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Symptoms of anxiety and depression often coexist, and evidence suggests that this has a genetic basis, among other possible causes. However, the current classification of comorbid generalised anxiety disorder (GAD) and depression (anxious depression) in the Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition; DSM-5) does not fully reflect the high prevalence of anxiety symptoms in people with depression and the International Classification of Diseases (10th and 11th revisions) has tended to identify anxious depression with minor disorders seen in primary care. As a result, few dedicated therapeutic trials have been conducted in patients with anxious depression, and specific treatment guidelines and recommendations are lacking. Fortunately, there is considerable therapeutic overlap between anxiety and depression, such that many agents with antidepressant efficacy are also effective for symptoms of GAD. The initial treatment of a patient with depression and symptoms of anxiety should be with an agent that is approved for both major depressive disorder and GAD, such as a selective serotonin reuptake inhibitor. There is an obvious need for greater recognition of anxious depression in order to boost the volume of high-quality clinical data, which should translate over time into better, more specific treatment recommendations and improved outcomes.

This narrative review summarizes and discusses the implications of the Diagnostic and Statistical Manual of Mental Disorders (DSM)-5 and the upcoming International Classification of Diseases (ICD)-11 classification systems on the prevalence of bipolar disorder and on the validity of the DSM-5 diagnosis of bipolar disorder according to the Robin and Guze criteria of diagnostic validity. Here we review and discuss current data on the prevalence of bipolar disorder diagnosed according to DSM-5 versus DSM-IV, and data on characteristics of bipolar disorder in the two diagnostic systems in relation to extended Robin and Guze criteria: 1) clinical presentation, 2) associations with para-clinical data such as brain imaging and blood-based biomarkers, 3) delimitation from other disorders, 4) associations with family history / genetics, 5) prognosis and long-term follow-up, and 6) treatment effects. The review highlights that few studies have investigated consequences for the prevalence of the diagnosis of bipolar disorder and for the validity of the diagnosis. Findings from these studies suggest a substantial decrease in the point prevalence of a diagnosis of bipolar with DSM-5 compared with DSM-IV, ranging from 30-50%, but a smaller decrease in the prevalence during lifetime, corresponding to a 6% reduction. It is concluded that it is likely that the use of DSM-5 and ICD-11 will result in diagnostic delay and delayed early intervention in bipolar disorder. Finally, we recommend areas for future research. (c) 2021 Elsevier B.V. and ECNP. All rights reserved.

Background Bipolar disorder (BD) is associated with excess and premature cardiovascular mortality. Elevated blood pressure (BP) is a leading contributor to cardiovascular risk. However, few studies have examined BP in BD in comparison to other psychiatric disorders. Furthermore, the association between BP and mood instability is not presently clear despite increasing interest in repurposing existing antihypertensive medications as possible novel BD treatments. Thus we examined BP differences between BD and borderline personality disorder (BPD), a disorder with a similar symptom profile through chronic mood instability. Methods A total of 106 adults (38 BD, 25 BPD, and 43 healthy controls), evaluated in the Automated Monitoring of Symptom Severity (AMoSS) study, completed a week-long home blood pressure monitoring assessment and ecological momentary assessment of mood. We examined group-wise differences in mean BP and BP variability and their association with mood instability. Results BD individuals had a significantly wider resting pulse pressure (40.8 ± 7.4, mmHg) compared to BPD (35.7 ± 5.3, mmHg, P = 0.03) and control participants (37.3 ± 6.3, mmHg, P = 0.036). Systolic BP was negatively associated with sad mood instability, and all measures of mean BP (systolic, diastolic, and mean arterial pressure) were negatively associated with positive mood instability. Conclusions This study demonstrates BP differences between BD and healthy and clinical controls that are within a normotensive range. Early pulse pressure widening may be a modifiable pathophysiological feature of BD that confers later cardiovascular risk. BP may be an important transdiagnostic predictor of mood instability and a potential explicit treatment target.

Bipolar disorder (BD) might be associated with higher infection rates of coronavirus disease (COVID-19) which in turn could result in worsening the clinical course and outcome. This may be due to a high prevalence of somatic comorbidities and an increased risk of delays in and poorer treatment of somatic disease in patients with severe mental illness in general. Vaccination is the most important public health intervention to tackle the ongoing pandemic. We undertook a systematic review regarding the data on vaccinations in individuals with BD. Proportion of prevalence rates, efficacy and specific side effects of vaccinations and in individuals with BD were searched. Results show that only five studies have investigated vaccinations in individuals with BD, which substantially limits the interpretation of overall findings. Studies on antibody production after vaccinations in BD are very limited and results are inconsistent. Also, the evidence-based science on side effects of vaccinations in individuals with BD so far is poor. (c) 2021 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY license ( http://creativecommons.org/licenses/by/4.0/ )

BackgroundDepressed patients often focus on negative life events. Effective antidepressant therapy reverses this negative emotional bias (NEB) within 1 week. Clinical therapeutic effect usually requires 4–6 weeks. The value of implementing NEB monitoring for the personalisation of antidepressant therapy is unknown.ObjectiveTo estimate the likely outcome and cost consequences of adopting the P1vital Oxford Emotional Test Battery (ETB) for this purpose in routine primary care in England.MethodsA hybrid decision analytic model (decision tree plus Markov model) was developed to estimate the cost-effectiveness of ETB monitoring versus no ETB over 52 weeks using quality-adjusted life years (QALYs). Differences in depression severity, episode type and analytical perspectives were considered. Input data were derived from relevant guidelines, literature, national databases, expert opinion and the developers for the year 2013. Multiple sensitivity analyses addressed uncertainty.FindingsThe mean number of ETB tests is 2.162 per newly diagnosed patient and 2.166 per patient with recurrent depression. The incremental cost-effectiveness of ETB versus ‘no ETB’ is £4355/QALY from the healthcare perspective. From the broader societal perspective, ETB is more effective and cost saving.ConclusionsMonitoring negative emotional bias in primary care in England for personalised antidepressant treatment using ETB seems as an effective and cost-effective option under all considered scenarios (including worst case). Its main economic value seems to lie in reduced productivity loss as opposed to healthcare savings.Clinical implicationsThe test supports accelerated application of evidence-based depression care. Further optimisation and implementation in the ongoing European PReDicT trial is ongoing.

Background/Aims: TrueColours ulcerative colitis (TCUC) is a comprehensive web-based program that functions through email, providing direct links to questionnaires. Several similar programs are available, however patient perspectives are unexplored. Methods: A pilot study was conducted to determine feasibility, usability and patient perceptions of real-time data collection (daily symptoms, fortnightly quality of life, 3 monthly outcomes). TCUC was adapted from a web-based program for patients with relapsing-remitting bipolar disorder, using validated UC indices. A semi-structured interview was developed and audio-recorded face-to-face interviews were conducted after 6 months of interaction with TCUC. Transcripts were coded in NVivo11, a qualitative data analysis software package. An inductive approach and thematic analysis was conducted. Results: TCUC was piloted in 66 patients for 6 months. Qualitative analysis currently defies statistical appraisal beyond "data saturation," even if it has more influence on clinical practice than quantitative data. A total of 28 face-to-face interviews were conducted. Six core themes emerged: awareness, control, decision-making, reassurance, communication and burden of treatment. There was a transcending overarching theme of patient empowerment, which cut across all aspects of the TCUC experience. Conclusions: Patient perception of the impact of real-time data collection was extremely positive. Patients felt empowered as a product of the self-monitoring format of TCUC, which may be a way of improving self-management of UC whilst also decreasing the burden on the individual and healthcare services.

