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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_014110599.2: c.866G>A; XP_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.

Background: Evidence for the effectiveness of treatments in early-onset psychosis is sparse. Current guidance for the treatment of early-onset psychosis is mostly extrapolated from trials in adult populations. The UK National Institute for Health and Care Excellence has recommended evaluation of the clinical effectiveness and cost-effectiveness of antipsychotic drugs versus psychological intervention (cognitive behavioural therapy [CBT] and family intervention) versus the combination of these treatments for early-onset psychosis. The aim of this study was to establish the feasibility of a randomised controlled trial of antipsychotic monotherapy, psychological intervention monotherapy, and antipsychotics plus psychological intervention in adolescents with first-episode psychosis., Methods: We did a multicentre pilot and feasibility trial according to a randomised, single-blind, three-arm, controlled design. We recruited participants from seven UK National Health Service Trust sites. Participants were aged 14-18 years; help-seeking; had presented with first-episode psychosis in the past year; were under the care of a psychiatrist; were showing current psychotic symptoms; and met ICD-10 criteria for schizophrenia, schizoaffective disorder, or delusional disorder, or met the entry criteria for an early intervention for psychosis service. Participants were assigned (1:1:1) to antipsychotics, psychological intervention (CBT with optional family intervention), or antipsychotics plus psychological intervention. Randomisation was via a web-based randomisation system, with permuted blocks of random size, stratified by centre and family contact. CBT incorporated up to 26 sessions over 6 months plus up to four booster sessions, and family intervention incorporated up to six sessions over 6 months. Choice and dose of antipsychotic were at the discretion of the treating consultant psychiatrist. Participants were followed up for a maximum of 12 months. The primary outcome was feasibility (ie, data on trial referral and recruitment, session attendance or medication adherence, retention, and treatment acceptability) and the proposed primary efficacy outcome was total score on the Positive and Negative Syndrome Scale (PANSS) at 6 months. Primary outcomes were analysed by intention to treat. Safety outcomes were reported according to as-treated status, for all patients who had received at least one session of CBT or family intervention, or at least one dose of antipsychotics. The study was prospectively registered with ISRCTN, ISRCTN80567433., Findings: Of 101 patients referred to the study, 61 patients (mean age 16·3 years [SD 1·3]) were recruited from April 10, 2017, to Oct 31, 2018, 18 of whom were randomly assigned to psychological intervention, 22 to antipsychotics, and 21 to antipsychotics plus psychological intervention. The trial recruitment rate was 68% of our target sample size of 90 participants. The study had a low referral to recruitment ratio (around 2:1), a high rate of retention (51 [84%] participants retained at the 6-month primary endpoint), a high rate of adherence to psychological intervention (defined as six or more sessions of CBT; in 32 [82%] of 39 participants in the monotherapy and combined groups), and a moderate rate of adherence to antipsychotic medication (defined as at least 6 consecutive weeks of exposure to antipsychotics; in 28 [65%] of 43 participants in the monotherapy and combined groups). Mean scores for PANSS total at the 6-month primary endpoint were 68·6 (SD 17·3) for antipsychotic monotherapy (6·2 points lower than at randomisation), 59·8 (13·7) for psychological intervention (13·1 points lower than at randomisation), and 62·0 (15·9) for antipsychotics plus psychological intervention (13·9 points lower than at randomisation). A good clinical response at 6 months (defined as ≥50% improvement in PANSS total score) was achieved in four (22%) of 18 patients receiving antipsychotic monotherapy, five (31%) of 16 receiving psychological intervention, and five (29%) of 17 receiving antipsychotics plus psychological intervention. In as-treated groups, serious adverse events occurred in eight [35%] of 23 patients in the combined group, two [13%] of 15 in the antipsychotics group, four [24%] of 17 in the psychological intervention group, and four [80%] of five who did not receive any treatment. No serious adverse events were considered to be related to participation in the trial., Interpretation: This trial is the first to show that a head-to-head clinical trial comparing psychological intervention, antipsychotics, and their combination is safe in young people with first-episode psychosis. However, the feasibility of a larger trial is unclear because of site-specific recruitment challenges, and amendments to trial design would be needed for an adequately powered clinical and cost-effectiveness trial that provides robust evidence., Funding: National Institute for Health Research., (Copyright © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

