Optimizing functional recovery in young individuals with severe mental illness constitutes a major healthcare priority. The current study sought to quantify the cognitive and clinical factors underpinning academic and vocational engagement in a transdiagnostic and prospective youth mental health cohort. The primary outcome measure was ‘not in education, employment or training’ (‘NEET’) status.

A clinical sample of psychiatric out-patients aged 15–25 years (n = 163) was assessed at two time points, on average, 24 months apart. Functional status, and clinical and neuropsychological data were collected. Bayesian structural equation modelling was used to confirm the factor structure of predictors and cross-lagged effects at follow-up.

Individually, NEET status, cognitive dysfunction and negative symptoms at baseline were predictive of NEET status at follow-up (p < 0.05). Baseline cognitive functioning was the only predictor of follow-up NEET status in the multivariate Bayesian model, while controlling for baseline NEET status. For every 1 s.d. deficit in cognition, the probability of being disengaged at follow-up increased by 40% (95% credible interval 19–58%). Baseline NEET status predicted poorer negative symptoms at follow-up (β = 0.24, 95% credible interval 0.04–0.43).

Disengagement with education, employment or training (i.e. being NEET) was reported in about one in four members of this cohort. The initial level of cognitive functioning was the strongest determinant of future NEET status, whereas being academically or vocationally engaged had an impact on future negative symptomatology. If replicated, these findings support the need to develop early interventions that target cognitive phenotypes transdiagnostically.

Persistent complex bereavement disorder (PCBD) is a protracted form of grief included in DSM Section 3 indicating a need for more research. Two other criteria sets [prolonged grief disorder (PGD) and complicated grief (CG) disorder] are also currently in use by researchers. This study evaluates rates of diagnosis of each proposed criteria set in a clinical sample of bereaved individuals participating in clinical research.

Two groups in which persistent grief was judged to be present or absent completed an assessment instrument that included items needed to diagnose PCBD as well as PGD and CG. One group included grief treatment-seeking participants in our multicenter National Institute of Mental Health (NIMH)-sponsored study who scored ⩾30 on the Inventory of Complicated Grief (ICG) and the other comprised bereaved adults enrolled in clinical research studies who scored <20 on the ICG. Rates of diagnosis were determined for proposed PCBD, PGD and CG criteria.

PCBD criteria diagnosed 70 [95% confidence interval (CI) 64.2–75.8] % of the grief treatment-seeking group, PGD criteria identified 59.6 (95% CI 53.4–65.8) % of these individuals and CG criteria identified 99.6 (95% CI 98.8–100.0) %. None of the three proposed criteria identified any cases in the bereaved comparison group.

Both proposed DSM-5 criteria for PCBD and criteria for PGD appear to be too restrictive as they failed to identify substantial numbers of treatment-seeking individuals with clinically significant levels of grief-related distress and impairment. Use of CG criteria or a similar algorithm appears to be warranted.

Identifying youth who may engage in future substance use could facilitate early identification of substance use disorder vulnerability. We aimed to identify biomarkers that predicted future substance use in psychiatrically un-well youth.

LASSO regression for variable selection was used to predict substance use 24.3 months after neuroimaging assessment in 73 behaviorally and emotionally dysregulated youth aged 13.9 (s.d. = 2.0) years, 30 female, from three clinical sites in the Longitudinal Assessment of Manic Symptoms (LAMS) study. Predictor variables included neural activity during a reward task, cortical thickness, and clinical and demographic variables.

Future substance use was associated with higher left middle prefrontal cortex activity, lower left ventral anterior insula activity, thicker caudal anterior cingulate cortex, higher depression and lower mania scores, not using antipsychotic medication, more parental stress, older age. This combination of variables explained 60.4% of the variance in future substance use, and accurately classified 83.6%.

These variables explained a large proportion of the variance, were useful classifiers of future substance use, and showed the value of combining multiple domains to provide a comprehensive understanding of substance use development. This may be a step toward identifying neural measures that can identify future substance use disorder risk, and act as targets for therapeutic interventions.

There is growing recognition of the importance of both functioning and quality of life (QoL) outcomes in the treatment of depressive disorders, but the meta-analytic evidence is scarce. The objective of this meta-analysis of randomized controlled trials (RCTs) was to determine the absolute and relative effects of psychotherapy, pharmacotherapy and their combination on functioning and QoL in patients with depression.

One hundred and fifty-three outcome trials involving 29 879 participants with depressive disorders were identified through database searches in Pubmed, PsycINFO and the Cochrane Central Register of Controlled Trials.