Controversy continues with regard to antidepressants and withdrawal. Recent debates have focused on the prevalence and length of withdrawal, and some continue to state that withdrawal from these compounds constitutes ‘addiction’. In this editorial we examine the evidence underlying these recent debates. We acknowledge gaps in knowledge, and make suggestions for how the field can progress.

BackgroundLithium is the best documented maintenance treatment in bipolar disorder, but its use varies considerably across and within countries. It is not known whether regional differences in lithium prescription rates translate to differing regional outcomes.AimsTo estimate associations between county specific lithium prescription rates and county specific recurrence odds of bipolar disorder in Sweden.MethodData from 14,616 patients with bipolar I disorder, bipolar II disorder, or bipolar disorder not otherwise specified were extracted from the Swedish national quality assurance register for bipolar disorders (BipoläR). Lithium prescription frequencies were calculated for 21 counties. Logistic regression analyses were run adjusted for confounders, with any type of recurrence as primary outcome, and incident elated and depressive episodes as secondary outcomes. Subsets of patients with bipolar I, II and not otherwise specified disorder were also analysed separately.ResultsLithium prescription rates for populations with all bipolar subtypes ranged across counties from 37.7 to 84.9% (mean 52.4%). Higher regional prescription rates were significantly associated with lower rate of any type of recurrence. The association was stronger when bipolar I disorder was analysed separately.ConclusionsThe advantages for lithium use long acknowledged for bipolar I disorder are also seen for the rest of the bipolar spectrum. Results suggest that population level outcomes of bipolar disorder could be improved by increasing the number of patients using lithium.

Psychotic experiences (PE) are associated with poorer functioning, higher distress and the onset of serious mental illness. Environmental exposures (e.g. childhood abuse) are associated with the development of PE. However, which specific exposures convey risk for each type or dimension of PE has rarely been explored. The Oxford Wellbeing Life and Sleep (OWLS) survey includes 22 environmental risk factors for psychosis and was designed to examine how environmental risks are associated with specific dimensions of PE. Multivariate logistic regression models were fit using these risk factors to predict six dimensions of PE (perceptual abnormalities, persecutory ideation, bizarre ideas, cognitive disorganisation, delusional mood and negative symptoms). Models were built using only 70% of the data, and then fit to the remaining data to assess their generalisability and quality. 1789 (27.2% men; mean age = 27.6; SD = 10.9) survey responses were analysed. The risk factors predictive of the most PE were anxiety, social withdrawal during childhood and trauma. Cannabis and depression predicted three dimensions with both predicting bizarre ideas and persecutory ideation. Psychological abuse and sleep quality each predicted two dimensions (persecutory ideation and delusional mood). Risk factors predicting one PE dimension were age (predicting cognitive disorganisation), physical abuse (bizarre ideas), bullying and gender (persecutory ideation); and circadian phase (delusional mood). These results lend support for a continuum of psychosis, suggesting environmental risks for psychotic disorders also increase the risk of assorted dimensions of PE. Furthermore, it advocates the use of dimensional approaches when examining environmental exposures for PE given that environmental risks distribute differently across dimensions.

Background: Remote monitoring and digital phenotyping harbor potential to aid clinical diagnosis, predict episode course and recognize early signs of mental health crises. Digital communication metrics, such as phone call and short message service (SMS) use may represent novel biomarkers of mood and diagnosis in Bipolar Disorder (BD) and Borderline Personality Disorder (BPD).Materials and Methods: BD (n = 17), BPD (n = 17) and Healthy Control (HC, n = 21) participants used a smartphone application which monitored phone calls and SMS messaging, alongside self-reported mood. Linear mixed-effects regression models were used to assess the association between digital communications and mood symptoms, mood state, trait-impulsivity, diagnosis and the interaction effect between mood and diagnosis.Results: Transdiagnostically, self-rated manic symptoms and manic state were positively associated with total and outgoing call frequency and cumulative total, incoming and outgoing call duration. Manic symptoms were also associated with total and outgoing SMS frequency. Transdiagnostic depressive symptoms were associated with increased mean incoming call duration. For the different diagnostic groups, BD was associated with increased total call frequency and BPD with increased total and outgoing SMS frequency and length compared to HC. Depression in BD, but not BPD, was associated with decreased total and outgoing call frequency, mean total and outgoing call duration and total and outgoing SMS frequency. Finally, trait-impulsivity was positively associated with total call frequency, total and outgoing SMS frequency and cumulative total and outgoing SMS length.Conclusion: These results identify a general increase in phone call and SMS communications associated with self-reported manic symptoms and a diagnosis-moderated decrease in communications associated with depression in BD, but not BPD, participants. These findings may inform the development of clinical tools to aid diagnosis and remote symptom monitoring, as well as informing understanding of differential psychopathologies in BD and BPD.

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Depressed patients often do not respond to the first antidepressant prescribed, resulting in sequential trials of different medications. Personalised medicine offers a means of reducing this delay; however, the clinical effectiveness of personalised approaches to antidepressant treatment has not previously been tested. We assessed the clinical effectiveness of using a predictive algorithm, based on behavioural tests of affective cognition and subjective symptoms, to guide antidepressant treatment. We conducted a multicentre, open-label, randomised controlled trial in 913 medication-free depressed patients. Patients were randomly assigned to have their antidepressant treatment guided by a predictive algorithm or treatment as usual (TaU). The primary outcome was the response of depression symptoms, defined as a 50% or greater reduction in baseline score of the QIDS-SR-16 scale, at week 8. Additional prespecified outcomes included symptoms of anxiety at week 8, and symptoms of depression and functional outcome at weeks 8, 24 and 48. The response rate of depressive symptoms at week 8 in the PReDicT (55.9%) and TaU (51.8%) arms did not differ significantly (odds ratio: 1.18 (95% CI: 0.89-1.56), P = 0.25). However, there was a significantly greater reduction of anxiety in week 8 and a greater improvement in functional outcome at week 24 in the PReDicT arm. Use of the PReDicT test did not increase the rate of response to antidepressant treatment estimated by depressive symptoms but did improve symptoms of anxiety at week 8 and functional outcome at week 24. Our findings indicate that personalisation of antidepressant treatment may improve outcomes in depressed patients. This project received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 696802.

