Carers of patients with psychiatric disorders show high levels of anxiety and depression, possibly mediated through disruption of the hypothalamo–pituitary–adrenal (HPA) axis. Among carers of patients with treatment-resistant depression (TRD), we set out to determine the psychological and physiological (HPA axis) consequences of caring, and the association of these consequences with long-term outcome in patients.

Thirty-five informal carers of patients with severe TRD requiring in-patient treatment were recruited and compared with 23 controls. HPA-axis activity was assessed by measuring post-awaking salivary cortisol. The Involvement Evaluation Questionnaire (IEQ) and the General Health Questionnaire-12 (GHQ-12) were administered to measure carer burden and psychiatric caseness respectively. Independent t tests were used to compare differences between carers and controls and a linear regression model was used to determine the association of post-awakening cortisol with carer status while controlling for confounding variables. Data on long-term patient outcome (12 to 83 months), measured using the Hamilton Depression Rating Scale (HAMD), were also obtained and linear regression was used to determine the association between cortisol output in carers and remission status in patients.

Carers experienced high carer burden and high psychiatric caseness. Carers showed reduced cortisol output after awakening, calculated as the area under the curve with respect to ground (AUCg), which remained significant after controlling for potential confounders. In a linear regression model, non-remission in patients was associated with reduced cortisol output in carers.

Caring for patients with TRD is associated with adverse psychological and physiological changes suggesting hypocortisolism post-awakening. These changes are associated with poor patient outcome.

In order to reduce the high prevalence of depression, early interventions for people at risk of depression are warranted. This study evaluated the effectiveness of an early guided self-help programme based on acceptance and commitment therapy (ACT) for reducing depressive symptomatology.

Participants with mild to moderate depressive symptomatology were recruited from the general population and randomized to the self-help programme with extensive email support (n=125), the self-help programme with minimal email support (n=125) or to a waiting list control group (n=126). Participants completed measures before and after the intervention to assess depression, anxiety, fatigue, experiential avoidance, positive mental health and mindfulness. Participants in the experimental conditions also completed these measures at a 3-month follow-up.

In the experimental conditions significant reductions in depression, anxiety, fatigue, experiential avoidance and improvements in positive mental health and mindfulness were found, compared with the waiting list condition (effect sizes Cohen's d=0.51–1.00). These effects were sustained at the 3-month follow-up. There were no significant differences between the experimental conditions on the outcome measures.

The ACT-based self-help programme with minimal email support is effective for people with mild to moderate depressive symptomatology.

Antidepressant drug treatments increase the processing of positive compared to negative affective information early in treatment. Such effects have been hypothesized to play a key role in the development of later therapeutic responses to treatment. However, it is unknown whether these effects are a common mechanism of action for different treatment modalities. High-density negative ion (HDNI) treatment is an environmental manipulation that has efficacy in randomized clinical trials in seasonal affective disorder (SAD).

The current study investigated whether a single session of HDNI treatment could reverse negative affective biases seen in seasonal depression using a battery of emotional processing tasks in a double-blind, placebo-controlled randomized study.

Under placebo conditions, participants with seasonal mood disturbance showed reduced recognition of happy facial expressions, increased recognition memory for negative personality characteristics and increased vigilance to masked presentation of negative words in a dot-probe task compared to matched healthy controls. Negative ion treatment increased the recognition of positive compared to negative facial expression and improved vigilance to unmasked stimuli across participants with seasonal depression and healthy controls. Negative ion treatment also improved recognition memory for positive information in the SAD group alone. These effects were seen in the absence of changes in subjective state or mood.

These results are consistent with the hypothesis that early change in emotional processing may be an important mechanism for treatment action in depression and suggest that these effects are also apparent with negative ion treatment in seasonal depression.

Current classification of unipolar depression reflects the idea that prognosis is essential. However, do DSM categories of major depressive disorder (MDD), dysthymic disorder (Dysth) and double depression (DD=MDD+Dysth) indeed adequately represent clinically relevant course trajectories of unipolar depression? Our aim was to test DSM categories (MDD, Dysth and DD) in comparison with empirically derived prognostic categories, using a prospectively followed cohort of depressed patients.

A large sample (n=804) of out-patients with unipolar depression were derived from a prospective cohort study, the Netherlands Study of Depression and Anxiety (NESDA). Using latent class growth analysis (LCGA), empirically derived 2-year course trajectories were constructed. These were compared with DSM diagnoses and a wider set of putative predictors for class membership.