Compared to control conditions, psychotherapy and pharmacotherapy yielded small to moderate effect sizes for functioning and QoL, ranging from g = 0.31 to g = 0.43. When compared directly, initial analysis yielded no evidence that one of them was superior. After adjusting for publication bias, psychotherapy was more efficacious than pharmacotherapy (g = 0.21) for QoL. The combination of psychotherapy and medication performed significantly better for both outcomes compared to each treatment alone yielding small effect sizes (g = 0.32 to g = 0.39). Both interventions improved depression symptom severity more than functioning and QoL.

Despite the small number of comparative trials for some of the analyses, this study reveals that combined treatment is superior, but psychotherapy and pharmacotherapy alone are also efficacious for improving functioning and QoL. The overall relatively modest effects suggest that future tailoring of therapies could be warranted to better meet the needs of individuals with functioning and QoL problems.

As children mature, they become increasingly independent and less reliant on caregiver support. Changes in brain systems are likely to stimulate and guide this process. One mechanistic hypothesis suggests that changes in neural systems that process reward and threat support the increase in exploratory behavior observed in the transition to adolescence. This study examines the basic tenets of this hypothesis by performing functional magnetic resonance imaging (fMRI) during well-established reward and threat processing tasks in 40 children and adolescents, aged 9–15 years.

fMRI responses in the striatum and amygdala are fit to a model predicting that striatal reward and amygdala threat-responses will be unrelated in younger participants (aged 9–12 years), while older participants (aged 13–15 years) will differentially engage these structures.

Our data are consistent with this model. Activity in the striatum and amygdala are comparable in younger children, but in older children, they are inversely related; those more responsive to reward show a reduced threat-response. Analyses testing age as a continuous variable yield consistent results. In addition, the proportion of threat to reward-response relates to self-reported approach behavior in older but not younger youth, exposing behavioral relevance in the relative level of activity in these structures.

Results are consistent with the notion that both individual and developmental differences drive reward-seeking behavior in adolescence. While these response patterns may serve adaptive functions in the shift to independence, skew in these systems may relate to increased rates of emotional psychopathology and risk-taking observed in adolescence.

There are no existing longitudinal studies of inflammatory markers and atopic disorders in childhood and risk of hypomanic symptoms in adulthood. This study examined if childhood: (1) serum interleukin-6 (IL-6) and C-reactive protein (CRP); and (2) asthma and/or eczema are associated with features of hypomania in young adulthood.

Participants in the Avon Longitudinal Study of Parents and Children, a prospective general population UK birth cohort, had non-fasting blood samples for IL-6 and CRP measurement at the age of 9 years (n = 4645), and parents answered a question about doctor-diagnosed atopic illness before the age of 10 years (n = 7809). These participants completed the Hypomania Checklist at age 22 years (n = 3361).

After adjusting for age, sex, ethnicity, socio-economic status, past psychological and behavioural problems, body mass index and maternal postnatal depression, participants in the top third of IL-6 values at 9 years, compared with the bottom third, had an increased risk of hypomanic symptoms by age 22 years [adjusted odds ratio 1.77, 95% confidence interval (CI) 1.10–2.85, p < 0.001]. Higher IL-6 levels in childhood were associated with adult hypomania features in a dose–response fashion. After further adjustment for depression at the age of 18 years this association remained (adjusted odds ratio 1.70, 95% CI 1.03–2.81, p = 0.038). There was no evidence of an association of hypomanic symptoms with CRP levels, asthma or eczema in childhood.

Higher levels of systemic inflammatory marker IL-6 in childhood were associated with hypomanic symptoms in young adulthood, suggesting that inflammation may play a role in the pathophysiology of mania. Inflammatory pathways may be suitable targets for the prevention and intervention for bipolar disorder.

Observations in psychiatric in-patient settings are used to reduce suicide, self-harm, violence and absconding risk. The study aims were to describe the characteristics of in-patients who died by suicide under observation and examine their service-related antecedents.

A national consecutive case series in England and Wales (2006–2012) was examined.

There were 113 suicides by in-patients under observation, an average of 16 per year. Most were under intermittent observation. Five deaths occurred while patients were under constant observation. Patient deaths were linked with the use of less experienced staff or staff unfamiliar with the patient, deviation from procedures and absconding.

We identified key elements of observation that could improve safety, including only using experienced and skilled staff for the intervention and using observation levels determined by clinical need not resources.

