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Introduction: Self-harm amongst young people is becoming increasingly prevalent. Understanding, responding to, and supporting young people who self-harm is vital. Friends are typically the first and sometimes the only source of support sought by adolescents who self-harm. Despite their important role as confidants, friends' perspectives and experiences remain poorly understood., Methods: We conducted retrospective qualitative semi-structured interviews, prompted by an adapted version of the Card Sort Task for Self-Harm (CaTS-FF), about the experiences of nine female young adults (18-20 years old) who supported a friend who self-harmed during adolescence. Data were analyzed using thematic analysis., Results: Four themes were developed: (1) "I did not realize my friend was on the road to self-harm": Friends' reactions to self-harm; (2) "That's what friends do": the role of friends; (3) The impact of supporting a friend who self-harms; and (4) "They were quite formative years": reflecting on growth through the experience., Discussion: The present findings highlight the complex experiences of young people supporting a friend who self-harms. Despite being willing to take on the role of a supporter, participants experienced a range of difficult emotions and consequences. The temporal transition running through the four themes reflects the evolving nature of participants' attitudes, knowledge, and friendships. Overall, results highlight the unmet needs of adolescents supporting young people who self-harm, as well as identifying potential pathways to "support the supporters" toward resilience., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Bilello, Townsend, Broome and Burnett Heyes.)

Sleep problems are extremely common during the postpartum period. The role of sleep in the development of postpartum psychosis (PP) is, however, still under-researched. This narrative review aims to (1) provide a summary of the existing evidence for the associations between sleep problems and PP, (2) discuss the relevant risk factors associated with sleep problems and PP, and (3) suggest future lines of research in this area. Some of the existing literature suggests an association between sleep problems, specifically insomnia, sleep loss and sleep disruption during pregnancy and postpartum, and PP, with the most relevant risk factors including history of bipolar disorder and time of delivery. However, it is still unclear whether the previously mentioned sleep problems are a symptom of, or a trigger for PP. Thus, further research is needed to identify the specific role of sleep problems in PP, using longitudinal designs and more objective measures of sleep. This will allow appropriate detection, intervention and support for women experiencing and/or at risk for PP.

Bullying is a modifiable risk factor for poor mental health across childhood and adolescence. It is also socially patterned, with increased prevalence rates in more disadvantaged settings. The current study aimed to better understand whether school-level disadvantage is associated with different types of bullying roles, and whether it is a moderator in the association between bullying and children's mental health. Cross-sectional data were used from 4727 children aged 6-11 years, from 57 primary schools across England and Wales. The child data included previous bullying involvement and bullying role characteristics (bully, victim, bully-victim, reinforcer, defender, outsider), and the teacher-reported data included each child's mental health (emotional symptoms and externalizing) problems. School-level disadvantage was calculated from the proportion of children in the school eligible to receive free school meals (an indicator of disadvantage). Children in more disadvantaged schools were more likely to report being bully perpetrators, bully-victims, and engage less in defending behaviors during a bullying incident. Children from more disadvantaged schools who reported bullying others showed fewer emotional symptoms than those from less disadvantaged schools. There was no other evidence of moderation by school-level disadvantage between bullying roles and emotional and externalizing problems. The findings highlight the potential for school-based interventions targeting children's emotional and social development, targeting bullying, and promoting defending behaviors, particularly in more disadvantaged settings.

This editorial reflects on current methodological trends in translational research in mental health. It aims to build a bridge between two fields that are frequently siloed off from each other: interventional research and phenomenologically informed research. Recent years have witnessed a revival of phenomenological approaches in mental health, often - but not only - as a means of connecting the subjective character of experience with neurobiological explanatory accounts of illness. Rich phenomenological knowledge accrued in schizophrenia, and wider psychosis research, has opened up new opportunities for improving prediction, early detection, diagnosis, prognostic stratification, treatment and ethics of care. Novel qualitative studies of delusions and hallucinations have challenged longstanding assumptions about their nature and meaning, uncovering highly complex subjective dimensions that are not adequately captured by quantitative methodologies. Interdisciplinary and participatory research efforts, informed by phenomenological insights, have prompted revisions of pre-established narratives of mental disorder dominated by a dysfunction framework and by researcher-centric outcome measures. Despite these recent advances, there has been relatively little effort to integrate and translate phenomenological insights across applied clinical research, with the goal of producing more meaningful, patient-valued results. It is our contention that phenomenological psychopathology - as the basic science of psychiatry - represents an important methodology for advancing evidence-based practices in mental health, and ultimately improving real-world outcomes. Setting this project into motion requires a greater emphasis on subjectivity and the structures of experience, more attention to the quality and patient-centredness of outcome measures, and the identification of treatment targets that matter most to patients.

Can delusions, in the context of psychosis, enhance a person's sense of meaningfulness? The case described here suggests that, in some circumstances, they can. This prompts further questions into the complexities of delusion as a lived phenomenon, with important implications for the clinical encounter. While assumptions of meaninglessness are often associated with concepts of 'disorder', 'harm' and 'dysfunction', we suggest that meaning can nonetheless be found within what is commonly taken to be incomprehensible or even meaningless. A phenomenological and value-based approach appears indispensable for clinicians facing the seemingly paradoxical coexistence of harmfulness and meaningfulness.