In this Personal View, we discuss the history and concept of self-disturbance in relation to the pathophysiology and subjective experience of schizophrenia in terms of three approaches: the perceptual anomalies approach of the early Heidelberg School of Psychiatry, the ipseity model, and the predictive coding framework. Despite the importance of these approaches, there has been a notable absence of efforts to compare them and consider how they might be integrated. This Personal View compares the three approaches and offers suggestions as to how they might work together, which represents a novel position. We view self-disturbances as transformations of self that form the inseparable background against which psychotic symptoms emerge. Integrating computational psychiatric approaches with those used by phenomenologists in the first two listed approaches, we argue that delusions and hallucinations are inferences produced under extraordinary conditions and are both statistically and experientially as real for patients as other mental events. Such inferences still approximate Bayes-optimality, given the personal, neurobiological, and environmental circumstances, and might be the only ones available to minimise prediction error. The added contribution we hope to make focuses on how the dialogue between neuroscience and phenomenology might improve clinical practice. We hope this Personal View will act as a timely primer and bridging point for the different approaches of computational psychiatry and phenomenological psychopathology for interested clinicians., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

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.)

Autism traits are found at elevated rates in individuals with schizophrenia spectrum disorders, however, there is a lack of evidence regarding potential clinical impact. The current research aimed to examine potential associations between autism traits and symptoms of psychosis, social and role functioning, and quality of life. 99 individuals experiencing a first episode of psychosis took part in a cross-sectional interview and self-report questionnaire which assessed current symptoms of psychosis, autism traits, functioning, and quality of life. Participants were found to have a high level of autism traits. Higher autism traits were associated with poorer quality of life, functioning, and current psychotic symptoms. Receiver operating characteristic curve (ROC) analyses indicated that optimal AQ cut-off scores to predict severity of psychosis symptoms, functioning, and quality of life were lower than those used to suggest likely autism-spectrum diagnosis. Results suggest that autism traits are associated with poorer clinical presentation in first-episode psychosis populations, even in those whose traits fall below potentially diagnostic thresholds for autism. Psychosis services should be prepared to adequately address the needs of individuals with higher autism traits., (Copyright © 2019 Elsevier B.V. All rights reserved.)

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.

Background: Impulsivity may be an important risk factor in terms of future self-harm. However, the extent of this, whether it may relate to self-harm that is new in onset and/or repetition of self-harm, and the detail of any interaction with mood instability (MI) and childhood sexual abuse (CSA) requires detailed examination., Aims: We used the 2000 Adult Psychiatry Morbidity Survey and an 18-month follow-up data to test hypotheses relating to the role of impulsivity, CSA and MI in the inception and persistence of self-harm., Methods: We assessed associations of impulsivity with (1) suicidal self-harm (SSH) and (2) non-SSH (NSSH) at baseline and follow-up, controlling for confounders including MI. Finally, we tested whether impulsivity mediated the relationship between CSA and self-harm., Results: A total of 8,580 respondents were assessed at baseline and 2,406 at follow-up as planned. Impulsivity significantly predicted emergence of new NSSH at 18-month follow-up even after adjustment for MI and other confounders. Impulsivity did not significantly predict repetition of NSSH, or repetition or new inception of SSH, even before inclusion of MI in the model. However, the absolute numbers involved were small. Cross-sectionally, impulsivity was a stronger mediator of the link between CSA and SSH (13.1%) than that between CSA and NSSH (4.8%)., Conclusion: Impulsivity may increase the risk of future development of NSSH independently of MI, which is clinically important for risk assessment. The involvement of impulsivity in the repetition of self-harm generally appears less certain. However, impulsivity may have a role in SSH in the context of previous CSA.

