This study evaluated in a rigorous 18-month randomized controlled trial the efficacy of an enhanced vocational intervention for helping individuals with a recent first schizophrenia episode to return to and remain in competitive work or regular schooling.

Individual Placement and Support (IPS) was adapted to meet the goals of individuals whose goals might involve either employment or schooling. IPS was combined with a Workplace Fundamentals Module (WFM) for an enhanced, outpatient, vocational intervention. Random assignment to the enhanced integrated rehabilitation program (N = 46) was contrasted with equally intensive clinical treatment at UCLA, including social skills training groups, and conventional vocational rehabilitation by state agencies (N = 23). All patients were provided case management and psychiatric services by the same clinical team and received oral atypical antipsychotic medication.

The IPS–WFM combination led to 83% of patients participating in competitive employment or school in the first 6 months of intensive treatment, compared with 41% in the comparison group (p < 0.005). During the subsequent year, IPS–WFM continued to yield higher rates of schooling/employment (92% v. 60%, p < 0.03). Cumulative number of weeks of schooling and/or employment was also substantially greater with the IPS–WFM intervention (45 v. 26 weeks, p < 0.004).

The results clearly support the efficacy of an enhanced intervention focused on recovery of participation in normative work and school settings in the initial phase of schizophrenia, suggesting potential for prevention of disability.

Obsessive-compulsive disorder (OCD) has been associated with cognitive deficits, particularly with executive functions. These findings support fronto-striatal dysfunction in OCD. However, it is not certain whether these findings are trait features of OCD. In recent years, a number of studies have investigated cognitive functions in unaffected relatives of OCD (OCDrel) but the findings of these studies are contradictory.

A systematic review in Pubmed and Scopus databases was performed until 18 March 2019, to locate the studies comparing cognitive functions of OCDrel with healthy controls and OCD patients (OCDpt). A random-effects meta-analysis was conducted.

Current meta-analysis included 16 studies including 527 OCDrel, 445 OCDpt and 639 healthy controls. Healthy controls overperformed OCDpt in all cognitive domains (d = 0.36–0.86). OCDrel underperformed healthy controls in inhibition (d = 0.58, CI = 0.29–0.86), planning (d = 0.45, CI = 0.28–0.63), decision-making (d = 0.58, CI = 0.19–0.98). OCDrel also had small-sized deficits in set-shifting (d = 0.37, CI = 0.04–0.69) and visual memory (d = 0.28, CI = 0.08–0.49). OCDpt underperformed OCDrel in visual memory (d = 0.45, CI = 0.22–0.67) and set-shifting (d = 0.23, CI = 0.04–0.42).

Current findings suggest that abnormalities in inhibition, planning/problem solving and reward-based decision-making are shared features of OCDrel and OCDpt and might be trait markers related to vulnerability for developing OCD. Visual memory and set-shifting deficits might potentially be biomarkers of incipient illness or subthreshold OCD presentation among OCDrel. Further exploration of cognitive heterogeneity in OCDrel and investigating the effects of the subtypes of OCD in probands on cognitive impairment in OCDrel are needed.

Altered heart rate variability (HRV), an index of autonomic nervous system function, has been reported in generalized anxiety disorder (GAD), but the results have been mixed. Thus, the present study, using a large sample size and better methodology, aims to examine whether GAD is associated with impaired HRV, both at rest and in response to posture challenges.

In total, 1832 participants were recruited in this study, consisting of 682 patients with GAD (including 326 drug- and comorbidity-free GAD patients) and 1150 healthy controls. Short-term HRV was measured during the supine-standing-supine test (5-min per position). Propensity score matching (PSM), a relatively novel method, was used to control for potential confounders.

After PSM algorithm, drug- and comorbidity-free GAD patients had reductions in resting (baseline) high-frequency power (HF), an index for parasympathetic modulation, and increases in the low-frequency/HF ratio (LF/HF), an index for sympathovagal balance as compared to matched controls. Furthermore, the responses of HF and LF/HF to posture changes were all attenuated when compared with matched controls. Effect sizes, given by Cohen's d, for resting HF and HF reactivity were 0.42 and 0.36–0.42, respectively.