Five course trajectories were identified, ranging from mild severity and rapid remission to high severity and chronic course trajectory. Contrary to expectations, more than 50% of Dysth and DD were allocated to classes with favorable course trajectories, suggesting that current DSM categories do not adequately represent course trajectories. The class with the most favorable course trajectory differed on several characteristics from other classes (younger age, more females, less childhood adversity, less somatic illnesses, lower neuroticism, higher extraversion). Older age, earlier age of onset and lower extraversion predicted poorest course trajectory.

MDD, Dysth and DD did not adequately match empirically derived course trajectories for unipolar depression. For the future classification of unipolar depression, it may be wise to retain the larger, heterogeneous category of unipolar depression, adopting cross-cutting dimensions of severity and duration to further characterize patients.

Familial liability to both severe and common mental disorder predicts psychotic disorder and psychotic symptoms, and may be used as a proxy in models examining interaction between genetic risk and the environment at individual and contextual levels.

In a representative general population sample (n=4011) in Izmir, Turkey, the full spectrum of expression of psychosis representing (0) no symptoms, (1) subclinical psychotic experiences, (2) low-impact psychotic symptoms, (3) high-impact psychotic symptoms and (4) full-blown clinical psychotic disorder was assessed in relation to mental health problems in the family (proxy for familial liability) and the wider social environment. Quality of the wider social environment was assessed in an independent sample using contextual measures of informal social control, social disorganization, unemployment and low income, aggregated to the neighbourhood level.

The association between familial liability to severe mental illness and expression of psychosis spectrum was stronger in more deprived neighbourhoods [e.g. this association increased from β=0.33 (p=0.01) in low-unemployment neighbourhoods to β=0.92 (p<0.001) in high-unemployment neighbourhoods] and in neighbourhoods high in social control, while neighbourhood variables did not modify the association between familial liability to common mental disorder and the psychosis outcome. Neighbourhood variables mediated urbanicity effects.

Contextual effects may be important in moderating the expression of psychosis liability in populations, representing a specific pathway independent of the link between common mental disorder and psychosis.

The relationship between cannabis use and cognitive functioning in patients with psychosis has yielded contradictory findings. In individuals at genetic high risk for psychosis, information is sparse. The aim of this study was to assess the association between recency and frequency of cannabis use and cognitive functioning in patients with psychosis and their unaffected siblings.

We conducted a cross-sectional study in 956 patients with non-affective psychosis, 953 unaffected siblings, and 554 control subjects. Participants completed a cognitive test battery including assessments of verbal learning, set shifting, sustained attention, processing speed, working memory, acquired knowledge, reasoning and problem solving and social cognition. Cannabis use was assessed by urinalysis and by the Composite International Diagnostic Interview. Using random-effect regression models the main effects of cannabis (recency and frequency) and the interaction with status (patient, sibling, control) on cognitive functioning were assessed.

Current cannabis use was associated with poorer performance on immediate verbal learning, processing speed and working memory (Cohen's d −0.20 to −0.33, p<0.005). Lifetime cannabis use was associated with better performance on acquired knowledge, facial affect recognition and face identity recognition (Cohen's d+0.17 to +0.33, p<0.005). There was no significant interaction between cannabis and status on cognitive functioning.

Lifetime cannabis-using individuals might constitute a subgroup with a higher cognitive potential. The residual effects of cannabis may impair short-term memory and processing speed.

The National Psychiatric Morbidity Survey (NPMS) programme was partly designed to monitor trends in mental disorders, including depression, with comparable data spanning 1993 to 2007. Findings already published from this programme suggest that concerns about increasing prevalence of common mental disorders (CMDs) may be unfounded. This article focuses on depression and tests the hypothesis that successive birth cohorts experience the same prevalence of depression as they age.

We carried out a pseudo-cohort analysis of a sequence of three cross-sectional surveys of the English household population using identical diagnostic instruments. The main outcome was ICD-10 depressive episode or disorder. Secondary outcomes were the depression subscales of the Clinical Interview Schedule – Revised (CIS-R).

There were 8670, 6977 and 6815 participants in 1993, 2000 and 2007 respectively. In men, the prevalence of depression increased between cohorts born in 1943–1949 and 1950–1956 [odds ratio (OR) 2.5, 95% confidence interval (CI) 1.4–4.2], then remained relatively stable across subsequent cohorts. In women, there was limited evidence of change in prevalence of depression. Women born in 1957–1963, surveyed aged 44–50 years in 2007, had exceptionally high prevalence. It is not clear whether this represents a trend or a quirk of sampling.

