to moderate post-traumatic stress disorder were randomised with 82% retention at 16 weeks and 71% at 52 weeks. Nineteen participants and ten therapists were interviewed for the process evaluation. Interventions Up to 12 face-to-face, manualised, individual cognitive-behavioural therapy with a trauma focus sessions, each lasting 60–90 minutes, or to guided self-help using Spring, an eight-step online guided self-help programme based on cognitive-behavioural therapy with a trauma focus, with up to five face-to-face meetings of up to 3 hours in total and four brief telephone calls or e-mail contacts between sessions. Main outcome measures Primary outcome: the Clinician-Administered PTSD Scale for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, at 16 weeks post-randomisation. Secondary outcomes: included severity of post-traumatic stress disorder symptoms at 52 weeks, and functioning, symptoms of depression, symptoms of anxiety, alcohol use and perceived social support at both 16 and 52 weeks post-randomisation. Those assessing outcomes were blinded to group assignment. Results Non-inferiority was demonstrated at the primary end point of 16 weeks on the Clinician-Administered PTSD Scale for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition [mean difference 1.01 (one-sided 95% CI −∞ to 3.90, non-inferiority p = 0.012)]. Clinician-Administered PTSD Scale for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, score improvements of over 60% in both groups were maintained at 52 weeks but the non-inferiority results were inconclusive in favour of cognitive-behavioural therapy with a trauma focus at this timepoint [mean difference 3.20 (one-sided 95% confidence interval −∞ to 6.00, non-inferiority p = 0.15)]. Guided self-help using Spring was not shown to be more cost-effective than face-to-face cognitive-behavioural therapy with a trauma focus although there was no significant difference in accruing quality-adjusted life-years, incremental quality-adjusted life-years −0.04 (95% confidence interval −0.10 to 0.01) and guided self-help using Spring was significantly cheaper to deliver [£277 (95% confidence interval £253 to £301) vs. £729 (95% CI £671 to £788)]. Guided self-help using Spring appeared to be acceptable and well tolerated by participants. No important adverse events or side effects were identified. Limitations The results are not generalisable to people with post-traumatic stress disorder to more than one traumatic event. Conclusions Guided self-help using Spring for mild to moderate post-traumatic stress disorder to a single traumatic event appears to be non-inferior to individual face-to-face cognitive-behavioural therapy with a trauma focus and the results suggest it should be considered a first-line treatment for people with this condition. Future work Work is now needed to determine how best to effectively disseminate and implement guided self-help using Spring at scale. Trial registration This trial is registered as ISRCTN13697710. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 14/192/97) and is published in full in Health Technology Assessment; Vol. 27, No. 26. See the NIHR Funding and Awards website for further award information. Plain language summary Post-traumatic stress disorder is a common, disabling condition that can occur following major traumatic events. Typical symptoms include distressing reliving, avoidance of reminders and feeling a current sense of threat. First-choice treatments for post-traumatic stress disorder are individual, face-to-face talking treatments, of 12–16 hours duration, including cognitive behavioural therapy with a trauma focus. If equally effective treatments could be developed that take less time and can be largely undertaken in a flexible manner at home, this would improve accessibility, reduce waiting times and hence the burden of disease. RAPID was a randomised controlled trial using a web-based programme called Spring. The aim was to determine if trauma-focused guided self-help provided a faster and cheaper treatment for post-traumatic stress disorder than first-choice face-to-face therapy, while being equally effective. Guided self-help using Spring is delivered through eight steps. A therapist provides a 1-hour introductory meeting followed by four further, fortnightly sessions of 30 minutes each and four brief (around 5 minutes) telephone calls or e-mail contacts between sessions. At each session, the therapist reviews progress and guides the client through the programme, offering continued support, monitoring, motivation and problem-solving. One hundred and ninety-six people with post-traumatic stress disorder to a single traumatic event took part in the study. Guided self-help using Spring was found to be equally effective to first-choice face-to-face therapy at reducing post-traumatic stress disorder symptoms at 16 weeks. Very noticeable improvements were maintained at 52 weeks post-randomisation in both groups, when most results were inconclusive but in favour of face-to-face therapy. Guided self-help using Spring was significantly cheaper to deliver and appeared to be well-tolerated. It is noteworthy that not everyone benefitted from guided self-help using Spring, highlighting the importance of considering it on a person-by-person basis, and personalising interventions. But, the RAPID trial has demonstrated that guided self-help using Spring provides a low-intensity treatment option for people with post-traumatic stress disorder that is ready to be implemented in the National Health Service. Scientific summary Background Post-traumatic stress disorder (PTSD) is a common mental health condition that may develop following exposure to traumatic events that involve threatened or actual death, serious injury or sexual violence. PTSD causes significant distress to those affected by it, often co-occurs with other physical and mental health conditions and is associated with a large economic burden. Face-to-face, trauma-focused psychological treatments (TFPT) have been found to be the most effective currently available treatments for PTSD and are recommended first line by treatment guidelines across the world. Unfortunately, the limited number of suitably trained therapists available to deliver TFPT in the National Health Service often prevents timely access to treatment and some people find accessing and fully engaging with face-to-face TFPT difficult for other reasons, including work commitments, travel and childcare. Guided self-help (GSH) provides an alternative approach to the delivery of treatment by combining the use of self-help materials with regular guidance from a trained professional and requires less therapist time than recommended face-to-face TFPT. GSH has been shown to be effective for other mental conditions and, if effective for PTSD, GSH would offer a time-efficient and accessible treatment option, with the potential to reduce waiting times and intervention costs. Objectives The main aim of the RAPID trial was to determine the likely clinical and cost-effectiveness of GSH using Spring, an internet-based programme based on cognitive behavioural therapies with a trauma focus (CBT-TF), for mild to moderate PTSD. RAPID also aimed to describe the experience of receiving GSH using Spring from the recipient’s perspective, and the delivery of GSH using Spring from the therapist’s perspective. The objectives were to determine if: GSH using Spring was at least equivalent in effectiveness and cost-effective relative to individual face-to-face CBT-TF for people with PTSD, as judged by reduced symptoms of PTSD and improved quality of life. GSH using Spring improved functioning and reduced symptoms of depression, symptoms of anxiety, alcohol use and perceived social support. Specific factors may impact effectiveness and successful roll-out of GSH for PTSD in the NHS. Methods RAPID was a multicentre pragmatic randomised controlled non-inferiority trial with assessors masked to treatment allocation. Individual randomisation was used. Economic evaluation was undertaken to determine cost-effectiveness and nested process evaluation to assess fidelity and adherence, dose and factors that may influence outcome (including context, acceptability, and facilitators and barriers, measured qualitatively). GSH using Spring was not expected to be more effective than face-to-face CBT-TF, and therefore, a non-inferiority design was chosen. Participants were recruited from NHS Improving Access to Psychological Therapy services based in primary care in England, and NHS psychological treatment settings based in primary and secondary care in Scotland and Wales. Wide eligibility criteria were used to ensure good external validity. Participants were aged 18 or over, had mild to moderate PTSD as their primary diagnosis, had regular access to the internet and gave informed consent to take part. Exclusion criteria were inability to read and write fluently in English, previous completion of a course of TFPT for PTSD, current PTSD symptoms to more than one traumatic event, current engagement in psychological therapy, psychosis, substance dependence, active suicide risk and change in psychotropic medication in the past 4 weeks. Participants were randomised to receive up to 12 face-to-face, manualised, individual CBT-TF sessions, each lasting 60–90 minutes, or to GSH using Spring. Spring is a manualised, eight-step online GSH programme based on CBT-TF. An initial meeting of 1 hour between the therapist and the person with PTSD is followed by four subsequent fortnightly meetings of 30 minutes, with four brief telephone calls or e-mail contacts between sessions. The primary outcome was the severity of symptoms of PTSD over the previous week as measured by the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) at 16 weeks post-randomisation. Secondary outcomes included severity of PTSD symptoms at 52 weeks, and functioning, symptoms of depression, symptoms of anxiety, alcohol use, and perceived social support at both 16 and 52 weeks post-randomisation. Resource use was also collected to support the health economic evaluation. Semistructured interviews were conducted with 19 participants and 10 therapists as part of the process evaluation, to gather perspectives of receiving and delivering the interventions, to examine underlying mechanisms and factors influencing future implementation. Results One hundred and ninety-six participants were randomised with 82% retention at 16 weeks and 71% at 52 weeks. There were no serious imbalances observed in the baseline data between the two groups. Non-inferiority (margin of 5 points) was demonstrated at the primary endpoint of 16 weeks on the CAPS-5 using the intention to treat principle [mean difference 1.0, 95% one-sided confidence interval (CI) (−∞, 3.9, non-inferiority p = 0.012)]. This was also the case for all secondary outcomes at this time point, except for client satisfaction that was inconclusive but in favour of CBT-TF. At 52 weeks post-randomisation, non-inferiority was shown for Multidimensional Scale for Perceived Social Support (MSPSS), Alcohol Use Disorders Test and GSES; non-inferiority was not shown for the other outcomes but the results, which were inconclusive, were in favour of CBT-TF. Further examination of the Impact of Event Scale-Revised (IES-R) longitudinal measurements indicated that while the GSH group maintained their reduction (improvement) in IES-R scores between the 16- and 52-week assessments, the CBT-TF group continued to improve at a slow rate over the same period. There were no subgroup effects that showed any evidence of difference between the interventions including gender (pre-specified), mode of data collection or assessments conducted after the introduction of the COVID-19 lockdown. Spring was cheaper to deliver than face-to-face CBT TF [£277 (95% CI £253 to £301) vs. £729 (95% CI £671 to £788)]. When total costs were included, Spring was £572 (95% CI £64.96 to £1080.14) cheaper and produced but derived fewer quality-adjusted life-years (QALYs) compared to CBT-TF, −0.04 (95% CI −0.10 to 0.01). At a willingness-to-pay threshold of £30,000 per QALY gained, the probability of GSH being cost-effective was 29.74%. The process data provided evidence of acceptability of the overall trial methodology, although key points were identified for consideration in future randomised controlled design, especially concerning burden and impact of outcome measures on participants and how they are delivered and explained. Intervention acceptability was indicated for both GSH and CBT-TF interventions, although there was a preference for face-to-face treatment. Therapeutic relationship was an important factor highlighted in the acceptability of the interventions. Flexibility identified with GSH was seen as positive and some activities within Spring were described as more helpful than others. Conclusions Implications for health care GSH using Spring was found to be non-inferior to face-to-face CBT-TF at treating people with mild to moderate PTSD. Significant gains were maintained in the GSH using Spring group at 52 weeks but some ongoing improvements in the CBT-TF group appeared to result in largely inconclusive findings with respect to non-inferiority at 52 weeks. The additional benefits of GSH using Spring with respect to time, cost and convenience, and having another evidence-based treatment option could be argued as outweighing what appear to be minor differences at 52 weeks. The results of the RAPID trial should herald a step change in the approach of services to the provision of evidence-based treatment to people with mild to moderate PTSD. There is now an urgent need to make GSH using Spring available as a low-intensity treatment option for people with PTSD. Future research implications How best to effectively disseminate and implement GSH using Spring at scale, to maximise its impact, is a key research question. This includes identification of the specific skill set and competencies required by a guiding clinician to foster effective alliance and engagement, and the optimal level of training and supervision required for the provision of GSH using Spring. The optimal amount of guidance is unclear. The quantitative and qualitative results strongly suggest that the current number of facilitation sessions is right for most people but that some people could probably benefit with more. Research into the impact of increased flexibility in delivery and more personalised adaptations is desirable. Research is also required to understand the extent to which individuals may or may not be excluded from internet-based treatments due to language and literacy issues, and online access issues, and how best to address these. Trial registration This trial is registered as ISRCTN13697710. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 14/192/97) and is published in full in Health Technology Assessment; Vol. 27, No. 26. See the NIHR Funding and Awards website for further award information.

Published
2023
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3. Prevalence and correlates of self-stigma in Post-Traumatic Stress Disorder (PTSD)

Author

Catrin Lewis, Stan Zammit, Ian Jones, and Jonathan I. Bisson

Subjects
stress disorders, post-traumatic, self-stigma, psychological distress, epidemiology, Psychiatry, RC435-571
Abstract

Background: Self-stigma refers to the internalisation of negative societal views and stereotypes. Self-stigma has been well-characterised in the context of mental disorders such as schizophrenia but has received little attention in relation to post-traumatic stress disorder (PTSD). Objective: This work aimed to determine the prevalence of self-stigma in a sample of adults with PTSD and to establish factors associated with the internalisation of stigma in this population. Method: Participants were 194 adults (mean age 46.07 (SD = 12.39); 64.4% female; 96.6% white Caucasian; residing in the UK), who self-reported a diagnosis of PTSD and currently screened positive for the disorder according to the PTSD Checklist for DSM-5 (PCL-5). Structured interviews and validated self-report questionnaires were used to ascertain clinical and sociodemographic information for analysis. Results: The prevalence of self-stigma measured by the Internalized Stigma of Mental Illness Scale (ISMIS) was 41.2% (95% CI 34.24–48.22). There was no evidence of an association between self-stigma and gender (β = −2.975 (95% CI −7.046–1.097) p = .151), age (β = 0.007 (95% CI −0.152–0.165) p = .953), sexual trauma (β = 0.904 (95% CI −3.668–5.476) p = .697), military trauma (β = −0.571 (95% CI −4.027–7.287) p = .571). Self-stigma was associated with lower income and higher levels of anxiety (β = 5.722 (95% CI 2.922–8.522) p =

Published
2022
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4. The effect of the COVID-19 pandemic on mental health in individuals with pre-existing mental illness

Author

Katie J. S. Lewis, Catrin Lewis, Alice Roberts, Natalie A. Richards, Claudia Evison, Holly A. Pearce, Keith Lloyd, Alan Meudell, Bethan M. Edwards, Catherine A. Robinson, Rob Poole, Ann John, Jonathan I. Bisson, and Ian Jones

Subjects
COVID-19, depression, anxiety disorders, pre-existing mental illness, post-traumatic stress disorder, Psychiatry, RC435-571
Abstract

Background There is evidence that the COVID-19 pandemic has negatively affected mental health, but most studies have been conducted in the general population. Aims To identify factors associated with mental health during the COVID-19 pandemic in individuals with pre-existing mental illness. Method Participants (N = 2869, 78% women, ages 18–94 years) from a UK cohort (the National Centre for Mental Health) with a history of mental illness completed a cross-sectional online survey in June to August 2020. Mental health assessments were the GAD-7 (anxiety), PHQ-9 (depression) and WHO-5 (well-being) questionnaires, and a self-report question on whether their mental health had changed during the pandemic. Regressions examined associations between mental health outcomes and hypothesised risk factors. Secondary analyses examined associations between specific mental health diagnoses and mental health. Results A total of 60% of participants reported that mental health had worsened during the pandemic. Younger age, difficulty accessing mental health services, low income, income affected by COVID-19, worry about COVID-19, reduced sleep and increased alcohol/drug use were associated with increased depression and anxiety symptoms and reduced well-being. Feeling socially supported by friends/family/services was associated with better mental health and well-being. Participants with a history of anxiety, depression, post-traumatic stress disorder or eating disorder were more likely to report that mental health had worsened during the pandemic than individuals without a history of these diagnoses. Conclusions We identified factors associated with worse mental health during the COVID-19 pandemic in individuals with pre-existing mental illness, in addition to specific groups potentially at elevated risk of poor mental health during the pandemic.

Published
2022
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6. The reconsolidation using rewind study (RETURN): trial protocol

Author

Laurence Astill Wright, Kali Barawi, Natalie Simon, Catrin Lewis, David Muss, Neil P. Roberts, Neil J Kitchiner, and Jonathan I Bisson

Subjects
ptsd, rct, rewind technique, rewind therapy, protocol, Psychiatry, RC435-571
Abstract

Background: An increasing body of research highlights reconsolidation-based therapies as emerging treatments for post-traumatic stress disorder (PTSD). The Rewind Technique is a non-pharmacological reconsolidation-based therapy with promising early results, which now requires evaluation through an RCT. Objectives: This is a preliminary efficacy RCT to determine if the Rewind Technique is likely to be a good candidate to test against usual care in a future pragmatic efficacy RCT. Methods: 40 participants will be randomised to receive either the Rewind Technique immediately, or after an 8 week wait. The primary outcome will be PTSD symptom severity as measured by the Clinician-Administered PTSD Scale for DSM5 (CAPS-5) at 8 and 16 weeks post-randomisation. Secondary outcome measures include the PTSD Checklist (PCL-5), International Trauma Questionnaire (ITQ), Patient Health Questionnaire (PHQ-9), the General Anxiety Disorder-7 (GAD-7), Insomnia Severity Index, the Euro-Qol-5D (EQ5D-5 L), the prominence of re-experiencing specific symptoms (CAPS-5) and an intervention acceptability questionnaire to measure tolerability of the intervention. Conclusions: This study will be the first RCT to assess the Rewind Technique. Using a cross-over methodology we hope to rigorously assess the efficacy and tolerability of Rewind using pragmatic inclusion criteria. Potential challenges include participant recruitment and retention. Trial registration: ISRCTN91345822

Published
2021
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7. Pharmacological-assisted Psychotherapy for Post Traumatic Stress Disorder: a systematic review and meta-analysis

Author

Mathew D. Hoskins, Robert Sinnerton, Anna Nakamura, Jack F. G. Underwood, Alan Slater, Catrin Lewis, Neil P. Roberts, Jonathan I. Bisson, Matthew Lee, and Liam Clarke

Subjects
ptsd, pharmacological therapy, drug-assisted therapy, mdma, d-cycloserine, ssri, snri, Psychiatry, RC435-571
Abstract

Background: Pharmacological-assisted psychotherapies, using conventional and novel drug agents, are increasingly being used both in clinical and experimental research settings, respectively. Objective: To determine the efficacy of conventional and novel pharmacological-assisted psychotherapies in reducing PTSD symptom severity. Method: A systematic review and meta-analysis of randomised-controlled trials were undertaken; 21 studies were included. Results: MDMA-assisted therapy was found to statistically superior to active and inactive placebo-assisted therapy in reduction of PTSD symptoms (standardised mean difference −1.09, 95% CI −1.60 to −0.58). There was no evidence of superiority over placebo for any other intervention. Conclusions: MDMA-assisted therapy demonstrated an impressive effect size; however, it is difficult to have confidence at this stage in this intervention due to the small numbers of participants included, and more research in this area is needed. There was no evidence to support the efficacy of any other drug-assisted interventions.

Published
2021
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8. Pharmacological therapy for post-traumatic stress disorder: a systematic review and meta-analysis of monotherapy, augmentation and head-to-head approaches

Author

Mathew D. Hoskins, Jack Bridges, Robert Sinnerton, Anna Nakamura, Jack F. G. Underwood, Alan Slater, Matthew R. D. Lee, Liam Clarke, Catrin Lewis, Neil P. Roberts, and Jonathan I. Bisson

Subjects
ptsd, pharmacological therapy, medication, systematic review, meta-analysis, Psychiatry, RC435-571
Abstract

Background: Pharmacological approaches are widely used for post-traumatic stress disorder (PTSD) despite uncertainty over efficacy. Objectives: To determine the efficacy of all pharmacological approaches, including monotherapy, augmentation and head-to-head approaches (drug versus drug, drug versus psychotherapy), in reducing PTSD symptom severity. Method: A systematic review and meta-analysis of randomised controlled trials were undertaken; 115 studies were included. Results: Selective serotonin reuptake inhibitors (SSRIs) were found to be statistically superior to placebo in reduction of PTSD symptoms but the effect size was small (standardised mean difference −0.28, 95% CI −0.39 to −0.17). For individual monotherapy agents compared to placebo in two or more studies, we found small statistically significant evidence for the antidepressants fluoxetine, paroxetine, sertraline, venlafaxine and the antipsychotic quetiapine. For pharmacological augmentation, we found small statistically significant evidence for prazosin and risperidone. Conclusions: Some medications have a small positive effect on reducing PTSD symptom severity and can be considered as potential monotherapy treatments; these include fluoxetine, paroxetine, sertraline, venlafaxine and quetiapine. Two medications, prazosin and risperidone, also have a small positive effect when used to augment pharmacological monotherapy. There was no evidence of superiority for one intervention over another in the small number of head-to-head comparison studies.

Published
2021
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9. Dropout from psychological therapies for post-traumatic stress disorder (PTSD) in adults: systematic review and meta-analysis

Author

Catrin Lewis, Neil P. Roberts, Samuel Gibson, and Jonathan I. Bisson

Subjects
post-traumatic stress disorder, trauma, psychological, therapy, dropout, review, Psychiatry, RC435-571
Abstract

Background: Despite the established efficacy of psychological therapies for post-traumatic stress disorder (PTSD) there has been little systematic exploration of dropout rates. Objective: To ascertain rates of dropout across different modalities of psychological therapy for PTSD and to explore potential sources of heterogeneity. Method: A systematic review of dropout rates from randomized controlled trials (RCTs) of psychological therapies was conducted. The pooled rate of dropout from psychological therapies was estimated and reasons for heterogeneity explored using meta-regression. Results:: The pooled rate of dropout from RCTs of psychological therapies for PTSD was 16% (95% CI 14–18%). There was evidence of substantial heterogeneity across studies. We found evidence that psychological therapies with a trauma-focus were significantly associated with greater dropout. There was no evidence of greater dropout from therapies delivered in a group format; from studies that recruited participants from clinical services rather than via advertisements; that included only military personnel/veterans; that were limited to participants traumatized by sexual traumas; that included a higher proportion of female participants; or from studies with a lower proportion of participants who were university educated. Conclusions: Dropout rates from recommended psychological therapies for PTSD are high and this appears to be particularly true of interventions with a trauma focus. There is a need to further explore the reasons for dropout and to look at ways of increasing treatment retention.

Published
2020
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10. Psychological therapies for post-traumatic stress disorder in adults: systematic review and meta-analysis

Author

Catrin Lewis, Neil P. Roberts, Martin Andrew, Elise Starling, and Jonathan I. Bisson

Subjects
ptsd, systematic review, psychological therapy, Psychiatry, RC435-571
Abstract

Background: Psychological therapies are the recommended first-line treatment for post-traumatic stress disorder (PTSD). Previous systematic reviews have grouped theoretically similar interventions to determine differences between broadly distinct approaches. Consequently, we know little regarding the relative efficacy of the specific manualized therapies commonly applied to the treatment of PTSD. Objective: To determine the effect sizes of manualized therapies for PTSD. Methods: We undertook a systematic review following Cochrane Collaboration guidelines. A pre-determined definition of clinical importance was applied to the results and the quality of evidence was appraised using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. Results: 114 randomized-controlled trials (RCTs) of 8171 participants were included. There was robust evidence that the therapies broadly defined as CBT with a trauma focus (CBT-T), as well as Eye Movement Desensitization and Reprocessing (EMDR), had a clinically important effect. The manualized CBT-Ts with the strongest evidence of effect were Cognitive Processing Therapy (CPT); Cognitive Therapy (CT); and Prolonged Exposure (PE). There was also some evidence supporting CBT without a trauma focus; group CBT with a trauma focus; guided internet-based CBT; and Present Centred Therapy (PCT). There was emerging evidence for a number of other therapies. Conclusions: A recent increase in RCTs of psychological therapies for PTSD, results in a more confident recommendation of CBT-T and EMDR as the first-line treatments. Among the CBT-Ts considered by the review CPT, CT and PE should be the treatments of choice. The findings should guide evidence informed shared decision-making between patient and clinician.