Background: Reducing bullying is a public health priority. KiVa, a school-based anti-bullying programme, is effective in reducing bullying in Finland and requires rigorous testing in other countries, including the UK. This trial aims to test the effectiveness and cost-effectiveness of KiVa in reducing child reported bullying in UK schools compared to usual practice. The trial is currently on-going. Recruitment commenced in October 2019, however due to COVID-19 pandemic and resulting school closures was re-started in October 2020., Methods: Design: Two-arm pragmatic multicentre cluster randomised controlled trial with an embedded process and cost-effectiveness evaluation., Participants: 116 primary schools from four areas; North Wales, West Midlands, South East and South West England. Outcomes will be assessed at student level (ages 7-11 years; n = approximately 13,000 students)., Intervention: KiVa is a whole school programme with universal actions that places a strong emphasis on changing bystander behaviour alongside indicated actions that provide consistent strategies for dealing with incidents of bullying. KiVa will be implemented over one academic year., Comparator: Usual practice., Primary Outcome: Student-level bullying-victimisation assessed through self-report using the extensively used and validated Olweus Bully/Victim questionnaire at baseline and 12-month follow-up., Secondary Outcomes: student-level bullying-perpetration; student mental health and emotional well-being; student level of, and roles in, bullying; school related well-being; school attendance and academic attainment; and teachers' self-efficacy in dealing with bullying, mental well-being, and burnout., Sample Size: 116 schools (58 per arm) with an assumed ICC of 0.02 will provide 90% power to identify a relative reduction of 22% with a 5% significance level., Randomisation: recruited schools will be randomised on 1:1 basis stratified by Key-Stage 2 size and free school meal status. Process evaluation: assess implementation fidelity, identify influences on KiVa implementation, and examine intervention mechanisms. Economic evaluation: Self-reported victimisation, Child Health Utility 9D, Client Service Receipt Inventory, frequency of services used, and intervention costs. The health economic analysis will be conducted from a schools and societal perspective., Discussion: This two-arm pragmatic multicentre cluster randomised controlled trial will evaluate the KiVa anti-bullying intervention to generate evidence of the effectiveness, cost-effectiveness and scalability of the programme in the UK. Our integrated process evaluation will assess implementation fidelity, identify influences on KiVa implementation across England and Wales and examine intervention mechanisms. The integrated health economic analysis will be conducted from a schools and societal perspective. Our trial will also provide evidence regarding the programme impact on inequalities by testing whether KiVa is effective across the socio-economic gradient., Trial Registration: Trials ISRCTN 12300853 Date assigned 11/02/2020., (© 2022. The Author(s).)

Background: Preventing psychotic disorders and effective treatment in first-episode psychosis are key priorities for the National Institute for Health and Care Excellence. This review assessed the evidence base for the cost-effectiveness of health and social care interventions for people at risk of psychosis and for first-episode psychosis., Methods: Electronic searches were conducted using the PsycINFO, MEDLINE and Embase databases to identify relevant published full economic evaluations published before August 2020. Full-text English-language studies reporting a full economic evaluation of a health or social care intervention aiming to reduce or prevent symptoms in people at risk of psychosis or experiencing first-episode psychosis were included. Screening, data extraction, and critical appraisal were performed using pre-specified criteria and forms based on the NHS Economic Evaluation Database (EED) handbook and Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklist for economic evaluations. The protocol was registered on the PROSPERO database (CRD42018108226). Results were summarised qualitatively., Results: Searching identified 1,628 citations (1,326 following the removal of duplications). After two stages of screening 14 studies met the inclusion criteria and were included in the review. Interventions were varied and included multidisciplinary care, antipsychotic medication, psychological therapy, and assertive outreach. Evidence was limited in the at-risk group with only four identified studies, though all interventions were found to be cost-effective with a high probability (> 80%). A more substantial evidence base was identified for first-episode psychosis (11 studies), with a focus on early intervention (7/11 studies) which again had positive conclusions though with greater uncertainty., Conclusions: Study findings generally concluded interventions were cost-effective. The evidence for the population who are at-risk of psychosis was limited, and though there were more studies for the population with first-episode psychosis, limitations of the evidence base (including generalisability and heterogeneity across the methods used) affect the certainty of conclusions., (© 2022. The Author(s).)

Psychosis is a major mental illness with first onset in young adults. The prognosis is poor in around half of the people affected, and difficult to predict. The few tools available to predict prognosis have major weaknesses which limit their use in clinical practice. We aimed to develop and validate a risk prediction model of symptom nonremission in first-episode psychosis. Our development cohort consisted of 1027 patients with first-episode psychosis recruited between 2005 and 2010 from 14 early intervention services across the National Health Service in England. Our validation cohort consisted of 399 patients with first-episode psychosis recruited between 2006 and 2009 from a further 11 English early intervention services. The one-year nonremission rate was 52% and 54% in the development and validation cohorts, respectively. Multivariable logistic regression was used to develop a risk prediction model for nonremission, which was externally validated. The prediction model showed good discrimination C-statistic of 0.73 (0.71, 0.75) and adequate calibration with intercept alpha of 0.12 (0.02, 0.22) and slope beta of 0.98 (0.85, 1.11). Our model improved the net-benefit by 15% at a risk threshold of 50% compared to the strategy of treating all, equivalent to 15 more detected nonremitted first-episode psychosis individuals per 100 without incorrectly classifying remitted cases. Once prospectively validated, our first episode psychosis prediction model could help identify patients at increased risk of nonremission at initial clinical contact., (© The Author(s) 2021. Published by Oxford University Press on behalf of the University of Maryland's school of medicine, Maryland Psychiatric Research Center.)

In the healthy brain, homeostatic balance between excitation and inhibition maintains neural stability. Reduced inhibition may explain shared symptoms observed in autism and psychosis. Here we review evidence suggesting that altered levels of gamma-aminobutyric acid (GABA) may underlie both disorders, providing a potential cross-diagnostic therapeutic target.