There is no evidence of an increase in the prevalence of depression in male cohorts born since 1950. In women, there is limited evidence of increased prevalence. Demand for mental health services may stabilize or even fall for men.

Electronic medical records (EMR) provide a unique opportunity for efficient, large-scale clinical investigation in psychiatry. However, such studies will require development of tools to define treatment outcome.

Natural language processing (NLP) was applied to classify notes from 127 504 patients with a billing diagnosis of major depressive disorder, drawn from out-patient psychiatry practices affiliated with multiple, large New England hospitals. Classifications were compared with results using billing data (ICD-9 codes) alone and to a clinical gold standard based on chart review by a panel of senior clinicians. These cross-sectional classifications were then used to define longitudinal treatment outcomes, which were compared with a clinician-rated gold standard.

Models incorporating NLP were superior to those relying on billing data alone for classifying current mood state (area under receiver operating characteristic curve of 0.85–0.88 v. 0.54–0.55). When these cross-sectional visits were integrated to define longitudinal outcomes and incorporate treatment data, 15% of the cohort remitted with a single antidepressant treatment, while 13% were identified as failing to remit despite at least two antidepressant trials. Non-remitting patients were more likely to be non-Caucasian (p<0.001).

The application of bioinformatics tools such as NLP should enable accurate and efficient determination of longitudinal outcomes, enabling existing EMR data to be applied to clinical research, including biomarker investigations. Continued development will be required to better address moderators of outcome such as adherence and co-morbidity.

The perinatal or early life environment may influence the development of mental illness in adulthood. It is not clear how, or when, any such influences might be mediated. Foetal exposure to maternal stress in the intrauterine environment has been suggested as a possible mediator of foetal origins of mental illness but the postnatal environment may also be of importance. This study aimed to test the foetal origins hypothesis by using retrograde and antegrade interbirth intervals (time to mother's most recent and next deliveries respectively) as proxy measures of antenatal and postnatal maternal stress.

Linked datasets of the Scottish Morbidity Record (SMR) were used to identify a birth cohort. Where applicable, the dates of each mother's most recent previous and/or next subsequent delivery were noted, allowing birth intervals to be calculated. The cohort was followed up into young adulthood, using self-harm, substance misuse, psychotic disorder and affective disorder as outcome measures. Data were analysed using Cox regression.

No significant relationship was observed between affective disorders and interbirth interval, neither retrograde nor antegrade. Short (<18-month) antegrade birth intervals were independently associated with increased risk of psychotic disorder and self-harm. Long (>72-month) retrograde intervals were associated with increased risk of self-harm and substance misuse.

The data do not provide evidence for the foetal origins of mental disorders but, in the cases of psychotic disorders, and of self-harm, suggest that the early postnatal rather than the antenatal environment may be of greater importance.

Depression following myocardial infarction (MI) independently increases risk for early cardiac morbidity and mortality. Studies suggest that somatic, but not cognitive, depressive symptoms are responsible for the increased risk. However, the effects of somatic depressive symptoms at follow-up, after sufficient time has elapsed to allow for physical recovery from the initial infarction, are not known. Our aim was to examine the relationship between cognitive and somatic depressive symptom dimensions at baseline and 12 months post-MI and subsequent mortality and cardiovascular morbidity.

Patients were 2442 depressed and/or socially isolated men and women with acute MI included in the Enhancing Recovery in Coronary Heart Disease (ENRICHD) clinical trial. We used principal components analysis (PCA) of the Beck Depression Inventory (BDI) items to derive subscales measuring cognitive and somatic depressive symptom dimensions, and Cox regression with Bonferroni correction for multiple testing to examine the contribution of these dimensions to all-cause mortality, cardiovascular mortality, and first recurrent non-fatal MI.

After adjusting for medical co-morbidity and Bonferroni correction, the somatic depressive symptom dimension assessed proximately following MI did not significantly predict any endpoints. At 12 months post-MI, however, this dimension independently predicted subsequent all-cause [hazard ratio (HR) 1.43, 95% confidence interval (CI) 1.13–1.81] and cardiovascular mortality (HR 1.60, 95% CI 1.17–2.18). No significant associations were found between the cognitive depressive symptom dimension and any endpoints after Bonferroni correction.