Published
2020
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11. A systematic review of factors associated with outcome of psychological treatments for post-traumatic stress disorder

Author

Kali S. Barawi, Catrin Lewis, Natalie Simon, and Jonathan I. Bisson

Subjects
psychological intervention, randomized control trial, post-traumatic stress disorder, treatment outcome, Psychiatry, RC435-571
Abstract

Objective Psychological interventions for post-traumatic stress disorder (PTSD) are not always effective and can leave some individuals with enduring symptoms. Little is known about factors that are associated with better or worse treatment outcome. Our objective was to address this gap. Method We undertook a systematic review following Cochrane Collaboration Guidelines. We included 126 randomized controlled trials (RCTs) of psychological interventions for PTSD and examined factors that were associated with treatment outcome, in terms of severity of PTSD symptoms post-treatment, and recovery or remission. Results Associations were neither consistent nor strong. Two factors were associated with smaller reductions in severity of PTSD symptoms post-treatment: comorbid diagnosis of depression, and higher PTSD symptom severity at baseline assessment. Higher education, adherence to homework and experience of a more recent trauma were associated with better treatment outcome. Conclusion Identifying and understanding why certain factors are associated with treatment outcome is vital to determine which individuals are most likely to benefit from particular treatments and to develop more effective treatments in the future. There is an urgent need for consistent and standardized reporting of factors associated with treatment outcome in all clinical trials.

Published
2020
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12. Non-pharmacological and non-psychological approaches to the treatment of PTSD: results of a systematic review and meta-analyses

Author

Jonathan I. Bisson, Marieke van Gelderen, Neil P. Roberts, and Catrin Lewis

Subjects
non-pharmacological, non-psychological, systematic review, ptsd treatment, Psychiatry, RC435-571
Abstract

Background Non-pharmacological and non-psychological approaches to the treatment of post-traumatic stress disorder (PTSD) have often been excluded from systematic reviews and meta-analyses. Consequently, we know little regarding their efficacy. Objective To determine the effect sizes of non-pharmacological and non-psychological treatment approaches for PTSD. Method We undertook a systematic review and meta-analyses following Cochrane Collaboration guidelines. A pre-determined definition of clinical importance was applied to the results and the quality of evidence was appraised using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. Results 30 randomised controlled trials (RCTs) of a range of heterogeneous non-psychological and non-pharmacological interventions (28 in adults, two in children and adolescents) were included. There was emerging evidence for six different approaches (acupuncture, neurofeedback, saikokeishikankyoto (a herbal preparation), somatic experiencing, transcranial magnetic stimulation, and yoga). Conclusions Given the level of evidence available, it would be premature to offer non-pharmacological and non-psychological interventions routinely, but those with evidence of efficacy provide alternatives for people who do not respond to, do not tolerate or do not want more conventional evidence-based interventions. This review should stimulate further research in this area.

Published
2020
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13. Sleep disturbance in post-traumatic stress disorder (PTSD): a systematic review and meta-analysis of actigraphy studies

Author

Catrin Lewis, Katie Lewis, Neil Kitchiner, Samantha Isaac, Ian Jones, and Jonathan I. Bisson

Subjects
stress disorders, post-traumatic, sleep, review, actigraphy, Psychiatry, RC435-571
Abstract

Background Sleep disturbance has been described as a ‘hallmark’ symptom of posttraumatic stress disorder (PTSD). Although there are robust findings of self-reported sleep disturbance in PTSD, evidence of sleep disturbance measured using actigraphy is less certain. Objective To conduct a systematic review and meta-analysis to determine whether there are any significant differences between individuals with and without PTSD in actigraph-derived sleep measures. Method Case-control studies comparing participants with current PTSD to those without PTSD were eligible for inclusion. Sleep parameters of interest were: (1) total sleep time; (2) sleep onset latency; (3) wake after sleep onset (WASO); and (4) sleep efficiency. Data were meta-analysed as standardised mean differences (SMDs) and potential sources of heterogeneity were explored through meta-regression. Six actigraphy studies with 405 participants were included. Results There was no evidence of a statistically significant difference between those with and without PTSD in total sleep time (SMD 0.09, 95%CI −0.23 to 0.42); WASO (SMD 0.18, 95%CI −0.06 to 0.43); sleep latency (SMD 0.32, 95%CI −0.04 to 0.69); or sleep efficiency (SMD −0.28, 95%CI −0.78 to 0.21). Conclusions Further high-quality research is required to determine whether there is a true difference in sleep between those with and without PTSD.

Published
2020
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14. Active duty and ex-serving military personnel with post-traumatic stress disorder treated with psychological therapies: systematic review and meta-analysis

Author

Neil J. Kitchiner, Catrin Lewis, Neil P. Roberts, and Jonathan I. Bisson

Subjects
military personnel, post-traumatic stress disorder, psychological therapies, systematic review and meta-analysis, Psychiatry, RC435-571
Abstract

Background: Post-traumatic stress disorder (PTSD) is a major cause of morbidity amongst active duty and ex-serving military personnel. In recent years increasing efforts have been made to develop more effective treatments. Objective: To determine which psychological therapies are efficacious in treating active duty and ex-serving military personnel with post-traumatic stress disorder (PTSD). Method: A systematic review was undertaken according to Cochrane Collaboration Guidelines. The primary outcome measure was reduction in PTSD symptoms and the secondary outcome dropout. Results: Twenty-four studies with 2386 participants were included. Evidence demonstrated that CBT with a trauma focus (CBT-TF) was associated with the largest evidence of effect when compared to waitlist/usual care in reducing PTSD symptoms post treatment (10 studies; n = 524; SMD −1.22, −1.78 to −0.66). Group CBT-TF was less effective when compared to individual CBT-TF at reducing PTSD symptoms post treatment (1 study; n = 268; SMD −0.35, −0.11 to −0.59). Eye Movement Desensitization and Reprocessing (EMDR) therapy was not effective when compared to waitlist/usual care at reducing PTSD symptoms post treatment (4 studies; n = 92; SMD −0.83, −1.75 to 0.10). There was evidence of greater dropout from CBT-TF therapies compared to waitlist and Present Centred Therapy. Conclusions: The evidence, albeit limited, supports individual CBT-TF as the first-line psychological treatment of PTSD in active duty and ex-serving personnel. There is evidence for Group CBT-TF, but this is not as strong as for individual CBT-TF. EMDR cannot be recommended as a first line therapy at present and urgently requires further evaluation. Lower effect sizes than for other populations with PTSD and high levels of drop-out suggest that CBT-TF in its current formats is not optimally acceptable and further research is required to develop and evaluate more effective treatments for PTSD and complex PTSD in active duty and ex-serving military personnel.

Published
2019
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15. Pragmatic RAndomised controlled trial of a trauma-focused guided self-help Programme versus InDividual trauma-focused cognitive Behavioural therapy for post-traumatic stress disorder (RAPID): trial protocol

Author

Claire Nollett, Catrin Lewis, Neil Kitchiner, Neil Roberts, Katy Addison, Lucy Brookes-Howell, Sarah Cosgrove, Katherine Cullen, Anke Ehlers, Sarah Heke, Mark Kelson, Karina Lovell, Kim Madden, Kirsten McEwan, Rachel McNamara, Ceri Phillips, Timothy Pickles, Natalie Simon, and Jonathan Bisson

Subjects
PTSD, Post-traumatic stress disorder, RCT, Randomised controlled trial, Guided self-help, Trauma focused, Psychiatry, RC435-571
Abstract

Abstract Background There is good evidence that trauma-focused therapies for Post-Traumatic Stress Disorder are effective. However, they are not always feasible to deliver due a shortage of trained therapists and demands on the patient. An online trauma-focused Guided Self-Help (GSH) programme which could overcome these barriers has shown promise in a pilot study. This study will be the first to evaluate GSH against standard face-to-face therapy to assess its suitability for use in the NHS. Methods The study is a large-scale multi-centre pragmatic randomised controlled non-inferiority trial, with assessors masked to treatment allocation. One hundred and ninety-two participants will be randomly allocated to receive either face-to-face trauma-focused cognitive behaviour therapy (TFCBT) or trauma-focused online guided self-help (GSH). The primary outcome will be the severity of symptoms of PTSD over the previous week as measured by the Clinician Administered PTSD Scale for DSM5 (CAPS-5) at 16 weeks post-randomisation. Secondary outcome measures include PTSD symptoms over the previous month as measured by the CAPS-5 at 52 weeks plus the Impact of Event Scale – revised (IES-R), Work and Social Adjustment Scale (WSAS), Patient Health Questionnaire-9 (PHQ-9), General Anxiety Disorder-7 (GAD-7), Alcohol Use Disorders Test (AUDIT-O), Multidimensional Scale for Perceived Social Support (MSPSS), short Post-Traumatic Cognitions Inventory (PTCI), Insomnia Severity Index (ISI) and General Self Efficacy Scale (GSES) measured at 16 and 52 weeks post-randomisation. Changes in health-related quality of life will be measured by the EQ-5D and the level of healthcare resource utilisation for health economic analysis will be determined by an amended version of the Client Socio-Demographic and Service Receipt Inventory European Version. The Client Satisfaction Questionnaire (CSQ) will be collected at 16 weeks post-randomisation to evaluate treatment satisfaction. Discussion This study will be the first to compare online GSH with usual face-to-face therapy for PTSD. The strengths are that it will test a rigorously developed intervention in a real world setting to inform NHS commissioning. The potential challenges of delivering such a pragmatic study may include participant recruitment, retention and adherence, therapist retention, and fidelity of intervention delivery. Trial registration ISRCTN13697710 registered on 20/12/2016.

Published
2018
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16. Adverse Childhood Experiences, Support, and the Perception of Ability to Work in Adults with Disability.

Author

Sophia Miryam Schüssler-Fiorenza Rose, Jessica G Eslinger, Lindsey Zimmerman, Jamie Scaccia, Betty S Lai, Catrin Lewis, and Eva Alisic

Subjects
Medicine, Science
Abstract

OBJECTIVE:To examine the impact of adverse childhood experiences (ACEs) and support on self-reported work inability of adults reporting disability. PARTICIPANTS:Adults (ages 18-64) who participated in the Behavioral Risk Factor Surveillance System in 2009 or 2010 and who reported having a disability (n = 13,009). DESIGN AND MAIN OUTCOME MEASURES:The study used a retrospective cohort design with work inability as the main outcome. ACE categories included abuse (sexual, physical, emotional) and family dysfunction (domestic violence, incarceration, mental illness, substance abuse, divorce). Support included functional (perceived emotional/social support) and structural (living with another adult) support. Logistic regression was used to adjust for potential confounders (age, sex and race) and to evaluate whether there was an independent effect of ACEs on work inability after adding other important predictors (support, education, health) to the model. RESULTS:ACEs were highly prevalent with almost 75% of the sample reporting at least one ACE category and over 25% having a high ACE burden (4 or more categories). ACEs were strongly associated with functional support. Participants experiencing a high ACE burden had a higher adjusted odds ratio (OR) [95% confidence interval] of 1.9 [1.5-2.4] of work inability (reference: zero ACEs). Good functional support (adjusted OR 0.52 [0.42-0.63]) and structural support (adjusted OR 0.48 [0.41-0.56]) were protective against work inability. After adding education and health to the model, ACEs no longer appeared to have an independent effect. Structural support remained highly protective, but functional support only appeared to be protective in those with good physical health. CONCLUSIONS:ACEs are highly prevalent in working-age US adults with a disability, particularly young adults. ACEs are associated with decreased support, lower educational attainment and worse adult health. Health care providers are encouraged to screen for ACEs. Addressing the effects of ACEs on health and support, in addition to education and retraining, may increase ability to work in those with a disability.

Published
2016
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17. The Relationship of Attention-Deficit/Hyperactivity Disorder With Posttraumatic Stress Disorder

Author

Frank R. Wendt, Miguel Garcia-Argibay, Brenda Cabrera-Mendoza, Unnur A. Valdimarsdóttir, Joel Gelernter, Murray B. Stein, Michel G. Nivard, Adam X. Maihofer, Caroline M. Nievergelt, Henrik Larsson, Manuel Mattheisen, Renato Polimanti, Sandra M. Meier, Karmel W. Choi, Jonathan R.I. Coleman, Nikolaos P. Daskalakis, Christy A. Denckla, Elizabeth Ketema, Rajendra A. Morey, Andrew Ratanatharathorn, Katy Torres, Aliza P. Wingo, Clement C. Zai, Allison E. Aiello, Lynn M. Almli, Ananda B. Amstadter, Soren B. Andersen, Ole A. Andreassen, Paul A. Arbisi, Allison E. Ashley-Koch, S. Bryn Austin, Esmina Avdibegovic, Anders D. Borglum, Dragan Babic, Marie Bækvad-Hansen, Dewleen G. Baker, Jean C. Beckham, Laura J. Bierut, Jonathan I. Bisson, Marco P. Boks, Elizabeth A. Bolger, Bekh Bradley, Meghan Brashear, Gerome Breen, Richard A. Bryant, Angela C. Bustamante, Jonas Bybjerg-Grauholm, Joseph R. Calabrese, Jose Miguel Caldas-de-Almeida, Chia-Yen Chen, Anders M. Dale, Shareefa Dalvie, Jürgen Deckert, Douglas L. Delahanty, Michelle F. Dennis, Seth G. Disner, Katharina Domschke, Laramie E. Duncan, Alma Dzubur Kulenovic, Christopher R. Erbes, Alexandra Evans, Lindsay A. Farrer, Norah C. Feeny, Janine D. Flory, David Forbes, Carol E. Franz, Sandro Galea, Melanie E. Garrett, Aarti Gautam, Bizu Gelaye, Elbert Geuze, Charles F. Gillespie, Aferdita Goci Uka, Scott D. Gordon, Guia Guffanti, Rasha Hammamieh, Michael A. Hauser, Andrew C. Heath, Sian M.J. Hemmings, David Michael Hougaard, Miro Jakovljevic, Marti Jett, Eric Otto Johnson, Ian Jones, Tanja Jovanovic, Xue-Jun Qin, Karen-Inge Karstoft, Milissa L. Kaufman, Ronald C. Kessler, Alaptagin Khan, Nathan A. Kimbrel, Anthony P. King, Nastassja Koen, Henry R. Kranzler, William S. Kremen, Bruce R. Lawford, Lauren A.M. Lebois, Catrin Lewis, Israel Liberzon, Sarah D. Linnstaedt, Mark W. Logue, Adriana Lori, Bozo Lugonja, Jurjen J. Luykx, Michael J. Lyons, Jessica L. Maples-Keller, Charles Marmar, Nicholas G. Martin, Douglas Maurer, Matig R. Mavissakalian, Alexander McFarlane, Regina E. McGlinchey, Katie A. McLaughlin, Samuel A. McLean, Divya Mehta, Rebecca Mellor, Vasiliki Michopoulos, William Milberg, Mark W. Miller, Charles Phillip Morris, Ole Mors, Preben Bo Mortensen, Elliot C. Nelson, Merete Nordentoft, Sonya B. Norman, Meaghan O’Donnell, Holly K. Orcutt, Matthew S. Panizzon, Edward S. Peters, Alan L. Peterson, Matthew Peverill, Robert H. Pietrzak, Melissa A. Polusny, John P. Rice, Victoria B. Risbrough, Andrea L. Roberts, Alex O. Rothbaum, Barbara O. Rothbaum, Peter Roy-Byrne, Kenneth J. Ruggiero, Ariane Rung, Bart P.F. Rutten, Nancy L. Saccone, Sixto E. Sanchez, Dick Schijven, Soraya Seedat, Antonia V. Seligowski, Julia S. Seng, Christina M. Sheerin, Derrick Silove, Alicia K. Smith, Jordan W. Smoller, Scott R. Sponheim, Dan J. Stein, Jennifer S. Stevens, Martin H. Teicher, Wesley K. Thompson, Edward Trapido, Monica Uddin, Robert J. Ursano, Leigh Luella van den Heuvel, Miranda Van Hooff, Eric Vermetten, Christiaan Vinkers, Joanne Voisey, Yunpeng Wang, Zhewu Wang, Thomas Werge, Michelle A. Williams, Douglas E. Williamson, Sherry Winternitz, Christiane Wolf, Erika J. Wolf, Rachel Yehuda, Keith A. Young, Ross McD. Young, Hongyu Zhao, Lori A. Zoellner, Magali Haas, Heather Lasseter, Allison C. Provost, Rany M. Salem, Jonathan Sebat, Richard Shaffer, Tianying Wu, Stephan Ripke, Mark J. Daly, Kerry J. Ressler, Karestan C. Koenen, Biological Psychology, APH - Mental Health, APH - Methodology, Anatomy and neurosciences, Psychiatry, and Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep

Subjects
Genome-wide association study, Epidemiology, Siblings, PTSD, Mendelian Randomization Analysis, Comorbidities, SDG 3 - Good Health and Well-being, Humans, ADHD, Attention Deficit Disorder with Hyperactivity/epidemiology, Stress Disorders, Post-Traumatic/genetics, Biological Psychiatry, Causal inference
Abstract

Background: Attention-deficit/hyperactivity disorder (ADHD) and posttraumatic stress disorder (PTSD) are associated, but it is unclear if this is a causal relationship or confounding. We used genetic analyses and sibling comparisons to clarify the direction of this relationship. Methods: Linkage disequilibrium score regression and 2-sample Mendelian randomization were used to test for genetic correlation (r g) and bidirectional causal effects using European ancestry genome-wide association studies of ADHD (20,183 cases and 35,191 controls) and 6 PTSD definitions (up to 320,369 individuals). Several additional variables were included in the analysis to verify the independence of the ADHD-PTSD relationship. In a population-based sibling comparison (N = 2,082,118 individuals), Cox regression models were fitted to account for time at risk, a range of sociodemographic factors, and unmeasured familial confounders (via sibling comparisons). Results: ADHD and PTSD had consistent r g (r g range, 0.43–0.52; p < .001). ADHD genetic liability was causally linked with increased risk for PTSD (β = 0.367; 95% CI, 0.186–0.552; p = 7.68 × 10 −5). This result was not affected by heterogeneity, horizontal pleiotropy (Mendelian randomization Egger intercept = 4.34 × 10 −4, p = .961), or other phenotypes and was consistent across PTSD datasets. However, we found no consistent associations between PTSD genetic liability and ADHD risk. Individuals diagnosed with ADHD were at a higher risk for developing PTSD than their undiagnosed sibling (hazard ratio = 2.37; 95% CI, 1.98–3.53). Conclusions: Our findings add novel evidence supporting the need for early and effective treatment of ADHD, as patients with this diagnosis are at significantly higher risk to develop PTSD later in life.

Published
2023

18. Posttraumatic growth related to the COVID‐19 pandemic among individuals with lived experience of psychiatric disorder

Author

Catrin Lewis, Katie Lewis, Bethan Edwards, Claudia Evison, Ann John, Holly Pearce, Lawrence Raisanen, Natalie Richards, Alice Roberts, Ian Jones, and Jonathan I. Bisson

Subjects
Adult, Stress Disorders, Post-Traumatic, Psychiatry and Mental health, Clinical Psychology, Adaptation, Psychological, Humans, COVID-19, Longitudinal Studies, Posttraumatic Growth, Psychological, Pandemics
Abstract

Although the COVID-19 pandemic has been shown to be detrimental to mental health, it may hold a parallel potential for positive change. Little is known about posttraumatic growth (PTG) as a potential outcome for individuals with lived experience of psychiatric disorders following trauma exposure, especially in the context of the COVID-19 pandemic. Participants were 1,424 adults with lived experience of a psychiatric disorder who took part in a longitudinal study of mental health during the COVID-19 pandemic conducted by the National Centre for Mental Health. PTG was measured using the Posttraumatic Growth Inventory-Short Form (PTGI-SF). Factors hypothesized to be associated with PTG were investigated using linear regression. The mean participant PTGI score was 12.64 (SD = 11.01). On average, participants reported the highest scores on items related to appreciation of life and lowest on those related to spiritual change subscale. We found the strongest evidence of associations between higher levels of PTG and higher scores on assessment items related to perceived social support, B = 2.86; perceptions of the pandemic as traumatic, B = 4.89; and higher psychological well-being, B = 0.40. Taken together, we did not observe evidence of widespread PTG related to the COVID-19 pandemic among individuals with lived experiences of psychiatric disorders.

Published
2022

19. COVID‐19‐related posttraumatic stress disorder in adults with lived experience of psychiatric disorder

Author

Catrin Lewis, Katie Lewis, Alice Roberts, Claudia Evison, Bethan Edwards, Ann John, Keith Lloyd, Holly Pearce, Rob Poole, Natalie Richards, Catherine Robinson, Ian Jones, and Jonathan I. Bisson

Subjects
Adult, Stress Disorders, Post-Traumatic, Psychiatry and Mental health, Clinical Psychology, International Classification of Diseases, ICD-11, Humans, COVID-19, PTSD, Longitudinal Studies, collective trauma, Pandemics
Abstract

Background\ud Prevalence estimates of COVID-19-related posttraumatic stress disorder (PTSD) have ranged from 1% to over 60% in the general population. Individuals with lived experience of a psychiatric disorder may be particularly vulnerable to COVID-19-related PTSD but this has received inadequate attention.\ud \ud Methods\ud Participants were 1571 adults with lived experience of psychiatric disorder who took part in a longitudinal study of mental health during the COVID-19 pandemic. PTSD was assessed by the International Trauma Questionnaire (ITQ) anchored to the participant's most troubling COVID-19-related experiencevent. Factors hypothesised to be associated with traumatic stress symptoms were investigated by linear regression.\ud \ud Results\ud 40.10% of participants perceived some aspect of the pandemic as traumatic. 5.28% reported an ICD-11 PTSD qualifying COVID-19 related traumatic exposure and 0.83% met criteria for probable ICD-11 COVID-19-related PTSD. Traumatic stress symptoms were associated with younger age, lower income, lower social support, and financial worries, and lived experience of PTSD/complex PTSD. Depression and anxiety measured in June 2020 predicted traumatic stress symptoms at follow-up approximately 20 weeks later in November 2020.\ud \ud Conclusions\ud We did not find evidence of widespread COVID-19-related PTSD among individuals with lived experience of a psychiatric disorder. There is a need for future research to derive valid prevalence estimates of COVID-19-related PTSD.

Published
2022

20. Eye movement desensitization and reprocessing for the treatment and early intervention of trauma among first responders: A systematic review

Author

Heather Morris, Kostas Hatzikiriakidis, Melissa Savaglio, Jenny Dwyer, Catrin Lewis, Robyn Miller, and Helen Skouteris

Subjects
Psychotherapy, Stress Disorders, Post-Traumatic, Psychiatry and Mental health, Clinical Psychology, Treatment Outcome, Eye Movement Desensitization Reprocessing, Eye Movements, Emergency Responders, Humans
Abstract

First responders are exposed to repetitive work-related trauma and, thus, are at risk of developing posttraumatic stress disorder (PTSD). Eye-movement desensitization and reprocessing (EMDR) is a psychotherapy intervention designed to treat symptoms of posttraumatic stress. We conducted a systematic review to examine the viability of EMDR among first responders. The primary aim of this review was to identify studies that have trialed EMDR among first responders and evaluate its effectiveness in reducing trauma-related symptoms; a secondary aim was to identify whether EMDR has been used as an early intervention for this cohort and determine its effectiveness as such. Four databases were searched. Studies were included if they evaluated the extent to which EMDR was effective in alleviating symptoms stemming from work-related trauma exposure among first responders. The findings from each study were reported descriptively, and eight studies that evaluated the efficacy of EMDR in this population were included. There was substantial variation in how EMDR was implemented, particularly in the type, duration, frequency, and timing. The findings suggest that EMDR can alleviate symptoms of work-related trauma exposure among first responders; however, findings regarding early intervention were inconclusive, and a methodological quality assessment revealed that all studies were classified as being of either weak or medium quality. Although this review provides preliminary insights into the effectiveness of EMDR for first responders, the conclusions that can be drawn from the literature are limited, and the findings highlight several gaps in the literature.