Importance: Cognitive deficits are core features of mental disorders and are important in predicting long-term prognosis. However, it is still unknown whether individual patterns of cognitive deficits predate specific mental disorders., Objective: To investigate the specificity of the associations of attention, working memory, and inhibition in childhood with borderline personality disorder (BPD), psychosis, depression, and hypomania in adolescence and young adulthood., Design, Setting, and Participants: This cohort study obtained data from the Avon Longitudinal Study of Parents and Children in the United Kingdom. All pregnant women resident in Avon, United Kingdom, with an expected date of delivery from April 1, 1991, and December 31, 1992, were eligible. Data analysis was conducted from April 1 to September 30, 2020. The sample initially comprised 13 988 participants who were alive at 1 year of age. For this study, data were available for 6333 individuals reporting on any psychopathological measure at ages 11 to 12 years, 4903 individuals at ages 17 to 18 years, and 2963 individuals at 22 to 23 years., Exposures: Sustained attention, selective attention, and attentional control were assessed with the Test of Everyday Attention for Children at age 8 years, and working memory and inhibition were assessed at age 10 years with the Counting Span Task and the stop-signal paradigm, respectively., Main Outcomes and Measures: Symptoms of BPD were assessed at ages 11 to 12 years, psychotic experiences and depression were examined at ages 17 to 18 years, and hypomania was examined at ages 22 to 23 years., Results: Among 5315 individuals included in the statistical analysis, 2551 (48.0%) were male and 2764 (52.0) were female. Higher sustained attention at 8 years was associated with decreased risk of BPD symptoms at ages 11 to 12 years (adjusted odds ratio [aOR], 0.964; 95% CI, 0.933-0.996; P = .03), better performance on inhibition at age 10 years with decreased risk of psychotic experiences at ages 17 to 18 years (aOR, 0.938; 95% CI, 0.890-0.989; P = .02), higher sustained attention at age 8 years with decreased risk of depressive symptoms at ages 17 to 18 years (aOR, 0.969; 95% CI 0.938-0.9997; P = .048), and better performance in working memory at age 10 years with decreased risk of hypomania symptoms at ages 22 to 23 years (aOR, 0.694; 95% CI, 0.529-0.911; P = .008). After controlling for potential psychopathological overlay, all the associations remained, except for working memory and hypomania. Higher sustained attention at age 8 years was associated with decreased risk of BPD symptoms at ages 11 to 12 years (β = -0.05; P < .001) and of depression at ages 17 to 18 years (β = -0.03; P = .04), and better performance in inhibition at age 10 years was associated with decreased risk of psychotic experiences at ages 17 to 18 years (β = -0.03; P = .04)., Conclusions and Relevance: These findings suggest that specific cognitive deficits in childhood are distinctively associated with different psychopathological symptoms in young people. Furthermore, these results suggest the potential of early cognitive interventions in childhood as a way of modifying or attenuating risk for subsequent psychopathological symptoms.

Women in academic publishing and academic psychiatry face many challenges of gender inequality, including significant pay differentials, poor visibility in senior positions and a male-dominated hierarchical system. We discuss this problem and outline how the BJPsych plans to tackle these issues it in its own publishing.

The ability to identify biomarkers of psychosis risk is essential in defining effective preventive measures to potentially circumvent the transition to psychosis. Using samples of people at clinical high risk for psychosis (CHR) and Healthy controls (HC) who were administered a task fMRI paradigm, we used a framework for labelling time windows of fMRI scans as 'integrated' FC networks to provide a granular representation of functional connectivity (FC). Periods of integration were defined using the 'cartographic profile' of time windows and k-means clustering, and sub-network discovery was carried out using Network Based Statistics (NBS). There were no network differences between CHR and HC groups. Within the CHR group, using integrated FC networks, we identified a sub-network negatively associated with longitudinal changes in the severity of psychotic symptoms. This sub-network comprised brain areas implicated in bottom-up sensory processing and in integration with motor control, suggesting it may be related to the demands of the fMRI task. These data suggest that extracting integrated FC networks may be useful in the investigation of biomarkers of psychosis risk., (© 2020 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

Dogs provide highly valuable models of human disease due to the similarity in phenotype presentation and the ease of genetic analysis. Seven Saluki puppies were investigated for neurological abnormalities including seizures and altered behavior. Magnetic resonance imaging showed a diffuse, marked reduction in cerebral cortical thickness, and symmetrical T2 hyperintensity in specific brain regions. Cerebral cortical atrophy with vacuolation (status spongiosus) was noted on necropsy. Genome-wide association study of 7 affected and 28 normal Salukis revealed a genome-wide significantly associated region on CFA 35. Whole-genome sequencing of three confirmed cases from three different litters revealed a homozygous missense variant within the aldehyde dehydrogenase 5 family member A1 ( ALDH5A1 ) gene (XM&#95;014110599.2: c.866G>A; XP&#95;013966074.2: p.(Gly288Asp). ALDH5A1 encodes a succinic semialdehyde dehydrogenase (SSADH) enzyme critical in the gamma-aminobutyric acid neurotransmitter (GABA) metabolic pathway. Metabolic screening of affected dogs showed markedly elevated gamma-hydroxybutyric acid in serum, cerebrospinal fluid (CSF) and brain, and elevated succinate semialdehyde in urine, CSF and brain. SSADH activity in the brain of affected dogs was low. Affected Saluki dogs had striking similarities to SSADH deficiency in humans although hydroxybutyric aciduria was absent in affected dogs. ALDH5A1 -related SSADH deficiency in Salukis provides a unique translational large animal model for the development of novel therapeutic strategies.