Somatic symptoms of depression at 12 months post-MI in patients at increased psychosocial risk predicted subsequent mortality. Psychosocial interventions aimed at improving cardiac prognosis may be enhanced by targeting somatic depressive symptoms, with particular attention to somatic symptom severity at 12 months post-MI.

Studies have suggested that patients with schizophrenia are impaired at recognizing emotions. Recently, it has been shown that the neuropeptide oxytocin can have beneficial effects on social behaviors.

To examine emotion recognition deficits in patients and see whether oxytocin could improve these deficits, we carried out two experiments. In the first experiment we recruited 30 patients with schizophrenia and 29 age- and IQ-matched control subjects, and gave them an emotion recognition task. Following this, we carried out a second experiment in which we recruited 21 patients with schizophrenia for a double-blind, placebo-controlled cross-over study of the effects of oxytocin on the same emotion recognition task.

In the first experiment we found that patients with schizophrenia had a deficit relative to controls in recognizing emotions. In the second experiment we found that administration of oxytocin improved the ability of patients to recognize emotions. The improvement was consistent and occurred for most emotions, and was present whether patients were identifying morphed or non-morphed faces.

These data add to a growing literature showing beneficial effects of oxytocin on social–behavioral tasks, as well as clinical symptoms.

Suicide is the 11th leading cause of death in the USA. Suicide rates vary across ethnic groups. Whether suicide behavior differs by ethnic groups in the USA in the same way as observed for suicide death is a matter of current discussion. The aim of this report was to compare the lifetime prevalence of suicide ideation and attempt among four main ethnic groups (Asians, Blacks, Hispanics, and Whites) in the USA.

Suicide ideation and attempts were assessed using the World Mental Health version of the Composite International Diagnostic Interview (WMH-CIDI). Discrete time survival analysis was used to examine risk for lifetime suicidality by ethnicity and immigration among 15 180 participants in the Collaborative Psychiatric Epidemiological Surveys (CPES), a group of cross-sectional surveys.

Suicide ideation was most common among Non-Hispanic Whites (16.10%), least common among Asians (9.02%) and intermediate among Hispanics (11.35%) and Non-Hispanic Blacks (11.82%). Suicide attempts were equally common among Non-Hispanic Whites (4.69%), Hispanics (5.11%) and Non-Hispanic Blacks (4.15%) and less common among Asians (2.55%). These differences in the crude prevalence rates of suicide ideation decreased but persisted after control for psychiatric disorders, but disappeared for suicide attempt. Within ethnic groups, risk for suicidality was low among immigrants prior to migration compared to the US born, but equalized over time after migration.

Ethnic differences in suicidal behaviors are explained partly by differences in psychiatric disorders and low risk prior to arrival in the USA. These differences are likely to decrease as the US-born proportion of Hispanics and Asians increases.

Depression and anxiety disorders (ADs) are highly co-morbid, but the reason for this co-morbidity is unclear. One possibility is that they predispose one another. An informative way to examine interactions between disorders without the confounds present in patient populations is to manipulate the psychological processes thought to underlie the pathological states in healthy individuals. In this study we therefore asked whether a model of the sad mood in depression can enhance psychophysiological responses (startle) to a model of the anxiety in ADs. We predicted that sad mood would increase anxious anxiety-potentiated startle responses.

In a between-subjects design, participants (n=36) completed either a sad mood induction procedure (MIP; n=18) or a neutral MIP (n=18). Startle responses were assessed during short-duration predictable electric shock conditions (fear-potentiated startle) or long-duration unpredictable threat of shock conditions (anxiety-potentiated startle).

Induced sadness enhanced anxiety- but not fear-potentiated startle.

This study provides support for the hypothesis that sadness can increase anxious responding measured by the affective startle response. This, taken together with prior evidence that ADs can contribute to depression, provides initial experimental support for the proposition that ADs and depression are frequently co-morbid because they may be mutually reinforcing.

Non-suicidal self-injury (NSSI) is the deliberate and direct injuring of body tissue without suicidal intent for purposes not socially sanctioned. Few studies have examined the correlates of NSSI among young adults. This study aimed to identify predictors of lifetime and past-year NSSI, and describe motives for NSSI and disclosure of NSSI to others.

Interviews were conducted annually with 1081 students enrolled in the College Life Study, a prospective longitudinal study conducted at a large public mid-Atlantic university. NSSI characteristics were assessed at Year 4. Demographic and predictor variables were assessed during Years 1 to 4. Multivariate logistic regression models were used to identify correlates of lifetime NSSI and predictors of past-year NSSI.