Published
2022

21. Early intervention for residential out-of-home care staff using eye movement desensitization and reprocessing (EMDR)

Author

Heather Morris, Kostas Hatzikiriakidis, Jenny Dwyer, Catrin Lewis, Nick Halfpenny, Robyn Miller, and Helen Skouteris

Subjects
Clinical Psychology, Social Psychology
Abstract

Residential out-of-home care (OoHC) staff regularly experience workplace-related trauma. This may contribute to the future development of a trauma- or stressor-related disorder. Eye movement desensitization and reprocessing (EMDR) is an effective treatment for stress disorders but is largely unstudied in OoHC staff. The objective of the current study was to determine if EMDR, provided early within 3 months of an incident, reduced trauma symptom severity in OoHC staff.During a 3-year pilot study (2018-2020), a trained clinician delivered the Recent Traumatic Episode Protocol (R-TEP) and Group Traumatic Episode Protocol (G-TEP) EMDR to OoHC staff from one community service organization in Victoria, Australia. Retrospective data from the Posttraumatic Stress Disorder Checklist for DSM-5 (PCL-5) were deidentified and analyzed using descriptive statistics and analysis of variance. Due to the COVID-19 pandemic, individual EMDR (R-TEP) was provided via telehealth in 2020 in comparison with face-to-face sessions during 2018-2019.Overall, a significant decrease in PCL-5 scores was seen from baseline to follow up, and staff who received R-TEP or G-TEP experienced reductions in symptoms. Both face-to-face and online modalities showed significant reductions in PCL-5 scores. No significant differences were found between the online or face-to-face modes of delivery, suggesting both options are effective. No adverse reactions were reported among the 144 staff who participated.This study provides evidence for the efficacy of EMDR in reducing traumatic stress symptom severity for residential OoHC staff. A larger, prospective research study is needed. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Published
2022

22. Trauma exposure and co-occurring ICD-11 post-traumatic stress disorder and complex post-traumatic stress disorder in adults with lived experience of psychiatric disorder

Author

Catrin Lewis, Katie Lewis, Alice Roberts, Bethan Edwards, Claudia Evison, Ann John, Alan Meudell, Patrick Parry, Holly Pearce, Natalie Richards, Ian Jones, and Jonathan I. Bisson

Subjects
Adult, Stress Disorders, Post-Traumatic, Psychiatry and Mental health, comorbidity, International Classification of Diseases, Surveys and Questionnaires, Humans, complex post-traumatic stress disorder (CPTSD), Anxiety, post-traumatic stress disorder (PTSD), Anxiety Disorders
Abstract

Objective: To establish factors associated with ICD-11 post-traumatic stress disorder (PTSD) and complex PTSD (CPTSD) in a large sample of adults with lived experience of psychiatric disorder and examine the psychiatric burden associated with the two disorders. Methods: One thousand three hundred and five adults were recruited from the National Centre for Mental Health (NCMH) cohort. ICD-11 PTSD/CPTSD were assessed with the International Trauma Questionnaire (ITQ). Binary logistic regression was used to determine factors associated with both PTSD and CPTSD. One-way between-groups analysis of variance was conducted to examine the burden associated with the two disorders in terms of symptoms of anxiety, depression, and psychological wellbeing. For post-hoc pairwise comparisons, the Tukey HSD test was used, and the magnitude of between-group differences assessed using Cohen's d. Results: Probable ICD-11 CPTSD was more common than PTSD within the sample (PTSD 2.68%; CPTSD 12.72%). We found evidence that PTSD was associated with interpersonal trauma and household income under £20,000 a year. CPTSD was also associated with interpersonal trauma, higher rates of personality disorder, and lower rates of bipolar disorder. Those with probable-CPTSD had higher levels of current anxiety and depressive symptoms and lower psychological wellbeing in comparison to those with probable-PTSD and those with neither disorder. Conclusions: CPTSD was more prevalent than PTSD in our sample of people with lived experience of psychiatric disorder. Our findings indicate a need for routine screening for trauma histories and PTSD/CPTSD in clinical settings and a greater focus on the need for interventions to treat CPTSD.

Published
2022

23. Psychological first aid

Author

Catrin Lewis and Jonathan I. Bisson

Abstract

Psychological first aid (PFA) is a framework to address the psychosocial needs of individuals and communities in the acute aftermath of trauma. It is an evidence-informed set of principles that provides immediate support to affected individuals, with the aim of reducing distress, promoting adaptive functioning, enhancing resiliency, and mitigating the negative psychological sequalae of trauma. This chapter aims to introduce PFA and outline the core facets of the approach. The evolution of PFA will be considered alongside a summary of the research findings on which it is based. Widely used PFA frameworks will be described and discussed. Finally, the evidence base for PFA will be explored and recommendations for future research will be presented.

Published
2022

24. Associations between comorbid anxiety and sleep disturbance in people with bipolar disorder: Findings from actigraphy and subjective sleep measures

Author

Daniel J, Oakes, Holly A, Pearce, Cerian, Roberts, Phillip G, Gehrman, Catrin, Lewis, Ian, Jones, and Katie J S, Lewis

Subjects
Male, Sleep Wake Disorders, Psychiatry and Mental health, Clinical Psychology, Bipolar Disorder, Humans, Female, Anxiety, Sleep, Actigraphy, Anxiety Disorders
Abstract

Background\ud Studies show that comorbid anxiety disorders are common in people with bipolar disorder. However, little is known about whether this anxiety is associated with sleep disturbance. We investigated, in individuals with bipolar disorder, whether comorbid anxiety disorder is associated with sleep disturbance.\ud \ud Methods\ud Participants were 101 (64% female) currently euthymic individuals with a history of bipolar disorder. Sleep disturbances were assessed using self-report measures of sleep quality (Pittsburgh Sleep Quality Index, PSQI) and six weeks of sleep monitoring using actigraphy. Bipolar disorder and comorbid anxiety diagnoses were assessed using the Mini International Neuropsychiatric Interview. Multiple regression analyses examined associations between comorbid anxiety and sleep disturbance, whilst controlling for confounding covariates known to impact on sleep.\ud \ud Results\ud A comorbid anxiety disorder was associated with increased sleep disturbance as measured using the PSQI global score (B = 3.58, 95% CI 1.85–5.32, P

Published
2022

25. Enhancing Discovery of Genetic Variants for Posttraumatic Stress Disorder Through Integration of Quantitative Phenotypes and Trauma Exposure Information

Author

Alma Dzubur Kulenovic, Michael J. Lyons, Elizabeth A. Bolger, Kenneth J. Ruggiero, Zhewu Wang, Laramie E. Duncan, Bozo Lugonja, Joanne Voisey, José Miguel Caldas-de-Almeida, Regina E. McGlinchey, Laura J. Bierut, Michael A. Hauser, Jean C. Beckham, Dan J. Stein, Alexander C. McFarlane, Elbert Geuze, Victoria B. Risbrough, Douglas Maurer, Christy A. Denckla, Seth G. Disner, William P. Milberg, Erika J. Wolf, Scott R. Sponheim, Caroline M. Nievergelt, Henry R. Kranzler, Clement C. Zai, Antonia V. Seligowski, Miro Jakovljević, Katharina Domschke, Paul A. Arbisi, Thomas Werge, Vasiliki Michopoulos, Joel Gelernter, Sarah D. Linnstaedt, Nastassja Koen, Sonya B. Norman, Nicholas G. Martin, Janine D. Flory, Meghan M Brashear, Melissa A. Polusny, Nathan A. Kimbrel, Douglas L. Delahanty, Milissa L. Kaufman, Peter Roy-Byrne, Magali Haas, Monica Uddin, Matig R. Mavissakalian, William S. Kremen, Ole A. Andreassen, Marco P. Boks, Matthew S. Panizzon, Christiaan H. Vinkers, Bart P. F. Rutten, Heather Lasseter, Richard A. Shaffer, Aferdita Goci, Jessica L. Maples-Keller, Israel Liberzon, Melanie E. Garrett, Alicia K. Smith, Catrin Lewis, Dewleen G. Baker, Murray B. Stein, Xuejun Qin, Nikolaos P. Daskalakis, Sherry Winternitz, Douglas E. Williamson, Alex O. Rothbaum, David Forbes, Leigh van den Heuvel, Scott D. Gordon, Edward J. Trapido, Marti Jett, Ole Mors, Adam X. Maihofer, Christina M. Sheerin, Lori A. Zoellner, A.C. Bustamante, David M. Hougaard, Alexandra Evans, Chia-Yen Chen, Robert H. Pietrzak, Rachel Yehuda, Allison C. Provost, Matthew Peverill, Aarti Gautam, Bruce R. Lawford, Derrick Silove, Bekh Bradley, Gerome Breen, Charles F. Gillespie, Allison E. Ashley-Koch, Kerry J. Ressler, Christiane Wolf, Renato Polimanti, Jonathan Ian Bisson, Adriana Lori, Lynn M. Almli, Norah C. Feeny, Jonas Bybjerg-Grauholm, Guia Guffanti, Søren Bo Andersen, Anders D. Børglum, Elizabeth Ketema, Andrea L. Roberts, Marie Bμkvad-Hansen, Ross McD. Young, Jürgen Deckert, Jonathan Sebat, Rajendra A. Morey, P. B. Mortensen, Lindsay A. Farrer, Yunpeng Wang, Karestan C. Koenen, Joseph R. Calabrese, Bizu Gelaye, Jurjen J. Luykx, Andrew Ratanatharathorn, Charles P. Morris, S. Bryn Austin, Miranda Van Hooff, Edward S. Peters, Katie A. McLaughlin, Anthony P. King, Jonathan R. I. Coleman, Holly K. Orcutt, Keith A. Young, Samuel A. McLean, Jennifer S. Stevens, Rasha Hammamieh, Robert J. Ursano, Mark W. Miller, Allison E. Aiello, Charles R. Marmar, Esmina Avdibegović, Katy Torres, Elliot C. Nelson, Rany M. Salem, Martin H. Teicher, Rebecca Mellor, Karen-Inge Karstoft, Aliza P. Wingo, Alaptagin Khan, Michelle A. Williams, Dick Schijven, Merete Nordentoft, Ananda B. Amstadter, Shareefa Dalvie, Michelle F. Dennis, Mark J. Daly, Mark W. Logue, Soraya Seedat, Julia S. Seng, Carol E. Franz, Stephan Ripke, Karmel W. Choi, Sandro Galea, Richard A. Bryant, Ian Jones, Anders M. Dale, Wesley K. Thompson, Lauren A.M. Lebois, Sixto E. Sanchez, Ronald C. Kessler, Tanja Jovanovic, Divya Mehta, Jordan W. Smoller, Eric O. Johnson, John P. Rice, Andrew C. Heath, Nancy L. Saccone, Barbara O. Rothbaum, Alan L. Peterson, Meaghan O'Donnell, Sian M. J. Hemmings, Eric Vermetten, Dragan Babić, Hongyu Zhao, Tianying Wu, Christopher R. Erbes, Ariane Rung, NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM), Centro de Estudos de Doenças Crónicas (CEDOC), Psychiatrie & Neuropsychologie, RS: MHeNs - R3 - Neuroscience, MUMC+: MA Psychiatrie (3), Anatomy and neurosciences, Psychiatry, and Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep

Subjects
Oncology, Multivariate analysis, LD SCORE REGRESSION, Genome-wide association study, THOUSANDS, Medical and Health Sciences, Stress Disorders, Post-Traumatic, GWAS, Stress Disorders, Psychiatry, Genome-Wide Association Study / methods, Traumatic stress, PROLIFERATION, PTSD, Single Nucleotide, Biological Sciences, Post-Traumatic Stress Disorder (PTSD), Anxiety Disorders, Mental Health, Phenotype, Cohort, Polymorphism, Single Nucleotide / genetics, medicine.medical_specialty, Stress Disorders, Post-Traumatic / genetics, Quantitative trait locus, Polymorphism, Single Nucleotide, Genetic correlation, behavioral disciplines and activities, Trauma, Heritability, Internal medicine, PSYCHIATRIC GENOMICS, mental disorders, medicine, Genetics, Humans, Genetic Predisposition to Disease, Polymorphism, GENOME-WIDE ASSOCIATION, METAANALYSIS, Biological Psychiatry, Genetic association, business.industry, Prevention, Human Genome, Psychology and Cognitive Sciences, PheWAS, Brain Disorders, Post-Traumatic, RISK-FACTORS, business, Genome-Wide Association Study
Abstract

Funding Information: This work was supported by the National Institute of Mental Health / U.S. Army Medical Research and Development Command (Grant No. R01MH106595 [to CMN, IL, MBS, KJRe, and KCK], National Institutes of Health (Grant No. 5U01MH109539 to the Psychiatric Genomics Consortium ), and Brain & Behavior Research Foundation (Young Investigator Grant [to KWC]). Genotyping of samples was provided in part through the Stanley Center for Psychiatric Genetics at the Broad Institute supported by Cohen Veterans Bioscience . Statistical analyses were carried out on the LISA/Genetic Cluster Computer ( https://userinfo.surfsara.nl/systems/lisa ) hosted by SURFsara. This research has been conducted using the UK Biobank resource (Application No. 41209). This work would have not been possible without the financial support provided by Cohen Veterans Bioscience, the Stanley Center for Psychiatric Genetics at the Broad Institute, and One Mind. Funding Information: MBS has in the past 3 years received consulting income from Actelion, Acadia Pharmaceuticals, Aptinyx, Bionomics, BioXcel Therapeutics, Clexio, EmpowerPharm, GW Pharmaceuticals, Janssen, Jazz Pharmaceuticals, and Roche/Genentech and has stock options in Oxeia Biopharmaceuticals and Epivario. In the past 3 years, NPD has held a part-time paid position at Cohen Veterans Bioscience, has been a consultant for Sunovion Pharmaceuticals, and is on the scientific advisory board for Sentio Solutions for unrelated work. In the past 3 years, KJRe has been a consultant for Datastat, Inc., RallyPoint Networks, Inc., Sage Pharmaceuticals, and Takeda. JLM-K has received funding and a speaking fee from COMPASS Pathways. MU has been a consultant for System Analytic. HRK is a member of the Dicerna scientific advisory board and a member of the American Society of Clinical Psychopharmacology Alcohol Clinical Trials Initiative, which during the past 3 years was supported by Alkermes, Amygdala Neurosciences, Arbor Pharmaceuticals, Dicerna, Ethypharm, Indivior, Lundbeck, Mitsubishi, and Otsuka. HRK and JG are named as inventors on Patent Cooperative Treaty patent application number 15/878,640, entitled “Genotype-guided dosing of opioid agonists,” filed January 24, 2018. RP and JG are paid for their editorial work on the journal Complex Psychiatry. OAA is a consultant to HealthLytix. All other authors report no biomedical financial interests or potential conflicts of interest. Funding Information: This work was supported by the National Institute of Mental Health/ U.S. Army Medical Research and Development Command (Grant No. R01MH106595 [to CMN, IL, MBS, KJRe, and KCK], National Institutes of Health (Grant No. 5U01MH109539 to the Psychiatric Genomics Consortium), and Brain & Behavior Research Foundation (Young Investigator Grant [to KWC]). Genotyping of samples was provided in part through the Stanley Center for Psychiatric Genetics at the Broad Institute supported by Cohen Veterans Bioscience. Statistical analyses were carried out on the LISA/Genetic Cluster Computer (https://userinfo.surfsara.nl/systems/lisa) hosted by SURFsara. This research has been conducted using the UK Biobank resource (Application No. 41209). This work would have not been possible without the financial support provided by Cohen Veterans Bioscience, the Stanley Center for Psychiatric Genetics at the Broad Institute, and One Mind. This material has been reviewed by the Walter Reed Army Institute of Research. There is no objection to its presentation and/or publication. The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting true views of the U.S. Department of the Army or the Department of Defense. We thank the investigators who comprise the PGC-PTSD working group and especially the more than 206,000 research participants worldwide who shared their life experiences and biological samples with PGC-PTSD investigators. We thank Mark Zervas for his critical input. Full acknowledgments are in Supplement 1. MBS has in the past 3 years received consulting income from Actelion, Acadia Pharmaceuticals, Aptinyx, Bionomics, BioXcel Therapeutics, Clexio, EmpowerPharm, GW Pharmaceuticals, Janssen, Jazz Pharmaceuticals, and Roche/Genentech and has stock options in Oxeia Biopharmaceuticals and Epivario. In the past 3 years, NPD has held a part-time paid position at Cohen Veterans Bioscience, has been a consultant for Sunovion Pharmaceuticals, and is on the scientific advisory board for Sentio Solutions for unrelated work. In the past 3 years, KJRe has been a consultant for Datastat, Inc. RallyPoint Networks, Inc. Sage Pharmaceuticals, and Takeda. JLM-K has received funding and a speaking fee from COMPASS Pathways. MU has been a consultant for System Analytic. HRK is a member of the Dicerna scientific advisory board and a member of the American Society of Clinical Psychopharmacology Alcohol Clinical Trials Initiative, which during the past 3 years was supported by Alkermes, Amygdala Neurosciences, Arbor Pharmaceuticals, Dicerna, Ethypharm, Indivior, Lundbeck, Mitsubishi, and Otsuka. HRK and JG are named as inventors on Patent Cooperative Treaty patent application number 15/878,640, entitled ?Genotype-guided dosing of opioid agonists,? filed January 24, 2018. RP and JG are paid for their editorial work on the journal Complex Psychiatry. OAA is a consultant to HealthLytix. All other authors report no biomedical financial interests or potential conflicts of interest. Publisher Copyright: © 2021 Society of Biological Psychiatry Background: Posttraumatic stress disorder (PTSD) is heritable and a potential consequence of exposure to traumatic stress. Evidence suggests that a quantitative approach to PTSD phenotype measurement and incorporation of lifetime trauma exposure (LTE) information could enhance the discovery power of PTSD genome-wide association studies (GWASs). Methods: A GWAS on PTSD symptoms was performed in 51 cohorts followed by a fixed-effects meta-analysis (N = 182,199 European ancestry participants). A GWAS of LTE burden was performed in the UK Biobank cohort (N = 132,988). Genetic correlations were evaluated with linkage disequilibrium score regression. Multivariate analysis was performed using Multi-Trait Analysis of GWAS. Functional mapping and annotation of leading loci was performed with FUMA. Replication was evaluated using the Million Veteran Program GWAS of PTSD total symptoms. Results: GWASs of PTSD symptoms and LTE burden identified 5 and 6 independent genome-wide significant loci, respectively. There was a 72% genetic correlation between PTSD and LTE. PTSD and LTE showed largely similar patterns of genetic correlation with other traits, albeit with some distinctions. Adjusting PTSD for LTE reduced PTSD heritability by 31%. Multivariate analysis of PTSD and LTE increased the effective sample size of the PTSD GWAS by 20% and identified 4 additional loci. Four of these 9 PTSD loci were independently replicated in the Million Veteran Program. Conclusions: Through using a quantitative trait measure of PTSD, we identified novel risk loci not previously identified using prior case-control analyses. PTSD and LTE have a high genetic overlap that can be leveraged to increase discovery power through multivariate methods. publishersversion published

Published
2022

26. Rare copy number variation in posttraumatic stress disorder

Author

Adam X, Maihofer, Worrawat, Engchuan, Guillaume, Huguet, Marieke, Klein, Jeffrey R, MacDonald, Omar, Shanta, Bhooma, Thiruvahindrapuram, Martineau, Jean-Louis, Zohra, Saci, Sebastien, Jacquemont, Stephen W, Scherer, Elizabeth, Ketema, Allison E, Aiello, Ananda B, Amstadter, Esmina, Avdibegović, Dragan, Babic, Dewleen G, Baker, Jonathan I, Bisson, Marco P, Boks, Elizabeth A, Bolger, Richard A, Bryant, Angela C, Bustamante, Jose Miguel, Caldas-de-Almeida, Graça, Cardoso, Jurgen, Deckert, Douglas L, Delahanty, Katharina, Domschke, Boadie W, Dunlop, Alma, Dzubur-Kulenovic, Alexandra, Evans, Norah C, Feeny, Carol E, Franz, Aarti, Gautam, Elbert, Geuze, Aferdita, Goci, Rasha, Hammamieh, Miro, Jakovljevic, Marti, Jett, Ian, Jones, Milissa L, Kaufman, Ronald C, Kessler, Anthony P, King, William S, Kremen, Bruce R, Lawford, Lauren A M, Lebois, Catrin, Lewis, Israel, Liberzon, Sarah D, Linnstaedt, Bozo, Lugonja, Jurjen J, Luykx, Michael J, Lyons, Matig R, Mavissakalian, Katie A, McLaughlin, Samuel A, McLean, Divya, Mehta, Rebecca, Mellor, Charles Phillip, Morris, Seid, Muhie, Holly K, Orcutt, Matthew, Peverill, Andrew, Ratanatharathorn, Victoria B, Risbrough, Albert, Rizzo, Andrea L, Roberts, Alex O, Rothbaum, Barbara O, Rothbaum, Peter, Roy-Byrne, Kenneth J, Ruggiero, Bart P F, Rutten, Dick, Schijven, Julia S, Seng, Christina M, Sheerin, Michael A, Sorenson, Martin H, Teicher, Monica, Uddin, Robert J, Ursano, Christiaan H, Vinkers, Joanne, Voisey, Heike, Weber, Sherry, Winternitz, Miguel, Xavier, Ruoting, Yang, Ross, McD Young, Lori A, Zoellner, Rany M, Salem, Richard A, Shaffer, Tianying, Wu, Kerry J, Ressler, Murray B, Stein, Karestan C, Koenen, Jonathan, Sebat, Caroline M, Nievergelt, MUMC+: MA Psychiatrie (3), Psychiatrie & Neuropsychologie, RS: MHeNs - R3 - Neuroscience, Anatomy and neurosciences, Psychiatry, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, APH - Mental Health, Centro de Estudos de Doenças Crónicas (CEDOC), and NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)

Subjects
Stress Disorders, Post-Traumatic, Cellular and Molecular Neuroscience, Psychiatry and Mental health, Genome, SDG 3 - Good Health and Well-being, DNA Copy Number Variations, Humans, Brain, Genetic Predisposition to Disease, Molecular Biology, Polymorphism, Single Nucleotide, Genome-Wide Association Study
Abstract

Funding Information: This work was supported by the National Institute of Mental Health/U.S. Army Medical Research and Development Command (Grant No. R01MH106595 [to CMN, MBS, KJRe, and KCK]), and National Institutes of Health (Grant No. 5U01MH109539 [to the Psychiatric Genomics Consortium] and Grant No. U19 MH069056 [to BWD])). Financial support for the PTSD PGC was provided by the Cohen Veterans Bioscience, Stanley Center for Psychiatric Research at the Broad Institute, and One Mind. Genotyping of samples was provided in part through the Stanley Center for Psychiatric Genetics at the Broad Institute supported by Cohen Veterans Bioscience Statistical analyses were carried out on the LISA/Genetic Cluster Computer ( https://userinfo.surfsara.nl/systems/lisa ) hosted by SURFsara. This research has been conducted using the UK Biobank resource (Application No. 41209). Posttraumatic stress disorder (PTSD) is a heritable (h2 = 24–71%) psychiatric illness. Copy number variation (CNV) is a form of rare genetic variation that has been implicated in the etiology of psychiatric disorders, but no large-scale investigation of CNV in PTSD has been performed. We present an association study of CNV burden and PTSD symptoms in a sample of 114,383 participants (13,036 cases and 101,347 controls) of European ancestry. CNVs were called using two calling algorithms and intersected to a consensus set. Quality control was performed to remove strong outlier samples. CNVs were examined for association with PTSD within each cohort using linear or logistic regression analysis adjusted for population structure and CNV quality metrics, then inverse variance weighted meta-analyzed across cohorts. We examined the genome-wide total span of CNVs, enrichment of CNVs within specified gene-sets, and CNVs overlapping individual genes and implicated neurodevelopmental regions. The total distance covered by deletions crossing over known neurodevelopmental CNV regions was significant (beta = 0.029, SE = 0.005, P = 6.3 × 10−8). The genome-wide neurodevelopmental CNV burden identified explains 0.034% of the variation in PTSD symptoms. The 15q11.2 BP1-BP2 microdeletion region was significantly associated with PTSD (beta = 0.0206, SE = 0.0056, P = 0.0002). No individual significant genes interrupted by CNV were identified. 22 gene pathways related to the function of the nervous system and brain were significant in pathway analysis (FDR q < 0.05), but these associations were not significant once NDD regions were removed. A larger sample size, better detection methods, and annotated resources of CNV are needed to explore this relationship further. publishersversion published

Published
2022

27. Managing the risk of post-traumatic stress disorder (PTSD): best practice for prevention, detection and treatment

Author

Catrin Lewis and Jonathan I. Bisson

Subjects
Stress Disorders, Post-Traumatic, Psychiatry and Mental health, mental disorders, Humans, behavioral disciplines and activities
Abstract

In this issue, Bonde and colleagues1 present a comprehensive systematic review of the time course of symptoms in post-traumatic stress disorder (PTSD) with delayed expression. Finding that in most cases PTSD is preceded by traumatic stress symptoms during the first year, they conclude a need to monitor traumatic stress symptoms after trauma exposure to identify those at risk of developing PTSD. This work draws attention to the prevalence of traumatic stress symptoms after trauma exposure, as well as indicating the potential to identify those likely to develop PTSD at a later point in time based on earlier symptoms. This indicates the value of revisiting what we know about best practice in managing the risk of PTSD.