The liability-threshold model of psychosis risk predicts stronger phenotypic manifestation of the polygenic risk score (PRS) in the healthy relatives of patients, as compared with healthy comparison subjects.

First-degree relatives of patients with psychotic disorder (871 siblings and 812 parents) and healthy comparison subjects (n = 523) were interviewed three times in 6 years. Repeated measures of two psychosis phenotypes, the Community Assessment of Psychic Experiences (CAPE; self-report – subscales of positive, negative and depressive symptoms) and the Structured Interview for Schizotypy – Revised (SIS-R; clinical interview – subscales of positive and negative schizotypy), were examined for association with PRS. Interview-based lifetime rate of depressive and manic episodes were also examined, as was association with repeated measures of intelligence quotient (IQ).

In the relatives, PRS was associated with CAPE/SIS-R total score (respectively, B = 0.12, 95% CI 0.02–0.22 and B = 0.11, 95% CI 0.02–0.20), the SIS-R positive subscale (B = 0.16, 95% CI 0.04–0.28), the CAPE depression subscale (B = 0.21, 95% CI 0.07–0.34), any lifetime affective episode (OR 3.1, 95% CI 1.04–9.3), but not with IQ (B = −1.8, 95% CI −8.0 to 4.4). In the controls, similar associations were apparent between PRS on the one hand and SIS-R total score, SIS-R positive, SIS-R negative, any lifetime affective episode and, in contrast, lower IQ (B = −8.5, 95% CI −15.5 to −1.6).

In non-ill people, polygenic risk for psychotic disorder is expressed pleiotropically in the domain of neurodevelopment, emotion regulation and attribution of salience. In subjects at elevated genetic risk, emerging expression of neurodevelopmental alterations may create floor effects, obscuring genetic associations.

Valid consent for treatment or research participation requires that an individual has decision-making capacity (DMC), which is the ability to make a specific decision. There is evidence that the psychopathology of schizophrenia can compromise DMC. The objective of this review was to examine the presence or absence of DMC in schizophrenia and the socio-demographic/psychopathological factors associated.

We searched three databases Embase, Ovid MEDLINE(R), and PsycINFO for studies reporting data on the proportion of DMC for treatment and research (DMC-T and DMC-R), and/or socio-demographic/psychopathological associations with ability to make such decisions, in people with schizophrenia and related illnesses.

A total of 40 studies were identified. While high levels of heterogeneity limited direct comparison, meta-analysis of inpatient data showed that DMC-T was present in 48% of people. Insight was strongly associated with DMC-T. Neurocognitive deficits were strongly associated with lack of DMC-R and to a lesser extent DMC-T. With the exception of years of education, there was no evidence for an association with socio-demographic factors.

Insight and neurocognitive deficits are most closely associated with DMC in schizophrenia. The lack of an association with socio-demographic factors dispels common misperceptions regarding DMC and characteristics such as age. Although our results reveal a wide spectrum of DMC-T and DMC-R in schizophrenia, this could be partly due to the complexity of the DMC construct and the heterogeneity of existing studies. To facilitate systematic review research, there is a need for improvement within research study design and increased consistency of concepts and tools.

The ecological validity of retrospective measures of social functioning is currently unknown in patients with schizophrenia. In the present study, patients with a diagnosis of non-affective psychosis were compared with controls on two measures of social functioning: the Social Functioning Scale (SFS) and daily-life measures collected with the Experience Sampling Methodology (ESM). The associations between both measures were examined in each group of participants to test for the ecological validity of the SFS.

A total of 126 participants with a non-affective psychotic disorder and 109 controls completed the SFS and a 6-day momentary ESM protocol assessing various aspects of social functioning. Multiple linear and multilevel regression analyses were performed to test for group differences in social functioning level and examine associations between the two assessment techniques.

Lower social functioning was observed in patients compared with controls on retrospective and momentary measures. The SFS interpersonal domain (social engagement/withdrawal and interpersonal behaviour dimensions) was associated with the percentage of time spent alone and negative appraisal of social interactions. The SFS activity domain (pro-social and recreational activities dimensions) was negatively associated with time spent in leisure activities.

The SFS showed some degree of ecological validity at assessing broad aspects of social functioning. Low scores on the SFS social engagement/withdrawal and interpersonal behaviour dimensions captured social isolation and social avoidance in daily life, but not lack of interest in socializing. Ecological validity of the SFS activity domain was low. ESM offers a rich alternative to classical assessment techniques of social functioning.