The prevalence of past-year and lifetime NSSI was 2% and 7% respectively (>70% were female for both lifetime and past-year NSSI). Seven percent of NSSI cases self-injured once, whereas almost half self-injured six or more times. Independent predictors of past-year NSSI were maternal depression, non-heterosexual orientation, affective dysregulation and depression. Independent predictors of lifetime NSSI were depression, non-heterosexual orientation, paternal depression and female sex. One in six participants with NSSI had attempted suicide by young adulthood. The three most commonly reported motives for NSSI were mental distress, coping and situational stressors. Most (89%) told someone about their NSSI, most commonly a friend (68%).

This study identified unique predictors of NSSI, which should help to elucidate its etiology and has implications for early identification and interventions.

Interpersonal sensitivity is a personality trait described as excessive awareness of both the behaviour and feelings of others. Although interpersonal sensitivity has been found to be one of the vulnerability factors to depression, there has been little interest in its relationship with the prodromal phase of psychosis. The aims of this study were to examine the level of interpersonal sensitivity in a sample of individuals with an at-risk mental state (ARMS) for psychosis and its relationship with other psychopathological features.

Method. Sixty-two individuals with an ARMS for psychosis and 39 control participants completed a series of self-report questionnaires, including the Interpersonal Sensitivity Measure (IPSM), the Prodromal Questionnaire (PQ), the Ways of Coping Questionnaire (WCQ) and the Depression and Anxiety Stress Scale (DASS).

Individuals with an ARMS reported higher interpersonal sensitivity compared to controls. Associations between interpersonal sensitivity, positive psychotic symptoms (i.e. paranoid ideation), avoidant coping and symptoms of depression, anxiety and stress were also found.

This study suggests that being ‘hypersensitive’ to interpersonal interactions is a psychological feature of the putatively prodromal phase of psychosis. The relationship between interpersonal sensitivity, attenuated positive psychotic symptoms, avoidant coping and negative emotional states may contribute to long-term deficits in social functioning. We illustrate the importance, when assessing a young client with a possible ARMS, of examining more subtle and subjective symptoms in addition to attenuated positive symptoms.

Relatively little is known about the environmental and genetic contributions to gambling frequency and disordered gambling (DG), the full continuum of gambling-related problems that includes pathological gambling (PG).

A web-based sample (n=43 799 including both members of 609 twin and 303 sibling pairs) completed assessments of number of lifetime gambling episodes, DSM-IV criteria for PG, alcohol, nicotine and caffeine intake, and nicotine dependence (ND) and DSM-III-R criteria for lifetime major depression (MD). Twin modeling was performed using Mx.

In the entire cohort, symptoms of DG indexed a single dimension of liability. Symptoms of DG were weakly related to caffeine intake and moderately related to MD, consumption of cigarettes and alcohol, and ND. In twin and sibling pairs, familial resemblance for number of times gambled resulted from both familial–environmental (c2=42%) and genetic factors (a2=32%). For symptoms of DG, resemblance resulted solely from genetic factors (a2=83%). Bivariate analyses indicated a low genetic correlation between symptoms of DG and MD (ra=+0.14) whereas genetic correlations with DG symptoms were substantially higher with use of alcohol, caffeine and nicotine, and ND (ranging from +0.29 to +0.80). The results were invariant across genders.

Whereas gambling participation is determined by shared environmental and genetic factors, DG constitutes a single latent dimension that is largely genetically determined and more closely related to externalizing than internalizing behaviors. Because these findings are invariant across genders, they suggest that the etiological factors of DG are likely to be similar in men and women.

Cross-sectional surveys of older people commonly find associations between higher levels of depressive symptoms and poorer cognitive performance, but the direction of effect is unclear. We examined whether there was a bidirectional relationship between depressive symptoms and general cognitive ability in non-demented older people, and explored the role of physical health, smoking, exercise, social class and education as potential confounders of this association and as possible determinants of the rate of change of cognitive decline and depressive symptoms.

The English Longitudinal Study of Ageing consists of people aged 50 years and over. Cognitive function and self-reported depressive symptoms were measured in 2002–2003, 2004–2005, 2006–2007 and 2008–2009. We fitted linear piecewise models with fixed knot positions to allow different slopes for different age groups. Analyses are based on 8611 people.