Published
2022

28. Guided, internet based, cognitive behavioural therapy for post-traumatic stress disorder: pragmatic, multicentre, randomised controlled non-inferiority trial (RAPID)

Author

Jonathan I Bisson, Cono Ariti, Katherine Cullen, Neil Kitchiner, Catrin Lewis, Neil P Roberts, Natalie Simon, Kim Smallman, Katy Addison, Vicky Bell, Lucy Brookes-Howell, Sarah Cosgrove, Anke Ehlers, Deborah Fitzsimmons, Paula Foscarini-Craggs, Shaun R S Harris, Mark Kelson, Karina Lovell, Maureen McKenna, Rachel McNamara, Claire Nollett, Tim Pickles, and Rhys Williams-Thomas

Subjects
Adult, Stress Disorders, Post-Traumatic, Internet, Treatment Outcome, Cognitive Behavioral Therapy, Humans, General Medicine, Anxiety, Anxiety Disorders
Abstract

ObjectiveTo determine if guided internet based cognitive behavioural therapy with a trauma focus (CBT-TF) is non-inferior to individual face-to-face CBT-TF for mild to moderate post-traumatic stress disorder (PTSD) to one traumatic event.DesignPragmatic, multicentre, randomised controlled non-inferiority trial (RAPID).SettingPrimary and secondary mental health settings across the UK’s NHS.Participants196 adults with a primary diagnosis of mild to moderate PTSD were randomised in a 1:1 ratio to one of two interventions, with 82% retention at 16 weeks and 71% retention at 52 weeks. 19 participants and 10 therapists were purposively sampled and interviewed for evaluation of the process.InterventionsUp to 12 face-to-face, manual based, individual CBT-TF sessions, each lasting 60-90 minutes; or guided internet based CBT-TF with an eight step online programme, with up to three hours of contact with a therapist and four brief telephone calls or email contacts between sessions.Main outcome measuresPrimary outcome was the Clinician Administered PTSD Scale for DSM-5 (CAPS-5) at 16 weeks after randomisation (diagnosis of PTSD based on the criteria of theDiagnostic and Statistical Manual of Mental Disorders, fifth edition, DSM-5). Secondary outcomes included severity of PTSD symptoms at 52 weeks, and functioning, symptoms of depression and anxiety, use of alcohol, and perceived social support at 16 and 52 weeks after randomisation.ResultsNon-inferiority was found at the primary endpoint of 16 weeks on the CAPS-5 (mean difference 1.01, one sided 95% confidence interval −∞ to 3.90, non-inferiority P=0.012). Improvements in CAPS-5 score of more than 60% in the two groups were maintained at 52 weeks, but the non-inferiority results were inconclusive in favour of face-to-face CBT-TF at this time point (3.20, −∞ to 6.00, P=0.15). Guided internet based CBT-TF was significantly (PConclusionsGuided internet based CBT-TF for mild to moderate PTSD to one traumatic event was non-inferior to individual face-to-face CBT-TF and should be considered a first line treatment for people with this condition.Trial registrationISRCTN13697710.

Published
2022

29. Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors

Author

Niamh Mullins, JooEun Kang, Adrian I. Campos, Jonathan R.I. Coleman, Alexis C. Edwards, Hanga Galfalvy, Daniel F. Levey, Adriana Lori, Andrey Shabalin, Anna Starnawska, Mei-Hsin Su, Hunna J. Watson, Mark Adams, Swapnil Awasthi, Michael Gandal, Jonathan D. Hafferty, Akitoyo Hishimoto, Minsoo Kim, Satoshi Okazaki, Ikuo Otsuka, Stephan Ripke, Erin B. Ware, Andrew W. Bergen, Wade H. Berrettini, Martin Bohus, Harry Brandt, Xiao Chang, Wei J. Chen, Hsi-Chung Chen, Steven Crawford, Scott Crow, Emily DiBlasi, Philibert Duriez, Fernando Fernández-Aranda, Manfred M. Fichter, Steven Gallinger, Stephen J. Glatt, Philip Gorwood, Yiran Guo, Hakon Hakonarson, Katherine A. Halmi, Hai-Gwo Hwu, Sonia Jain, Stéphane Jamain, Susana Jiménez-Murcia, Craig Johnson, Allan S. Kaplan, Walter H. Kaye, Pamela K. Keel, James L. Kennedy, Kelly L. Klump, Dong Li, Shih-Cheng Liao, Klaus Lieb, Lisa Lilenfeld, Chih-Min Liu, Pierre J. Magistretti, Christian R. Marshall, James E. Mitchell, Eric T. Monson, Richard M. Myers, Dalila Pinto, Abigail Powers, Nicolas Ramoz, Stefan Roepke, Vsevolod Rozanov, Stephen W. Scherer, Christian Schmahl, Marcus Sokolowski, Michael Strober, Laura M. Thornton, Janet Treasure, Ming T. Tsuang, Stephanie H. Witt, D. Blake Woodside, Zeynep Yilmaz, Lea Zillich, Rolf Adolfsson, Ingrid Agartz, Tracy M. Air, Martin Alda, Lars Alfredsson, Ole A. Andreassen, Adebayo Anjorin, Vivek Appadurai, María Soler Artigas, Sandra Van der Auwera, M. Helena Azevedo, Nicholas Bass, Claiton H.D. Bau, Bernhard T. Baune, Frank Bellivier, Klaus Berger, Joanna M. Biernacka, Tim B. Bigdeli, Elisabeth B. Binder, Michael Boehnke, Marco P. Boks, Rosa Bosch, David L. Braff, Richard Bryant, Monika Budde, Enda M. Byrne, Wiepke Cahn, Miguel Casas, Enrique Castelao, Jorge A. Cervilla, Boris Chaumette, Sven Cichon, Aiden Corvin, Nicholas Craddock, David Craig, Franziska Degenhardt, Srdjan Djurovic, Howard J. Edenberg, Ayman H. Fanous, Jerome C. Foo, Andreas J. Forstner, Mark Frye, Janice M. Fullerton, Justine M. Gatt, Pablo V. Gejman, Ina Giegling, Hans J. Grabe, Melissa J. Green, Eugenio H. Grevet, Maria Grigoroiu-Serbanescu, Blanca Gutierrez, Jose Guzman-Parra, Steven P. Hamilton, Marian L. Hamshere, Annette Hartmann, Joanna Hauser, Stefanie Heilmann-Heimbach, Per Hoffmann, Marcus Ising, Ian Jones, Lisa A. Jones, Lina Jonsson, René S. Kahn, John R. Kelsoe, Kenneth S. Kendler, Stefan Kloiber, Karestan C. Koenen, Manolis Kogevinas, Bettina Konte, Marie-Odile Krebs, Mikael Landén, Jacob Lawrence, Marion Leboyer, Phil H. Lee, Douglas F. Levinson, Calwing Liao, Jolanta Lissowska, Susanne Lucae, Fermin Mayoral, Susan L. McElroy, Patrick McGrath, Peter McGuffin, Andrew McQuillin, Sarah E. Medland, Divya Mehta, Ingrid Melle, Yuri Milaneschi, Philip B. Mitchell, Esther Molina, Gunnar Morken, Preben Bo Mortensen, Bertram Müller-Myhsok, Caroline Nievergelt, Vishwajit Nimgaonkar, Markus M. Nöthen, Michael C. O’Donovan, Roel A. Ophoff, Michael J. Owen, Carlos Pato, Michele T. Pato, Brenda W.J.H. Penninx, Jonathan Pimm, Giorgio Pistis, James B. Potash, Robert A. Power, Martin Preisig, Digby Quested, Josep Antoni Ramos-Quiroga, Andreas Reif, Marta Ribasés, Vanesa Richarte, Marcella Rietschel, Margarita Rivera, Andrea Roberts, Gloria Roberts, Guy A. Rouleau, Diego L. Rovaris, Dan Rujescu, Cristina Sánchez-Mora, Alan R. Sanders, Peter R. Schofield, Thomas G. Schulze, Laura J. Scott, Alessandro Serretti, Jianxin Shi, Stanley I. Shyn, Lea Sirignano, Pamela Sklar, Olav B. Smeland, Jordan W. Smoller, Edmund J.S. Sonuga-Barke, Gianfranco Spalletta, John S. Strauss, Beata Świątkowska, Maciej Trzaskowski, Gustavo Turecki, Laura Vilar-Ribó, John B. Vincent, Henry Völzke, James T.R. Walters, Cynthia Shannon Weickert, Thomas W. Weickert, Myrna M. Weissman, Leanne M. Williams, Naomi R. Wray, Clement C. Zai, Allison E. Ashley-Koch, Jean C. Beckham, Elizabeth R. Hauser, Michael A. Hauser, Nathan A. Kimbrel, Jennifer H. Lindquist, Benjamin McMahon, David W. Oslin, Xuejun Qin, Esben Agerbo, Anders D. Børglum, Gerome Breen, Annette Erlangsen, Tõnu Esko, Joel Gelernter, David M. Hougaard, Ronald C. Kessler, Henry R. Kranzler, Qingqin S. Li, Nicholas G. Martin, Andrew M. McIntosh, Ole Mors, Merete Nordentoft, Catherine M. Olsen, David Porteous, Robert J. Ursano, Danuta Wasserman, Thomas Werge, David C. Whiteman, Cynthia M. Bulik, Hilary Coon, Ditte Demontis, Anna R. Docherty, Po-Hsiu Kuo, Cathryn M. Lewis, J. John Mann, Miguel E. Rentería, Daniel J. Smith, Eli A. Stahl, Murray B. Stein, Fabian Streit, Virginia Willour, Douglas M. Ruderfer, Manuel Mattheisen, Abdel Abdellaoui, Mark J. Adams, Till F.M. Andlauer, Silviu-Alin Bacanu, Marie Bækvad-Hansen, Aartjan T.F. Beekman, Julien Bryois, Henriette N. Buttenschøn, Jonas Bybjerg-Grauholm, Na Cai, Jane Hvarregaard Christensen, Toni-Kim Clarke, Lucía Colodro-Conde, Baptiste Couvy-Duchesne, Nick Craddock, Gregory E. Crawford, Gail Davies, Eske M. Derks, Nese Direk, Conor V. Dolan, Erin C. Dunn, Thalia C. Eley, Valentina Escott-Price, Farnush Farhadi Hassan Kiadeh, Hilary K. Finucane, Josef Frank, Héléna A. Gaspar, Michael Gill, Fernando S. Goes, Scott D. Gordon, Shantel Marie Weinsheimer, Jürgen Wellmann, Gonneke Willemsen, Yang Wu, Hualin S. Xi, Jian Yang, Futao Zhang, Volker Arolt, Dorret I. Boomsma, Udo Dannlowski, E.J.C. de Geus, J. Raymond Depaulo, Enrico Domenici, Katharina Domschke, Jakob Grove, Lynsey S. Hall, Christine Søholm Hansen, Thomas F. Hansen, Stefan Herms, Ian B. Hickie, Georg Homuth, Carsten Horn, Jouke-Jan Hottenga, David M. Howard, Rick Jansen, Eric Jorgenson, James A. Knowles, Isaac S. Kohane, Julia Kraft, Warren W. Kretzschmar, Zoltán Kutalik, Yihan Li, Penelope A. Lind, Donald J. MacIntyre, Dean F. MacKinnon, Robert M. Maier, Wolfgang Maier, Jonathan Marchini, Hamdi Mbarek, Christel M. Middeldorp, Evelin Mihailov, Lili Milani, Francis M. Mondimore, Grant W. Montgomery, Sara Mostafavi, Matthias Nauck, Bernard Ng, Michel G. Nivard, Dale R. Nyholt, Paul F. O’Reilly, Hogni Oskarsson, Caroline Hayward, Andrew C. Heath, Glyn Lewis, Pamela A.F. Madden, Patrik K. Magnusson, Andres Metspalu, Sara A. Paciga, Nancy L. Pedersen, Jodie N. Painter, Carsten Bøcker Pedersen, Marianne Giørtz Pedersen, Roseann E. Peterson, Wouter J. Peyrot, Danielle Posthuma, Jorge A. Quiroz, Per Qvist, John P. Rice, Brien P. Riley, Saira Saeed Mirza, Robert Schoevers, Eva C. Schulte, Ling Shen, Engilbert Sigurdsson, Grant C.B. Sinnamon, Johannes H. Smit, Hreinn Stefansson, Stacy Steinberg, Jana Strohmaier, Katherine E. Tansey, Henning Teismann, Alexander Teumer, Wesley Thompson, Pippa A. Thomson, Thorgeir E. Thorgeirsson, Matthew Traylor, Jens Treutlein, Vassily Trubetskoy, André G. Uitterlinden, Daniel Umbricht, Albert M. van Hemert, Alexander Viktorin, Peter M. Visscher, Yunpeng Wang, Bradley T. Webb, Roy H. Perlis, David J. Porteous, Catherine Schaefer, Kari Stefansson, Henning Tiemeier, Rudolf Uher, Patrick F. Sullivan, Kevin S. O’Connell, Brandon Coombes, Zhen Qiao, Thomas D. Als, Sigrid Børte, Alexander W. Charney, Ole Kristian Drange, Michael J. Gandal, Saskia P. Hagenaars, Masashi Ikeda, Nolan Kamitaki, Kristi Krebs, Georgia Panagiotaropoulou, Brian M. Schilder, Laura G. Sloofman, Bendik S. Winsvold, Hong-Hee Won, Liliya Abramova, Kristina Adorjan, Mariam Al Eissa, Diego Albani, Ney Alliey-Rodriguez, Verneri Antilla, Anastasia Antoniou, Ji Hyun Baek, Michael Bauer, Eva C. Beins, Sarah E. Bergen, Armin Birner, Erlend Bøen, Murielle Brum, Ben M. Brumpton, Nathalie Brunkhorst-Kanaan, William Byerley, Murray Cairns, Miquel Casas, Pablo Cervantes, Cristiana Cruceanu, Alfredo Cuellar-Barboza, Julie Cunningham, David Curtis, Piotr M. Czerski, Anders M. Dale, Nina Dalkner, Friederike S. David, Amanda L. Dobbyn, Athanassios Douzenis, Torbjørn Elvsåshagen, I. Nicol Ferrier, Alessia Fiorentino, Tatiana M. Foroud, Liz Forty, Oleksandr Frei, Nelson B. Freimer, Louise Frisén, Katrin Gade, Julie Garnham, Ian R. Gizer, Katherine Gordon-Smith, Tiffany A. Greenwood, José Guzman-Parra, Kyooseob Ha, Magnus Haraldsson, Martin Hautzinger, Urs Heilbronner, Dennis Hellgren, Peter A. Holmans, Laura Huckins, Jessica S. Johnson, Janos L. Kalman, Yoichiro Kamatani, Sarah Kittel-Schneider, Maria Koromina, Thorsten M. Kranz, Michiaki Kubo, Ralph Kupka, Steven A. Kushner, Catharina Lavebratt, Markus Leber, Heon-Jeong Lee, Shawn E. Levy, Catrin Lewis, Martin Lundberg, Sigurdur H. Magnusson, Adam Maihofer, Dolores Malaspina, Eirini Maratou, Lina Martinsson, Nathaniel W. McGregor, James D. McKay, Helena Medeiros, Vincent Millischer, Jennifer L. Moran, Derek W. Morris, Thomas W. Mühleisen, Niamh O’Brien, Claire O’Donovan, Loes M. Olde Loohuis, Lilijana Oruc, Sergi Papiol, Antonio F. Pardiñas, Amy Perry, Andrea Pfennig, Evgenia Porichi, Towfique Raj, Mark H. Rapaport, J. Raymond DePaulo, Eline J. Regeer, Fabio Rivas, Julian Roth, Panos Roussos, Fanny Senner, Sally Sharp, Paul D. Shilling, Claire Slaney, Janet L. Sobell, Maria Soler Artigas, Anne T. Spijker, Dan J. Stein, Chikashi Terao, Claudio Toma, Paul Tooney, Evangelia-Eirini Tsermpini, Marquis P. Vawter, Helmut Vedder, Simon Xi, Wei Xu, Jessica Mei Kay Yang, Allan H. Young, Hannah Young, Peter P. Zandi, Hang Zhou, null HUNT All-In Psychiatry, Gulja Babadjanova, Lena Backlund, Susanne Bengesser, Douglas H.R. Blackwood, Vaughan J. Carr, Stanley Catts, Dimitris Dikeos, Bruno Etain, Panagiotis Ferentinos, Micha Gawlik, Elliot S. Gershon, Frans Henskens, Jan Hillert, Kyung Sue Hong, Christina M. Hultman, Kristian Hveem, Nakao Iwata, Assen V. Jablensky, George Kirov, Christine Lochner, Carmel Loughland, Carol A. Mathews, Francis J. McMahon, Patricia Michie, Bryan Mowry, Benjamin M. Neale, Caroline M. Nievergelt, Ketil J. Oedegaard, Tomas Olsson, Chris Pantelis, George P. Patrinos, Eva Z. Reininghaus, Takeo Saito, Ulrich Schall, Martin Schalling, Rodney J. Scott, Eystein Stordal, Arne E. Vaaler, Eduard Vieta, Irwin D. Waldman, John-Anker Zwart, John I. Nurnberger, Arianna Di Florio, Roger A.H. Adan, Tetsuya Ando, Harald Aschauer, Jessica H. Baker, Vladimir Bencko, Andreas Birgegård, Joseph M. Boden, Ilka Boehm, Claudette Boni, Vesna Boraska Perica, Katharina Buehren, Roland Burghardt, Laura Carlberg, Matteo Cassina, Maurizio Clementi, Roger D. Cone, Philippe Courtet, James J. Crowley, Unna N. Danner, Oliver S.P. Davis, Martina de Zwaan, George Dedoussis, Daniela Degortes, Janiece E. DeSocio, Danielle M. Dick, Christian Dina, Monika Dmitrzak-Weglarz, Elisa Docampo Martinez, Laramie E. Duncan, Karin Egberts, Morten Mattingsdal, Sara McDevitt, Ingrid Meulenbelt, Nadia Micali, James Mitchell, Karen Mitchell, Palmiero Monteleone, Alessio Maria Monteleone, Melissa A. Munn-Chernoff, Benedetta Nacmias, Marie Navratilova, Ioanna Ntalla, Julie K. O’Toole, Leonid Padyukov, Aarno Palotie, Jacques Pantel, Hana Papezova, Richard Parker, John F. 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A., Keski-Rahkonen, A., Kiezebrink, K., Kim, Y. -R., Kirk, K. M., Klareskog, L., Knudsen, G. P. S., Larsen, J. T., Le Hellard, S., Leppa, V. M., Lichtenstein, P., Lin, B. D., Lundervold, A., Luykx, J., Maj, M., Mannik, K., Marsal, S., Stuber, G. D., Szatkiewicz, J. P., Tachmazidou, I., Tenconi, E., Tortorella, A., Tozzi, F., Tsitsika, A., Tyszkiewicz-Nwafor, M., Tziouvas, K., van Elburg, A. A., van Furth, E. F., Wade, T. D., Wagner, G., Walton, E., Whiteman, D. C., Wichmann, H. E., Widen, E., Yao, S., Zeggini, E., Zerwas, S., Zipfel, S., Jungkunz, M., Dietl, L., Schwarze, C. E., Dahmen, N., Schott, B. H., Mobascher, A., Crivelli, S., Dennis, M. F., Harvey, P. D., Carter, B. W., Huffman, J. E., Jacobson, D., Madduri, R., Olsen, M. K., Pestian, J., Gaziano, J. M., Muralidhar, S., Ramoni, R., Beckham, J., Chang, K. -M., O'Donnell, C. J., Tsao, P. S., Breeling, J., Huang, G., Romero, J. P. C., Moser, J., Whitbourne, S. B., Brewer, J. V., Aslan, M., Connor, T., Argyres, D. P., Stephens, B., Brophy, M. T., Humphries, D. E., Selva, L. E., Do, N., Shayan, S., Cho, K., Pyarajan, S., Hauser, E., Sun, Y., Zhao, H., Wilson, P., Mcardle, R., Dellitalia, L., Mattocks, K., Harley, J., Zablocki, C. J., Whittle, J., Jacono, F., Gutierrez, S., Gibson, G., Hammer, K., Kaminsky, L., Villareal, G., Kinlay, S., Xu, J., Hamner, M., Mathew, R., Bhushan, S., Iruvanti, P., Godschalk, M., Ballas, Z., Ivins, D., Mastorides, S., Moorman, J., Gappy, S., Klein, J., Ratcliffe, N., Florez, H., Okusaga, O., Murdoch, M., Sriram, P., Yeh, S. S., Tandon, N., Jhala, D., Aguayo, S., Cohen, D., Sharma, S., Liangpunsakul, S., Oursler, K. A., Whooley, M., Ahuja, S., Constans, J., Meyer, P., Greco, J., Rauchman, M., Servatius, R., Gaddy, M., Wallbom, A., Morgan, T., Stapley, T., Sherman, S., Ross, G., Tsao, P., Strollo, P., Boyko, E., Meyer, L., Gupta, S., Huq, M., Fayad, J., Hung, A., Lichy, J., Hurley, R., Robey, B., Striker, R., Erlangsen, A., Kessler, R. C., Porteous, D., Ursano, R. J., Wasserman, D., Coon, H., Demontis, D., Docherty, A. R., Kuo, P. -H., Mann, J. J., Renteria, M. E., Stein, M. B., Willour, V., Psychiatry, Biological Psychology, APH - Methodology, APH - Mental Health, APH - Health Behaviors & Chronic Diseases, AMS - Sports, AMS - Ageing & Vitality, APH - Personalized Medicine, Amsterdam Neuroscience - Complex Trait Genetics, Complex Trait Genetics, Institute for Molecular Medicine Finland, Centre of Excellence in Complex Disease Genetics, Aarno Palotie / Principal Investigator, Genomics of Neurological and Neuropsychiatric Disorders, HUS Psychiatry, Department of Public Health, Clinicum, Nuorisopsykiatria, Faculty Common Matters (Faculty of Social Sciences), Samuli Olli Ripatti / Principal Investigator, Complex Disease Genetics, Biostatistics Helsinki, Anna Keski-Rahkonen / Principal Investigator, Elisabeth Ingrid Maria Widen / Principal Investigator, Genomic Discoveries and Clinical Translation, Internal medicine, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, APH - Digital Health, Mullins N., Kang J., Campos A.I., Coleman J.R.I., Edwards A.C., Galfalvy H., Levey D.F., Lori A., Shabalin A., Starnawska A., Su M.-H., Watson H.J., Adams M., Awasthi S., Gandal M., Hafferty J.D., Hishimoto A., Kim M., Okazaki S., Otsuka I., Ripke S., Ware E.B., Bergen A.W., Berrettini W.H., Bohus M., Brandt H., Chang X., Chen W.J., Chen H.-C., Crawford S., Crow S., DiBlasi E., Duriez P., Fernandez-Aranda F., Fichter M.M., Gallinger S., Glatt S.J., Gorwood P., Guo Y., Hakonarson H., Halmi K.A., Hwu H.-G., Jain S., Jamain S., Jimenez-Murcia S., Johnson C., Kaplan A.S., Kaye W.H., Keel P.K., Kennedy J.L., Klump K.L., Li D., Liao S.-C., Lieb K., Lilenfeld L., Liu C.-M., Magistretti P.J., Marshall C.R., Mitchell J.E., Monson E.T., Myers R.M., Pinto D., Powers A., Ramoz N., Roepke S., Rozanov V., Scherer S.W., Schmahl C., Sokolowski M., Strober M., Thornton L.M., Treasure J., Tsuang M.T., Witt S.H., Woodside D.B., Yilmaz Z., Zillich L., Adolfsson R., Agartz I., Air T.M., Alda M., Alfredsson L., Andreassen O.A., Anjorin A., Appadurai V., Soler 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Kamitaki N., Krebs K., Panagiotaropoulou G., Schilder B.M., Sloofman L.G., Winsvold B.S., Won H.-H., Abramova L., Adorjan K., Al Eissa M., Albani D., Alliey-Rodriguez N., Antilla V., Antoniou A., Baek J.H., Bauer M., Beins E.C., Bergen S.E., Birner A., Boen E., Brum M., Brumpton B.M., Brunkhorst-Kanaan N., Byerley W., Cairns M., Cervantes P., Cruceanu C., Cuellar-Barboza A., Cunningham J., Curtis D., Czerski P.M., Dale A.M., Dalkner N., David F.S., Dobbyn A.L., Douzenis A., Elvsashagen T., Ferrier I.N., Fiorentino A., Foroud T.M., Forty L., Frei O., Freimer N.B., Frisen L., Gade K., Garnham J., Gelernter J., Gizer I.R., Gordon-Smith K., Greenwood T.A., Ha K., Haraldsson M., Hautzinger M., Heilbronner U., Hellgren D., Holmans P.A., Huckins L., Johnson J.S., Kalman J.L., Kamatani Y., Kittel-Schneider S., Koromina M., Kranz T.M., Kranzler H.R., Kubo M., Kupka R., Kushner S.A., Lavebratt C., Leber M., Lee H.-J., Levy S.E., Lewis C., Lundberg M., Magnusson S.H., Maihofer A., Malaspina D., Maratou E., Martinsson L., McGregor N.W., McKay J.D., Medeiros H., Millischer V., Moran J.L., Morris D.W., Muhleisen T.W., O'Brien N., O'Donovan C., Olde Loohuis L.M., Oruc L., Papiol S., Pardinas A.F., Perry A., Pfennig A., Porichi E., Raj T., Rapaport M.H., Regeer E.J., Rivas F., Roth J., Roussos P., Ruderfer D.M., Senner F., Sharp S., Shilling P.D., Slaney C., Sobell J.L., Artigas M.S., Spijker A.T., Stein D.J., Terao C., Toma C., Tooney P., Tsermpini E.-E., Vawter M.P., Vedder H., Xi S., Xu W., Kay Yang J.M., Young A.H., Young H., Zandi P.P., Zhou H., HUNT All-In Psychiatry, Babadjanova G., Backlund L., Bengesser S., Blackwood D.H.R., Carr V.J., Catts S., Dikeos D., Etain B., Ferentinos P., Gawlik M., Gershon E.S., Henskens F., Hillert J., Hong K.S., Hultman C.M., Hveem K., Iwata N., Jablensky A.V., Kirov G., Lochner C., Loughland C., Mathews C.A., McMahon F.J., Michie P., Mowry B., Neale B.M., Nievergelt C.M., Oedegaard K.J., Olsson T., Pantelis C., Patrinos G.P., Reininghaus E.Z., Saito T., Schall U., Schalling M., Scott R.J., Weickert C.S., Stordal E., Vaaler A.E., Vieta E., Waldman I.D., Zwart J.-A., Nurnberger J.I., Stahl E.A., Di Florio A., Adan R.A.H., Ando T., Aschauer H., Baker J.H., Bencko V., Birgegard A., Boden J.M., Boehm I., Boni C., Perica V.B., Buehren K., Bulik C.M., Burghardt R., Carlberg L., Cassina M., Clementi M., Cone R.D., Courtet P., Crowley J.J., Danner U.N., Davis O.S.P., de Zwaan M., Dedoussis G., Degortes D., DeSocio J.E., Dick D.M., Dina C., Dmitrzak-Weglarz M., Martinez E.D., Duncan L.E., Egberts K., Mattingsdal M., McDevitt S., Meulenbelt I., Micali N., Mitchell J., Mitchell K., Monteleone P., Monteleone A.M., Munn-Chernoff M.A., Nacmias B., Navratilova M., Ntalla I., Olsen C.M., O'Toole J.K., Padyukov L., Palotie A., Pantel J., Papezova H., Parker R., Pearson J.F., Ehrlich S., Escaramis G., Espeseth T., Estivill X., Farmer A., Favaro A., Fischer K., Floyd J.A.B., Focker M., Foretova L., Forzan M., Franklin C.S., Gambaro G., Giuranna J., Giusti-Rodriquez P., Gonidakis F., Gordon S., Mayora M.G., Guillaume S., Hanscombe K.B., Hatzikotoulas K., Hebebrand J., Helder S.G., Henders A.K., Herpertz-Dahlmann B., Herzog W., Hinney A., Horwood L.J., Hubel C., Petersen L.V., Purves K.L., Raevuori A., Reichborn-Kjennerud T., Ricca V., Ripatti S., Ritschel F., Roberts M., Rybakowski F., Santonastaso P., Scherag A., Schmidt U., Schork N.J., Schosser A., Seitz J., Slachtova L., Slagboom P.E., Slof-Op 't Landt M.C.T., Slopien A., Soranzo N., Sorbi S., Southam L., Steen V.W., Huckins L.M., Hudson J.I., Imgart H., Inoko H., Janout V., Jordan J., Julia A., Kalsi G., Kaminska D., Kaprio J., Karhunen L., Karwautz A., Kas M.J.H., Kennedy M.A., Keski-Rahkonen A., Kiezebrink K., Kim Y.-R., Kirk K.M., Klareskog L., Knudsen G.P.S., Larsen J.T., Le Hellard S., Leppa V.M., Lichtenstein P., Lin B.D., Lundervold A., Luykx J., Maj M., Mannik K., Marsal S., Stuber G.D., Szatkiewicz J.P., Tachmazidou I., Tenconi E., Tortorella A., Tozzi F., Tsitsika A., Tyszkiewicz-Nwafor M., Tziouvas K., van Elburg A.A., van Furth E.F., Wade T.D., Wagner G., Walton E., Whiteman D.C., Wichmann H.E., Widen E., Yao S., Zeggini E., Zerwas S., Zipfel S., Jungkunz M., Dietl L., Schwarze C.E., Dahmen N., Schott B.H., Mobascher A., Crivelli S., Dennis M.F., Harvey P.D., Carter B.W., Huffman J.E., Jacobson D., Madduri R., Olsen M.K., Pestian J., Gaziano J.M., Muralidhar S., Ramoni R., Beckham J., Chang K.-M., O'Donnell C.J., Tsao P.S., Breeling J., Huang G., Romero J.P.C., Moser J., Whitbourne S.B., Brewer J.V., Aslan M., Connor T., Argyres D.P., Stephens B., Brophy M.T., Humphries D.E., Selva L.E., Do N., Shayan S., Cho K., Pyarajan S., Hauser E., Sun Y., Zhao H., Wilson P., McArdle R., Dellitalia L., Mattocks K., Harley J., Zablocki C.J., Whittle J., Jacono F., Gutierrez S., Gibson G., Hammer K., Kaminsky L., Villareal G., Kinlay S., Xu J., Hamner M., Mathew R., Bhushan S., Iruvanti P., Godschalk M., Ballas Z., Ivins D., Mastorides S., Moorman J., Gappy S., Klein J., Ratcliffe N., Florez H., Okusaga O., Murdoch M., Sriram P., Yeh S.S., Tandon N., Jhala D., Aguayo S., Cohen D., Sharma S., Liangpunsakul S., Oursler K.A., Whooley M., Ahuja S., Constans J., Meyer P., Greco J., Rauchman M., Servatius R., Gaddy M., Wallbom A., Morgan T., Stapley T., Sherman S., Ross G., Tsao P., Strollo P., Boyko E., Meyer L., Gupta S., Huq M., Fayad J., Hung A., Lichy J., Hurley R., Robey B., Striker R., Erlangsen A., Kessler R.C., Porteous D., Ursano R.J., Wasserman D., Coon H., Demontis D., Docherty A.R., Kuo P.-H., Mann J.J., Renteria M.E., Stein M.B., and Willour V.