Serotonergic psychedelic drugs, such as psilocin (4-hydroxy-N,N-dimethyltryptamine), profoundly alter the quality of consciousness through mechanisms which are incompletely understood. Growing evidence suggests that a single psychedelic experience can positively impact long-term psychological well-being, with relevance for the treatment of psychiatric disorders, including depression. A prominent factor associated with psychiatric disorders is disturbed sleep, and the sleep-wake cycle is implicated in the regulation of neuronal firing and activity homeostasis. It remains unknown to what extent psychedelic agents directly affect sleep, in terms of both acute arousal and homeostatic sleep regulation. Here, chronic in vivo electrophysiological recordings were obtained in mice to track sleep-wake architecture and cortical activity after psilocin injection. Administration of psilocin led to delayed REM sleep onset and reduced NREM sleep maintenance for up to approximately 3 hours after dosing, and the acute EEG response was associated primarily with an enhanced oscillation around 4 Hz. No long-term changes in sleep-wake quantity were found. When combined with sleep deprivation, psilocin did not alter the dynamics of homeostatic sleep rebound during the subsequent recovery period, as reflected in both sleep amount and EEG slow wave activity. However, psilocin decreased the recovery rate of sleep slow wave activity following sleep deprivation in the local field potentials of electrodes targeting medial prefrontal and surrounding cortex. It is concluded that psilocin affects both global vigilance state control and local sleep homeostasis, an effect which may be relevant for its antidepressant efficacy.

Objective : To examine the evolution of dementia in HIV-positive injecting drug users (IDU) in Edinburgh. Design : Case-control study. Participants : Twenty six (6%) out of 404 patients in the Edinburgh cohort of HIV-positive IDU who have developed HIV-1-associated dementia in the 10 years since infection and seroconversion. Methods : Patients were tested repeatedly, where possible, on a range of neuropsychological and neurophysiological measures. The results from patients with dementia were compared with those of age, sex and IQ-matched non-demented HIV-positive controls from the cohort. An auditory event-related potential (P3 or P300), a neurophysiological measure of cognitive function, detected the onset of a marked slowing of cognitive and psychomotor functions. Neuropsychological measures that involve the speed of information processing such as the Trail-Making task also identified the early stages of dementia. Results : Dementia was associated with a more advanced stage of systemic disease, increased rates of decline in CD4 cell counts and markedly reduced survival compared with the non-demented controls. No evidence for a protective effect of treatment with zidovudine was detected. Conclusion : In the first 10 years after infection with HIV-1 dementia is an individual development, not the clinical extreme of general intellectual impairment, and had occurred in at least 6% of our IDU cohort. Future questions concern the long-term rate of dementia, the critical neuropathological change and the true potential for early treatment.

Background Anxiety is highly prevalent in people diagnosed with bipolar disorder (BD), and can persist between acute episodes of mania and depression. Recent studies indicate that people with BD are prone to experiencing frequent, intrusive and emotional mental images which further fuel their levels of anxiety and mood instability. These intrusive emotional mental images represent a specific target for treatment for this disorder with the potential to reduce anxiety and improve mood stability. A new brief structured psychological intervention for BD called Imagery Based Emotion Regulation (IBER) has been developed, which translates experimental work in the area of imagery and emotion into a skills training programme to improve the regulation of intrusive and distressing emotional mental images in BD. A feasibility trial is required in order to assess whether a full randomised controlled trial is indicated in order to evaluate this approach. Methods The design is a two-arm feasibility randomised controlled trial (RCT), with 1:1 randomisation stratified by trial site and minimised on medication status and anxiety severity. Participants are 60 individuals diagnosed with bipolar disorder and experiencing at least a mild level of anxiety. Sites are defined by the geographical boundaries of two National Health Service (NHS) Trusts, with recruitment from NHS teams, GP surgeries and self-referral. The intervention is up to 12 sessions of Imagery Based Emotion Regulation within 16 weeks. The comparator is NHS standard care. The primary aim is to assess the feasibility of conducting a powered multi-site RCT to evaluate effectiveness. Measures of anxiety, depression, mania, mood stability and health care use will be conducted at baseline, end of treatment and at 16-week follow-up. Discussion This is the first feasibility trial of an imagery-based intervention for the treatment of anxiety in bipolar disorder. If the trial proves feasible, a large multi-site trial will be required. Trial registration ISRCTN16321795. Registered on October 16, 2018. 10.1186/ISRCTN16321795

Bipolar disorder is a chronic neuropsychiatric condition associated with mood instability, where patients present significant sleep and circadian rhythm abnormalities. Currently, the pathophysiology of bipolar disorder remains elusive, but treatment with lithium continues as the benchmark pharmacotherapy, functioning as a potent mood stabilizer in most, but not all patients. Lithium is well documented to induce period lengthening and amplitude enhancement of the circadian clock. Based on this, we sought to investigate whether lithium differentially impacts circadian rhythms in bipolar patient cell lines and crucially if lithium’s effect on the clock is fundamental to its mood-stabilizing effects. We analyzed the circadian rhythms of bipolar patient-derived fibroblasts (n = 39) and their responses to lithium and three further chronomodulators. Here we show, relative to controls (n = 23), patients exhibited a wider distribution of circadian period (p

Antidepressants must be taken for weeks before response can be assessed with many patients not responding to the first medication prescribed. This often results in long delays before effective treatment is started. Antidepressants induce changes in the processing of emotional stimuli early in the course of treatment. In the current study we assessed whether changes in emotional processing and subjective symptoms over the first week of antidepressant treatment predicted clinical response after 4-8 weeks of treatment. Such a predictive test may shorten the time taken to initiate effective treatment in depressed patients. Seventy-four depressed primary care patients completed measures of emotional bias and subjective symptoms before starting antidepressant treatment and then again 1 week later. Response to treatment was assessed after 4-6 weeks. The performance of classifiers based on these measures was assessed using a leave-one-out validation procedure with the best classifier then tested in an independent sample from a second study of 239 patients. The combination of a facial emotion recognition task and subjective symptoms predicted response with 77% accuracy in the training sample and 60% accuracy in the independent study, significantly better than possible using baseline response rates. The face based measure of emotional bias provided good quality data with high acceptability ratings. Changes in emotional processing can provide a sensitive early measure of antidepressant efficacy for individual patients. Early treatment induced changes in emotional processing may be used to guide antidepressant therapy and reduce the time taken for depressed patients to return to good mental health.

Depression and anxiety are negative emotional states familiar to us all through personal experience. Less familiar are severe states of depression, in particular, which can actually shorten the lives of sufferers by over a decade. The relationship of these very severe states of illness to the milder cases more common earlier in development is important. Most patients who have suffered from depression will suffer from further episodes during their lifetime, and an early onset may make recurrence more likely. A number of factors increase the risk for depression, including family history, stressful life events, early life experiences, personality (particularly the traits of neuroticism and perfectionism) and mood lability (marked ups and downs). Sleep disturbance may both provoke and/or signal the onset of mood disorder. Sleep is therefore doubly important as a gateway to treatment. Understanding more about how sleep interacts with the established risk factors would allow vulnerable young people to be identified earlier for more effective intervention. Early identification of sleep disorder and depression allows psychological treatments to be used, which are less effective once a full depressive episode and a cascade of neurobiological and psychological effects have occurred.