GAD is associated with altered sympathovagal balance, characterized by attenuation in both resting vagal modulation and vagal reactivity, with an almost medium effect size (Cohen's d ≈ 0.4), regardless of medication use or comorbidity status.

We aim to (1) determine whether a behavioural sleep intervention for children with attention-deficit/hyperactivity disorder (ADHD) leads to sustained benefits; and (2) examine the factors associated with treatment response.

This study was a randomised controlled trial of 244 children (5–13 years) with ADHD from Victoria, Australia. All participants had a moderate/severe sleep problem that met American Academy of Sleep Medicine criteria for an eligible sleep disorder by parent report. The two-session intervention covered sleep hygiene and standardised behavioural strategies. The control group received usual care. Parent- and teacher-reported outcomes at 12 months included sleep, ADHD severity, quality of life, daily functioning, behaviour, and parent mental health. Adjusted mixed effects regression analyses examined 12 month outcomes. Interaction analyses were used to determine moderators of intervention outcomes over time. The trial was registered with ISRCTN, http://www.controlled-trials.com (ISRCTN68819261).

Intervention children were less likely to have a moderate/severe sleep problem by parent report at 12 months compared to usual care children (28.4% v. 46.5%, p = 0.03). Children in the intervention group fared better than the usual care group in terms of parent-reported ADHD symptoms (Cohen's d: −0.3, p < 0.001), quality of life (d: 0.4, p < 0.001), daily functioning (d: −0.5, p < 0.001), and behaviour (d: −0.3, p = 0.005) 12 months later. The benefits of the intervention over time in terms of sleep were less for children not taking ADHD medication and children with parents experiencing depression.

A behavioural sleep intervention for ADHD is associated with small sustained improvements in child wellbeing. Children who are not taking ADHD medication or have parents with depression may require follow-up booster sleep sessions.

Whereas genetic susceptibility increases the risk for major depressive disorder (MDD), non-genetic protective factors may mitigate this risk. In a large-scale prospective study of US Army soldiers, we examined whether trait resilience and/or unit cohesion could protect against the onset of MDD following combat deployment, even in soldiers at high polygenic risk.

Data were analyzed from 3079 soldiers of European ancestry assessed before and after their deployment to Afghanistan. Incident MDD was defined as no MDD episode at pre-deployment, followed by a MDD episode following deployment. Polygenic risk scores were constructed from a large-scale genome-wide association study of major depression. We first examined the main effects of the MDD PRS and each protective factor on incident MDD. We then tested the effects of each protective factor on incident MDD across strata of polygenic risk.

Polygenic risk showed a dose–response relationship to depression, such that soldiers at high polygenic risk had greatest odds for incident MDD. Both unit cohesion and trait resilience were prospectively associated with reduced risk for incident MDD. Notably, the protective effect of unit cohesion persisted even in soldiers at highest polygenic risk.

Polygenic risk was associated with new-onset MDD in deployed soldiers. However, unit cohesion – an index of perceived support and morale – was protective against incident MDD even among those at highest genetic risk, and may represent a potent target for promoting resilience in vulnerable soldiers. Findings illustrate the value of combining genomic and environmental data in a prospective design to identify robust protective factors for mental health.

Despite extensive research, symptom structure of posttraumatic stress disorder (PTSD) is highly debated. The network approach to psychopathology offers a novel method for understanding and conceptualizing PTSD. However, extant studies have mainly used small samples and self-report measures among sub-clinical populations, while also overlooking co-morbid depressive symptoms.

PTSD symptom network topology was estimated in a sample of 1489 treatment-seeking veteran patients based on a clinician-rated PTSD measure. Next, clinician-rated depressive symptoms were incorporated into the network to assess their influence on PTSD network structure. The PTSD-symptom network was then contrasted with the network of 306 trauma-exposed (TE) treatment-seeking patients not meeting full criteria for PTSD to assess corresponding network differences. Finally, a directed acyclic graph (DAG) was computed to estimate potential directionality among symptoms, including depressive symptoms and daily functioning.

The PTSD symptom network evidenced robust reliability. Flashbacks and getting emotionally upset by trauma reminders emerged as the most central nodes in the PTSD network, regardless of the inclusion of depressive symptoms. Distinct clustering emerged for PTSD and depressive symptoms within the comorbidity network. DAG analysis suggested a key triggering role for re-experiencing symptoms. Network topology in the PTSD sample was significantly distinct from that of the TE sample.