Subjects
LD SCORE REGRESSION, Genome-wide association study, Suicide, Attempted, 3124 Neurology and psychiatry, 0302 clinical medicine, Risk Factors, Insomnia, Suicide attempt, GWAS, Suïcidi, Depression (differential diagnoses), Cause of death, Psychiatry, 0303 health sciences, Factors de risc en les malalties, Mental Disorders, Genetic Correlation, Genome-wide Association Study, Pleiotropy, Polygenicity, Suicide, Suicide Attempt, DEPRESSION, 3. Good health, Genetic correlation, Genome-Wide Association Study, Humans, Polymorphism, Single Nucleotide, Depressive Disorder, Major, Mental illness, Cohort, SEX, medicine.symptom, Human, medicine.medical_specialty, Risk factors in diseases, BF, Locus (genetics), BEHAVIORS, Psykiatri, EVENTS, 03 medical and health sciences, SDG 3 - Good Health and Well-being, medicine, ddc:610, GENOME-WIDE ASSOCIATION, IDEATION, Socioeconomic status, METAANALYSIS, Biological Psychiatry, 030304 developmental biology, business.industry, Risk Factor, Genetic architecture, THOUGHTS, RC0321, business, Malalties mentals, 030217 neurology & neurosurgery
Abstract

Statistical analyses were carried out on the NL Genetic Cluster Computer (http://www.geneticcluster.org) hosted by SURFsara and the Mount Sinai high performance computing cluster (http://hpc.mssm.edu), which is supported by the Office of Research Infrastructure of the National Institutes of Health (Grant Nos. S10OD018522 and S10OD026880). This work was conducted in part using the resources of the Advanced Computing Center for Research and Education at Vanderbilt University, Nashville, TN. This work was funded by the National Institutes of Health (Grant Nos. R01MH116269 and R01MH121455 [to DMR]), NIGMS of the National Institutes of Health (Grant No. T32GM007347 [to JK]), and the Brain & Behavior Research Foundation (NARSAD Young Investigator Award No. 29551 [to NM])., BACKGROUND: Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. METHODS: We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors. RESULTS: Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged. CONCLUSIONS: Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders., Office of Research Infrastructure of the National Institutes of Health S10OD018522 S10OD026880, United States Department of Health & Human Services, National Institutes of Health (NIH) - USA R01MH116269 R01MH121455, NIH National Institute of General Medical Sciences (NIGMS) T32GM007347 NARSAD 29551

Published
2022

30. Childhood stress impairs social function through AVP-dependent mechanisms

Author

Holly Watkin, Catrin Lewis, Jeremy Hall, Caroline Best, Kerrie L. Thomas, Lowenna Rule, Amanda J. Drake, Nichola M. Brydges, and Jessica Hall

Subjects
Male, Vasopressin, Indoles, Pyrrolidines, Relcovaptan, Adverse Childhood Experiences, Borderline Personality Disorder, Stress (linguistics), Sexual Maturation, Young adult, Borderline personality disorder, Behavior, Animal, Middle Aged, Psychiatry and Mental health, Female, Supraoptic Nucleus, Antidiuretic Hormone Receptor Antagonists, hormones, hormone substitutes, and hormone antagonists, medicine.drug, Adult, medicine.medical_specialty, endocrine system, Vasopressins, Molecular neuroscience, Article, lcsh:RC321-571, Cellular and Molecular Neuroscience, Young Adult, Internal medicine, medicine, Genetics, Animals, Humans, Protein Precursors, Social Behavior, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, Biological Psychiatry, Aged, Neurophysins, business.industry, Antagonist, Mental illness, medicine.disease, Rats, Arginine Vasopressin, Disease Models, Animal, Endocrinology, Oxytocin, business, Stress, Psychological, Paraventricular Hypothalamic Nucleus
Abstract

Impaired social function is a core feature of many psychiatric illnesses. Adverse experiences during childhood increase risk for mental illness, however it is currently unclear whether stress early in life plays a direct role in the development of social difficulties. Using a rat model of pre-pubertal stress (PPS), we investigated effects on social behaviour, oxytocin and arginine vasopressin (AVP) in the periphery (plasma) and centrally in the paraventricular and supraoptic hypothalamic nuclei. We also explored social performance and AVP expression (plasma) in participants with borderline personality disorder (BPD) who experienced a high incidence of childhood stress. Social behaviour was impaired and AVP expression increased in animals experiencing PPS and participants with BPD. Behavioural deficits in animals were rescued through administration of the AVPR1a antagonist Relcovaptan (SR49059). AVP levels and recognition of negative emotions were significantly correlated in BPD participants only. In conclusion, early life stress plays a role in the precipitation of social dysfunction, and AVP mediates at least part of this effect.

Published
2019

31. 13 The effect of continuous positive airway pressure (CPAP) on key plasma metabolites identifying obstructive sleep apnoea hypopnoea syndrome (OSAHS)

Author

Sarah Bowen, Keir Lewis, Catrin Lewis, Sarah Thomas, Scott O’Rourke, and Luis A. J. Mur

Subjects
Cardiometabolic risk, medicine.medical_specialty, RC705-779, medicine.diagnostic_test, business.industry, medicine.medical_treatment, Polysomnography, respiratory tract diseases, Diagnostic modalities, Diseases of the respiratory system, Metabolomic profiling, Excessive daytime somnolence, Internal medicine, Q exactive, medicine, Cardiology, Medicine, Continuous positive airway pressure, business, Pre and post
Abstract

We recently applied untargeted metabolomic profiling on the plasma obtained from consecutive attenders referred for conventional Level 3 home-sleep studies with excessive daytime somnolence, comparing 17 OSAHS patients (AHI≥15, Epworth Score 13.5±4.5) with 16 age, gender, and BMI matched sleepy subjects (sleepy snorers (SS)) with negative home polysomnography tests (AHI We reported 6 biologically plausible plasma metabolites that can differentiate OSAHS from SS of similar phenotype with an AUC of 0.982 (95% CI: 0.9-1.0) (figure 1), with these key metabolites being essential lipids involved in protein synthesis and the formation of antioxidative, antiglycating, and free radical scavenging dipeptides. We now report early changes in these biomarkers following CPAP in those with OSAHS. 11 OSAHS patients with AHI≥15 (63.6% male, Age 54.4±6.9, BMI 34.2±4.0, AHI 47.6±25.6, Epworth 13.7±4.8) were commenced on standard auto-adjustment CPAP devices (Phillips DreamStation set at 4 to 18 cm H2O). Mean use of CPAP was 6.6±1.4 hours and average residual AHI was 6.9±6.0. Plasma was sampled pre and post treatment (42-70 days treatment), and metabolomically assessed using the Q Exactive Hybrid Quadrupole-Orbitrap mass spectrometry platform. 16 sleepy snorers with AHI Our previously reported biomarkers associated with processes such as oxidative stress, inflammation, and dysregulation of energy homeostasis improve with short-term treatment with CPAP towards the level of sleepy snorers of similar age, phenotype, and no OSAHS (figure 2). We feel these metabolites have significant potential in the future care pathways of OSAHS, and could reflect the cardiometabolic risk associated with OSAHS better than current diagnostic modalities. Reference O’Rourke, et al. Plasma metabolomics identifies OSAHS. ERS Congress 2021.

Published
2021

33. High prevalence of somatisation in ICD-11 complex PTSD: A cross sectional cohort study

Author

Grace W.K. Ho, Laurence Astill Wright, Jonathan Ian Bisson, Catrin Lewis, Natalie Simon, Philip Hyland, Neil P. Roberts, and Eoin McElroy

Subjects
Complex ptsd, behavioral disciplines and activities, Article, Cohort Studies, Stress Disorders, Post-Traumatic, Self organisation, International Classification of Diseases, mental disorders, Prevalence, Humans, Medicine, High prevalence, business.industry, Symptom severity, PTSD, CPTSD, Mental health, Patient Health Questionnaire, Psychiatry and Mental health, Clinical Psychology, Cross-Sectional Studies, Cohort, Somatisation, business, Cohort study, Clinical psychology
Abstract

Background While research demonstrates that somatisation is highly correlated with post-traumatic stress disorder (PTSD), the relationship between International Classification of Diseases 11th edition (ICD-11) PTSD, complex PTSD (CPTSD) and somatisation has not previously been determined. Objective To determine the relationship between frequency and severity of somatisation and ICD-11 PTSD/CPTSD. Method This cross-sectional study included 222 individuals recruited to the National Centre for Mental Health (NCMH) PTSD cohort. We assessed rates of Patient Health Questionnaire 15 (PHQ-15) somatisation stratified by ICD-11 PTSD/CPTSD status. Path analysis was used to explore the relationship between PTSD/CPTSD and somatisation, including number of traumatic events, age, and gender as controls. Results 70% (58/83) of individuals with CPTSD had high PHQ-15 somatisation symptom severity compared with 48% (12/25) of those with PTSD (chi-square: 95.1, p value, Highlights • People with CPTSD had a higher prevalence of co-morbid somatisation. • People with CPTSD had a worse somatisation symptom severity. • The core features of PTSD predicted somatisation.

Published
2021

34. Advances in repetitive transcranial magnetic stimulation for posttraumatic stress disorder: a systematic review

Author

Fuad Issa, Sheila A.M. Rauch, Bradley E. Belsher, Marija Spanovic Kelber, Derek J. Smolenski, Jonathan Ian Bisson, Erin H Beech, Madhavi K. Reddy, and Catrin Lewis

Subjects
medicine.medical_specialty, medicine.medical_treatment, behavioral disciplines and activities, law.invention, Stress Disorders, Post-Traumatic, 03 medical and health sciences, 0302 clinical medicine, Physical medicine and rehabilitation, Randomized controlled trial, law, mental disorders, Humans, Medicine, Biological Psychiatry, Depression (differential diagnoses), business.industry, Transcranial Magnetic Stimulation, Neuromodulation (medicine), 030227 psychiatry, Quality of evidence, Transcranial magnetic stimulation, Psychiatry and Mental health, Posttraumatic stress, Treatment Outcome, business, 030217 neurology & neurosurgery
Abstract

Repetitive transcranial magnetic stimulation (rTMS) as a treatment for posttraumatic stress disorder (PTSD) has gained interest over the past two decades. However, it has yet to be recommended in major treatment guidelines. We conducted a systematic review of randomized controlled trials to examine the efficacy of rTMS for PTSD. Thirteen studies with 549 participants were included in this review. We compared the effects of (1) rTMS versus sham, and (2) high-frequency (HF) versus low-frequency (LF) rTMS, on posttreatment PTSD scores and other secondary outcomes. We calculated the standardized mean differences (SMD) to determine the direction of effects, and unstandardized mean differences to estimate the magnitude of efficacy. At post-treatment, rTMS was superior to sham comparison in reducing PTSD (SMD = −1.13, 95% CI: −2.10 to −0.15) and depression severity (SMD = −0.83, 95% CI: −1.30 to −0.36). The quality of evidence, however, was rated very low due to small samples sizes, treatment heterogeneity, inconsistent results, and an imprecise pooled effect. HF rTMS was associated with slightly improved, albeit imprecise, outcomes compared to LF rTMS on PTSD (SMD = −0.19, 95% CI: −1.39 to 1.00) and depression (SMD = −1.09, 95% CI: −1.65 to −0.52) severity. Further research is required to advance the evidence on this treatment.

Published
2021

35. Internet-based psychological therapies: A qualitative study of National Health Service commissioners and managers views

Author

Lucy Brookes-Howell, Neil P. Roberts, Neil J Kitchiner, Matt Ploszajski, Jonathan Ian Bisson, Kim Smallman, Natalie Simon, and Catrin Lewis

Subjects
Medical education, Internet, Cognitive Behavioral Therapy, business.industry, SARS-CoV-2, Compromise, media_common.quotation_subject, Psychological intervention, COVID-19, National health service, State Medicine, Therapeutic relationship, Psychiatry and Mental health, Clinical Psychology, Arts and Humanities (miscellaneous), Intervention (counseling), Developmental and Educational Psychology, Humans, The Internet, Quality (business), business, Psychology, Pandemics, media_common, Qualitative research
Abstract

To explore in-depth the views on Internet-based psychological therapies and their implementation from the perspective of National Health Service (NHS) commissioners and managers.Qualitative interview study.Ten NHS commissioners and managers participated in a semi-structured, co-produced interview. Each transcribed interview was double-coded and thematically analysed using The Framework Method.Interviews generated three main themes. (1) Capacity issues across psychological therapy services create barriers to face-to-face therapies, and Internet-based interventions offer a solution. (2) Despite reservations, there is growing acceptance of Internet-based therapies. Different ways of connecting with patients are required, and Internet-based treatments are accessible and empowering treatment options, with guided self-help (GSH) preferred. Internet-based interventions may however exclude some individuals and be a threat to the therapeutic relationship between patient and practitioner. (3) Successful roll-out of Internet-based interventions would be facilitated by a strong empirical- or practice-based evidence, a national coordinated approach and timely training and supervision. Barriers to the roll-out include digital intervention set-up costs and delays due to NHS inflexibility.The study highlights factors influencing access to Internet-based therapies, important given the rapid evolution of e-therapies, and particularly timely given increasing use of remote therapies due to COVID-19 restrictions. Interviewees were open to Internet-based approaches, particularly GSH interventions, so long as they do not compromise on therapy quality. Interviewees acknowledged implementation may be challenging, and recommendations were offered.There is a shift in practice and increasingly positive views from NHS staff around remote psychological therapies and different ways of connecting with patients, particularly since the COVID-19 pandemic. There is a strong preference for Internet-based psychological interventions that are guided and that include built-in outcome measures co-produced with service users. There is a need to raise awareness of the growing evidence base for Internet-based psychological therapies, including research examining therapeutic alliance across Internet-based and face-to-face therapies. Challenges implementing Internet-based psychological therapies include therapist resistance to changing working practices in general, and inflexibility of the NHS, and national, coordinated implementation efforts are encouraged.