Background: Bullying is a widespread phenomenon that has captured attention from mental health researchers. Several studies have assessed bullying prevalence with some methodological concerns., Objectives: Preliminary, we analyzed the psychometric properties of two bullying scales for victimization (the multidimensional peer victimization scale - MPVS) and for perpetration (the bully subscale of the Illinois bully scale - IBS-B); then, we estimated bullying prevalence; finally, we evaluated the effect of gender and classroom on the phenomenon., Participants and Setting: 2959 students from the metropolitan city of Naples constituted the sample., Methods: Data collection was obtained using a multi-assessment approach that included both single-item questions and intensity scales in order to compare the two methods., Results: The two scales resulted valid and showed good reliability. The MPVS displayed a 1-factor second order model. The IBS-B had a mono-factorial structure. Both showed full invariance for gender and classroom. Prevalence of victimization was 37% whereas that for perpetration was 21%. As expected we obtained several bullying prevalence results depending on the specificity of questions and in particular repetitiveness of episodes. There was a good correspondence between results of single-item questions and multi-item scales. Finally results demonstrated several differences for gender and classroom attended., Conclusion: In this epidemiological study the multi-assessment approach identified different but complementary features of bullying phenomena. The use of the two measurement approaches allowed us to obtain more precise and exhaustive information on bullying prevalence and compare it with previous findings., (Crown Copyright © 2018. Published by Elsevier Ltd. All rights reserved.)

Background: This study aims to understand suicidal ideation and suicide attempts among transgender individuals through an in-depth analysis of a nation-wide population general survey in China., Methods: Transgender Men (TM) and Women (TW) were investigated through a cross-sectional survey. A structured questionnaire was used to investigate participants' demographic information, perceived sexuality conflicts, childhood adversity and mental health conditions. Logistic regression models were utilized to investigate risk factors associated with suicidal ideation and suicide attempts in these groups. We also conducted a quasi-meta-analysis in order to compare the prevalence of suicidal ideation and attempted suicide between general and transgender populations in China., Results: A total of 1309 participants across 32 provinces and municipalities in China took part in this survey, out of 2060 valid questionnaires. In this transgender population, the lifetime prevalence of suicidal ideation and an attempt at suicide were 56.4% and 16.1%, respectively. This estimated prevalence rate is far greater than in Chinese community samples. For all transgender people, disliking birth-assigned sex, seeking sex reassignment surgery, having intense conflicts with parents, lifetime history of suffering from major depressive disorder, a recent episode of depression, self-harm, and seeking mental health services were significantly associated with increased risk of suicidal ideation. An education level of high school or equivalent, being married and/or separated/divorced, having intense conflicts with parents, or self-harm and seeking mental health services were all significantly associated with increased risk of suicide attempt. Although most risk factors for TM and TW were equivalent across groups, differences were observed in both suicidal ideation and suicide attempt models., Limitations: The cross-sectional study design and lack of follow-up data are limitations of this study., Conclusions: This is the first study to examine suicide within a Chinese transgender population. The clinical implications of these findings for Chinese mental health professionals are discussed. Also, the evidence from this study can be used to inform the practices of suicide prevention workers, and policy makers working with the transgender population., (Copyright © 2018 Elsevier B.V. All rights reserved.)

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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Background: Affective instability (AI) is transdiagnostic, and associated with suicidality and healthcare use. It has rarely been compared between diagnoses or to controls. We investigated: whether AI differs between clinical cases and controls and between diagnoses; how different AI components are correlated; and whether AI is associated with functioning in clinical cases., Methods: Cases (N = 69) from psychiatric services had a diagnosis of borderline personality disorder, bipolar disorder, major depression or psychosis and were compared to primary care controls (N = 25). Participants completed the affective lability scale (ALS), affective intensity measure (AIM), affective control scale (ACS), scored mood fluctuation rate and the WHO-DAS., Results: There was a significant difference in affective lability between cases and controls and across diagnostic groups (p < 0.001). Compared to controls, cases showed lower affective control (p < 0.05). There were no differences in affective intensity between cases and controls or between diagnostic groups, or in mood fluctuation rate between groups. ALS score (p < 0.001), and total number of medications (p < 0.046), were associated with functioning, independent of diagnosis., Limitations: The sample size was modest. Cases were not in an acute illness episode and this could bias estimates of group difference towards the null., Conclusion: Individuals with mental disorder demonstrate higher levels of affective lability and lower affect control than those without mental disorder. In contrast affective intensity may not be useful in demarcating abnormal affective experience. Independent of diagnosis, affective instability, as measured by affect lability, adversely impacts day-to-day functioning. It could be an important target for clinical intervention., (Copyright © 2018. Published by Elsevier B.V.)