Background:Cognitive behavioral therapy (CBT) is an efficacious intervention for generalized anxiety disorder (GAD). Digital CBT may provide a scalable means of delivering CBT at a population level. We investigated the efficacy of a novel digital CBT program in those with GAD for outcomes of anxiety, worry, depressive symptoms, sleep difficulty, wellbeing, and participant‐specific quality of life. Methods:This online, two‐arm parallel‐group superiority randomized controlled trial compared digital CBT with waitlist control in 256 participants with moderate‐to‐severe symptoms of GAD. Digital CBT (Daylight), was delivered using participants’ own smartphones. Online assessments took place at baseline (Week 0; immediately preceding randomization), mid‐intervention (Week 3; from randomization), post‐intervention (Week 6; primary endpoint), and follow‐up (Week 10). Results:Overall, 256 participants were randomized and intention‐to‐treat analysis foundDaylightreduced symptoms of anxiety compared with waitlist control at post‐intervention, reflecting a large effect size (adjusted difference [95% CI]: 3.22 [2.14, 4.31],d = 1.08). Significant improvements were found for measures of worry; depressive symptoms, sleep difficulty, wellbeing, and participant‐specific quality of life. Conclusion:Digital CBT (Daylight) appears to be safe and efficacious for symptoms of anxiety, worry, and further measures of mental health compared with waitlist control in individuals with GAD.

This chapter was edited from Professor Pichot’s contribution to the last edition. It presents a history of psychiatry from the perspective of doctors. It is not a historigraphy of mental illness, that is a history of how it has been described or written about by other groups or individuals. Nor is it a history of the people who have suffered with mental illness over the centuries. It describes the evolution of what is sometimes called the medical model of severe mental illness, starting with the founders of humane care, such as Pinel, and moving to the idea of an objective psychopathology, the confounding by psychological explanation, and the continuing conflicts between those favouring biological opposed to social approaches to aetiology and treatment.

BACKGROUND People with intellectual disabilities (IDs) have very high rates of osteoporosis and fractures, to which their widespread vitamin D deficiency and other factors could contribute. We aimed to assess in people with IDs previously treated for vitamin D deficiency (1) long-term adherence to vitamin D supplementation and (2) bone mineral density (BMD), as an indicator for risk of fractures, according to vitamin D supplementation and other factors. METHOD We recorded height, weight, medical, pharmacological, dietary and lifestyle assessment. Blood sample were taken for vitamin D and related analytes. dual-energy X-ray absorptiometry for BMD was performed. RESULTS Of 51 study participants (mean [standard deviation, SD] age 51.5 [13.6] years, 57% male), 41 (80.4%) were taking vitamin D and 10 were not. Mean [SD] serum vitamin D was 81.3 [21.3] vs. 25.2 [10.2] nmol/L (P

Objectives: For the first time to present a systematic review of observational studies on the efficiency of lithium monotherapy in comparison with other maintenance mood stabilizers and in combination. Methods: As part of the International Society for Bipolar Disorders (ISBD) Task Force on Lithium Treatment we undertook a systematic literature search of non-randomized controlled observational studies on 1) lithium monotherapy versus treatment with another maintenance mood stabilizer in monotherapy 2) lithium in combination with other mood stabilizers versus monotherapy. Results: In eight out of nine identified studies including more than a total of 14.000 patients, maintenance lithium monotherapy was associated with improved outcome compared with another mood stabilizer in monotherapy including valproate, lamotrigine, olanzapine, quetiapine, unspecified anticonvulsants, carbamazepine/lamotrigine, unspecified atypical antipsychotics and unspecified antipsychotics. Among the four identified studies including a total of more than 4.000 patients comparing maintenance combination therapy with maintenance monotherapy, a few combination therapies were found to be superior to monotherapy in some analyses, but many were not. Conclusions: The results show the superiority in real life of lithium monotherapy compared with monotherapy with other maintenance mood stabilizers. The four largest register-based studies largely addressed confounding, but, as ever, residual confounding cannot be excluded. Nevertheless, the observational findings substantially add to the findings from randomized controlled trials, whose designs often limit the validity of comparison between medicines.

This ECNP meeting was designed to build bridges between different constituencies of mental illness treatment researchers from a range of backgrounds with a specific focus on enhancing the development of novel, evidence based, psychological treatments. In particular we wished to explore the potential for basic neuroscience to support the development of more effective psychological treatments, just as this approach is starting to illuminate the actions of drugs. To fulfil this aim, a selection of clinical psychologists, psychiatrists and neuroscientists were invited to sit at the same table. The starting point of the meeting was the proposition that we know certain psychological treatments work, but we have only an approximate understanding of why they work. The first task in developing a coherent mental health science would therefore be to uncover the mechanisms (at all levels of analysis) of effective psychological treatments. Delineating these mechanisms, a task that will require input from both the clinic and the laboratory, will provide a key foundation for the rational optimisation of psychological treatments. As reviewed in this paper, the speakers at the meeting reviewed recent advances in the understanding of clinical and cognitive psychology, neuroscience, experimental psychopathology, and treatment delivery technology focussed primarily on anxiety disorders and depression. We started by asking three rhetorical questions: What has psychology done for treatment? What has technology done for psychology? What has neuroscience done for psychology? We then addressed how research in five broad research areas could inform the future development of better treatments: Attention, Conditioning, Compulsions and addiction, Emotional Memory, and Reward and emotional bias. Research in all these areas (and more) can be harnessed to neuroscience since psychological therapies are a learning process with a biological basis in the brain. Because current treatment approaches are not fully satisfactory, there is an imperative to understand why not. And when psychological therapies do work we need to understand why this is the case, and how we can improve them. We may be able to improve accessibility to treatment without understanding mechanisms. But for treatment innovation and improvement, mechanistic insights may actually help. Applying neuroscience in this way will become an additional mission for ECNP.

Background Antidepressant medication is commonly used to treat depression. However, many patients do not respond to the first medication prescribed and improvements in symptoms are generally only detectable by clinicians 4–6 weeks after the medication has been initiated. As a result, there is often a long delay between the decision to initiate an antidepressant medication and the identification of an effective treatment regimen. Previous work has demonstrated that antidepressant medications alter subtle measures of affective cognition in depressed patients, such as the appraisal of facial expression. Furthermore, these cognitive effects of antidepressants are apparent early in the course of treatment and can also predict later clinical response. This trial will assess whether an electronic test of affective cognition and symptoms (the Predicting Response to Depression Treatment Test; PReDicT Test) can be used to guide antidepressant treatment in depressed patients and, therefore, hasten treatment response compared to a control group of patients treated as usual. Methods/design The study is a randomised, two-arm, multi-centre, open-label, clinical investigation of a medical device, the PReDicT Test. It will be conducted in five European countries (UK, France, Spain, Germany and the Netherlands) in depressed patients who are commencing antidepressant medication. Patients will be randomised to treatment guided by the PReDicT Test (PReDicT arm) or to Treatment as Usual (TaU arm). Patients in the TaU arm will be treated as per current standard guidelines in their particular country. Patients in the PReDicT arm will complete the PReDicT Test after 1 (and if necessary, 2) weeks of treatment. If the test indicates non-response to the treatment, physicians will be advised to immediately alter the patient’s antidepressant therapy by dose escalation or switching to another compound. The primary outcome of the study is the proportion of patients showing a clinical response (defined as 50% or greater decrease in baseline scores of depression measured using the Quick Inventory of Depressive Symptoms – Self-Rated questionnaire) at week 8. Health economic and acceptability data will also be collected and analysed. Discussion This trial will test the clinical efficacy, cost-effectiveness and acceptability of using the novel PReDicT Test to guide antidepressant treatment selection in depressed patients. Trial registration ClinicalTrials.gov, ID: NCT02790970. Registered on 30 March 2016. Electronic supplementary material The online version of this article (doi:10.1186/s13063-017-2247-2) contains supplementary material, which is available to authorized users.