Mean cognitive function declined with age; there was no trend in the trajectory of depressive symptoms. Better cognitive function was associated with less depression up to the age of 80 years. Greater depression was associated with a slightly faster rate of cognitive decline but only in people aged 60–80 years. There were no consistent associations across age groups between sex, smoking, education, social class, exercise or number of chronic physical illnesses and the rate of change of cognitive decline or depressive symptoms.

In this longitudinal study of older people, there was no consistent evidence that being more depressed led to an acceleration in cognitive decline and no support for the hypothesis that there might be reciprocal dynamic influences between cognitive ability and depressive symptoms.

Social cognition has been identified as a significant construct for schizophrenia research with relevance to diagnosis, assessment, treatment and functional outcome. However, social cognition has not been clearly understood in terms of its relationships with neurocognition and functional outcomes. The present study sought to examine the empirical independence of social cognition and neurocognition; to investigate the possible causal structure among social cognition, neurocognition and psychosocial functioning.

The sample consists of 130 individuals diagnosed with schizophrenia. All participants were recruited as they were admitted to four community-based psychosocial rehabilitation programs. Social cognition, neurocognition and psychosocial functioning were measured at baseline and 12 months. The empirical independence of social cognition and neurocognition was tested using confirmatory factor analysis (CFA) and the possible causal structure among social cognition, neurocognition and psychosocial functioning was investigated using latent difference score (LDS) analysis.

A two-factor model of social cognition and neurocognition fit the data very well, indicating the empirical independence of social cognition, whereas the longitudinal CFA results show that the empirical independence of neurocognition and social cognition is maintained over time. The results of the LDS analysis support a causal model that indicates that neurocognition underlies and is causally primary to social cognition, and that neurocognition and social cognition are causally primary to functional outcome.

Social cognition and neurocognition could have independent and distinct upward causal effects on functional outcome. It is also suggested that the approaches for remediation of neurocognition and social cognition might need to be distinct.

Children of depressed mothers not only have higher risk of depression, but also may experience both elevated and continuing exposure to stressful experiences. The study tested hypotheses of the intergenerational transmission of stress and depression and examined the role of early childhood adversity and maternal depression in the interplay between youth depression and stress over 20 years.

In a longitudinal community study of 705 families selected for history or absence of maternal depression, mothers and youth were studied from pregnancy to age 5 years and at youth ages 15 and 20 years. Youth and maternal depression were assessed with diagnostic interviews, acute and chronic interview-based stress assessment in the youth and contemporaneous measures of childhood adversity obtained between pregnancy and youth age 5 years.

Regression analyses indicated evidence of intergenerational transmission and continuity of depression over time, continuity of acute and chronic stress and reciprocal predictive associations between depression and stress. Maternal depression and exposure to adversities by child's age 5 years contributed to the youth's continuing experiences of depression and stress. An overall path model was consistent with stress continuity and intergenerational transmission and highlighted the mediating role of age 15 youth chronic interpersonal stress.

Youth of depressed mothers are at risk not only for depression but also for continuing experiences of acute and chronic stress from childhood to age 20. The associations among depression and stress are bidirectional and portend continuing experiences of depression and further stress.

Although individuals vulnerable to psychosis show brain volumetric abnormalities, structural alterations underlying different probabilities for later transition are unknown. The present study addresses this issue by means of voxel-based morphometry (VBM).

We investigated grey matter volume (GMV) abnormalities by comparing four neuroleptic-free groups: individuals with first episode of psychosis (FEP) and with at-risk mental state (ARMS), with either long-term (ARMS-LT) or short-term ARMS (ARMS-ST), compared to the healthy control (HC) group. Using three-dimensional (3D) magnetic resonance imaging (MRI), we examined 16 FEP, 31 ARMS, clinically followed up for on average 3 months (ARMS-ST, n=18) and 4.5 years (ARMS-LT, n=13), and 19 HC.

The ARMS-ST group showed less GMV in the right and left insula compared to the ARMS-LT (Cohen's d 1.67) and FEP groups (Cohen's d 1.81) respectively. These GMV differences were correlated positively with global functioning in the whole ARMS group. Insular alterations were associated with negative symptomatology in the whole ARMS group, and also with hallucinations in the ARMS-ST and ARMS-LT subgroups. We found a significant effect of previous antipsychotic medication use on GMV abnormalities in the FEP group.

GMV abnormalities in subjects at high clinical risk for psychosis are associated with negative and positive psychotic symptoms, and global functioning. Alterations in the right insula are associated with a higher risk for transition to psychosis, and thus may be related to different transition probabilities.