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.

Object: There have been significantly fewer community-based, epidemiological studies focusing on PTSD and its socio-demographic correlates among the Chinese than Western populations., Method: The multistage household cluster random sampling method was used to select participants from18 districts and counties in Beijing; a total of 16,032 participants were assessed; face-to-face interviews and data collection was conducted using the semi-structured clinical interview for DSM-IV-TR Axis I Disorders-Patient Edition (SCID-I/P)., Result: The lifetime PTSD prevalence was 0.3%. Older age, low educational level, low personal monthly income, urban living, unemployment and being a farmer were all significantly associated with an increased risk of PTSD. Multivariate analysis showed that farmers and the unemployed were significantly associated with a higher risk for PTSD., Conclusions: The prevalence rates of PTSD in Beijing were low compared with that of Western countries. Farming occupation and unemployment were independent risk factors for PTSD., (Copyright © 2017 Elsevier B.V. All rights reserved.)

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.)

Background: Clinical outcomes in people identified as at ultra-high risk (UHR) for psychosis are remarkably heterogeneous, and are difficult to predict on the basis of the presenting clinical features. Individuals at UHR are at risk of poor functional outcome regardless of development of psychotic disorder. The aim of the present study was to assess whether there is a relationship between functional neuroimaging measures at presentation and functional outcome as measured by the GAF three years after scanning., Methods: Functional magnetic resonance imaging (fMRI) data were collected during an object working memory task in 34 ultra-high risk (UHR) subjects and 20 healthy controls. On the basis of their GAF scores at follow up, the UHR participants were divided into subgroups with good and poor functional outcomes, respectively., Results: At baseline, the UHR group differed from controls in showing altered frontal and cuneus/posterior cingulate activation. Significant group x task interactions were found in the left cuneus and posterior cingulate gyrus, reflecting differential responses to the task conditions. Within the UHR sample, the subgroup with a poor functional outcome exhibited altered activation in frontal, temporal and striatal regions, and reduced deactivation within default-mode network regions, relative to those with a good outcome. Within the whole UHR sample, in these regions the local task response was correlated with the GAF score at follow up., Conclusions: The findings suggest a potential role of functional neuroimaging in the prediction of outcomes in people at high clinical risk of psychosis., (Copyright © 2016 Elsevier B.V. All rights reserved.)

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: The models of mental disorders held by all mental health professionals are implicit in their attitudes and inform all aspects of theory and practice. The present study aims to explore the attitudes of trainee clinical psychologists towards mental disorders by building on a study conducted by Harland et al. () with psychiatrists. In so doing, the present study contributes to an evidence base that can inform the development of clinical training programs and multidisciplinary working., Methods: The Maudsley Attitude Questionnaire was administered in an online survey of trainee clinical psychologists (n = 289)., Results: Analyses of variance revealed main effects of model, and of diagnostic category, and a significant interaction effect between model and diagnostic category. Principal component analysis revealed a biological-psychosocial continuum and cognitive/behavioural and psychodynamic/spiritual dimensions. Comparisons with Harland et al.'s () psychiatrists revealed large differences, particularly in biological and social constructionist model endorsement., Conclusion: Results suggest that the attitudes of psychologists and psychiatrists continue to sit at opposite ends of a biological-psychosocial continuum. However, an area of consensus regarding psychotherapeutic models was indicated. Training courses can be reassured that strong opinions tended to reflect the evidence base. Future research with similarly large representative samples from different disciplines would allow findings of the current study to be better contextualized. Copyright © 2016 John Wiley & Sons, Ltd., Key Practitioner Message: The models of mental disorders held by clinical psychologists are implicit in their attitudes and inform all aspects of theory and practice. We found that trainee clinical psychologists continue to favour psychosocial over biological understandings of mental disorders, giving the cognitive, behavioural and psychodynamic models equal value overall, and stronger attitudes were supported by the evidence base. We found that trainee clinical psychologists organized their attitudes around a biological-psychosocial continuum and cognitive/behavioural and psychodynamic/spiritual dimensions. These findings may be useful for those involved in developing clinical training programs and multidisciplinary working because they provide an insight into the attitudes of emerging clinical psychologists., (Copyright © 2016 John Wiley & Sons, Ltd.)