Published
2021

36. The reconsolidation using rewind study (RETURN): trial protocol

Author

David Muss, Neil J Kitchiner, Laurence Astill Wright, Neil P. Roberts, Jonathan Ian Bisson, Natalie Simon, Kali Barawi, and Catrin Lewis

Subjects
medicine.medical_specialty, TEPT, RC435-571, law.invention, rewind technique, Study Protocol, Randomized controlled trial, law, Intervention (counseling), Terapia de Rebobinado, medicine, ptsd, Rewind疗法方案, protocol, ECA, rct, Protocol (science), Psychiatry, Protocolo, business.industry, Técnica de Rebobinado, rewind therapy, Rewind技术, Test (assessment), Patient Health Questionnaire, Tolerability, Physical therapy, Anxiety, Memory consolidation, medicine.symptom, business, Research Article
Abstract

Background: An increasing body of research highlights reconsolidation-based therapies as emerging treatments for post-traumatic stress disorder (PTSD). The Rewind Technique is a non-pharmacological reconsolidation-based therapy with promising early results, which now requires evaluation through an RCT. Objectives: This is a preliminary efficacy RCT to determine if the Rewind Technique is likely to be a good candidate to test against usual care in a future pragmatic efficacy RCT. Methods: 40 participants will be randomised to receive either the Rewind Technique immediately, or after an 8 week wait. The primary outcome will be PTSD symptom severity as measured by the Clinician-Administered PTSD Scale for DSM5 (CAPS-5) at 8 and 16 weeks post-randomisation. Secondary outcome measures include the PTSD Checklist (PCL-5), International Trauma Questionnaire (ITQ), Patient Health Questionnaire (PHQ-9), the General Anxiety Disorder-7 (GAD-7), Insomnia Severity Index, the Euro-Qol-5D (EQ5D-5 L), the prominence of re-experiencing specific symptoms (CAPS-5) and an intervention acceptability questionnaire to measure tolerability of the intervention. Conclusions: This study will be the first RCT to assess the Rewind Technique. Using a cross-over methodology we hope to rigorously assess the efficacy and tolerability of Rewind using pragmatic inclusion criteria. Potential challenges include participant recruitment and retention. Trial registration: ISRCTN91345822, HIGHLIGHTS This study will be the first RCT to rigorously assess the efficacy and tolerability of the Rewind Technique.

Published
2021

37. Genome-wide association study of more than 40,000 bipolar disorder cases provides new insights into the underlying biology

Author

James McKay, Frank Bellivier, Mark A. Frye, Bertram Müller-Myhsok, Fermín Mayoral, I. Nicol Ferrier, Marion Leboyer, Fabian Streit, Dan J. Stein, James L. Kennedy, Christine Søholm Hansen, Scott D. Gordon, Beata Świątkowska, Valentina Escott-Price, Michael Bauer, Lina Martinsson, Donald J. MacIntyre, Oleksandr Frei, Daniel J. Smith, Sara A. Paciga, Takeo Saito, Jennifer L. Moran, Verneri Antilla, C Pantelis, Tomas Olsson, Swapnil Awasthi, Lena Backlund, Eirini Maratou, Martin Schalling, John B. Vincent, Niamh Mullins, Sarah E. Bergen, Niamh L. O'Brien, Marco P. Boks, Carsten Bøcker Pedersen, Mikael Landén, Franziska Degenhardt, Hang Zhou, Margarita Rivera, Andrew M. McIntosh, Manuel Mattheisen, Shawn Levy, Roy H. Perlis, John P. Rice, Sigurdur H. Magnusson, Amanda Dobbyn, Michael Conlon O'Donovan, Julien Bryois, Wolfgang Maier, John-Anker Zwart, J. Raymond DePaulo, Martin Alda, Laura G. Sloofman, Friederike Sophie David, James A. Knowles, Aiden Corvin, Thomas G. Schulze, Markus M. Nöthen, Nolan Kamitaki, Nina Dalkner, Brandon J. Coombes, Gustavo Turecki, Allan H. Young, Caroline M. Nievergelt, Patricia T. Michie, Ingrid Agartz, Towfique Raj, Diego Albani, Maria Grigoroiu-Serbanescu, Bernhard T. Baune, Kyooseob Ha, Vincent Millischer, Engilbert Sigurdsson, Eva C. Beins, Nicholas G. Martin, Gulja Babadjanova, Josef Frank, Eva Z. Reininghaus, Patrick F. Sullivan, Ian R. Gizer, Guy A. Rouleau, Carmel M. Loughland, Christine Lochner, Thorsten M. Kranz, Amy Perry, Arne E. Vaaler, Mariam M. Al Eissa, Simon Xi, Claire O'Donovan, Josep Antoni Ramos-Quiroga, Ketil J. Oedegaard, Helmut Vedder, Carol A. Mathews, Panagiotis Ferentinos, Tim B. Bigdeli, Derek W. Morris, Per Hoffmann, Mark Hyman Rapaport, Peter P. Zandi, Michael John Owen, Douglas M. Ruderfer, Anders D. Børglum, Catharina Lavebratt, Thorgeir E. Thorgeirsson, Paul A. Tooney, Michiaki Kubo, Steven A. Kushner, Jan Hillert, Loes M. Olde Loohuis, Anastasia Antoniou, Murielle Brum, Chikashi Terao, Nathaniel W. McGregor, Fabio Rivas, James B. Potash, Kevin S. O’Connell, Susanne Lucae, Brian M. Schilder, Katrin Gade, Stephan Ripke, Kristina Adorjan, Kari Stefansson, Tiffany A. Greenwood, Panos Roussos, Sarah Kittel-Schneider, Steven A. McCarroll, Sergi Papiol, Heon Jeong Lee, Assen Jablensky, Liliya Abramova, Dennis Hellgren, Jonas Bybjerg-Grauholm, Martin Lundberg, Hong-Hee Won, William Byerley, Lars Alfredsson, Joel Gelernter, Andrew McQuillin, Claire Slaney, Marta Ribasés, Stephanie H. Witt, Yoichiro Kamatani, Kyung Sue Hong, Marie Bækvad-Hansen, María Soler Artigas, Julie M. Cunningham, Fanny Senner, Stacy Steinberg, Paul D. Shilling, Nakao Iwata, Eystein Stordal, Armin Birner, Sarah E. Medland, Miquel Casas, Ben Michael Brumpton, Erlend Bøen, Bryan J. Mowry, Jolanta Lissowska, Francis J. McMahon, Howard J. Edenberg, Grant W. Montgomery, John I. Nurnberger, Stéphane Jamain, Claudio Toma, Ney Alliey-Rodriguez, Ole Mors, Micha Gawlik, David Curtis, Catrin Lewis, Evangelia-Eirini Tsermpini, Georgia Panagiotaropoulou, Marcella Rietschel, Jessica Yang, Ian Jones, Eduard Vieta, Ole A. Andreassen, Richard M. Myers, Dimitris Dikeos, Melissa J. Green, Janet L. Sobell, Maria Koromina, Piotr M. Czerski, Lilijana Oruc, Sven Cichon, Udo Dannlowski, Bruno Etain, Monika Budde, Alessia Fiorentino, Naomi R. Wray, Qingqin S. Li, Murray J. Cairns, Jonathan R. I. Coleman, Jose Guzman-Parra, Andreas J. Forstner, Hannah Young, Alfredo B. Cuellar-Barboza, Julian Roth, Torbjørn Elvsåshagen, Zhen Qiao, Thomas Werge, Athanassios Douzenis, Cristiana Cruceanu, Rolf Adolfsson, Peter Holmans, Vaughan J. Carr, Thomas W. Weickert, Masashi Ikeda, Joanna M. Biernacka, Lea Sirignano, Adam X. Maihofer, Ralph W. Kupka, John Strauss, Anders M. Dale, Elliot S. Gershon, Jakob Grove, Arianna Di Florio, Helena Medeiros, Ingrid Melle, Preben Bo Mortensen, Kristi Krebs, Saskia P. Hagenaars, Liz Forty, Stanley V. Catts, David M. Hougaard, Marianne Giørtz Pedersen, Andreas Reif, Toni-Kim Clarke, Anne T. Spijker, Danielle Posthuma, Manolis Kogevinas, Michael Boehnke, Rosa Bosch, Gerome Breen, Benjamin M. Neale, Jessica S. Johnson, Katherine Gordon-Smith, Cristina Sánchez-Mora, Alexander W. Charney, Henry R. Kranzler, Digby Quested, René S. Kahn, Lili Milani, Merete Nordentoft, Nathalie Brunkhorst-Kanaan, Laura M. Huckins, James T.R. Walters, Sigrid Børte, Antonio F. Pardiñas, Kristian Hveem, Julie Garnham, Jacob Lawrence, Vassily Trubetskoy, Rodney J. Scott, Nicholas Bass, Carlos N. Pato, Andrea Pfennig, Wei Xu, Calwing Liao, Nicholas John Craddock, Thomas Damm Als, Christina M. Hultman, Fernando S. Goes, Adebayo Anjorin, Evgenia Porichi, Frans Henskens, Nelson B. Freimer, Janice M. Fullerton, Cathryn M. Lewis, Srdjan Djurovic, Roel A. Ophoff, Phil Lee, Peter McGuffin, Gunnar Morken, George P. Patrinos, Alessandro Serretti, Cynthia Shannon Weickert, Pablo Cervantes, Bendik S. Winsvold, Tatiana Foroud, Tõnu Esko, Ulrich Schall, Michele T. Pato, Ji Hyun Baek, John R. Kelsoe, Olav B. Smeland, Janos Kalman, Eva C. Schulte, Joanna Hauser, Urs Heilbronner, Magnús Haraldsson, Martin Hautzinger, Lea Zillich, Eline J. Regeer, Douglas Blackwood, Laura J. Scott, Jordan W. Smoller, Michael J. Gandal, Marquis P. Vawter, Philip B. Mitchell, Ole Kristian Drange, Peter R. Schofield, Susanne Bengesser, Stefan Herms, George Kirov, Markus Leber, Louise Frisén, Thomas W. Mühleisen, Susan L. McElroy, Irwin D. Waldman, Wade H. Berrettini, Sally I. Sharp, Minsoo Kim, Lisa Jones, Eli A. Stahl, Hreinn Stefansson, Esben Agerbo, Dolores Malaspina, Complex Trait Genetics, Amsterdam Neuroscience - Complex Trait Genetics, Psychiatry, APH - Mental Health, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, Human genetics, Amsterdam Neuroscience - Compulsivity, Impulsivity & Attention, Amsterdam Reproduction & Development (AR&D), APH - Digital Health, Mullins N., Forstner A.J., O'Connell K.S., Coombes B., Coleman J.R.I., Qiao Z., Als T.D., Bigdeli T.B., Borte S., Bryois J., Charney A.W., Drange O.K., Gandal M.J., Hagenaars S.P., Ikeda M., Kamitaki N., Kim M., Krebs K., Panagiotaropoulou G., Schilder B.M., Sloofman L.G., Steinberg S., Trubetskoy V., Winsvold B.S., Won H.-H., Abramova L., Adorjan K., Agerbo E., Al Eissa M., Albani D., Alliey-Rodriguez N., Anjorin A., Antilla V., Antoniou A., Awasthi S., Baek J.H., Baekvad-Hansen M., Bass N., Bauer M., Beins E.C., Bergen S.E., Birner A., Bocker Pedersen C., Boen E., Boks M.P., Bosch R., Brum M., Brumpton B.M., Brunkhorst-Kanaan N., Budde M., Bybjerg-Grauholm J., Byerley W., Cairns M., Casas M., Cervantes P., Clarke T.-K., Cruceanu C., Cuellar-Barboza A., Cunningham J., Curtis D., Czerski P.M., Dale A.M., Dalkner N., David F.S., Degenhardt F., Djurovic S., Dobbyn A.L., Douzenis A., Elvsashagen T., Escott-Price V., Ferrier I.N., Fiorentino A., Foroud T.M., Forty L., Frank J., Frei O., Freimer N.B., Frisen L., Gade K., Garnham J., Gelernter J., Giortz Pedersen M., Gizer I.R., Gordon S.D., Gordon-Smith K., Greenwood T.A., Grove J., Guzman-Parra J., Ha K., Haraldsson M., Hautzinger M., Heilbronner U., Hellgren D., Herms S., Hoffmann P., Holmans P.A., Huckins L., Jamain S., Johnson J.S., Kalman J.L., Kamatani Y., Kennedy J.L., Kittel-Schneider S., Knowles J.A., Kogevinas M., Koromina M., Kranz T.M., Kranzler H.R., Kubo M., Kupka R., Kushner S.A., Lavebratt C., Lawrence J., Leber M., Lee H.-J., Lee P.H., Levy S.E., Lewis C., Liao C., Lucae S., Lundberg M., MacIntyre D.J., Magnusson S.H., Maier W., Maihofer A., Malaspina D., Maratou E., Martinsson L., Mattheisen M., McCarroll S.A., McGregor N.W., McGuffin P., McKay J.D., Medeiros H., Medland S.E., Millischer V., Montgomery G.W., Moran J.L., Morris D.W., Muhleisen T.W., O'Brien N., O'Donovan C., Olde Loohuis L.M., Oruc L., Papiol S., Pardinas A.F., Perry A., Pfennig A., Porichi E., Potash J.B., Quested D., Raj T., Rapaport M.H., DePaulo J.R., Regeer E.J., Rice J.P., Rivas F., Rivera M., Roth J., Roussos P., Ruderfer D.M., Sanchez-Mora C., Schulte E.C., Senner F., Sharp S., Shilling P.D., Sigurdsson E., Sirignano L., Slaney C., Smeland O.B., Smith D.J., Sobell J.L., Soholm Hansen C., Soler Artigas M., Spijker A.T., Stein D.J., Strauss J.S., Swiatkowska B., Terao C., Thorgeirsson T.E., Toma C., Tooney P., Tsermpini E.-E., Vawter M.P., Vedder H., Walters J.T.R., Witt S.H., Xi S., Xu W., Yang J.M.K., Young A.H., Young H., Zandi P.P., Zhou H., Zillich L., Adolfsson R., Agartz I., Alda M., Alfredsson L., Babadjanova G., Backlund L., Baune B.T., Bellivier F., Bengesser S., Berrettini W.H., Blackwood D.H.R., Boehnke M., Borglum A.D., Breen G., Carr V.J., Catts S., Corvin A., Craddock N., Dannlowski U., Dikeos D., Esko T., Etain B., Ferentinos P., Frye M., Fullerton J.M., Gawlik M., Gershon E.S., Goes F.S., Green M.J., Grigoroiu-Serbanescu M., Hauser J., Henskens F., Hillert J., Hong K.S., Hougaard D.M., Hultman C.M., Hveem K., Iwata N., Jablensky A.V., Jones I., Jones L.A., Kahn R.S., Kelsoe J.R., Kirov G., Landen M., Leboyer M., Lewis C.M., Li Q.S., Lissowska J., Lochner C., Loughland C., Martin N.G., Mathews C.A., Mayoral F., McElroy S.L., McIntosh A.M., McMahon F.J., Melle I., Michie P., Milani L., Mitchell P.B., Morken G., Mors O., Mortensen P.B., Mowry B., Muller-Myhsok B., Myers R.M., Neale B.M., Nievergelt C.M., Nordentoft M., Nothen M.M., O'Donovan M.C., Oedegaard K.J., Olsson T., Owen M.J., Paciga S.A., Pantelis C., Pato C., Pato M.T., Patrinos G.P., Perlis R.H., Posthuma D., Ramos-Quiroga J.A., Reif A., Reininghaus E.Z., Ribases M., Rietschel M., Ripke S., Rouleau G.A., Saito T., Schall U., Schalling M., Schofield P.R., Schulze T.G., Scott L.J., Scott R.J., Serretti A., Shannon Weickert C., Smoller J.W., Stefansson H., Stefansson K., Stordal E., Streit F., Sullivan P.F., Turecki G., Vaaler A.E., Vieta E., Vincent J.B., Waldman I.D., Weickert T.W., Werge T., Wray N.R., Zwart J.-A., Biernacka J.M., Nurnberger J.I., Cichon S., Edenberg H.J., Stahl E.A., McQuillin A., Di Florio A., Ophoff R.A., Andreassen O.A., IMRB - 'Neuropsychiatrie translationnelle' [Créteil] (U955 Inserm - UPEC), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre International de Recherche contre le Cancer - International Agency for Research on Cancer (CIRC - IARC), Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Optimisation thérapeutique en Neuropsychopharmacologie (OPTeN (UMR_S_1144 / U1144)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Etain, Bruno

Subjects
Multifactorial Inheritance, Bipolar Disorder, [SDV.MHEP.PSM] Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Medizin, Genome-wide association study, Major Histocompatibility Complex/genetics, Major Histocompatibility Complex, 0302 clinical medicine, Risk Factors, MESH: Risk Factors, MESH: Bipolar Disorder, Chromosomes, Human, Spectrum disorder, Genetics, 0303 health sciences, Bipolar Disorder/genetics, MESH: Genetic Predisposition to Disease, MESH: Case-Control Studies, Phenotype, Schizophrenia, Synaptic signaling, Case-Control Studie, Human, Quantitative Trait Loci, Biology, MESH: Phenotype, MESH: Chromosomes, Human, Article, 03 medical and health sciences, MESH: Major Histocompatibility Complex, SDG 3 - Good Health and Well-being, ddc:570, medicine, Humans, Genetic Predisposition to Disease, Bipolar disorder, Multifactorial Inheritance/genetics, MESH: Genome, Human, 030304 developmental biology, MESH: Humans, Genome, Human, Risk Factor, Chromosomes, Human/genetics, Mental illness, medicine.disease, MESH: Quantitative Trait Loci, Human genetics, Psychologie, Case-Control Studies, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, MESH: Genome-Wide Association Study, Expression quantitative trait loci, MESH: Multifactorial Inheritance, Quantitative Trait Loci/genetics, 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract

International audience; Bipolar disorder is a heritable mental illness with complex etiology. We performed a genome-wide association study of 41,917 bipolar disorder cases and 371,549 controls of European ancestry, which identified 64 associated genomic loci. Bipolar disorder risk alleles were enriched in genes in synaptic signaling pathways and brain-expressed genes, particularly those with high specificity of expression in neurons of the prefrontal cortex and hippocampus. Significant signal enrichment was found in genes encoding targets of antipsychotics, calcium channel blockers, antiepileptics and anesthetics. Integrating expression quantitative trait locus data implicated 15 genes robustly linked to bipolar disorder via gene expression, encoding druggable targets such as HTR6, MCHR1, DCLK3 and FURIN. Analyses of bipolar disorder subtypes indicated high but imperfect genetic correlation between bipolar disorder type I and II and identified additional associated loci. Together, these results advance our understanding of the biological etiology of bipolar disorder, identify novel therapeutic leads and prioritize genes for functional follow-up studies.

Published
2021

38. Pharmacological-assisted Psychotherapy for Post Traumatic Stress Disorder: a systematic review and meta-analysis

Author

Matthew R. D. Lee, Neil P. Roberts, Jonathan Ian Bisson, Jack F. G. Underwood, R. Sinnerton, Alan Slater, Mathew Hoskins, Anna Nakamura, Catrin Lewis, and Liam Clarke

Subjects
ISRS, 050103 clinical psychology, medicine.medical_specialty, drug-assisted therapy, d-cycloserine, Psychological intervention, RC435-571, Placebo, Mean difference, 03 medical and health sciences, 0302 clinical medicine, 药物治疗, Intervention (counseling), Medicine, ptsd, 0501 psychology and cognitive sciences, Stage (cooking), ISRN, snri, Psychiatry, Clinical Research Article, business.industry, 05 social sciences, Traumatic stress, D-cicloserina, ssri, Experimental research, terapia asistida por fármacos, 030227 psychiatry, mdma, D-环丝氨酸, Meta-analysis, Terapia farmacológica, Physical therapy, 药物辅助治疗, business, pharmacological therapy, Research Article
Abstract

Background: Pharmacological-assisted psychotherapies, using conventional and novel drug agents, are increasingly being used both in clinical and experimental research settings, respectively. Objective: To determine the efficacy of conventional and novel pharmacological-assisted psychotherapies in reducing PTSD symptom severity. Method: A systematic review and meta-analysis of randomised-controlled trials were undertaken; 21 studies were included. Results: MDMA-assisted therapy was found to statistically superior to active and inactive placebo-assisted therapy in reduction of PTSD symptoms (standardised mean difference −1.09, 95% CI −1.60 to −0.58). There was no evidence of superiority over placebo for any other intervention. Conclusions: MDMA-assisted therapy demonstrated an impressive effect size; however, it is difficult to have confidence at this stage in this intervention due to the small numbers of participants included, and more research in this area is needed. There was no evidence to support the efficacy of any other drug-assisted interventions., Summary HIGHLIGHTS • We found that MDMA-assisted therapy is a novel and promising new treatment for severe PTSD. • Despite demonstrating an impressive effect size, more research is needed due to the small numbers of participants included. • We did not find evidence to recommend any other drug-assisted psychological intervention.