Psychosis has been proposed to develop from dysfunction in a hippocampal-striatal-midbrain circuit, leading to aberrant salience processing. Here, we used functional magnetic resonance imaging (fMRI) during novelty salience processing to investigate this model in people at clinical high risk (CHR) for psychosis according to their subsequent clinical outcomes. Seventy-six CHR participants as defined using the Comprehensive Assessment of At-Risk Mental States (CAARMS) and 31 healthy controls (HC) were studied while performing a novelty salience fMRI task that engaged an a priori hippocampal-striatal-midbrain circuit of interest. The CHR sample was then followed clinically for a mean of 59.7 months (~5 y), when clinical outcomes were assessed in terms of transition (CHR-T) or non-transition (CHR-NT) to psychosis (CAARMS criteria): during this period, 13 individuals (17%) developed a psychotic disorder (CHR-T) and 63 did not. Functional activation and effective connectivity within a hippocampal-striatal-midbrain circuit were compared between groups. In CHR individuals compared to HC, hippocampal response to novel stimuli was significantly attenuated (P = .041 family-wise error corrected). Dynamic Causal Modelling revealed that stimulus novelty modulated effective connectivity from the hippocampus to the striatum, and from the midbrain to the hippocampus, significantly more in CHR participants than in HC. Conversely, stimulus novelty modulated connectivity from the midbrain to the striatum significantly less in CHR participants than in HC, and less in CHR participants who subsequently developed psychosis than in CHR individuals who did not become psychotic. Our findings are consistent with preclinical evidence implicating hippocampal-striatal-midbrain circuit dysfunction in altered salience processing and the onset of psychosis., (© The Author(s) 2019. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Body dissatisfaction is associated with subsequent eating disorders and weight gain. One-off exposure to bodies of different sizes changes perception of others' bodies, and perception of and satisfaction with own body size. The effect of repeated exposure to bodies of different sizes has not been assessed. We randomized women into three groups, and they spent 5 min twice a day for a week completing a one-back task using images of women modified to appear either under, over, or neither over- nor underweight. We tested the effects on their perception of their own and others' body size, and satisfaction with own size. Measures at follow-up were compared between groups, adjusted for baseline measurements. In 93 women aged 18-30 years, images of other women were perceived as larger following exposure to underweight women (and vice versa) ( p < 0.001). There was no evidence for a difference in our primary outcome measure (visual analogue scale own size) or in satisfaction with own size. Avatar-constructed ideal ( p = 0.03) and avatar-constructed perceived own body size ( p = 0.007) both decreased following exposure to underweight women, possibly due to adaptation affecting how the avatar was perceived. Repeated exposure to different sized bodies changes perception of the size of others' bodies, but we did not find evidence that it changes perceived own size., Competing Interests: We declare we have no competing interests., (© 2020 The Authors.)

Background: The concurrence of sleep and socio-emotional development in children is well accepted. However, the predictive role of sleep problems in infancy and the development of emotional and behavioural problems later in childhood remain still unclear. Therefore, in this study we examined the associations between sleep problems in early childhood and internalising, externalising and dysregulation symptoms in toddlers., Methods: 1679 families entered the study during pregnancy and 936 children participated at 24 months. Parent-reported sleep duration, sleep-onset latency, night wakings, proportion of daytime sleep and bedtime at 3, 8, 18 and 24 months were assessed with two sleep questionnaires. Externalising, internalising and dysregulation problems at 24 months were examined with the Brief Infant-Toddler Social and Emotional Assessment., Results: Short sleep duration at 3 and 8 months, more night wakings at 3, 8, 18 and 24 months and greater proportion of daytime sleep at 24 months were associated with internalising symptoms. Shorter sleep duration at 8, 18 and 24 months and longer sleep-onset latency and more night wakings at all time points, in addition to earlier bedtime at 8 months and greater proportion of daytime sleep at 24 months, were related to dysregulation. Finally, more night wakings at 3 and 24 months, and longer sleep-onset latency at 24 months were associated with externalising problems., Conclusion: Shorter sleep and poorer sleep quality in infancy were prospectively related to emotional and behavioural symptoms in toddlers, and these associations were strongest for internalising and dysregulation symptoms. This study contributes to the recent research on the role of early sleep problems in socio-emotional development, suggesting that shorter sleep duration, longer sleep-onset latency and higher waking frequency are related to internalising, externalising and dysregulation symptoms in toddlers, and thus it might be beneficial to provide early interventions for those infants reporting these sleep problems., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Outcomes for people with first-episode psychosis are highly heterogeneous. Few reliable validated methods are available to predict the outcome for individual patients in the first clinical contact. In this study, we aimed to build multivariable prediction models of 1-year remission and recovery outcomes using baseline clinical variables in people with first-episode psychosis., Methods: In this machine learning approach, we applied supervised machine learning, using regularised regression and nested leave-one-site-out cross-validation, to baseline clinical data from the English Evaluating the Development and Impact of Early Intervention Services (EDEN) study (n=1027), to develop and internally validate prediction models at 1-year follow-up. We assessed four binary outcomes that were recorded at 1 year: symptom remission, social recovery, vocational recovery, and quality of life (QoL). We externally validated the prediction models by selecting from the top predictor variables identified in the internal validation models the variables shared with the external validation datasets comprised of two Scottish longitudinal cohort studies (n=162) and the OPUS trial, a randomised controlled trial of specialised assertive intervention versus standard treatment (n=578)., Findings: The performance of prediction models was robust for the four 1-year outcomes of symptom remission (area under the receiver operating characteristic curve [AUC] 0·703, 95% CI 0·664-0·742), social recovery (0·731, 0·697-0·765), vocational recovery (0·736, 0·702-0·771), and QoL (0·704, 0·667-0·742; p<0·0001 for all outcomes), on internal validation. We externally validated the outcomes of symptom remission (AUC 0·680, 95% CI 0·587-0·773), vocational recovery (0·867, 0·805-0·930), and QoL (0·679, 0·522-0·836) in the Scottish datasets, and symptom remission (0·616, 0·553-0·679), social recovery (0·573, 0·504-0·643), vocational recovery (0·660, 0·610-0·710), and QoL (0·556, 0·481-0·631) in the OPUS dataset., Interpretation: In our machine learning analysis, we showed that prediction models can reliably and prospectively identify poor remission and recovery outcomes at 1 year for patients with first-episode psychosis using baseline clinical variables at first clinical contact., Funding: Lundbeck Foundation., (Copyright © 2019 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Adolescent-onset psychosis is associated with more severe symptoms and poorer outcomes than adult-onset psychosis. The National Institute for Clinical Excellence (NICE) recommend that adolescents with first episode psychosis (FEP) should be offered a combination of antipsychotic medication (APs), cognitive behavioural therapy (CBT) and family intervention (FI). The evidence for APs in treating psychosis is limited in adolescents compared to adults. Nevertheless, it indicates that APs can reduce overall symptoms in adolescents but may cause more severe side effects, including cardiovascular and metabolic effects, than in adults. CBT and FI can improve outcomes in adults, but there are no studies of psychological interventions (PI) in patients under 18 years old. Given this limited evidence base, NICE made a specific research recommendation for determining the clinical and cost effectiveness of APs versus PI versus both treatments for adolescent FEP., Methods/design: The current study aimed to establish the feasibility and acceptability of conducting such a trial by recruiting 14-18-year-olds with a first episode of psychosis into a feasibility prospective randomised open blinded evaluation (PROBE) design, three-arm, randomised controlled trial of APs alone versus PI alone versus a combination of both treatments. We aimed to recruit 90 participants from Early Intervention and Child and Adolescent Mental Health Teams in seven UK sites. APs were prescribed by participants' usual psychiatrists. PI comprised standardised cognitive behavioural therapy and family intervention sessions., Discussion: This is the first study to compare APs to PI in an adolescent population with FEP. Recruitment finished on 31 October 2018. The study faced difficulties with recruitment across most sites due to factors including clinician and service-user treatment preferences., Trial Registration: Current controlled trial with ISRCTN, ISRCTN80567433 . Registered on 27 February 2017.