Contains fulltext : 191289.pdf (Publisher’s version ) (Open Access) Despite decades of research, the pathophysiology of bipolar disorder (BD) is still not well understood. Structural brain differences have been associated with BD, but results from neuroimaging studies have been inconsistent. To address this, we performed the largest study to date of cortical gray matter thickness and surface area measures from brain magnetic resonance imaging scans of 6503 individuals including 1837 unrelated adults with BD and 2582 unrelated healthy controls for group differences while also examining the effects of commonly prescribed medications, age of illness onset, history of psychosis, mood state, age and sex differences on cortical regions. In BD, cortical gray matter was thinner in frontal, temporal and parietal regions of both brain hemispheres. BD had the strongest effects on left pars opercularis (Cohen's d=-0.293; P=1.71 x 10(-21)), left fusiform gyrus (d=-0.288; P=8.25 x 10(-21)) and left rostral middle frontal cortex (d=-0.276; P=2.99 x 10(-19)). Longer duration of illness (after accounting for age at the time of scanning) was associated with reduced cortical thickness in frontal, medial parietal and occipital regions. We found that several commonly prescribed medications, including lithium, antiepileptic and antipsychotic treatment showed significant associations with cortical thickness and surface area, even after accounting for patients who received multiple medications. We found evidence of reduced cortical surface area associated with a history of psychosis but no associations with mood state at the time of scanning. Our analysis revealed previously undetected associations and provides an extensive analysis of potential confounding variables in neuroimaging studies of BD.

BackgroundClinical trials have examined the efficacy of drugs to prevent relapse in patients with bipolar disorder, however, their design often limits generalisation to routine clinical practice.AimsTo estimate the effectiveness of drugs used for maintenance treatment in bipolar disorder.MethodWe used national registers to identify 35022 individuals diagnosed with bipolar disorder and information on lithium, valproate, carbamazepine, lamotrigine, quetiapine and olanzapine treatment from 2006 to 2009. The main outcome was psychiatric hospital admissions. We used stratified cox regression to compare periods on and off medication within the same individual.ResultsMedication with lithium, valproate, lamotrigine, olanzapine and quetiapine was associated with reduced rates of admission to hospital. Lithium was more effective than quetiapine and olanzapine. The effects of specific drugs depended on the polarity of the mood episode.ConclusionsOur findings complement results from randomised controlled trails, but suggest that lithium is more effective than both quetiapine and olanzapine in routine clinical practice.

Introduction: Lockdowns implemented in response to the COVID-19 pandemic are thought to impact mental health [1,2] Understanding the mechanisms underlying this impact is critical to mitigating it [3] We tested the hypothesis that one such mechanism involves impaired mood homeostasis (i e , failure to stabilize mood via mood-modifying activities) [4,5] Methods: In this ecological momentary assessment cohort study, students in the Netherlands reported their mood and activities 4 times a day between March 16 and 29, 2020 New and immediate lockdown measures were announced on March 23 The average change in mood an individual experienced when engaging in an activity was recorded as its pleasantness Mood homeostasis was defined as the extent to which participants preferentially engaged in pleasant activities at time t+1 when their mood was low at time t, thus stabilizing their mood Participants' history of mental illness was screened at baseline Using linear regressions we assessed (i) changes in mood homeostasis from before to during lockdown, (ii) their moderation by mental illness history, (iii) their association with changes in mood level, and (iv) their mediation by changes in range of activities undertaken How changes in mood homeostasis might impact the risk of depression was estimated using computer simulations Statistical significance was set at 2-sided P< 05 Results: Seventy-eight students were included Mood homeostasis was significantly higher before than during lockdown (0 37 vs 0 28;95% CI of the difference [0 03,0 15];P= 003) For every 0 1 point drop in mood homeostasis, average mood decreased by 1 9 points (95% CI, [1 3,3 6], P< 001) This is enough to bring someone's average mood from the population's mean to its bottom quartile The change in mood homeostasis from before to during lockdown was mediated by a reduction in the range of activities (proportion mediated: 11 9%, P< 001) Mood homeostasis dropped significantly more among people with (vs without) a history of mental illness (P< 001): from similar values before lockdown (0 31 vs 0 36;P= 37) to significantly different values during lockdown (0 13 vs 0 35;95% CI of the difference [0 11,0 33];P< 001) In computer simulations, changes in mood homeostasis attributed to the lockdown led to a 3-fold increase in the the yearly incidence of depressed mood episodes: from 9 0% (95% CI [6 6%,11 4%]) before lockdown to 28 2% (95% CI [23 6%,32 6%]) during lockdown Conclusions: Mood homeostasis appears to decrease during lockdown Larger decreases correlate with larger decreases in mood level The impact was larger for students with a history of mental illness The lack of a control group (as the lockdown was implemented nationally) is the main limitation of our study However, since the same participants were monitored before and during lockdown, the lockdown itself seems to be the most likely explanation for the observed difference Identifying interventions that increase mood homeostasis might be a promising avenue to mitigate the impact of lockdowns on mental health Table 1 No conflict of interest

Background: The limited reliability of depression diagnosis impedes research in psychiatry. This impediment is often attributed to biases in the reporting and recording of symptoms. But a fundamental and overlooked explanation may lie in the ambiguity of the very definition of depressed mood. Digital phenotyping enables isolating the effects of this ambiguity from other factors. Methods: We used data from two large independent ecological momentary assessment studies: the 58sec study for testing and the Emotion Sense study for replication. We compared the yearly incidences of depressed mood episodes from 125 interpretations of the ICD-10 criteria. We then assessed agreement between interpretations that lead to similar (and realistic) yearly incidences. Outcomes: In the 58sec and Emotion Sense studies, respectively 2042 and 2009 people reported their mood frequently for an average of 114 and 132 days. Vastly different yearly incidences of depressed mood episodes were observed for different interpretations of the ICD-10 criteria (0%–65.7% in the 58sec study, and 0.3%–52.8% in the Emotion Sense study). Interpretations leading to similar yearly incidence identified different depressive episodes (Cohen’s kappa as low as 0.25 in the 58sec study and 0.47 in the Emotion Sense study). Interpretation: A fundamental cause for the unreliability of depression diagnosis appears to lie in the ambiguity of the definition of depressed mood. Improving this definition with digital phenotyping can be achieved if measurements are combined with a representation of depressed mood along underlying dimensions. Our findings thus offer a potential bridge between conventional diagnostic practice and newer dimensional approaches to psychopathology. Funding Statement: National Institute of Health Research. Declaration of Interests: Prof Goodwin is Medical Director at P1vital products, holds shares in P1vital and P1Vital products and has served as consultant, advisor or CME speaker in the last 3 years for Beckley Psytech, Clerkenwell Health, Compass pathways, Evapharma, Janssen, Lundbeck, Medscape, Novartis, P1Vital, Sage, Servier. The other authors declare no conflict of interest. Ethics Approval Statement: The 58sec study was approved by the Ethics Committee of ESADE (Escuela Superior de Administracion y Direccion de Empresas) Business School, Barcelona, Spain. The Emotion Sense study was approved by the Research Ethics Committee of the University of Cambridge.