Flashbacks and psychological reactions to trauma reminders, along with their strong connections to other re-experiencing symptoms, have a pivotal role in the clinical presentation of combat-related PTSD among veterans. Depressive and posttraumatic symptoms constitute two separate diagnostic entities, but with meaningful between-disorder connections, suggesting two mutually-influential systems.

Little is known about the neural substrates of suicide risk in mood disorders. Improving the identification of biomarkers of suicide risk, as indicated by a history of suicide-related behavior (SB), could lead to more targeted treatments to reduce risk.

Participants were 18 young adults with a mood disorder with a history of SB (as indicated by endorsing a past suicide attempt), 60 with a mood disorder with a history of suicidal ideation (SI) but not SB, 52 with a mood disorder with no history of SI or SB (MD), and 82 healthy comparison participants (HC). Resting-state functional connectivity within and between intrinsic neural networks, including cognitive control network (CCN), salience and emotion network (SEN), and default mode network (DMN), was compared between groups.

Several fronto-parietal regions (k > 57, p < 0.005) were identified in which individuals with SB demonstrated distinct patterns of connectivity within (in the CCN) and across networks (CCN-SEN and CCN-DMN). Connectivity with some of these same regions also distinguished the SB group when participants were re-scanned after 1–4 months. Extracted data defined SB group membership with good accuracy, sensitivity, and specificity (79–88%).

These results suggest that individuals with a history of SB in the context of mood disorders may show reliably distinct patterns of intrinsic network connectivity, even when compared to those with mood disorders without SB. Resting-state fMRI is a promising tool for identifying subtypes of patients with mood disorders who may be at risk for suicidal behavior.

Although efficacious treatments for major depression are available, efficacy is suboptimal and recurrence is common. Effective preventive strategies could reduce disability associated with the disorder, but current options are limited. Cognitive bias modification (CBM) is a novel and safe intervention that attenuates biases associated with depression. This study investigated whether the delivery of a CBM programme designed to attenuate negative cognitive biases over a period of 1 year would decrease the incidence of major depression among adults with subthreshold symptoms of depression.

Randomised double-blind controlled trial delivered an active CBM intervention or a control intervention over 52 weeks. Two hundred and two community-dwelling adults who reported subthreshold levels of depression were randomised (100 intervention, 102 control). The primary outcome of interest was the incidence of major depressive episode assessed at 11, 27 and 52 weeks. Secondary outcomes included onset of clinically significant symptoms of depression, change in severity of depression symptoms and change in cognitive biases.

Adherence to the interventions was modest though did not differ between conditions. Incidence of major depressive episodes was low. Conditions did not differ in the incidence of major depressive episodes. Likewise, conditions did not differ in the incidence of clinically significant levels of depression, change in the severity of depression symptoms or change in cognitive biases.

Active CBM intervention did not decrease the incidence of major depressive episodes as compared to a control intervention. However, adherence to the intervention programme was modest and the programme failed to modify the expected mechanism of action.

Scientific interest in the therapeutic effects of classical psychedelics has increased in the past two decades. The psychological effects of these substances outside the period of acute intoxication have not been fully characterized. This study aimed to: (1) quantify the effects of psilocybin, ayahuasca, and lysergic acid diethylamide (LSD) on psychological outcomes in the post-acute period; (2) test moderators of these effects; and (3) evaluate adverse effects and risk of bias.

We conducted a systematic review and meta-analysis of experimental studies (single-group pre-post or randomized controlled trials) that involved administration of psilocybin, ayahuasca, or LSD to clinical or non-clinical samples and assessed psychological outcomes ⩾24 h post-administration. Effects were summarized by study design, timepoint, and outcome domain.

A total of 34 studies (24 unique samples, n = 549, mean longest follow-up = 55.34 weeks) were included. Classical psychedelics showed significant within-group pre-post and between-group placebo-controlled effects on a range of outcomes including targeted symptoms within psychiatric samples, negative and positive affect-related measures, social outcomes, and existential/spiritual outcomes, with large between-group effect in these domains (Hedges' gs = 0.84 to 1.08). Moderator tests suggest some effects may be larger in clinical samples. Evidence of effects on big five personality traits and mindfulness was weak. There was no evidence of post-acute adverse effects.