The enhanced error monitoring in patients with obsessive–compulsive disorder (OCD), typically measured with the error-related negativity (ERN), has been found to be temporally stable and independent of symptom expression. Here, we examined whether the error monitoring in patients with OCD could be experimentally modulated by individually tailored symptom provocation.

Twenty patients with OCD and 20 healthy controls performed a flanker task in which OCD-relevant or neutral pictures were presented prior to a flanker stimulus. An individualized stimulus set consisting of the most provoking images in terms of OCD symptoms was selected for each patient with OCD. Response-locked event-related potentials were recorded and used to examine the error-related brain activity.

Patients with OCD showed larger ERN amplitudes than did control subjects in both the OCD-symptom provocation and neutral conditions. Additionally, while patients with OCD exhibited a significant increase in the ERN under the OCD-symptom provocation condition when compared with the neutral condition, control subjects showed no variation in the ERN between the conditions.

Our results strengthen earlier findings of hyperactive error monitoring in OCD, as indexed by higher ERN amplitudes in patients with OCD than in controls. Importantly, we showed that the patients’ overactive error-signals were experimentally enhanced by individually tailored OCD-symptom triggers, thus suggesting convincing evidence between OCD-symptoms and ERN. Such findings imply that therapeutic interventions should target affective regulation in order to alleviate the perceived threatening value of OCD triggers.

Angry outbursts are an important feature of various stress-related disorders, and commonly lead to aggression towards other people. Findings regarding interpersonal anger have linked the ventromedial prefrontal cortex (vmPFC) to anger regulation and the locus coeruleus (LC) to aggression. Both regions were previously associated with traumatic and chronic stress symptoms, yet it is unclear if their functionality represents a consequence of, or possibly also a cause for, stress symptoms. Here we investigated the relationship between the neural trajectory of these indicators of anger and the development and manifestation of stress symptoms.

A total of 46 males (29 soldiers, 17 civilians) participated in a prospective functional magnetic resonance imaging experiment in which they played a modified interpersonal anger-provoking Ultimatum Game (UG) at two-points. Soldiers were tested at the beginning and end of combat training, while civilians were tested at the beginning and end of civil service. We assumed that combat training would induce chronic stress and result in increased stress symptoms.

Soldiers showed an increase in stress symptoms following combat training while civilians showed no such change following civil service. All participants were angered by the modified UG irrespective of time point. Higher post-combat training stress symptoms were associated with lower pre-combat training vmPFC activation and with higher activation increase in the LC between pre- and post-combat training.

Results suggest that during anger-provoking social interactions, flawed vmPFC functionality may serve as a causal risk factor for the development of stress symptoms, and heightened reactivity of the LC possibly reflects a consequence of stress-inducing combat training. These findings provide potential neural targets for therapeutic intervention and inoculation for stress-related psychopathological manifestations of anger.

Obsessive–compulsive disorder (OCD) is often co-morbid with depression. Using the methods of network analysis, we computed two networks that disclose the potentially causal relationships among symptoms of these two disorders in 408 adult patients with primary OCD and co-morbid depression symptoms.

We examined the relationship between the symptoms constituting these syndromes by computing a (regularized) partial correlation network via the graphical LASSO procedure, and a directed acyclic graph (DAG) via a Bayesian hill-climbing algorithm.

The results suggest that the degree of interference and distress associated with obsessions, and the degree of interference associated with compulsions, are the chief drivers of co-morbidity. Moreover, activation of the depression cluster appears to occur solely through distress associated with obsessions activating sadness – a key symptom that ‘bridges’ the two syndromic clusters in the DAG.

Bayesian analysis can expand the repertoire of network analytic approaches to psychopathology. We discuss clinical implications and limitations of our findings.

Evidence for a relationship between neurocognition and functional outcome in important areas of community living is robust in serious mental illness research. Dysfunctional attitudes (defeatist performance beliefs and asocial beliefs) have been identified as intervening variables in this causal chain. This study seeks to expand upon previous research by longitudinally testing the link between neurocognition and community participation (i.e. time in community-based activity) through dysfunctional attitudes and motivation.

Adult outpatients with serious mental illness (N = 175) participated, completing follow-up assessments approximately 6 months after initial assessment. Path analysis tested relationships between baseline neurocognition, emotion perception, functional skills, dysfunctional attitudes, motivation, and outcome (i.e. community participation) at baseline and follow-up.