Background and objectives Cognitive behavioral therapy (CBT) is a first-line treatment for anxiety, but it is not widely available as clinical guidelines recommend. We examined the feasibility and efficacy of a novel smartphone-based fully automated digital CBT intervention, ‘Daylight™‘, to improve symptoms of Generalized Anxiety Disorder (GAD). Methods In this multiple-baseline design, 21 adults (20 F; mean age 43yrs. range 19–65yrs.) with moderate-to-severe symptoms of GAD were randomized to one of three baseline durations (2-, 4-, or 6-weeks) and then received access to digital CBT. Participants completed daily ratings of anxiety and worry, weekly measures of anxiety, depressive symptoms, and sleep, and measures of anxiety, worry, wellbeing, quality of life, CBT skill acquisition, and work performance at initial assessment prior to baseline randomization, post-intervention, and follow-up. Results Digital CBT was found to be feasible in terms of engagement, satisfaction, and safety. For preliminary efficacy, improvements were detected in daily and weekly outcomes of anxiety for most participants. Despite individual differences, significant improvements occurred with the introduction of digital CBT and not during baseline. Overall, 70% of participants no longer had clinically significant symptoms of GAD, 61% no longer had significant depressive symptoms, and 40% no longer had significant sleep difficulty at post-intervention. Limitations The study sample was recruited using the internet and was mostly female, limiting the generalizability of the findings. Conclusions Findings support the feasibility and efficacy of Daylight. Further examination in randomized controlled trials is now warranted.

BackgroundThere is increasing evidence that smoking is a risk factor for severe mental illness, including bipolar disorder. Conversely, patients with bipolar disorder might smoke more (often) as a result of the psychiatric disorder.AimsWe conducted a bidirectional Mendelian randomisation (MR) study to investigate the direction and evidence for a causal nature of the relationship between smoking and bipolar disorder.MethodWe used publicly available summary statistics from genome-wide association studies on bipolar disorder, smoking initiation, smoking heaviness, smoking cessation and lifetime smoking (i.e. a compound measure of heaviness, duration and cessation). We applied analytical methods with different, orthogonal assumptions to triangulate results, including inverse-variance weighted (IVW), MR-Egger, MR-Egger SIMEX, weighted-median, weighted-mode and Steiger-filtered analyses.ResultsAcross different methods of MR, consistent evidence was found for a positive effect of smoking on the odds of bipolar disorder (smoking initiation ORIVW = 1.46, 95% CI 1.28–1.66, P = 1.44 × 10−8, lifetime smoking ORIVW = 1.72, 95% CI 1.29–2.28, P = 1.8 × 10−4). The MR analyses of the effect of liability to bipolar disorder on smoking provided no clear evidence of a strong causal effect (smoking heaviness betaIVW = 0.028, 95% CI 0.003–0.053, P = 2.9 × 10−2).ConclusionsThese findings suggest that smoking initiation and lifetime smoking are likely to be a causal risk factor for developing bipolar disorder. We found some evidence that liability to bipolar disorder increased smoking heaviness. Given that smoking is a modifiable risk factor, these findings further support investment into smoking prevention and treatment in order to reduce mental health problems in future generations.

Prospective monitoring of mood was started by Kraepelin who made and recorded frequent observations of his patients. During the last decade, the number of research studies using remotely collected electronic mood data has increased markedly. However, standardized measures and methods to collect, analyze and report electronic mood data are lacking. To get better understanding of the nature, correlates and implications of mood and mood instability, and to standardize this process, we propose guidelines for reporting of electronic mood data (eMOOD). This paper provides an overview of remotely collected electronic mood data in mood disorders and discusses why standardized reporting is necessary to evaluate and inform mood research in Psychiatry. Adherence to these guidelines will improve interpretation, reproducibility and future meta-analyses of mood monitoring in mood disorder research.

Study objectives Intrusive memories of psychological trauma are a core clinical feature of posttraumatic stress disorder (PTSD), and in the early period post-trauma may be a potential target for early intervention. Disrupted sleep in the weeks post-trauma is associated with later PTSD. The impact of sleep and intrusive memories immediately post-trauma, and their relation to later PTSD, is unknown. This study assessed the relationship between sleep duration on the first night following a real-life traumatic event and intrusive memories in the subsequent week, and how these might relate to PTSD symptoms at 2 months. Methods Patients (n = 87) recruited in the emergency department completed a sleep and intrusive memory diary from the day of their trauma and for the subsequent week, with optional actigraphy. PTSD, anxiety, and depression symptoms were assessed at 1 week and 2 months. Results A U-shaped relationship was observed between sleep duration on the first night and intrusive memories over the subsequent week: sleeping “too little” or “too much” was associated with more intrusive memories. Individuals who met Clinician-Administered PTSD Scale (CAPS) criteria for PTSD at 2 months had three times more intrusive memories in the first week immediately post-trauma than those who did not (M = 28.20 vs 9.96). Post hoc analysis showed that the absence of intrusive memories in the first week post-trauma was only observed in those who did not meet CAPS criteria for PTSD at 2 months. Conclusions Monitoring intrusive memories and sleep in the first week post-trauma, using a simple diary, may help identify individuals more vulnerable to later psychopathology.

Objectives: Emotional processing abnormalities have been implicated in bipolar disorder (BD) but studies are typically small and uncontrolled. Here, facial expression recognition was explored in a large and naturalistically recruited cohort of BD patients. Methods: 271 patients with BD completed the facial expression recognition task. The effects of current medication together with the influence of current mood state and diagnostic subtype were assessed whilst controlling for the effects of demographic variables. Results: Patients who were currently receiving treatment with lithium demonstrated significantly poorer accuracy in recognising angry faces, an effect that held in a monotherapy sub-analysis comparing those participants on lithium only and those who were medication-free. Accuracy in recognising angry faces was also lower amongst participants currently taking dopamine antagonists (antipsychotics). Higher levels of current depressive symptoms were linked to poorer accuracy at identifying happy faces. Conclusion: Use of lithium and possibly dopamine antagonists may be associated with reduced processing of anger cues in BD. Findings support the existence of mood-congruent negative biases associated with depressive symptoms in BD. Observational cohort studies provide opportunities to explore the substantial effects of demographic, psychometric and clinical variables on cognitive performance and emotional processing.

In 1997, neuropsychological and neuroimaging evidence supported the involvement of the frontal lobes and indeed the brain in depression. This was a challenge to conventional phenomenology and linked with the imperative to use neuroscience to understand major mental illness. Since that time, we are seeing ever more convincing evidence for the genetic basis of mental illness (including depression), relevant abnormality in grey and white matter and neuropsychological analysis of brain function. It has proved more difficult to pin down structural abnormality in major depression at the cellular level, but a focus on glial cells is increasingly justified by the evidence. Neuroscience continues to be a buttress against anti-scientific impulses in psychiatry and can help attract young people to enter it as a profession.