Schizophrenia-spectrum psychoses are highly complex and heterogeneous disorders that necessitate multiple lines of scientific inquiry and levels of explanation. In recent years, both computational and phenomenological approaches to the understanding of mental illness have received much interest, and significant progress has been made in both fields. However, there has been relatively little progress bridging investigations in these seemingly disparate fields. In this conceptual review and collaborative project from the 4th Meeting of the International Consortium on Hallucination Research, we aim to facilitate the beginning of such dialogue between fields and put forward the argument that computational psychiatry and phenomenology can in fact inform each other, rather than being viewed as isolated or even incompatible approaches. We begin with an overview of phenomenological observations on the interrelationships between auditory-verbal hallucinations (AVH) and delusional thoughts in general, before moving on to review several theoretical frameworks and empirical findings in the computational modeling of AVH. We then relate the computational models to the phenomenological accounts, with a special focus on AVH and delusions that involve the senses of agency and ownership of thought (delusions of thought interference). Finally, we offer some tentative directions for future research, emphasizing the importance of a mutual understanding between separate lines of inquiry.

Preclinical models propose that the onset of psychosis is associated with hippocampal hyperactivity, thought to be driven by cortical GABAergic interneuron dysfunction and disinhibition of pyramidal neurons. Recent neuroimaging studies suggest that resting hippocampal perfusion is increased in subjects at ultra-high risk (UHR) for psychosis, but how this may be related to GABA concentrations is unknown. The present study used a multimodal neuroimaging approach to address this issue in UHR subjects. Proton magnetic resonance spectroscopy and pulsed-continuous arterial spin labeling imaging were acquired to investigate the relationship between medial prefrontal (MPFC) GABA+ levels (including some contribution from macromolecules) and hippocampal regional cerebral blood flow (rCBF) in 36 individuals at UHR of psychosis, based on preclinical evidence that MPFC dysfunction is involved in hippocampal hyperactivity. The subjects were then clinically monitored for 2 years: during this period, 7 developed a psychotic disorder and 29 did not. At baseline, MPFC GABA+ levels were positively correlated with rCBF in the left hippocampus (region of interest analysis, p = 0.044 family-wise error corrected, FWE). This correlation in the left hippocampus was significantly different in UHR subjects who went on to develop psychosis relative to those who did not (p = 0.022 FWE), suggesting the absence of a correlation in the latter subgroup. These findings provide the first human evidence that MPFC GABA+ concentrations are related to resting hippocampal perfusion in the UHR state, and offer some support for a link between GABA levels and hippocampal function in the development of psychosis.

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We recently reported that resting hippocampal, basal ganglia and midbrain perfusion is elevated in people at ultra high risk (UHR) for psychosis. The present study sought to replicate our previous finding in an independent UHR cohort, and examined the relationship between resting perfusion in these regions, psychosis and depression symptoms, and traumatic experiences in childhood. Pseudo-Continuous Arterial Spin Labelling (p-CASL) imaging was used to measure resting cerebral blood flow (rCBF) in 77 UHR for psychosis individuals and 25 healthy volunteers in a case-control design. UHR participants were recruited from clinical early detection services at 3 sites in the South of England. Symptoms levels were assessed using the Comprehensive Assessment of At Risk Mental States (CAARMS), the Hamilton Depression Scale (HAM-D), and childhood trauma was assessed retrospectively using the Childhood Trauma Questionnaire (CTQ). Right hippocampal and basal ganglia rCBF were significantly increased in UHR subjects compared to controls, partially replicating our previous finding in an independent cohort. In UHR participants, positive symptoms were positively correlated with rCBF in the right pallidum. CTQ scores were positively correlated with rCBF values in the bilateral hippocampus and negatively associated with rCBF in the left prefrontal cortex. Elevated resting hippocampal and basal ganglia activity appears to be a consistent finding in individuals at high risk for psychosis, consistent with data from preclinical models of the disorder. The association with childhood trauma suggests that its influence on the risk of psychosis may be mediated through an effect on hippocampal function.