Background: Prediction of self-harm is limited clinically. Early identification of individuals likely to repeat self-harm could improve outcomes and reduce suicide risk. Various neurocognitive deficits have been found in people who self-harm, but the ability of these to predict repetition has yet to be established AIMS: Identify neurocognitive factors that may predict repetition of self-harm., Methods: Systematic narrative review of English language publications assessing neurocognitive functioning and self-harm repetition, searching multiple databases from inception to March 2015. Quality of studies was appraised. A narrative synthesis was performed., Results: 7026 unique records were identified, and 169 full-texts assessed. 15 unique studies provided data. No imaging studies could be included. Most studies assessed cognitive control or problem solving, but neither factor was consistently associated with repetition. However, specific tasks may show promise. Two studies in adolescents suggest that value-based decision-making impairments could be predictive of repetition. There were too few results for memory to draw specific conclusions., Conclusions: Selected studies suggest promise for particular neurocognitive factors and specific cognitive tasks in terms of repetition of self-harm., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

There is growing interest in whether the parenting strategies and offspring outcomes of mothers with borderline personality disorder (BPD) differ from those of mothers without BPD. We searched PsychINFO, PubMed, EMBASE, Web of Science, Scopus and ASSIA databases for studies examining parenting skills and attitudes among mothers with BPD/BPD symptoms and/or offspring outcomes. PRISMA reporting guidelines were followed. Of 10,067 abstracts screened, 101 full-text articles were retrieved and 33 met pre-determined criteria for qualitative synthesis. Overall, studies suggest that mothers with BPD/BPD symptoms are more likely to engage in maladaptive interactions with their offspring characterised by insensitive, overprotective, and hostile parenting compared to mothers without BPD/BPD symptoms. Adverse offspring outcomes include BPD symptoms, internalising (including depression) and externalising problems, insecure attachment patterns, and emotional dysregulation. Findings suggest that vulnerability from mother to offspring may be partly transmitted via maladaptive parenting and maternal emotional dysfunction. Conclusions were limited by study heterogeneity in methodology and construct definitions, as well as a paucity of clinical comparison groups. Prospective studies of mothers with BPD and their offspring from pregnancy onwards may further elucidate mechanisms of transmission and identify resilience factors across development. Parenting behaviour awareness, improving attachment behaviours and emotional regulation strategies may be important intervention targets., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Thyroid scintigraphy is commonly used for evaluation of cats with hyperthyroidism, with the thyroid-to-salivary ratio (T/S) being the most common method to quantify the degree of thyroid activity and disease. Calculation of thyroid-to-background ratios (T/B) or percent thyroidal uptake of (99m) TcO(-) 4 (TcTU) has only been reported in a few studies. The purpose of this prospective, cross-sectional study was to evaluate a number of quantitative scintigraphic indices as diagnostic tests for hyperthyroidism, including the T/S, three different T/B, TcTU, and estimated thyroid volume. Of 524 cats referred to our clinic for evaluation of suspected hyperthyroidism, the diagnosis was confirmed (n = 504) or excluded (n = 20) based on results of a serum thyroid panel consisting of thyroxine (T4 ), triiodothyronine (T3 ), free T4 (fT4 ), and thyroid-stimulating hormone (TSH) concentrations. In the hyperthyroid cats, median values for TcTU, T/S, and three T/B ratios were all significantly higher (P < 0.001) than values in euthyroid suspect cats or clinically normal cats. All scintigraphic parameters were relatively sensitive and specific as diagnostic tests for hyperthyroidism, but the T/S ratio had the highest test accuracy. The T/S ratio correlated strongly with the TcTU (r = 0.85). However, the TcTU had a higher and more significant correlation (P < 0.01) with serum T4 (r = 0.76 vs. 0.64), T3 (r = 0.77 vs. 0.64), and estimated thyroid volume (r = 0.62 vs. 0.38). Overall, calculation of TcTU is an accurate diagnostic test, but also appears to be the best parameter to predict the functional volume and metabolic activity of the feline adenomatous thyroid gland., (© 2016 American College of Veterinary Radiology.)