This cohort study investigates mood homeostasis in Dutch students before and during the coronavirus disease 2019 lockdown.

There is increasing evidence that smoking is a risk factor for severe mental illness, including bipolar disorder. Conversely, patients with bipolar disorder might smoke more (often) as a result of the psychiatric disorder. We aimed to investigate the direction and causal nature of the relationship between smoking and bipolar disorder we conducted a bidirectional Mendelian randomization (MR) study. Publicly available summary statistics from genome-wide association studies on bipolar disorder, smoking initiation, smoking heaviness, smoking cessation and lifetime smoking (i.e., a compound measure of heaviness, duration and cessation). We applied multiple analytical methods with different, orthogonal assumptions to triangulate results, including inverse-variance weighted (IVW), MR-Egger or Egger SIMEX, weighted median, weighted mode, and Steiger filtered analyses. Across different methods of MR, consistent evidence was found for a positive effect of smoking on the odds of bipolar disorder (smoking initiation ORIVW=1.46, 95% CI=1.28-1.66, P=1.44x10-8, lifetime smoking ORIVW=1.72, 95% CI=1.29-2.28, P=1.8x10-4). The MR analyses of the liability of bipolar disorder on smoking provided no clear evidence of a strong causal effect (smoking heaviness betaIVW=0.028, 95% CI= 0.003-0.053, P=2.9x10-2). These findings suggest that smoking initiation and lifetime smoking are likely to be a causal risk factor for developing bipolar disorder. We found some evidence that liability to bipolar disorder increased smoking heaviness. Given that smoking is a modifiable risk factor, these findings further support investment into smoking prevention and treatment in order to reduce mental health problems in future generations.

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Background Faecal calprotectin [FCal] levels are used as a surrogate marker for mucosal inflammation, but thresholds for defining endoscopic or histological disease activity in ulcerative colitis [UC] remain unclear. Methods Using validated indices, prospective measurements of FCal, symptoms [Simple Colitis Clinical Activity Index, SCCAI], endoscopic [Ulcerative Colitis Endoscopic Index of Severity, UCEIS] and histological activity [Nancy index] were made over 6 months in patients enrolled into the TrueColours UC web-based monitoring programme. Repeated measurements correlation was performed between FCal and SCCAI, UCEIS, and Nancy indices using definitions for remission and active disease [UCEIS: remission ≤1, active ≥4; Nancy: remission ≤1, active ≥2; combined criteria: remission UCEIS ≤1 and Nancy ≤1, active UCEIS ≥4 and Nancy ≥2]. Receiver operating characteristic curves investigated FCal thresholds after maximising sensitivity for active disease. Results In 39 patients followed prospectively for 6 months, correlation coefficients between FCal and SCCAI, UCEIS, and Nancy indices were 0.271 (95% confidence interval [CI] 0.114–0.415), 0.741 [95% CI 0.289–0.922], and 0.876 [95% CI 0.605–0.965], respectively. Median FCal thresholds for remission using endoscopic, histological, or combined criteria were 71 μg/g [range 8–624], 91 μg/g [range 8–858], and 67 μg/g [range 8–479], respectively. The FCal threshold above which active disease was confirmed was 187 μg/g for UCEIS (area under the curve [AUC] 0.915), 72 μg/g for Nancy [AUC 0.824], and 187 μg/g for combined endoscopic and histological criteria [AUC 0.936]. Conclusions Correlation between FCal and symptoms in UC is weak. In contrast, the correlation between FCal and endoscopic or histological activity is strong. An FCal ≥72 μg/g indicates histological inflammation [Nancy ≥2] and ≥187 μg/g indicates endoscopically active disease [UCEIS ≥4], whether combined with histopathology or not.

Objectives Although not licensed for acute bipolar depression, lamotrigine has evidence for efficacy in trials and its use is recommended in guidelines. So far there had been no prospective health economic evaluation of its use. Methods Cost‐utility analysis of the CEQUEL trial comparing quetiapine plus lamotrigine vs quetiapine monotherapy (and folic acid vs placebo in an add‐on factorial design) for patients with bipolar depression (n = 201) from the health and social care perspective. Differences in costs together with quality‐adjusted life years (QALYs) between the groups were assessed over 52 weeks using a regression‐based approach. Results Health‐related quality of life improved substantially for all randomization groups during follow‐up with no significant difference in QALYs between any of the comparisons (mean adjusted QALY difference: lamotrigine vs placebo −0.001 (95% CI: −0.05 to 0.05), folic acid vs placebo 0.002 (95% CI: −0.05 to 0.05)). While medication costs in the lamotrigine group were higher than in the placebo group (£647, P

Pain is regulated endogenously through both opioid and non-opioid mechanisms. We hypothesized that two novel pain modulation tasks, one drawing on context/expectations and one using voluntary reappraisal, would show differing levels of opioid dependence. Specifically, we expected that naloxone would block context-related analgesia, whereas mental imagery-based pain reappraisal would be opioid-independent.A double-blind, placebo-controlled intravenous naloxone versus saline crossover design was used. Twenty healthy volunteers completed the two modulation tasks with acute heat stimuli calibrated to induce moderate pain. In the mental imagery task, participants imagined either a “pleasant” or a “comparison” scenario during painful heat. In the relative relief task, moderate heat stimuli coincided with visual cues eliciting relief from the expectation of intense pain, and were compared with moderate heat stimuli delivered under the expectation of non-painful warmth. Both “pleasant imagery” and “relative relief” conditions significantly improved ratings of pain intensity and pleasantness during saline treatment. Indeed, the target stimuli in both tasks, which had been calibrated to induce moderate pain, were rated as mildly pleasant. Furthermore, consistently with the main hypothesis, blocking endogenous opioid signaling with naloxone did not significantly affect imagery-induced regulation of pain intensity or pleasantness. In contrast, the relative relief-induced pain regulation (i.e., context/expectation) was blocked by naloxone. We conclude that endogenous opioid signaling is necessary for expectation-related relative relief analgesia, but not for pain reappraisal through mental imagery. These results support mental imagery as a powerful and clinically relevant strategy for regulating pain affect also in patients where endogenous opioid mechanisms might be compromised.SIGNIFICANCE STATEMENTNeurotransmitter systems in the human brain can be probed through antagonist drugs. Studies using the opioid antagonist naloxone have demonstrated that the brain relies on both opioid and non-opioid mechanisms to downregulate pain. This holds clinical relevance given altered endogenous opioid processes in many chronic pain conditions. The present study used a double-blinded, placebo-controlled naloxone blockage of endogenous opioids in healthy humans to show differential opioid involvement in two pain modulation tasks. Context/expectation-driven (relative relief-related) analgesia was blocked by naloxone. In contrast, pain reappraisal through mental imagery was intact despite opioid receptor blockade, suggesting opioid independence. These results support mental imagery as a powerful, clinically relevant strategy for regulating pain as it does not rely on a functioning opioidergic system.