Published
2021

39. Psychometric properties of the PTSD Checklist for DSM-5 in a sample of trauma exposed mental health service users

Author

Anthony J. Downes, Catrin Lewis, Neil P. Roberts, Neil J Kitchiner, and Jonathan Ian Bisson

Subjects
Adult, Male, Mental Health Services, 050103 clinical psychology, medicine.medical_specialty, Adolescent, Psychometrics, psychometric assessment, RC435-571, Sample (statistics), PCL-5, Mental health service, DSM-5, mediciones auto reportadas, Stress Disorders, Post-Traumatic, 03 medical and health sciences, Young Adult, 0302 clinical medicine, mental disorders, medicine, Humans, 0501 psychology and cognitive sciences, Psychiatry, Aged, Psychiatric Status Rating Scales, Clinical Research Article, self-report measures, Post-traumatic stress disorder, psiquiátrico, 05 social sciences, Reproducibility of Results, Ptsd checklist, Middle Aged, Mental health, 030227 psychiatry, Checklist, Diagnostic and Statistical Manual of Mental Disorders, evaluación psicométrica, psychiatric, Female, Trastorno de estrés postraumático, Self Report, Psychology, 创伤后应激障碍,心理测评,PCL-5,精神病学,自我报告测量。, Research Article
Abstract

Background: PTSD self-report measures are frequently used in mental health services but very few have been evaluated in clinical samples that include civilians. The PCL-5 was developed to assess for DSM-5 PTSD. Objective: The aim of this study was to evaluate the psychometric properties of the PCL-5 in a sample of trauma-exposed mental health service users who were evidencing symptoms of PTSD. Method: Reliability and validity of the PCL-5 were investigated in a sample of 273 participants who reported past diagnosis for PTSD or who had screened positively for traumatic stress symptoms. Diagnostic utility was evaluated in comparison to the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5). Results: The PCL-5 demonstrated high internal consistency, good convergent and divergent validity, acceptable stability and good diagnostic utility. However, operating characteristics differed from those found in other samples. Scores of 43–44 provided optimal efficiency for diagnosing PTSD. A post hoc regression analysis showed that depression explained more of the variance in PCL-5 total score than the CAPS-5. Conclusion: Whilst the PCL-5 is psychometrically sound it appears to have difficulty differentiating self-reported depression and anxiety symptoms from PTSD in trauma-exposed mental health service users and clinicians should take care to assess full symptomatology when individuals screen positively on the PCL-5. Clinicians and researchers should also take care not to assume that operating characteristics of self-report PTSD measures are valid for mental health service users, when these have been established in other populations., HIGHLIGHTS • The PCL-5 demonstrated good psychometric properties in this sample of trauma-exposed mental health service users. • An optimal cut off score of 43-44 was higher than reported in other studies evaluating the PCL-5. • A post-hoc analysis suggested that the PCL-5 has difficulty differentiating self-reported depression and anxiety symptoms from PTSD. • Clinicians should undertake further assessment to establish differential diagnosis when PCL-5 scores are raised.

Published
2021

40. Dropout from psychological therapies for post-traumatic stress disorder (PTSD) in adults: systematic review and meta-analysis

Author

Neil P. Roberts, Catrin Lewis, Jonathan Ian Bisson, and Samuel Gibson

Subjects
Abandono, 中途退出, 050103 clinical psychology, Terapia Psicológica, education, MEDLINE, Psychological intervention, 创伤后应激障碍 (PTSD), review, RC435-571, Review Article, dropout, behavioral disciplines and activities, law.invention, 系统综述, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, health services administration, mental disorders, medicine, 0501 psychology and cognitive sciences, Trastorno de Estrés Postraumático (TEPT), Dropout (neural networks), health care economics and organizations, Post-traumatic stress disorder (PTSD), Psychiatry, therapy, Modalities, Meta-Análisis, business.industry, 05 social sciences, Revisión Sistemática, medicine.disease, 030227 psychiatry, Military personnel, trauma, 心理治疗, Meta-analysis, post-traumatic stress disorder, psychological, 元分析, business, • Dropout data from 116 Randomised Controlled Trials (RCTs) of psychological therapies for adults with PTSD was meta-analysed.• The pooled rate of dropout was 16% (95% CI 14–18%).• Meta-regression was conducted to explore possible predictors of dropout, Clinical psychology
Abstract

Background: Despite the established efficacy of psychological therapies for post-traumatic stress disorder (PTSD) there has been little systematic exploration of dropout rates.\ud Objective: To ascertain rates of dropout across different modalities of psychological therapy for PTSD and to explore potential sources of heterogeneity.\ud Method: A systematic review of dropout rates from randomized controlled trials (RCTs) of psychological therapies was conducted. The pooled rate of dropout from psychological therapies was estimated and reasons for heterogeneity explored using meta-regression.\ud Results:: The pooled rate of dropout from RCTs of psychological therapies for PTSD was 16% (95% CI 14–18%). There was evidence of substantial heterogeneity across studies. We found evidence that psychological therapies with a trauma-focus were significantly associated with greater dropout. There was no evidence of greater dropout from therapies delivered in a group format; from studies that recruited participants from clinical services rather than via advertisements; that included only military personnel/veterans; that were limited to participants traumatized by sexual traumas; that included a higher proportion of female participants; or from studies with a lower proportion of participants who were university educated.\ud Conclusions: Dropout rates from recommended psychological therapies for PTSD are high and this appears to be particularly true of interventions with a trauma focus. There is a need to further explore the reasons for dropout and to look at ways of increasing treatment retention.

Published
2020

41. Genome-wide association study of over 40,000 bipolar disorder cases provides new insights into the underlying biology

Author

Niamh Mullins, Andreas J. Forstner, Kevin S. O’Connell, Brandon Coombes, Jonathan R. I. Coleman, Zhen Qiao, Thomas D. Als, Tim B. Bigdeli, Sigrid Børte, Julien Bryois, Alexander W. Charney, Ole Kristian Drange, Michael J. Gandal, Saskia P. Hagenaars, Masashi Ikeda, Nolan Kamitaki, Minsoo Kim, Kristi Krebs, Georgia Panagiotaropoulou, Brian M. Schilder, Laura G. Sloofman, Stacy Steinberg, Vassily Trubetskoy, Bendik S. Winsvold, Hong-Hee Won, Liliya Abramova, Kristina Adorjan, Esben Agerbo, Mariam Al Eissa, Diego Albani, Ney Alliey-Rodriguez, Adebayo Anjorin, Verneri Antilla, Anastasia Antoniou, Swapnil Awasthi, Ji Hyun Baek, Marie Bækvad-Hansen, Nicholas Bass, Michael Bauer, Eva C. Beins, Sarah E. Bergen, Armin Birner, Carsten Bøcker Pedersen, Erlend Bøen, Marco P. Boks, Rosa Bosch, Murielle Brum, Ben M. Brumpton, Nathalie Brunkhorst-Kanaan, Monika Budde, Jonas Bybjerg-Grauholm, William Byerley, Murray Cairns, Miquel Casas, Pablo Cervantes, Toni-Kim Clarke, Cristiana Cruceanu, Alfredo Cuellar-Barboza, Julie Cunningham, David Curtis, Piotr M. Czerski, Anders M. Dale, Nina Dalkner, Friederike S. David, Franziska Degenhardt, Srdjan Djurovic, Amanda L. Dobbyn, Athanassios Douzenis, Torbjørn Elvsåshagen, Valentina Escott-Price, I. Nicol Ferrier, Alessia Fiorentino, Tatiana M. Foroud, Liz Forty, Josef Frank, Oleksandr Frei, Nelson B. Freimer, Louise Frisén, Katrin Gade, Julie Garnham, Joel Gelernter, Marianne Giørtz Pedersen, Ian R. Gizer, Scott D. Gordon, Katherine Gordon-Smith, Tiffany A. Greenwood, Jakob Grove, José Guzman-Parra, Kyooseob Ha, Magnus Haraldsson, Martin Hautzinger, Urs Heilbronner, Dennis Hellgren, Stefan Herms, Per Hoffmann, Peter A. Holmans, Laura Huckins, Stéphane Jamain, Jessica S. Johnson, Janos L. Kalman, Yoichiro Kamatani, James L. Kennedy, Sarah Kittel-Schneider, James A. Knowles, Manolis Kogevinas, Maria Koromina, Thorsten M. Kranz, Henry R. Kranzler, Michiaki Kubo, Ralph Kupka, Steven A. Kushner, Catharina Lavebratt, Jacob Lawrence, Markus Leber, Heon-Jeong Lee, Phil H. Lee, Shawn E. Levy, Catrin Lewis, Calwing Liao, Susanne Lucae, Martin Lundberg, Donald J. MacIntyre, Sigurdur H. Magnusson, Wolfgang Maier, Adam Maihofer, Dolores Malaspina, Eirini Maratou, Lina Martinsson, Manuel Mattheisen, Steven A. McCarroll, Nathaniel W. McGregor, Peter McGuffin, James D. McKay, Helena Medeiros, Sarah E. Medland, Vincent Millischer, Grant W. Montgomery, Jennifer L. Moran, Derek W. Morris, Thomas W. Mühleisen, Niamh O’Brien, Claire O’Donovan, Loes M. Olde Loohuis, Lilijana Oruc, Sergi Papiol, Antonio F. Pardiñas, Amy Perry, Andrea Pfennig, Evgenia Porichi, James B. Potash, Digby Quested, Towfique Raj, Mark H. Rapaport, J. Raymond DePaulo, Eline J. Regeer, John P. Rice, Fabio Rivas, Margarita Rivera, Julian Roth, Panos Roussos, Douglas M. Ruderfer, Cristina Sánchez-Mora, Eva C. Schulte, Fanny Senner, Sally Sharp, Paul D. Shilling, Engilbert Sigurdsson, Lea Sirignano, Claire Slaney, Olav B. Smeland, Daniel J. Smith, Janet L. Sobell, Christine Søholm Hansen, Maria Soler Artigas, Anne T. Spijker, Dan J. Stein, John S. Strauss, Beata Świątkowska, Chikashi Terao, Thorgeir E. Thorgeirsson, Claudio Toma, Paul Tooney, Evangelia-Eirini Tsermpini, Marquis P. Vawter, Helmut Vedder, James T. R. Walters, Stephanie H. Witt, Simon Xi, Wei Xu, Jessica Mei Kay Yang, Allan H. Young, Hannah Young, Peter P. Zandi, Hang Zhou, Lea Zillich, HUNT All-In Psychiatry, Rolf Adolfsson, Ingrid Agartz, Martin Alda, Lars Alfredsson, Gulja Babadjanova, Lena Backlund, Bernhard T. Baune, Frank Bellivier, Susanne Bengesser, Wade H. Berrettini, Douglas H. R. Blackwood, Michael Boehnke, Anders D. Børglum, Gerome Breen, Vaughan J. Carr, Stanley Catts, Aiden Corvin, Nicholas Craddock, Udo Dannlowski, Dimitris Dikeos, Tõnu Esko, Bruno Etain, Panagiotis Ferentinos, Mark Frye, Janice M. Fullerton, Micha Gawlik, Elliot S. Gershon, Fernando S. Goes, Melissa J. Green, Maria Grigoroiu-Serbanescu, Joanna Hauser, Frans Henskens, Jan Hillert, Kyung Sue Hong, David M. Hougaard, Christina M. Hultman, Kristian Hveem, Nakao Iwata, Assen V. Jablensky, Ian Jones, Lisa A. Jones, René S. Kahn, John R. Kelsoe, George Kirov, Mikael Landén, Marion Leboyer, Cathryn M. Lewis, Qingqin S. Li, Jolanta Lissowska, Christine Lochner, Carmel Loughland, Nicholas G. Martin, Carol A. Mathews, Fermin Mayoral, Susan L. McElroy, Andrew M. McIntosh, Francis J. McMahon, Ingrid Melle, Patricia Michie, Lili Milani, Philip B. Mitchell, Gunnar Morken, Ole Mors, Preben Bo Mortensen, Bryan Mowry, Bertram Müller-Myhsok, Richard M. Myers, Benjamin M. Neale, Caroline M. Nievergelt, Merete Nordentoft, Markus M. Nöthen, Michael C. O’Donovan, Ketil J. Oedegaard, Tomas Olsson, Michael J. Owen, Sara A. Paciga, Chris Pantelis, Carlos Pato, Michele T. Pato, George P. Patrinos, Roy H. Perlis, Danielle Posthuma, Josep Antoni Ramos-Quiroga, Andreas Reif, Eva Z. Reininghaus, Marta Ribasés, Marcella Rietschel, Stephan Ripke, Guy A. Rouleau, Takeo Saito, Ulrich Schall, Martin Schalling, Peter R. Schofield, Thomas G. Schulze, Laura J. Scott, Rodney J. Scott, Alessandro Serretti, Cynthia Shannon Weickert, Jordan W. Smoller, Hreinn Stefansson, Kari Stefansson, Eystein Stordal, Fabian Streit, Patrick F. Sullivan, Gustavo Turecki, Arne E. Vaaler, Eduard Vieta, John B. Vincent, Irwin D. Waldman, Thomas W. Weickert, Thomas Werge, Naomi R. Wray, John-Anker Zwart, Joanna M. Biernacka, John I. Nurnberger, Sven Cichon, Howard J. Edenberg, Eli A. Stahl, Andrew McQuillin, Arianna Di Florio, Roel A. Ophoff, and Ole A. Andreassen

Subjects
Genetics, 0303 health sciences, Druggability, Genome-wide association study, Biology, medicine.disease, 3. Good health, 03 medical and health sciences, 0302 clinical medicine, Gene expression, Expression quantitative trait loci, medicine, Bipolar disorder, Synaptic signaling, Prefrontal cortex, Gene, 030217 neurology & neurosurgery, 030304 developmental biology
Abstract

Bipolar disorder (BD) is a heritable mental illness with complex etiology. We performed a genome-wide association study (GWAS) of 41,917 BD cases and 371,549 controls of European ancestry, which identified 64 associated genomic loci. BD risk alleles were enriched in genes in synaptic signaling pathways and brain-expressed genes, particularly those with high specificity of expression in neurons of the prefrontal cortex and hippocampus. Significant signal enrichment was found in genes encoding targets of antipsychotics, calcium channel blockers, antiepileptics and anesthetics. Integrating eQTL data implicated 15 genes robustly linked to BD via gene expression, including druggable genes such as HTR6, MCHR1, DCLK3 and FURIN. This GWAS provides the best-powered BD polygenic scores to date, when applied in both European and diverse ancestry samples. Analyses of BD subtypes indicated high but imperfect genetic correlation between BD type I and II and identified additional associated loci. Together, these results advance our understanding of the biological etiology of BD, identify novel therapeutic leads and prioritize genes for functional follow-up studies.

Published
2020

42. Genome-wide association study of more than 40,000 bipolar disorder cases provides new insights into the underlying biology

Author

Niamh, Mullins, Andreas J, Forstner, Kevin S, O'Connell, Brandon, Coombes, Jonathan R I, Coleman, Zhen, Qiao, Thomas D, Als, Tim B, Bigdeli, Sigrid, Børte, Julien, Bryois, Alexander W, Charney, Ole Kristian, Drange, Michael J, Gandal, Saskia P, Hagenaars, Masashi, Ikeda, Nolan, Kamitaki, Minsoo, Kim, Kristi, Krebs, Georgia, Panagiotaropoulou, Brian M, Schilder, Laura G, Sloofman, Stacy, Steinberg, Vassily, Trubetskoy, Bendik S, Winsvold, Hong-Hee, Won, Liliya, Abramova, Kristina, Adorjan, Esben, Agerbo, Mariam, Al Eissa, Diego, Albani, Ney, Alliey-Rodriguez, Adebayo, Anjorin, Verneri, Antilla, Anastasia, Antoniou, Swapnil, Awasthi, Ji Hyun, Baek, Marie, Bækvad-Hansen, Nicholas, Bass, Michael, Bauer, Eva C, Beins, Sarah E, Bergen, Armin, Birner, Carsten, Bøcker Pedersen, Erlend, Bøen, Marco P, Boks, Rosa, Bosch, Murielle, Brum, Ben M, Brumpton, Nathalie, Brunkhorst-Kanaan, Monika, Budde, Jonas, Bybjerg-Grauholm, William, Byerley, Murray, Cairns, Miquel, Casas, Pablo, Cervantes, Toni-Kim, Clarke, Cristiana, Cruceanu, Alfredo, Cuellar-Barboza, Julie, Cunningham, David, Curtis, Piotr M, Czerski, Anders M, Dale, Nina, Dalkner, Friederike S, David, Franziska, Degenhardt, Srdjan, Djurovic, Amanda L, Dobbyn, Athanassios, Douzenis, Torbjørn, Elvsåshagen, Valentina, Escott-Price, I Nicol, Ferrier, Alessia, Fiorentino, Tatiana M, Foroud, Liz, Forty, Josef, Frank, Oleksandr, Frei, Nelson B, Freimer, Louise, Frisén, Katrin, Gade, Julie, Garnham, Joel, Gelernter, Marianne, Giørtz Pedersen, Ian R, Gizer, Scott D, Gordon, Katherine, Gordon-Smith, Tiffany A, Greenwood, Jakob, Grove, José, Guzman-Parra, Kyooseob, Ha, Magnus, Haraldsson, Martin, Hautzinger, Urs, Heilbronner, Dennis, Hellgren, Stefan, Herms, Per, Hoffmann, Peter A, Holmans, Laura, Huckins, Stéphane, Jamain, Jessica S, Johnson, Janos L, Kalman, Yoichiro, Kamatani, James L, Kennedy, Sarah, Kittel-Schneider, James A, Knowles, Manolis, Kogevinas, Maria, Koromina, Thorsten M, Kranz, Henry R, Kranzler, Michiaki, Kubo, Ralph, Kupka, Steven A, Kushner, Catharina, Lavebratt, Jacob, Lawrence, Markus, Leber, Heon-Jeong, Lee, Phil H, Lee, Shawn E, Levy, Catrin, Lewis, Calwing, Liao, Susanne, Lucae, Martin, Lundberg, Donald J, MacIntyre, Sigurdur H, Magnusson, Wolfgang, Maier, Adam, Maihofer, Dolores, Malaspina, Eirini, Maratou, Lina, Martinsson, Manuel, Mattheisen, Steven A, McCarroll, Nathaniel W, McGregor, Peter, McGuffin, James D, McKay, Helena, Medeiros, Sarah E, Medland, Vincent, Millischer, Grant W, Montgomery, Jennifer L, Moran, Derek W, Morris, Thomas W, Mühleisen, Niamh, O'Brien, Claire, O'Donovan, Loes M, Olde Loohuis, Lilijana, Oruc, Sergi, Papiol, Antonio F, Pardiñas, Amy, Perry, Andrea, Pfennig, Evgenia, Porichi, James B, Potash, Digby, Quested, Towfique, Raj, Mark H, Rapaport, J Raymond, DePaulo, Eline J, Regeer, John P, Rice, Fabio, Rivas, Margarita, Rivera, Julian, Roth, Panos, Roussos, Douglas M, Ruderfer, Cristina, Sánchez-Mora, Eva C, Schulte, Fanny, Senner, Sally, Sharp, Paul D, Shilling, Engilbert, Sigurdsson, Lea, Sirignano, Claire, Slaney, Olav B, Smeland, Daniel J, Smith, Janet L, Sobell, Christine, Søholm Hansen, Maria, Soler Artigas, Anne T, Spijker, Dan J, Stein, John S, Strauss, Beata, Świątkowska, Chikashi, Terao, Thorgeir E, Thorgeirsson, Claudio, Toma, Paul, Tooney, Evangelia-Eirini, Tsermpini, Marquis P, Vawter, Helmut, Vedder, James T R, Walters, Stephanie H, Witt, Simon, Xi, Wei, Xu, Jessica Mei Kay, Yang, Allan H, Young, Hannah, Young, Peter P, Zandi, Hang, Zhou, Lea, Zillich, Rolf, Adolfsson, Ingrid, Agartz, Martin, Alda, Lars, Alfredsson, Gulja, Babadjanova, Lena, Backlund, Bernhard T, Baune, Frank, Bellivier, Susanne, Bengesser, Wade H, Berrettini, Douglas H R, Blackwood, Michael, Boehnke, Anders D, Børglum, Gerome, Breen, Vaughan J, Carr, Stanley, Catts, Aiden, Corvin, Nicholas, Craddock, Udo, Dannlowski, Dimitris, Dikeos, Tõnu, Esko, Bruno, Etain, Panagiotis, Ferentinos, Mark, Frye, Janice M, Fullerton, Micha, Gawlik, Elliot S, Gershon, Fernando S, Goes, Melissa J, Green, Maria, Grigoroiu-Serbanescu, Joanna, Hauser, Frans, Henskens, Jan, Hillert, Kyung Sue, Hong, David M, Hougaard, Christina M, Hultman, Kristian, Hveem, Nakao, Iwata, Assen V, Jablensky, Ian, Jones, Lisa A, Jones, René S, Kahn, John R, Kelsoe, George, Kirov, Mikael, Landén, Marion, Leboyer, Cathryn M, Lewis, Qingqin S, Li, Jolanta, Lissowska, Christine, Lochner, Carmel, Loughland, Nicholas G, Martin, Carol A, Mathews, Fermin, Mayoral, Susan L, McElroy, Andrew M, McIntosh, Francis J, McMahon, Ingrid, Melle, Patricia, Michie, Lili, Milani, Philip B, Mitchell, Gunnar, Morken, Ole, Mors, Preben Bo, Mortensen, Bryan, Mowry, Bertram, Müller-Myhsok, Richard M, Myers, Benjamin M, Neale, Caroline M, Nievergelt, Merete, Nordentoft, Markus M, Nöthen, Michael C, O'Donovan, Ketil J, Oedegaard, Tomas, Olsson, Michael J, Owen, Sara A, Paciga, Chris, Pantelis, Carlos, Pato, Michele T, Pato, George P, Patrinos, Roy H, Perlis, Danielle, Posthuma, Josep Antoni, Ramos-Quiroga, Andreas, Reif, Eva Z, Reininghaus, Marta, Ribasés, Marcella, Rietschel, Stephan, Ripke, Guy A, Rouleau, Takeo, Saito, Ulrich, Schall, Martin, Schalling, Peter R, Schofield, Thomas G, Schulze, Laura J, Scott, Rodney J, Scott, Alessandro, Serretti, Cynthia, Shannon Weickert, Jordan W, Smoller, Hreinn, Stefansson, Kari, Stefansson, Eystein, Stordal, Fabian, Streit, Patrick F, Sullivan, Gustavo, Turecki, Arne E, Vaaler, Eduard, Vieta, John B, Vincent, Irwin D, Waldman, Thomas W, Weickert, Thomas, Werge, Naomi R, Wray, John-Anker, Zwart, Joanna M, Biernacka, John I, Nurnberger, Sven, Cichon, Howard J, Edenberg, Eli A, Stahl, Andrew, McQuillin, Arianna, Di Florio, Roel A, Ophoff, and Ole A, Andreassen

Subjects
Major Histocompatibility Complex, Multifactorial Inheritance, Bipolar Disorder, Phenotype, Genome, Human, Risk Factors, Case-Control Studies, Quantitative Trait Loci, Chromosomes, Human, Humans, Genetic Predisposition to Disease, Genome-Wide Association Study
Abstract

Bipolar disorder is a heritable mental illness with complex etiology. We performed a genome-wide association study of 41,917 bipolar disorder cases and 371,549 controls of European ancestry, which identified 64 associated genomic loci. Bipolar disorder risk alleles were enriched in genes in synaptic signaling pathways and brain-expressed genes, particularly those with high specificity of expression in neurons of the prefrontal cortex and hippocampus. Significant signal enrichment was found in genes encoding targets of antipsychotics, calcium channel blockers, antiepileptics and anesthetics. Integrating expression quantitative trait locus data implicated 15 genes robustly linked to bipolar disorder via gene expression, encoding druggable targets such as HTR6, MCHR1, DCLK3 and FURIN. Analyses of bipolar disorder subtypes indicated high but imperfect genetic correlation between bipolar disorder type I and II and identified additional associated loci. Together, these results advance our understanding of the biological etiology of bipolar disorder, identify novel therapeutic leads and prioritize genes for functional follow-up studies.