Body dissatisfaction is prevalent among women and associated with subsequent obesity and eating disorders. Exposure to images of bodies of different sizes has been suggested to change the perception of 'normal' body size in others. We tested whether exposure to different-sized (otherwise identical) bodies changes perception of own and others' body size, satisfaction with body size and amount of chocolate consumed. In Study 1, 90 18-25-year-old women with normal BMI were randomized into one of three groups to complete a 15 min two-back task using photographs of women either of 'normal weight' (Body Mass Index (BMI) 22-23 kg m -2 ), or altered to appear either under- or over-weight. Study 2 was identical except the 96 participants had high baseline body dissatisfaction and were followed up after 24 h. We also conducted a mega-analysis combining both studies. Participants rated size of others' bodies, own size, and satisfaction with size pre- and post-task. Post-task ratings were compared between groups, adjusting for pre-task ratings. Participants exposed to over- or normal-weight images subsequently perceived others' bodies as smaller, in comparison to those shown underweight bodies ( p  < 0.001). They also perceived their own bodies as smaller (Study 1, p  = 0.073; Study 2, p  = 0.018; mega-analysis, p  = 0.001), and felt more satisfied with their size (Study 1, p  = 0.046; Study 2, p  = 0.004; mega-analysis, p  = 0.006). There were no differences in chocolate consumption. This study suggests that a move towards using images of women with a BMI in the healthy range in the media may help to reduce body dissatisfaction, and the associated risk of eating disorders., Competing Interests: We declare we have no competing interests.

Auditory verbal hallucinations (AVH) often lead to distress and functional disability, and are frequently associated with psychotic illness. Previously both state and trait magnetic resonance imaging (MRI) studies of AVH have identified activity in brain regions involving auditory processing, language, memory and areas of default mode network (DMN) and salience network (SN). Current evidence is clouded by research mainly in participants on long-term medication, with chronic illness and by choice of seed regions made 'a priori'. Thus, the aim of this study was to elucidate the intrinsic functional connectivity in patients presenting with first episode psychosis (FEP). Resting state functional MRI data were available from 18 FEP patients, 9 of whom also experienced AVH of sufficient duration in the scanner and had symptom capture functional MRI (sc fMRI), together with 18 healthy controls. Symptom capture results were used to accurately identify specific brain regions active during AVH; including the superior temporal cortex, insula, precuneus, posterior cingulate and parahippocampal complex. Using these as seed regions, patients with FEP and AVH showed increased resting sb-FC between parts of the SN and the DMN and between the SN and the cerebellum, but reduced sb-FC between the claustrum and the insula, compared to healthy controls.It is possible that aberrant activity within the DMN and SN complex may be directly linked to impaired salience appraisal of internal activity and AVH generation. Furthermore, decreased intrinsic functional connectivity between the claustrum and the insula may lead to compensatory over activity in parts of the auditory network including areas involved in DMN, auditory processing, language and memory, potentially related to the complex and individual content of AVH when they occur.

Modern psychiatric epidemiology researches complex interactions between multiple variables in large datasets. This creates difficulties for causal inference. We argue for the use of probabilistic models represented by directed acyclic graphs (DAGs). These capture the dependence structure of multiple variables and, used appropriately, allow more robust conclusions about the direction of causation. We analyzed British national survey data to assess putative mediators of the association between bullying victimization and persecutory ideation. We compared results using DAGs and the Karlson-Holm-Breen (KHB) logistic regression commands in STATA. We analyzed data from the 2007 English National Survey of Psychiatric Morbidity, using the equivalent 2000 survey in an instant replication. Additional details of methods and results are provided in the supplementary material. DAG analysis revealed a richer structure of relationships than could be inferred using the KHB logistic regression commands. Thus, bullying had direct effects on worry, persecutory ideation, mood instability, and drug use. Depression, sleep and anxiety lay downstream, and therefore did not mediate the link between bullying and persecutory ideation. Mediation by worry and mood instability could not be definitively ascertained. Bullying led to hallucinations indirectly, via persecutory ideation and depression. DAG analysis of the 2000 dataset suggested the technique generates stable results. While causality cannot be fully determined from cross-sectional data, DAGs indicate the relationships providing the best fit. They thereby advance investigation of the complex interactions seen in psychiatry, including the mechanisms underpinning psychiatric symptoms. It may consequently be used to optimize the choice of intervention targets., (© The Author 2017. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center.)

Background: Treatment decision tools have been developed in many fields of medicine, including psychiatry, however benefits for patients have not been sustained once the support is withdrawn. We have developed a web-based computerised clinical decision support tool (CDST), which can provide patients and clinicians with continuous, up-to-date, personalised information about the efficacy and tolerability of competing interventions. To test the feasibility and acceptability of the CDST we conducted a focus group study, aimed to explore the views of clinicians, patients and carers., Methods: The CDST was developed in Oxford. To tailor treatments at an individual level, the CDST combines the best available evidence from the scientific literature with patient preferences and values, and with patient medical profile to generate personalised clinical recommendations. We conducted three focus groups comprising of three different participant types: consultant psychiatrists, participants with a mental health diagnosis and/or experience of caring for someone with a mental health diagnosis, and primary care practitioners and nurses. Each 1-h focus group started with a short visual demonstration of the CDST. To standardise the discussion during the focus groups, we used the same topic guide that covered themes relating to the acceptability and usability of the CDST. Focus groups were recorded and any identifying participant details were anonymised. Data were analysed thematically and managed using the Framework method and the constant comparative method., Results: The focus groups took place in Oxford between October 2016 and January 2017. Overall 31 participants attended (12 consultants, 11 primary care practitioners and 8 patients or carers). The main themes that emerged related to CDST applications in clinical practice, communication, conflicting priorities, record keeping and data management. CDST was considered a useful clinical decision support, with recognised value in promoting clinician-patient collaboration and contributing to the development of personalised medicine. One major benefit of the CDST was perceived to be the open discussion about the possible side-effects of medications. Participants from all the three groups, however, universally commented that the terminology and language presented on the CDST were too medicalised, potentially leading to ethical issues around consent to treatment., Conclusions: The CDST can improve communication pathways between patients, carers and clinicians, identifying care priorities and providing an up-to-date platform for implementing evidence-based practice, with regard to prescribing practices.