Objective: Auditory verbal hallucinations (AVHs) are core features of psychotic illness and remain significant in predicting poor outcome and risk. There has been a wide range of approaches to understanding these experiences., Method: A systematic literature review summarizing different methods of investigation and their results; phenomenology, descriptive psychopathology, psychological, cognitive neurobiology, and neuroimaging., Results: A number of 764 papers and texts were screened and 113 reviewed. Phenomenological studies are comparably few in number, and psychopathology remains based on concepts defined in the early 20th century. Psychological models focus on voice content and emotional reaction, and suggest a continuum of AVHs from normal experience. Neuropsychological models include AVHs as misattribution of inner speech, whilst functional neuroimaging studies focus on the spontaneous activity and connectivity of auditory networks., Conclusion: There has been a large growth in research on AVHs in recent decades dominated by neurobiological and neuroimaging studies. Future research should include focus on phenomenological aspects and AVHs change over the course of developing illness. Integration between branches of enquiry is needed, and the risk is that without this, models are proposed and investigated that bear scant relevance to the symptom itself., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

An impasse in negotiations between the Department of Health (DoH) and the British Medical Association in November this year led to an overwhelming vote for industrial action (IA) by junior doctors. At the time of writing, a last minute concession by DoH led to a deferment of IA to allow further negotiations mediated by the Advisory, Conciliation and Arbitration Service. However, IA by junior doctors remains a possibility if these negotiations stall again. Would the proposed action be ethically justifiable? Furthermore, is IA by doctors ever ethically defendable? Building on previous work, we explore important ethical considerations for doctors considering IA. The primary moral objection to doctors striking is often claimed to be risk of harm to patients. Other common arguments against IA by doctors include breaching their vocational responsibilities and possible damage to their relationship with patients and the public in general. These positions are in turn countered by claims of a greater long-term good and the legal and moral rights of employees to strike. Absolute restrictions appear to be hard to justify in the modern context, as does an unrestricted right to IA. We review these arguments, find that some common moral objections to doctors striking may be less relevant to the current situation, that a stronger contemporary objection to IA might be from a position of social justice and suggest criteria for ethically permissible doctor IA., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

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.

Purpose: To explore repetition, service provision and service engagement following presentation of young people to emergency services with self-harm., Methods: 969 patients who presented to accident and emergency services after self-harm were followed up prospectively for a period of 1 year. Data on rates, method, clinical history, initial service provision, engagement and repetition (defined as re-presenting to emergency services with further self-harm) were gathered from comprehensive electronic records., Results: Young people were less likely to repeat self-harm compared to those aged 25 and above. A psychiatric history and a history of childhood trauma were significant predictors of repetition. Young people were more likely to receive self-help as their initial service provision, and less likely to receive acute psychiatric care or a hospital admission. There were no differences in engagement with services between young people and those aged 25 and above., Conclusion: Younger individuals may be less vulnerable to repetition, and are less likely to represent to services with repeated self-harm. All young people who present with self-harm should be screened for mental illness and asked about childhood trauma. Whilst young people are less likely to be referred to psychiatric services, they do attend when referred. This may indicate missed opportunity for intervention.