Published
2020

43. Non-pharmacological and non-psychological approaches to the treatment of PTSD: results of a systematic review and meta-analyses

Author

Catrin Lewis, Neil P. Roberts, Marieke J. van Gelderen, and Jonathan Ian Bisson

Subjects
Psychiatry, 非药物, business.industry, Short Communication, Revisión sistemática, RC435-571, No psicológica, non-psychological, Tratamiento para el TEPT, 系统综述, non-pharmacological, Systematic review, systematic review, Ptsd treatment, PTSD治疗, ptsd treatment, Medicine, Other, business, Non pharmacological, Clinical psychology, No farmacológica, 非心理
Abstract

Background: Non-pharmacological and non-psychological approaches to the treatment of post-traumatic stress disorder (PTSD) have often been excluded from systematic reviews and meta-analyses. Consequently, we know little regarding their efficacy. Objective: To determine the effect sizes of non-pharmacological and non-psychological treatment approaches for PTSD. Method: We undertook a systematic review and meta-analyses following Cochrane Collaboration guidelines. A pre-determined definition of clinical importance was applied to the results and the quality of evidence was appraised using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. Results: 30 randomised controlled trials (RCTs) of a range of heterogeneous non- psychological and non-pharmacological interventions (28 in adults, two in children and adolescents) were included. There was emerging evidence for six different approaches (acupuncture, neurofeedback, saikokeishikankyoto (a herbal preparation), somatic experiencing, transcranial magnetic stimulation, and yoga). Conclusions: Given the level of evidence available, it would be premature to offer non- pharmacological and non-psychological interventions routinely, but those with evidence of efficacy provide alternatives for people who do not respond to, do not tolerate or do not want more conventional evidence-based interventions. This review should stimulate further research in this area.

Published
2020

44. Preventing the onset of post traumatic stress disorder

Author

Tracey Varker, Neil P. Roberts, Laurence Astill Wright, Andrea Phelps, Catrin Lewis, Jonathan Ian Bisson, Kimberley A Jones, and Marit Sijbrandij

Subjects
Adult, 050103 clinical psychology, medicine.medical_specialty, MEDLINE, Psychological intervention, PsycINFO, law.invention, Stress Disorders, Post-Traumatic, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, SDG 3 - Good Health and Well-being, law, Intervention (counseling), medicine, Humans, 0501 psychology and cognitive sciences, Intensive care medicine, Cognitive Behavioral Therapy, Prevention, 05 social sciences, Pharmacological, Traumatic stress, Post-incident, PTSD, Mental health, Acute Stress Disorder, 030227 psychiatry, Psychiatry and Mental health, Clinical Psychology, Psychological, Pre-incident, Psychology, Psychosocial
Abstract

Post-traumatic stress disorder (PTSD) is a common mental health condition that requires exposure to a traumatic event. This provides unique opportunities for prevention that are not available for other disorders. The aim of this review was to undertake a systematic review and evaluation of randomized controlled trials (RCTs) of interventions designed to prevent PTSD in adults. Searches involving Cochrane, Embase, Medline, PsycINFO, PILOTS and Pubmed databases were undertaken to identify RCTs of pre-incident preparedness and post-incident interventions until May 2019. Six pre-incident and 69 post-incident trials were identified that could be included in meta-analyses. The overall quality of the evidence was low. There was emerging evidence that some interventions may be helpful but an absence of evidence for any intervention that can be strongly recommended for universal, selected or indicated prevention before or within the first three months of a traumatic event. The strongest results were found for cognitive-behavioural therapy with a trauma focus (CBT-T) in individuals with a diagnosis of acute stress disorder which supports calls to detect and treat individuals with significant symptoms rather than providing blanket preventative interventions. Further research is required to optimally configure existing interventions with some evidence of effect and to develop novel interventions to address this major public health issue.

Published
2020

45. Psychological therapies for post-traumatic stress disorder in adults: systematic review and meta-analysis

Author

Martin Andrew, Jonathan Ian Bisson, Catrin Lewis, Neil P. Roberts, and Elise Starling

Subjects
050103 clinical psychology, Psychotherapist, medicine.medical_treatment, RC435-571, Psychological intervention, TEPT, behavioral disciplines and activities, 系统评价, 03 medical and health sciences, 0302 clinical medicine, systematic review, mental disorders, Medicine, revisión sistemática, 0501 psychology and cognitive sciences, Grading (education), Psychiatry, • This review informed the latest ISTSS treatment guidelines. It summarises the current evidence-base in relation to the effect of specific therapies for PTSD, business.industry, 05 social sciences, terapia psicológica, Traumatic stress, PTSD, 030227 psychiatry, Posttraumatic stress, Systematic review, 心理治疗, psychological therapy, Meta-analysis, Cognitive therapy, Cognitive processing therapy, Reviews that informed the ISTSS guidelines update, business
Abstract

Background: Psychological therapies are the recommended first-line treatment for posttraumatic\ud stress disorder (PTSD). Previous systematic reviews have grouped theoretically\ud similar interventions to determine differences between broadly distinct approaches.\ud Consequently, we know little regarding the relative efficacy of the specific manualised\ud therapies commonly applied to the treatment of PTSD.\ud Objective: To determine the effect sizes of manualised therapies for PTSD.\ud Methods: We undertook a systematic review following Cochrane Collaboration guidelines. A\ud pre determined definition of clinical importance was applied to the results and the quality of\ud evidence was appraised using the Grading of Recommendations, Assessment, Development\ud and Evaluations (GRADE) approach.\ud Results: 114 randomised controlled trials (RCTs) of 8171 participants were included. There\ud was robust evidence that the therapies broadly defined as CBT with a trauma focus (CBT-T),\ud as well as Eye Movement Desensitisation and Reprocessing (EMDR), had a clinically important\ud effect. The manualised CBT-Ts with the strongest evidence of effect were Cognitive\ud Processing Therapy (CPT); Cognitive Therapy (CT); and Prolonged Exposure (PE). There was\ud also some evidence supporting CBT without a trauma focus; group CBT with a trauma focus;\ud guided internet-based CBT; and Present Centred Therapy (PCT). There was emerging\ud evidence for a number of other therapies.\ud Conclusions: A recent increase in RCTs of psychological therapies for PTSD, results in a more\ud confident recommendation of CBT-T and EMDR as the first-line treatments. Among the CBTTs\ud considered by the review CPT, CT and PE should be the treatments of choice. The findings\ud should guide evidence informed shared decision making between patient and clinician.

Published
2020

46. Internet-based cognitive behavioural therapy for post-traumatic stress disorder: systematic review and meta- analysis

Author

Catrin Lewis, Natalie Simon, Neil P. Roberts, Andrew Bethell, and Jonathan Ian Bisson

Subjects
medicine.medical_specialty, Cognitive Behavioral Therapy, business.industry, Traumatic stress, Psychological intervention, Internet delivered, Cognition, behavioral disciplines and activities, Confidence interval, 030227 psychiatry, Stress Disorders, Post-Traumatic, 03 medical and health sciences, Psychiatry and Mental health, 0302 clinical medicine, Relative risk, Meta-analysis, mental disorders, Physical therapy, medicine, Effective treatment, Humans, business, 030217 neurology & neurosurgery, Internet-Based Intervention
Abstract

Objective\ud To determine whether Internet‐delivered cognitive behavioural therapy (i‐CBT) is an effective treatment for those who meet diagnostic criteria for post‐traumatic stress disorder (PTSD).\ud \ud Method\ud A systematic review was undertaken according to Cochrane Collaboration Guidelines. The primary outcome measures were reduction in PTSD symptoms and drop‐out. Categorical outcomes were meta‐analysed as risk ratios (RRs) and continuous outcomes as mean differences (MDs) or standardised mean differences (SMDs).\ud \ud Results\ud Ten studies with 720 participants were included. Evidence showed that i‐CBT may be associated with a clinically important reduction in post‐treatment PTSD symptoms compared with wait list (SMD −0.60, 95% confidence interval −0.97 to −0.24; N = 560); however, only three studies reported follow‐up data, and there was no evidence to support the maintenance of symptom improvement at follow‐up of 3–6 months. There was no evidence of a difference in PTSD symptoms between i‐CBT and Internet‐delivered non‐CBT post‐treatment. There was evidence of greater treatment effect from trauma‐focused i‐CBT than i‐CBT without a trauma focus, as well as evidence that treatment effect was increased by the provision of guidance.\ud \ud Conclusions\ud While the review found some beneficial effects of i‐CBT for PTSD post‐treatment, the quality of the evidence was very low because of the small number of included trials and there was insufficient evidence to support the maintenance of improvement at follow‐up of 3–6 months. Further work is required to establish non‐inferiority to current first‐line interventions; to determine long‐term efficacy; to explore mechanisms of effect; and to establish optimal levels of guidance.

Published
2019

47. Pharmacological prevention and early treatment of post-traumatic stress disorder and acute stress disorder: a systematic review and meta-analysis

Author

Marit Sijbrandij, Rob Sinnerton, Neil P. Roberts, Laurence Astill Wright, Jonathan Ian Bisson, Catrin Lewis, Clinical Psychology, and APH - Mental Health

Subjects
medicine.medical_specialty, Poison control, Pathogenesis, Placebo, Article, lcsh:RC321-571, Stress Disorders, Post-Traumatic, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, Internal medicine, Humans, Medicine, Escitalopram, Adverse effect, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, Stress Disorders, Traumatic, Acute, Biological Psychiatry, business.industry, Traumatic stress, SDG 10 - Reduced Inequalities, Acute Stress Disorder, 030227 psychiatry, Psychiatry and Mental health, Meta-analysis, Relative risk, Clinical pharmacology, Psychiatric disorders, business, 030217 neurology & neurosurgery, medicine.drug
Abstract

Post-traumatic stress disorder (PTSD) is a common mental disorder associated with significant distress and reduced functioning. Its occurrence after a severe traumatic event and association with characteristic neurobiological changes make PTSD a good candidate for pharmacological prevention and early treatment. The primary aim for this systematic review and meta-analysis was to assess whether pharmacological interventions when compared to placebo, or other pharmacological/psychosocial interventions resulted in a clinically significant reduction or prevention of symptoms, improved functioning or quality of life, presence of disorder, or adverse effects. A systematic search was undertaken to identify RCTs, which used early pharmacotherapy (within three months of a traumatic event) to prevent and treat PTSD and acute stress disorder (ASD) in children and adults. Using Cochrane Collaboration methodology, RCTs were identified and rated for risk of bias. Available data was pooled to calculate risk ratios (RR) for PTSD prevalence and standardised mean differences (SMD) for PTSD severity. 19 RCTs met the inclusion criteria; 16 studies with adult participants and three with children. The methodological quality of most trials was low. Only hydrocortisone in adults was found to be superior to placebo (3 studies, n = 88, RR: 0.21 (CI 0.05 to 0.89)) although this was in populations with severe physical illness, raising concerns about generalisability. No significant effects were found for the other pharmacotherapies investigated (propranolol, oxytocin, gabapentin, fish oil (1470 mg DHA/147 mg EPA), fish oil (224 mg DHA/22.4 mg EPA), dexamethasone, escitalopram, imipramine and chloral hydrate). Hydrocortisone shows the most promise, of pharmacotherapies subjected to RCTs, as an emerging intervention in the prevention of PTSD within three months after trauma and should be a target for further investigation. The limited evidence for hydrocortisone and its adverse effects mean it cannot be recommended for routine use, but, it could be considered as a preventative intervention for people with severe physical illness or injury, shortly after a traumatic event, as long as there are no contraindications. More research is needed using larger, high quality RCTs to establish the most efficacious use of hydrocortisone in different populations and optimal dosing, dosing window and route. There is currently a lack of evidence to suggest that other pharmacological agents are likely to be effective.

Published
2019

48. Early psychological intervention following recent trauma: A systematic review and meta-analysis

Author

Catrin Lewis, Neil J Kitchiner, Justin Kenardy, Neil P. Roberts, and Jonathan Ian Bisson

Subjects
050103 clinical psychology, prevención, lcsh:RC435-571, 早期干预, medicine.medical_treatment, Psychological intervention, Review Article, intervención temprana, 系统综述, law.invention, 03 medical and health sciences, 0302 clinical medicine, Trastorno de estres postraumático, Randomized controlled trial, prevention, systematic review, law, Intervention (counseling), lcsh:Psychiatry, Eye movement desensitization and reprocessing, medicine, 0501 psychology and cognitive sciences, psychological intervention, business.industry, 05 social sciences, 心理干预, Traumatic stress, Revisión Sistemática, • We found no clinically important evidence for the benefit of early intervention offered to all individuals exposed to a traumatic event, regardless of symptomatology.• There was evidence of a clinically important effect for trauma-focused CBT (CBT-T), brief EMDR and cognitive therapy without exposure.• Evidence was strongest for CBT-T, intervencion psicológica, Acute Stress Disorder, 预防, 030227 psychiatry, meta-analysis, early intervention, 创伤后应激障碍, Meta-analysis, Cognitive therapy, post-traumatic stress disorder, meta-análisis, 元分析, business, Clinical psychology
Abstract

Background: Post-traumatic stress disorder (PTSD) is a common and debilitating disorder which has a significant impact on the lives of sufferers. A number of early psychological interventions have been developed to try to prevent chronic difficulties. Objective: The objective of this study was to establish the current evidence for the effectiveness of multiple session early psychological interventions aimed at preventing or treating traumatic stress symptoms beginning within three months of trauma exposure. Methods: Randomized controlled trials of early multiple session psychological interventions aimed at preventing or reducing traumatic stress symptoms of individuals exposed to a traumatic event, fulfiling trauma criteria for an ICD or DSM diagnosis of PTSD were identified through a search of the Cochrane Common Mental Disorders Group Clinical Trials Registers database, the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, PsycINFO and PILOTS. Two authors independently extracted study details and data and completed risk of bias assessments. Analyses were undertaken using Review Manager software. Quality of findings were rated according to ‘Grades of Recommendation, Assessment, Development, and Evaluation’ (GRADE) and appraised for clinical importance. Results: Sixty-one studies evaluating a variety of interventions were identified. For individuals exposed to a trauma who were not pre-screened for traumatic stress symptoms there were no clinically important differences between any intervention and usual care. For individuals reporting traumatic stress symptoms we found clinically important evidence of benefits for trauma-focused cognitive-behavioural therapy (CBT-T), cognitive therapy without exposure and eye movement desensitization and reprocessing (EMDR). Differences were greatest for those diagnosed with acute stress disorder (ASD) and PTSD. Conclusions: There is evidence for the effectiveness of several early psychological interventions for individuals with traumatic stress symptoms following trauma exposure, especially for those meeting the diagnostic threshold for ASD or PTSD. Evidence is strongest for trauma-focused CBT. • We found no clinically important evidence for the benefit of early intervention offered to all individuals exposed to a traumatic event, regardless of symptomatology.• There was evidence of a clinically important effect for trauma-focused CBT (CBT-T), brief EMDR and cognitive therapy without exposure.• Evidence was strongest for CBT-T.

Published
2019

49. International meta-analysis of PTSD genome-wide association studies identifies sex- and ancestry-specific genetic risk loci

Author

Magali Haas, Nancy L. Saccone, Barbara O. Rothbaum, Jessica L. Maples-Keller, Aferdita Goci Uka, Soraya Seedat, Marie Bækvad-Hansen, Scott R. Sponheim, Sixto E. Sanchez, Nastassja Koen, Alma Dzubur-Kulenovic, Sonya B. Norman, Douglas Maurer, Julia S. Seng, Matig R. Mavissakalian, Wesley K. Thompson, Douglas L. Delahanty, Daniel F. Levey, Matthew S. Panizzon, Megan Brashear, Lindsay A. Farrer, Kenneth J. Ruggiero, John P. Rice, Robert H. Pietrzak, Lori A. Zoellner, Charles F. Gillespie, Lauren A.M. Lebois, Alaptagin Khan, Robert J. Ursano, Chia-Yen Chen, Yunpeng Wang, Karestan C. Koenen, Dewleen G. Baker, Joseph R. Calabrese, Jurjen J. Luykx, Andrew C. Heath, Shareefa Dalvie, Eric O. Johnson, Laura J. Bierut, Catrin Lewis, Henry R. Kranzler, Sarah McLeay, Caroline M. Nievergelt, Michelle F. Dennis, Miro Jakovljević, Merete Nordentoft, Michael A. Hauser, Alexander C. McFarlane, Mark J. Daly, Mark W. Logue, Ole Mors, Andrea L. Roberts, Adam X. Maihofer, S. Bryn Austin, Bart P. F. Rutten, Christiane Wolf, Erika J. Wolf, Sarah D. Linnstaedt, Janine D. Flory, Melanie E. Garrett, Christina M. Sheerin, Elbert Geuze, Alicia K. Smith, Christiaan H. Vinkers, Divya Mehta, Matthew Peverill, Bruce R. Lawford, Scott D. Gordon, José Miguel Caldas de Almeida, Miranda Van Hooff, Supriya Harnal, Edward S. Peters, Ross McD. Young, Derrick Silove, Jennifer A. Sumner, Gerome Breen, Allison E. Ashley-Koch, Michelle A. Williams, Antonia V. Seligowski, A.C. Bustamante, Dick Schijven, Joel Gelernter, Jordan W. Smoller, Nicholas G. Martin, Ananda B. Amstadter, Anthony P. King, Jonathan R. I. Coleman, Alexandra Evans, Alan L. Peterson, Kerry J. Ressler, Martin H. Teicher, Angela G. Junglen, Regina E. McGlinchey, Jonathan Ian Bisson, Adriana Lori, Karen-Inge Karstoft, Marti Jett, Bekh Bradley, Murray B. Stein, Michael J. Lyons, Nikolaos P. Daskalakis, Anders D. Børglum, Holly K. Orcutt, Sherry Winternitz, Carol E. Franz, Meaghan O'Donnell, Elizabeth A. Bolger, Seth G. Disner, William P. Milberg, Renato Polimanti, David Forbes, Alex O. Rothbaum, Edward J. Trapido, William S. Kremen, David M. Hougaard, Ronald C. Kessler, Dan J. Stein, Sian M. J. Hemmings, Tanja Jovanovic, Jonathan D. Wolff, Allison C. Provost, Stephan Ripke, Rachel Yehuda, Karmel W. Choi, Sandro Galea, Richard A. Bryant, Victoria B. Risbrough, Eric Vermetten, Dragan Babić, Ian Jones, Jürgen Deckert, Anders M. Dale, Rajendra A. Morey, Benjamin M. Neale, Melissa A. Polusny, Norah C. Feeny, Xue Jun Qin, Hongyu Zhao, Mark W. Miller, Guia Guffanti, Allison E. Aiello, Charles R. Marmar, Esmina Avdibegović, Torsten Klengel, Jennifer S. Stevens, Jean C. Beckham, Katharina Domschke, Katy Torres, Elliot C. Nelson, Laramie E. Duncan, Bozo Lugonja, Joanne Voisey, Milissa L. Kaufman, Ole A. Andreassen, Douglas E. Williamson, Paul A. Arbisi, Søren Bo Andersen, Thomas Werge, Monica Uddin, Katie A. McLaughlin, Zhewu Wang, Bizu Gelaye, Andrew Ratanatharathorn, Elizabeth G. Atkinson, Charles P. Morris, Preben Bo Mortensen, Christopher R. Erbes, Lynn M. Almli, Jonas Bybjerg-Grauholm, Alicia R. Martin, Nathan A. Kimbrel, Peter Roy-Byrne, Ariane Rung, Israel Liberzon, Leigh van den Heuvel, Marco P. Boks, Keith A. Young, Samuel A. McLean, Rasha Hammamieh, Centro de Estudos de Doenças Crónicas (CEDOC), NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM), MUMC+: MA Psychiatrie (3), Psychiatrie & Neuropsychologie, RS: MHeNs - R3 - Neuroscience, Anatomy and neurosciences, Psychiatry, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, and APH - Mental Health

Subjects
0301 basic medicine, Male, Genetics of the nervous system, SYMPTOMS, Chemistry(all), LD SCORE REGRESSION, General Physics and Astronomy, Datasets as Topic, EFFICIENT, Genome-wide association study, PTSD, genome, Biochemistry, Genome-wide association studies, Stress Disorders, Post-Traumatic, 0302 clinical medicine, POSTTRAUMATIC-STRESS-DISORDER, African Continental Ancestry Group / genetics, HUMAN DEMOGRAPHIC HISTORY, Ubiquitin-Protein Ligases / genetics, lcsh:Science, Post-traumatic stress disorder (PTSD), Veterans, TRAUMA, Genetics, Multidisciplinary, 3. Good health, SNP HERITABILITY, Meta-analysis, Cohort, Behavioural genetics, Female, Ubiquitin-Protein Ligases, Science, Black People, Stress Disorders, Post-Traumatic / genetics, Biology, Physics and Astronomy(all), General Biochemistry, Genetics and Molecular Biology, Article, White People, 03 medical and health sciences, Sex Factors, Genetic variation, mental disorders, medicine, Journal Article, SNP, Humans, Genetic Predisposition to Disease, European Continental Ancestry Group / genetics, Veterans / statistics & numerical data, PARKINSON DISEASE, Post-traumatic stress disorder, Biochemistry, Genetics and Molecular Biology(all), General Chemistry, PROFILES, Heritability, medicine.disease, PREVENTION, 030104 developmental biology, Genetic Loci, lcsh:Q, Human genome, 030217 neurology & neurosurgery, Genetics and Molecular Biology(all), Genome-Wide Association Study
Abstract

The risk of posttraumatic stress disorder (PTSD) following trauma is heritable, but robust common variants have yet to be identified. In a multi-ethnic cohort including over 30,000 PTSD cases and 170,000 controls we conduct a genome-wide association study of PTSD. We demonstrate SNP-based heritability estimates of 5–20%, varying by sex. Three genome-wide significant loci are identified, 2 in European and 1 in African-ancestry analyses. Analyses stratified by sex implicate 3 additional loci in men. Along with other novel genes and non-coding RNAs, a Parkinson’s disease gene involved in dopamine regulation, PARK2, is associated with PTSD. Finally, we demonstrate that polygenic risk for PTSD is significantly predictive of re-experiencing symptoms in the Million Veteran Program dataset, although specific loci did not replicate. These results demonstrate the role of genetic variation in the biology of risk for PTSD and highlight the necessity of conducting sex-stratified analyses and expanding GWAS beyond European ancestry populations., Post-traumatic stress disorder (PTSD) is a common mental health problem. Here, the authors report a GWAS from the Psychiatric Genomics Consortium in which they identify two risk loci in European ancestry and one locus in African ancestry individuals and find that PTSD is genetically correlated with several other psychiatric traits.

Published
2019

50. Early life stress impairs social function through AVP-dependent mechanisms

Author

Holly Watkin, Kerrie L. Thomas, Lowenna Rule, Nichola M. Brydges, Catrin Lewis, Amanda J. Drake, Jessica Hall, Jeremy Hall, and Caroline Best

Subjects
endocrine system, Vasopressin, business.industry, Relcovaptan, Early life stress, Antagonist, Mental illness, medicine.disease, Oxytocin, Social function, Medicine, business, Borderline personality disorder, hormones, hormone substitutes, and hormone antagonists, medicine.drug, Clinical psychology
Abstract

Impaired social function is a core feature of many psychiatric illnesses. Adverse experiences during childhood increase risk for mental illness, however it is currently unclear whether stress early in life plays a direct role in the development of social difficulties. Using an animal model of pre-pubertal stress (PPS), we investigated effects on social behaviour, oxytocin and arginine vasopressin (AVP). We also explored social performance and AVP expression in participants with borderline personality disorder (BPD) who experienced a high incidence of childhood stress. Social behaviour was impaired and AVP expression increased in animals experiencing PPS and participants with BPD. Behavioural deficits in animals were rescued through administration of the AVP receptor 1a antagonist Relcovaptan (SR49059). AVP levels and recognition of negative emotions were significantly correlated in BPD participants only. In conclusion, early life stress plays a profound role in the precipitation of social dysfunction, and AVP mediates at least part of this effect.

Published
2019

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