Background: Thyroid cysts are rare in cats and poorly documented., Objectives: To report distinguishing clinical features and treatment responses of cats with thyroid cysts., Animals: Forty client-owned cats., Methods: Retrospective review of medical records for cats with thyroid cysts confirmed by scintigraphy, ultrasound, magnetic resonance imaging, or necropsy at 4 referral centers between 2005 and 2016. Signalment, clinical findings, diagnostic testing, treatment, and outcome were recorded., Results: Cats ranged in age from 8 to 20 years with no apparent breed or sex predilection. 37 of 40 (93%) cats were hyperthyroid (duration, 1-96 months). Clinical findings included palpable neck mass (40/40, 100%), weight loss (15/40, 38%), dysphagia (8/40, 20%), decreased appetite (5/40, 13%), and dyspnea (4/40, 10%). Cysts were classified as small (≤8 cm 3 ) in 16 (40%) and large (>8 cm 3 ) in 24 (60%) cats. Of 25 cats treated with radioiodine, hyperthyroidism resolved in 23 (92%), whereas thyroid cysts resolved in 12 (50%). Radioiodine treatment resolved small cysts in 8 of 13 (62%) cats and large cysts in 4 of 11 (36%) cats. Eight cats, including 2 euthyroid cats, underwent thyroid-cystectomy; 3 with bilateral thyroid involvement were euthanized postoperatively for hypocalcemia. Excised cystic thyroid masses were identified as cystadenoma (4) and carcinoma (4)., Conclusions and Clinical Importance: Thyroid cysts are encountered in hyperthyroid and euthyroid cats with benign and malignant thyroid tumors. Radioiodine treatment alone inconsistently resolved thyroid cysts. Thyroid-cystectomy could be considered in cats with unilateral thyroid disease or when symptomatic cysts persist despite successful radioiodine treatment of hyperthyroidism., (Copyright © 2017 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)

Published reports of functional abnormalities in schizophrenia remain divergent due to lack of staging point-of-view and whole-brain analysis. To identify key functional-connectivity differences of first-episode (FE) and chronic patients from controls using resting-state functional MRI, and determine changes that are specifically associated with disease onset, a clinical staging model is adopted. We analyze functional-connectivity differences in prodromal, FE (mostly drug naïve), and chronic patients from their matched controls from 6 independent datasets involving a total of 789 participants (343 patients). Brain-wide functional-connectivity analysis was performed in different datasets and the results from the datasets of the same stage were then integrated by meta-analysis, with Bonferroni correction for multiple comparisons. Prodromal patients differed from controls in their pattern of functional-connectivity involving the inferior frontal gyri (Broca's area). In FE patients, 90% of the functional-connectivity changes involved the frontal lobes, mostly the inferior frontal gyrus including Broca's area, and these changes were correlated with delusions/blunted affect. For chronic patients, functional-connectivity differences extended to wider areas of the brain, including reduced thalamo-frontal connectivity, and increased thalamo-temporal and thalamo-sensorimoter connectivity that were correlated with the positive, negative, and general symptoms, respectively. Thalamic changes became prominent at the chronic stage. These results provide evidence for distinct patterns of functional-dysconnectivity across FE and chronic stages of schizophrenia. Importantly, abnormalities in the frontal language networks appear early, at the time of disease onset. The identification of stage-specific pathological processes may help to understand the disease course of schizophrenia and identify neurobiological markers crucial for early diagnosis., (© The Author 2016. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: In dimensional understanding of psychosis, auditory verbal hallucinations (AVH) are unitary phenomena present on a continuum from non-clinical voice hearing to severe mental illness. There is mixed evidence for this approach and a relative absence of research into subjective experience of AVH in early psychosis., Aims: To conduct primary research into the nature of subjective experience of AVH in first-episode psychosis., Method: A phenomenological study using diary and photo-elicitation qualitative techniques investigating the subjective experience of AVH in 25 young people with first-episode psychosis., Results: AVH are characterised by: (a) entity, as though from a living being with complex social interchange; and (b) control, exerting authority with ability to influence. AVH are also received with passivity, often accompanied by sensation in other modalities., Conclusions: A modern detailed phenomenological investigation, without presupposition, gives results that echo known descriptive psychopathology. However, novel findings also emerge that may be features of AVH in psychosis not currently captured with standardised measures., Declaration of Interest: None., Copyright and Usage: © The Royal College of Psychiatrists 2016. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) licence.