High risk of bias in several domains, heterogeneity across studies, and indications of publication bias for some models highlight the need for careful, large-scale, placebo-controlled randomized trials.

Autism Spectrum Disorder (ASD) and schizophrenia are neurodevelopmental disorders which share substantial overlap in cognitive deficits during adulthood. However, treatment evaluation in ASD and treatment comparisons across ASD and schizophrenia are limited by a dearth of empirical work establishing the validity of a standard cognitive battery across ASD and schizophrenia. Promisingly, the MATRICS Consensus Cognitive Battery (MCCB) has been validated in schizophrenia and encompasses cognitive domains that are impacted in ASD. Thus, this study aimed to establish MCCB's generalizability from schizophrenia to ASD.

Community-residing adults with schizophrenia (N = 100) and ASD (N = 113) underwent MCCB assessment. Using multigroup confirmatory factor analysis, MCCB's transdiagnostic validity was evaluated by examining whether schizophrenia and ASD demonstrate the same configuration, magnitude, and directionality of relationships within and among measures and their underlying cognitive domains.

Across schizophrenia and ASD, the same subsets of MCCB measures inform three cognitive domains: processing speed, attention/working memory, and learning. Except for group means in category fluency, continuous performance, and spatial span, both groups show vastly comparable factor structures and characteristics.

To our knowledge, this study is the first to establish the validity of a standard cognitive battery in adults with ASD and furthermore the first to establish a cognitive battery's comparability across ASD and schizophrenia. Cognitive domain scores can be compared across new samples using weighted sums of MCCB scores resulting from this study. These findings highlight MCCB's applicability to ASD and support its utility for standardizing treatment evaluation of cognitive outcomes across the autism-schizophrenia spectrum.

The interaction between positive, negative and depressive symptoms experienced by people with schizophrenia is complex. We used longitudinal data to test the hypothesis that depressive symptoms mediate the links between positive and negative symptoms.

We analyzed data from the European Schizophrenia Cohort, randomly sampled from outpatient services in France, Germany and the UK (N = 1208). Initial measures were repeated after 6 and 12 months. Depressive symptoms were identified using the Calgary Depression Scale for Schizophrenia (CDSS), while positive and negative symptoms were assessed with the Positive and Negative Syndrome Scale (PANSS). Latent variable structural equation modelling was used to investigate the mediating role of depression assessed at 6 months in relation to the longitudinal association between positive symptoms at baseline and negative symptoms at 12 months.

We found longitudinal associations between positive symptoms at baseline and negative symptoms at 12 months, as well as between both of these and CDSS levels at 6 months. However depression did not mediate the longitudinal association between PANSS scores; all the effect was direct.

Our findings are incompatible with a mediating function for depression on the pathway from positive to negative symptoms, at least on this timescale. The role of depression in schizophrenic disorders remains a challenge for categorical and hierarchical diagnostic systems alike. Future research should analyze specific domains of both depressive and negative symptoms (e.g. motivational and hedonic impairments). The clinical management of negative symptoms using antidepressant treatments may need to be reconsidered.

Schizophrenia is associated with robust hippocampal volume deficits but subregion volume deficits, their associations with cognition, and contributing genes remain to be determined.

Hippocampal formation (HF) subregion volumes were obtained using FreeSurfer 6.0 from individuals with schizophrenia (n = 176, mean age ± s.d. = 39.0 ± 11.5, 132 males) and healthy volunteers (n = 173, mean age ± s.d. = 37.6 ± 11.3, 123 males) with similar mean age, gender, handedness, and race distributions. Relationships between the HF subregion volume with the largest between group difference, neuropsychological performance, and single-nucleotide polymorphisms were assessed.