Background:Despite the global impact of bipolar disorder (BD), treatment success is limited. Challenges include syndromal and subsyndromal mood instability, comorbid anxiety, and uncertainty around mechanisms to target. The Oxford Mood Action Psychology Programme (OxMAPP) offered a novel approach within a cognitive behavioural framework, via mental imagery-focused cognitive therapy (ImCT).Aims:This clinical audit evaluated referral rates, clinical outcomes and patient satisfaction with the OxMAPP service.Method:Eleven outpatients with BD received ImCT in addition to standard psychiatric care. Mood data were collected weekly from 6 months pre-treatment to 6 months post-treatment via routine mood monitoring. Anxiety was measured weekly from start of treatment until 1 month post-treatment. Patient feedback was provided via questionnaire.Results:Referral and treatment uptake rates indicated acceptability to referrers and patients. From pre- to post-treatment, there was (i) a significant reduction in the duration of depressive episode relapses, and (ii) a non-significant trend towards a reduction in the number of episodes, with small to medium effect size. There was a large effect size for the reduction in weekly anxiety symptoms from assessment to 1 month follow-up. Patient feedback indicated high levels of satisfaction with ImCT, and underscored the importance of the mental imagery focus.Conclusions:This clinical audit provides preliminary evidence that ImCT can help improve depressive and anxiety symptoms in BD as part of integrated clinical care, with high patient satisfaction and acceptability. Formal assessment designs are needed to further test the feasibility and efficacy of the new ImCT treatment on anxiety and mood instability.

Objectives We previously demonstrated oxidative stress in bipolar patients and a relationship between the age of illness onset and glutathione, a principal antioxidant. In this study, we sought to replicate these findings in a new cohort of patients. Methods We recruited bipolar patients from the OXTEXT cohort, Warneford Hospital, Oxford, UK, of similar age and grouped them according to age of onset of illness. The early onset group comprised patients with onset 30 years. A third group, comprising age-matched healthy volunteers, was also included. Reduced and oxidised glutathione, cysteine, and cystine were determined in plasma, using high performance liquid chromatography. Mitochondrial DNA copy number, measured in whole blood, was also compared between patients and healthy controls. Results Significant increases in oxidative stress were observed in the patient groups, compared with the control group; however, no differences in glutathione-related oxidative stress measures were detected between the early and late onset bipolar patient groups. No differences were observed in the amount of mitochondrial DNA, and there was no correlation with mood state. Conclusion Using a more accurate method to quantify oxidative stress than in our previous study, we show that oxidative stress is a consistent feature of bipolar disorder. Although we did not reproduce our finding correlating age of onset of illness to oxidative stress, we have shown, once again, that oxidative stress is a consistent feature of bipolar disorder.

BackgroundAdjunctive antidepressant therapy is commonly used to treat acute bipolar depression but few studies have examined this strategy.AimsTo examine the efficacy of agomelatine v. placebo as adjuncts to lithium or valproate in bipolar depression.MethodPatients who were currently depressed despite taking lithium or valproate for at least 6 weeks were randomised to treatment with agomelatine (n = 172) or placebo (n = 172) for 8 weeks of acute therapy and 44 weeks of continuation therapy (trial registration: ISRCTN28588282).ResultsNo significant differences in improvement of depressive symptoms were observed between the two groups either at 8 weeks or 52 weeks on the primary efficacy measure of change in Montgomery–Åsberg Depression Rating Scale scores from baseline to end-point. Adverse events including switches into mania/hypomania were low and similar in both groups.ConclusionsAgomelatine adjunctive therapy was not superior to placebo adjunctive therapy for acute bipolar depression.

The anxiety disorders include generalized anxiety disorder, specific phobia, social phobia, agoraphobia, and panic disorder. In addition to the specific symptoms of these disorders, there may be a common experience of anxiety and even dysphoria across the conditions, and of course recourse to the same drug or choice of drugs for treatment. This overlap probably occurs because of universal dimensions of distress or negative affectivity, a shared genetic predisposition, and a common neurobiology Evidence of shared genes is still based mainly on twin studies, but the shared neurobiology can be investigated directly by the investigation of emotional or cognitive bias either behaviorally or using functional brain imaging. This intermediate phenotype can then provide a substrate for understanding and developing medicines and psychological treatments.Los trastornos de ansiedad incluyen el trastorno de ansiedad generalizada, la fobia específica, la fobia social, la agorafobia y el trastorno de pánico. Además de los síntomas específicos de estos trastornos, en estas condiciones puede existir una experiencia común de ansiedad e incluso disforia y, por supuesto, el hecho de recurrir al mismo fármaco o a la elección de medicamentos para el tratamiento. Esta sobreposición se debe probablemente a las dimensiones universales del distrés o afectividad negativa, a una predisposición genética compartida y a una neurobiología común. Todavía la evidencia de genes compartidos se basa principalmente en estudios en gemelos, pero la neurobiología compartida puede ser investigada directamente por medio de la investigación de sesgos emocionales o cognitivos ya sea a través del comportamiento o empleando imágenes cerebrales funcionales. Este fenotipo intermedio puede proporcionar entonces un sustrato para la comprensión y el desarrollo de medicamentos y terapias psicológicas.L'anxiété généralisée, la phobie spécifique, la phobie sociale, l'agoraphobie et le trouble panique font partie des troubles anxieux. En plus des symptômes propres à ces troubles, il peut cependant exister un vécu commun d'anxiété et même de dysphorie entre ces pathologies, nécessitant bien sûr un recours au même médicament ou au même choix de médicament pour le traitement. Les dimensions universelles de la souffrance ou de l'affectivité négative, une prédisposition génétique partagée et une neurobiologie commune sont probablement à l'origine de ce chevauchement. Les données des gènes partagés sont toujours fondées sur des études de jumeaux, mais la neurobiologie partagée peut être étudiée directement par la recherche de biais émotionnels ou cognitifs soit de façon comportementale ou en utilisant l'imagerie cérébrale fonctionnelle. Ce phénotype intermédiaire peut alors fournir un substrat pour comprendre et développer des médicaments et des traitements psychologiques.

International audience; Bipolar disorder is associated with impaired decision-making. Little is known about how treatment, especially lithium, influences decision-making abilities in bipolar patients when euthymic. We aimed at testing for an association between lithium medication and decision-making performance in remitted bipolar patients. Decision-making was measured using the Iowa Gambling Task in 3 groups of subjects: 34 and 56 euthymic outpatients with bipolar disorder, treated with lithium (monotherapy and lithium combined with anticonvulsant or antipsychotic) and without lithium (anticonvulsant, antipsychotic and combination treatment), respectively, and 152 matched healthy controls. Performance was compared between the 3 groups. In the 90 euthymic patients, the relationship between different sociodemographic and clinical variables and decision-making was assessed by stepwise multivariate regression analysis. Euthymic patients with lithium (p=0.007) and healthy controls (p=0.001) selected significantly more cards from the safe decks than euthymic patients without lithium, with no significant difference between euthymic patients with lithium and healthy controls (p=0.9). In the 90 euthymic patients, the stepwise linear multivariate regression revealed that decision-making was significantly predicted (p