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.

Despite both having some shared features, evidence linking psychosis and adult attention deficit hyperactivity disorder (ADHD) is sparse and inconsistent. Hypotheses tested were (1) adult ADHD symptoms are associated with auditory hallucinations, paranoid ideation and psychosis (2) links between ADHD symptoms and psychosis are mediated by prescribed ADHD medications, use of illicit drugs, and dysphoric mood. The Adult Psychiatric Morbidity Survey 2007 (N=7403) provided data for regression and multiple mediation analyses. ADHD symptoms were coded from the ADHD Self-Report Scale (ASRS). Higher ASRS total score was significantly associated with psychosis, paranoid ideation and auditory hallucinations despite controlling for socio-demographic variables, verbal IQ, autism spectrum disorder traits, childhood conduct problems, hypomanic and dysphoric mood. An ASRS score indicating probable ADHD diagnosis was also significantly associated with psychosis. The link between higher ADHD symptoms and psychosis, paranoia and auditory hallucinations was significantly mediated by dysphoric mood, but not by use of amphetamine, cocaine or cannabis. In conclusion, higher levels of adult ADHD symptoms and psychosis are linked and dysphoric mood may form part of the mechanism. Our analyses contradict the traditional clinical view that the main explanation for people with ADHD symptoms developing psychosis is illicit drugs., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

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.)

Objectives: To evaluate the neurobiological, psychophysical and behavioural measures of affective instability in clinical populations., Data Sources: A range of medical and psychological science electronic databases were searched (including MEDLINE, EMBASE, and PsycINFO). Hand searching and reference checking are also included., Review Methods: Reviews, systematic reviews, experimental and cross-sectional studies, providing affective instability in neurobiological and behavioural measurements in clinical populations. Studies were selected, data were extracted and quality was appraised., Results: Twenty-nine studies were included, 6 of which were review studies (one a meta-analysis) and 23 of which were primary studies, across a wide variety of disorders including ADHD, bipolar affective disorder, schizophrenia, severe mood dysregulation, major depression, and borderline personality disorder., Conclusions: The bulk of the studies converge on the role of the amygdala, particularly in borderline personality disorders, and how it connects with other areas of the brain. Future research needs to extend these findings across diagnoses and development., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: Individuals with an "Attenuated Psychosis Syndrome" (APS) have a 20-40% chance of developing a psychotic disorder within two years; however it is difficult to predict which of them will become ill on the basis of their clinical symptoms alone. We examined whether P50 gating deficits could help to discriminate individuals with APS and also those who are particularly likely to make a transition to psychosis., Method: 36 cases meeting PACE (Personal Assessment and Crisis Evaluation) criteria for the APS, all free of antipsychotics, and 60 controls performed an auditory conditioning-testing experiment while their electroencephalogram was recorded. The P50 ratio and its C-T difference were compared between groups. Subjects received follow-up for up to 2 years to determine their clinical outcome., Results: The P50 ratio was significantly higher and C-T difference lower in the APS group compared to controls. Of the individuals with APS who completed the follow-up (n=36), nine (25%) developed psychosis. P50 ratio and the C-T difference did not significantly differ between those individuals who developed psychosis and those who did not within the APS group., Conclusion: P50 deficits appear to be associated with the pre-clinical phase of psychosis. However, due to the limitations of the study and its sample size, replication in an independent cohort is necessary, to clarify the role of P50 deficits in illness progression and whether this inexpensive and non-invasive EEG marker could be of clinical value in the prediction of psychosis outcomes amongst populations at risk., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Thyroid scintigraphy is currently the reference standard for diagnosing and staging cats with hyperthyroidism, but few studies describing the scintigraphic characteristics in a large number of cats have been reported. The objective of this study was to better characterize thyroid scintigraphy findings by evaluating 2096 consecutive cats with hyperthyroidism that were referred over a 3.5-year period. Of these cats, 2068 (98.7%) had a high thyroid-to-salivary ratio (>1.5), whereas 2014 (96.1%) were found to have a high thyroid-to-background ratio (>6.1). When the patterns of the cats' thyroid disease were recorded, 665 (31.7%) had unilateral disease, 1060 (50.6%) had bilateral-asymmetric disease (two thyroid lobes unequal in size), 257 (12.3%) had bilateral-symmetric disease (both lobes similar in size), and 81 (3.9%) had multifocal disease (≥3 areas of increased radionuclide uptake). The number of areas of (99m) TcO(-) 4 uptake in the 2096 cats ranged from 1 to 6 (median, 2), located in the cervical area in 2057 (98.1%), thoracic inlet in 282 (13.5%), and in the thoracic cavity in 115 (5.5%). Ectopic thyroid tissue (e.g. lingual or mediastinal) was diagnosed in 81 (3.9%) cats, whereas thyroid carcinoma was suspected in 35 (1.7%) of the cats. The results of this study support conclusions that most hyperthyroid cats have unilateral or bilateral thyroid nodules, but that multifocal disease will develop in a few cats that have ectopic thyroid disease or thyroid carcinoma. Both ectopic thyroid disease and thyroid carcinoma are relatively uncommon in hyperthyroid cats, with a respective prevalence of ∼4% and ∼2% in this study., (© 2014 American College of Veterinary Radiology.)