This study found a significant group by region interaction on hippocampal subregion volumes. Compared to healthy volunteers, individuals with schizophrenia had significantly smaller dentate gyrus (DG) (Cohen's d = −0.57), Cornu Ammonis (CA) 4, molecular layer of the hippocampus, hippocampal tail, and CA 1 volumes, when statistically controlling for intracranial volume; DG (d = −0.43) and CA 4 volumes remained significantly smaller when statistically controlling for mean hippocampal volume. DG volume showed the largest between group difference and significant positive associations with visual memory and speed of processing in the overall sample. Genome-wide association analysis with DG volume as the quantitative phenotype identified rs56055643 (β = 10.8, p < 5 × 10−8, 95% CI 7.0–14.5) on chromosome 3 in high linkage disequilibrium with MOBP. Gene-based analyses identified associations between SLC25A38 and RPSA and DG volume.

This study suggests that DG dysfunction is fundamentally involved in schizophrenia pathophysiology, that it may contribute to cognitive abnormalities in schizophrenia, and that underlying biological mechanisms may involve contributions from MOBP, SLC25A38, and RPSA.

Patients with bipolar disorder (BD) experience persistent impairments in both affective and non-affective cognitive function, which is associated with a worse course of illness and poor functional outcomes. Nevertheless, the temporal progression of cognitive dysfunction in BD remains unclear and the identification of objective endophenotypes can inform the aetiology of BD.

The present study is a cross-sectional investigation of cognitive baseline data from the longitudinal Bipolar Illness Onset-study. One hundred seventy-two remitted patients newly diagnosed with BD, 52 of their unaffected relatives (UR), and 110 healthy controls (HC) were compared on a large battery of behavioural cognitive tasks tapping into non-affective (i.e. neurocognitive) and affective (i.e. emotion processing and regulation) cognition.

Relative to HCs, patients with BD exhibited global neurocognitive deficits (ps < 0.001), as well as aberrant emotion processing and regulation (ps ⩽ 0.011); including decreased emotional reactivity to positive social scenarios, impaired ability to down-regulate positive emotion, as well as a specific deficit in the ability to recognise surprised facial expressions. Their URs also showed a trend towards difficulties identifying surprised faces (p = 0.075). No other differences in cognitive function were found for URs compared to HCs.

Neurocognitive deficits and impairments within emotion processing and regulation may be illness-related deficits of BD that present after illness-onset, whereas processing of emotional faces may represent an early risk marker of BD. However, longitudinal studies are needed to examine the association between cognitive impairments and illness progression in BD.

The hippocampus plays an important role in psychopathology and treatment outcome. While posterior hippocampus (PH) may be crucial for the learning process that exposure-based treatments require, affect-focused treatments might preferentially engage anterior hippocampus (AH). Previous studies have distinguished the different functions of these hippocampal sub-regions in memory, learning, and emotional processes, but not in treatment outcome. Examining two independent clinical trials, we hypothesized that anterior hippocampal volume would predict outcome of affect-focused treatment outcome [Interpersonal Psychotherapy (IPT); Panic-Focused Psychodynamic Psychotherapy (PFPP)], whereas posterior hippocampal volume would predict exposure-based treatment outcome [Prolonged Exposure (PE); Cognitive Behavioral Therapy (CBT); Applied Relaxation Training (ART)].

Thirty-five patients with posttraumatic stress disorder (PTSD) and 24 with panic disorder (PD) underwent structural magnetic resonance imaging (MRI) before randomization to affect-focused (IPT for PTSD; PFPP for PD) or exposure-based treatments (PE for PTSD; CBT or ART for PD). AH and PH volume were regressed with clinical outcome changes.

Baseline whole hippocampal volume did not predict post-treatment clinical severity scores in any treatment. For affect-focused treatments, but not exposure-based treatments, anterior hippocampal volume predicted clinical improvement. Smaller AH correlated with greater affect-focused treatment improvement. Posterior hippocampal volume did not predict treatment outcome.

This is the first study to explore associations between hippocampal volume sub-regions and treatment outcome in PTSD and PD. Convergent results suggest that affect-focused treatment may influence the clinical outcome through the ‘limbic’ AH, whereas exposure-based treatments do not. These preliminary, theory-congruent, therapeutic findings require replication in a larger clinical trial.

Prenatal infections have been proposed as a putative risk factor for a number of psychiatric outcomes across a continuum of severity. Evidence on eating disorders is scarce. We investigated whether exposure to prenatal maternal infections is associated with an increased risk of disordered eating and weight and shape concerns in adolescence in a large UK birth cohort.