Path models demonstrated two pathways to community participation. The first linked neurocognition and community participation through functional skills, defeatist performance beliefs, and motivation. A second pathway linked asocial beliefs and community participation, via a direct path passing through motivation. Model fit was excellent for models predicting overall community participation at baseline and, importantly, at follow-up.

The existence of multiple pathways to community participation in a longitudinal model supports the utility of multi-modal interventions for serious mental illness (i.e. treatment packages that build upon individuals’ strengths while addressing the array of obstacles to recovery) that feature dysfunctional attitudes and motivation as treatment targets.

The different patterns of Emotional Intelligence (EI) deficits in schizophrenia and bipolar I disorder are are not yet well understood. This study compares EI levels among these groups and highlights the potential impact of non-social cognition on EI.

Fifty-eight schizophrenia and 60 bipolar outpatients were investigated using the Mayer-Salovey-Caruso Emotional Intelligence Test (MSCEIT) and the Brief Assessment of Cognition in Schizophrenia (BACS). Analyses of covariance were performed with adjustment for the BACS composite score.

Compared to bipolar subjects, schizophrenia patients showed significantly lower levels in both EI and non-social cognition. After adjustment for the BACS composite score, the difference in EI was lost. The mediation analysis revealed that differences between schizophrenia and bipolar patients in strategic EI are almost fully attributable to the mediating effect of non-social cognition.

Our findings suggest that in both schizophrenia and bipolar patients EI is strongly influenced by non-social cognitive functioning. This has to be taken into account when interpreting MSCEIT data in comparative studies in serious mental illness and emphasizes the importance of cognitive remediation.

Recent theories suggest that poor working memory (WM) may be the cognitive underpinning of negative symptoms in people with schizophrenia. In this study, we first explore the effect of cognitive remediation (CR) on two clusters of negative symptoms (i.e. expressive and social amotivation), and then assess the relevance of WM gains as a possible mediator of symptom improvement.

Data were accessed for 309 people with schizophrenia from the NIMH Database of Cognitive Training and Remediation Studies and a separate study. Approximately half the participants received CR and the rest were allocated to a control condition. All participants were assessed before and after therapy and at follow-up. Expressive negative symptoms and social amotivation symptoms scores were calculated from the Positive and Negative Syndrome Scale. WM was assessed with digit span and letter-number span tests.

Participants who received CR had a significant improvement in WM scores (d = 0.27) compared with those in the control condition. Improvements in social amotivation levels approached statistical significance (d = −0.19), but change in expressive negative symptoms did not differ between groups. WM change did not mediate the effect of CR on social amotivation.

The results suggest that a course of CR may benefit behavioural negative symptoms. Despite hypotheses linking memory problems with negative symptoms, the current findings do not support the role of this cognitive domain as a significant mediator. The results indicate that WM improves independently from negative symptoms reduction.

Psychosocial and inflammatory factors have been associated with fatigue in breast cancer survivors. Nevertheless, the relative contribution and/or interaction of these factors with cancer-related fatigue have not been well documented.

This cross-sectional study enrolled 111 stage 0–III breast cancer patients treated with breast surgery followed by whole breast radiotherapy. Fatigue was measured by the total score of the Multidimensional Fatigue Inventory-20. Potential risk factors included inflammatory markers (plasma cytokines and their receptors and C-reactive protein; CRP), depressive symptoms (as assessed by the Inventory of Depressive Symptomatology–Self Reported), sleep (as assessed by the Pittsburgh Sleep Quality Index) and perceived stress (as assessed by the Perceived Stress Scale) as well as age, race, marital status, smoking history, menopause status, endocrine treatment, chemotherapy and cancer stage. Linear regression modeling was employed to examine risk factors of fatigue. Only risk factors with a significance level <0.10 were included in the initial regression model. A post-hoc mediation model using PROCESS SPSS was conducted to examine the association among depressive symptoms, sleep problems, stress, inflammation and fatigue.

At 1 year post-radiotherapy, depressive symptoms (p<0.0001) and inflammatory markers (CRP: p = 0.015; interleukin-1 receptor antagonist: p = 0.014; soluble tumor necrosis factor receptor-2: p = 0.009 in separate models) were independent risk factors of fatigue. Mediation analysis showed that depressive symptoms also mediated the associations of fatigue with sleep and stress.

Depressive symptoms and inflammation were independent risk factors for cancer-related fatigue at 1 year post-radiotherapy, and thus represent independent treatment targets for this debilitating symptom.