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.

Biases in cognition such as Jumping to Conclusions (JTC) and Verbal Self-Monitoring (VSM) are thought to underlie the formation of psychotic symptoms. This prospective study in people with an At Risk Mental State (ARMS) for psychosis examined how these cognitive biases changed over time, and predicted clinical and functional outcomes. Twenty-three participants were assessed at clinical presentation and a mean of 31 months later. Performance on a JTC and VSM tasks were measured at both time points. Relationships to symptom severity, level of function and the incidence of psychotic disorder were then examined. The levels of symptoms, function and VSM all improved over time, while JTC was stable. Five participants (22%) developed a psychotic disorder during the follow-up period, but the risk of transition was not related to performance on either task at baseline, or to longitudinal changes in task performance. JTC performance correlated with symptom severity at baseline and follow-up. Similarly, performance on the two tasks was not related to the level of functioning at follow-up. Thus, while the ARMS is associated with both VSM and JTC biases, neither predict the onset of psychosis or the overall functional outcome., (Copyright © 2014. Published by Elsevier Masson SAS.)

Background: Thyroid neoplasia is common in dogs, but there are few reports of dogs with ectopic, sublingual thyroid tumors., Objectives: To describe clinical features and outcomes of dogs with ectopic, sublingual thyroid neoplasia., Animals: Five hundred and forty-four dogs with thyroid neoplasia., Methods: This retrospective study reviewed the medical records of dogs referred for thyroid neoplasia between 1995 and 2013. Data extracted included signalment, extent of thyroid disease (eutopic or ectopic; metastasis), serum thyroxine (T4) concentration, treatment, and survival., Results: Of 544 dogs with thyroid neoplasia, 41 (7.5%) dogs had ectopic sublingual thyroid tumors. The clinical features of these 41 dogs were similar to the cohort group of 503 dogs with eutopic or ectopic mediastinal thyroid tumors, but dogs with sublingual tumors were younger and less likely to have metastatic disease (15% versus 30%, P < .05). Of the 41 dogs, 28 received treatment: 21 with surgery (which included partial hyoidectomy in 13), 7 with radioiodine alone, and 13 with surgery followed by administration of radioiodine. Overall median survival was 562 days (range, 1-1,850 days)., Conclusions and Clinical Importance: When compared with eutopic thyroid carcinomas, ectopic sublingual thyroid tumors generally have a less aggressive biologic behavior. Many dogs have prolonged survival, even without treatment, although death because of local tumor invasiveness or metastasis can develop in some dogs. Surgical thyroidectomy, including partial hyoidectomy, is generally effective for control of local disease. Administration of radioiodine, alone or in combination with surgical treatment, is recommended for multifocal disease or metastasis., (Copyright © 2014 by the American College of Veterinary Internal Medicine.)