We used data from the Avon Longitudinal Study of Parents and Children. The primary exposure was maternal experience of infections at any time in pregnancy. Study outcomes were presence of any, monthly or weekly disordered eating at 14 and 16 years of age, and weight and shape concerns at 14 years. We defined the causal effect of the exposure on these outcomes using a counterfactual framework adjusting our analyses for a number of hypothesised confounders, and imputing missing confounder data using multiple imputation.

In total, 4884 children had complete exposure and outcome data at age 14 years, and 4124 at 16 years. Exposed children had a greater risk of reporting weekly disordered eating at both age 14 [risk difference (RD) 0.9%, 95% confidence interval (CI) −0.01 to 1.9, p = 0.08] and 16 (RD 2.3%, 95% CI 0.6–3.9, p < 0.01), though evidence of an association was weak at age 14 years. Exposed children also had greater weight and shape concerns at age 14 years (mean difference 0.15, 95% CI 0.05–0.26, p < 0.01).

Exposure to prenatal maternal infection is associated with greater risk of disordered eating in adolescence. This association could be explained by in utero processes leading to impaired neurodevelopment or altered immunological profiles. Residual confounding cannot be excluded.

Although early life adversity (ELA) increases risk for psychopathology, mechanisms linking ELA with the onset of psychopathology remain poorly understood. Conceptual models have argued that ELA accelerates development. It is unknown whether all forms of ELA are associated with accelerated development or whether early maturation is a potential mechanism linking ELA with psychopathology. We examine whether two distinct dimensions of ELA – threat and deprivation – have differential associations with pubertal timing in girls, and evaluate whether accelerated pubertal timing is a mechanism linking ELA with the onset of adolescent psychopathology.

Data were drawn from a large, nationally representative sample of 4937 adolescent girls. Multiple forms of ELA characterized by threat and deprivation were assessed along with age at menarche (AAM) and the onset of DSM-IV fear, distress, externalizing, and eating disorders.

Greater exposure to threat was associated with earlier AAM (B = −0.1, p = 0.001). Each 1-year increase in AAM was associated with reduced odds of fear, distress, and externalizing disorders post-menarche (ORs = 0.74–0.85). Earlier AAM significantly mediated the association between exposure to threat and post-menarche onset of distress (proportion mediated = 6.2%), fear (proportion mediated = 16.3%), and externalizing disorders (proportion mediated = 2.9%).

Accelerated pubertal development in girls may be one transdiagnostic pathway through which threat-related experiences confer risk for the adolescent onset of mental disorders. Early pubertal maturation is a marker that could be used in both medical and mental health settings to identify trauma-exposed youth that are at risk for developing a mental disorder during adolescence in order to better target early interventions.

Both acute and chronic pain can disrupt reward processing. Moreover, prolonged prescription opioid use and depressed mood are common in chronic pain samples. Despite the prevalence of these risk factors for anhedonia, little is known about anhedonia in chronic pain populations.

We conducted a large-scale, systematic study of anhedonia in chronic pain, focusing on its relationship with opioid use/misuse, pain severity, and depression. Chronic pain patients across four distinct samples (N = 488) completed the Snaith–Hamilton Pleasure Scale (SHAPS), measures of opioid use, pain severity and depression, as well as the Current Opioid Misuse Measure (COMM). We used a meta-analytic approach to determine reference levels of anhedonia in healthy samples spanning a variety of countries and diverse age groups, extracting SHAPS scores from 58 published studies totaling 2664 psychiatrically healthy participants.

Compared to healthy samples, chronic pain patients showed higher levels of anhedonia, with ~25% of patients scoring above the standard anhedonia cut-off. This difference was not primarily driven by depression levels, which explained less than 25% of variance in anhedonia scores. Neither opioid use duration, dose, nor pain severity alone was significantly associated with anhedonia. Yet, there was a clear effect of opioid misuse, with opioid misusers (COMM ⩾13) reporting greater anhedonia than non-misusers. Opioid misuse remained a significant predictor of anhedonia even after controlling for pain severity, depression and opioid dose.

Study results suggest that both chronic pain and opioid misuse contribute to anhedonia, which may, in turn, drive further pain and misuse.