Objectives: Hyperthyroidism is common in cats, but there are no reports that evaluate its severity or underlying thyroid tumor disease based on disease duration (ie, time from original diagnosis). The objective of this study was to compare serum thyroxine (T4) concentrations and thyroid scintigraphic characteristics of cats referred for radioiodine treatment based on disease duration., Methods: This was a cross-sectional study of 2096 cats with hyperthyroidism. Cats were divided into five groups based on time from diagnosis: ⩽1 year (n = 1773); >1-2 years (n = 169); >2-3 years (n = 88); >3-4 years (n = 35); and >4-6.1 years (n = 31). Methimazole, administered to 996 (47.5%) cats, was stopped at least 1 week prior to examination to allow for serum T4 testing. Each thyroid scintiscan was evaluated for pattern (unilateral, bilateral, multifocal), location (cervical, thoracic inlet, chest) and size (small, medium, large, huge) of the thyroid tumor, as well as features suggesting malignancy., Results: Median serum T4 concentration increased with increasing disease duration from 100 nmol/l (⩽1 year) to 315 nmol/l (>4-6.1 years) (P <0.001). Prevalence of unilateral thyroid disease decreased, whereas multifocal disease (three or more tumor nodules) increased (P <0.001) with increasing disease duration. Median tumor volume in the five groups increased from 1.6 cm(3) (⩽1 year) to 6.4 cm(3) (>4-6.1 years). Prevalence of large (4-8 cm(3)) and huge (>8 cm(3)) thyroid tumors increased from 5.1% (⩽1 year) to 88.6% (>4-6.1 years), while the prevalence of intrathoracic tumor tissue increased from 3.4% (⩽1 year) to 32.3% (>4-6.1 years). Prevalence of suspected thyroid carcinoma (characterized by severe hyperthyroidism; huge, intrathoracic, multifocal tumors; refractory to methimazole treatment) increased with increasing disease duration from 0.4% (⩽1 year) to 19.3% (>4-6.1 years)., Conclusions and Relevance: Our results indicate that the prevalence of severe hyperthyroidism, large thyroid tumors, multifocal disease, intrathoracic thyroid masses and suspected malignant disease all increase with disease duration in cats referred for radioiodine therapy., (© ISFM and AAFP 2015.)

Over 800,000 people die by suicide each year globally, with non-fatal self-harm 20 times more common. With each episode of self-harm, the risks of future self-harm and suicide increase, as well as personal and healthcare costs. Therefore, early delineation of those at high risk of future self-harm is important. Historically, research has focused on clinical and demographic factors, but risk assessments based on these have low sensitivity to predict repetition. Various neurocognitive factors have been associated with self-harming behavior, but it is less certain if we can use these factors clinically (i) as risk markers to predict future self-harm and (ii) to become therapeutic targets for interventions. Recent systematic reviews and meta-analyses of behavioral tasks and fMRI studies point to an emerging hypothesis for neurocognition in self-harm: an underactive pre-frontal cortex is unable to respond appropriately to non-emotional stimuli, or inhibit a hyperactive emotionally-/threat-driven limbic system. However, there is almost no imaging data examining repetition of self-harm. Extrapolating from the non-repetition data, there may be several potential neurocognitive targets for interventions to prevent repeat self-harm: cognitive training; pharmacological regimes to promote non-emotional neurocognition; or other techniques, such as repetitive transcranial magnetic stimulation. Hence, there is an urgent need for imaging studies examining repetition and to test specific hypotheses. Until we investigate the functional neurocognitive basis underlying repetition of self-harm in a systematic manner using second-generational imaging techniques, we will be unable to inform third-generational imaging and potential future clinical applications.

Background: It is unknown whether prodromal services improve outcomes in those who go on to develop psychosis, and whether these patients are demographically different from the overall first-episode population., Aims: To compare sociodemographic features, duration of untreated psychosis, hospital admission and frequency of compulsory treatment in the first year after the onset of psychosis in patients who present to prodromal services with patients who did not present to services until the first episode of psychosis., Method: We compared two groups of patients with first-episode psychosis: one who made transition after presenting in the prodromal phase and the other who had presented with a first episode., Results: The patients who had presented before the first episode were more likely to be employed and less likely to belong to an ethnic minority group. They had a shorter duration of untreated psychosis, and were less likely to have been admitted to hospital and to have required compulsory treatment., Conclusions: Patients who develop psychosis after being engaged in the prodromal phase have a better short-term clinical outcome than patients who do not present until the first episode. Patients who present during first episodes may be more likely to have sociodemographic features associated with relatively poor outcomes., (© The Royal College of Psychiatrists 2015.)

Objective: To describe findings in dogs with exogenous thyrotoxicosis attributable to consumption of commercially available dog foods or treats containing high concentrations of thyroid hormone., Design: Retrospective and prospective case series., Animals: 14 dogs., Procedures: Medical records were retrospectively searched to identify dogs with exogenous thyrotoxicosis attributable to dietary intake. One case was found, and subsequent cases were identified prospectively. Serum thyroid hormone concentrations were evaluated before and after feeding meat-based products suspected to contain excessive thyroid hormone was discontinued. Scintigraphy was performed to evaluate thyroid tissue in 13 of 14 dogs before and 1 of 13 dogs after discontinuation of suspect foods or treats. Seven samples of 5 commercially available products fed to 6 affected dogs were analyzed for thyroxine concentration; results were subjectively compared with findings for 10 other commercial foods and 6 beef muscle or liver samples., Results: Total serum thyroxine concentrations were high (median, 8.8 μg/dL; range, 4.65 to 17.4 μg/dL) in all dogs at initial evaluation; scintigraphy revealed subjectively decreased thyroid gland radionuclide in 13 of 13 dogs examined. At ≥ 4 weeks after feeding of suspect food or treats was discontinued, total thyroxine concentrations were within the reference range for all dogs and signs associated with thyrotoxicosis, if present, had resolved. Analysis of tested food or treat samples revealed a median thyroxine concentration for suspect products of 1.52 μg of thyroxine/g, whereas that of unrelated commercial foods was 0.38 μg of thyroxine/g., Conclusions and Clinical Relevance: Results indicated that thyrotoxicosis can occur secondary to consumption of meat-based products presumably contaminated by thyroid tissue, and can be reversed by identification and elimination of suspect products from the diet.