Cognitive deficits are already present in early stages of schizophrenia. P3a and P3b event-related potentials (ERPs) are believed to underlie the processes of attention and working memory (WM), yet limited research has been performed on the associations between these parameters. Therefore, we explored possible associations between P3a/b amplitudes and cognition in a large cohort of antipsychotic-naïve, first-episode schizophrenia (AN-FES) patients and healthy controls (HC).

Seventy-three AN-FES patients and 93 age- and gender-matched HC were assessed for their P3a/b amplitude with an auditory oddball paradigm. In addition, subjects performed several subtests from the Cambridge Neuropsychological Test Automated Battery (CANTAB).

AN-FES patients had significantly reduced P3a/b amplitudes, as well as significantly lower scores on all cognitive tests compared with HC. Total group correlations revealed positive associations between P3b amplitude and WM and sustained attention and negative associations with all reaction time measures. These associations appeared mainly driven by AN-FES patients, where we found a similar pattern. No significant associations were found between P3b amplitude and cognitive measures in our HC. P3a amplitude did not correlate significantly with any cognitive measures in either group, nor when combined.

Our results provide further evidence for P3a/b amplitude deficits and cognitive deficits in AN-FES patients, which are neither due to antipsychotics nor to disease progress. Furthermore, our data showed significant, yet weak associations between P3b and cognition. Therefore, our data do not supply evidence for deficient P3a/b amplitudes as direct underlying factors for cognitive deficits in schizophrenia.

Neuropsychological investigations can help untangle the aetiological and phenomenological heterogeneity of schizophrenia but have scarcely been employed in the context of treatment-resistant (TR) schizophrenia. No population-based study has examined neuropsychological function in the first-episode of TR psychosis.

We report baseline neuropsychological findings from a longitudinal, population-based study of first-episode psychosis, which followed up cases from index admission to 10 years. At the 10-year follow up patients were classified as treatment responsive or TR after reconstructing their entire case histories. Of 145 cases with neuropsychological data at baseline, 113 were classified as treatment responsive, and 32 as TR at the 10-year follow-up.

Compared with 257 community controls, both case groups showed baseline deficits in three composite neuropsychological scores, derived from principal component analysis: verbal intelligence and fluency, visuospatial ability and executive function, and verbal memory and learning (p values⩽0.001). Compared with treatment responders, TR cases showed deficits in verbal intelligence and fluency, both in the extended psychosis sample (t = −2.32; p = 0.022) and in the schizophrenia diagnostic subgroup (t = −2.49; p = 0.017). Similar relative deficits in the TR cases emerged in sub-/sensitivity analyses excluding patients with delayed-onset treatment resistance (p values<0.01–0.001) and those born outside the UK (p values<0.05).

Verbal intelligence and fluency are impaired in patients with TR psychosis compared with those who respond to treatment. This differential is already detectable – at a group level – at the first illness episode, supporting the conceptualisation of TR psychosis as a severe, pathogenically distinct variant, embedded in aberrant neurodevelopmental processes.

Smoking is the largest single contributor to poor physical health and increased mortality in people with serious mental illnesses. The aim of the study was to investigate the utility of electronic cigarettes (e-cigarettes) as a harm reduction intervention in this population.

Fifty tobacco smokers with a psychotic disorder were enrolled onto a 24-week pilot study (ClinicalTrials.gov: NCT02212041) investigating the efficacy of a 6-week free e-cigarette intervention to reduce smoking. Cigarette and e-cigarette use was self-reported at weekly visits, and verified using carbon monoxide tests. Psychopathology, e-cigarette acceptability and adverse effects were assessed using standardised scales.

There was a significant (⩾50%) reduction in cigarettes consumed per day between baseline and week 6 [F(2.596,116.800) = 25.878, p < 0.001], and e-cigarette use was stable during this period [F(2.932,46.504) = 2.023, p = 0.115]. These changes were verified by significant carbon monoxide reductions between these time points [F(3.335,126.633) = 5.063, p = 0.002].

The provision of e-cigarettes is a potentially useful harm reduction intervention in smokers with a psychotic disorder.

Insomnia is effectively treated with online Cognitive Behavioral Therapy for Insomnia (CBT-I). Previous research has suggested the effects might not be limited to sleep and insomnia severity, but also apply to depressive symptoms. Results, however, are mixed.

In this randomized controlled trial we investigated the effects of guided online CBT-I on depression and insomnia in people suffering from symptoms of both. Participants (n = 104) with clinical insomnia and at least subclinical depression levels were randomized to (1) guided online CBT-I and sleep diary monitoring (i-Sleep) or (2) control group (sleep diary monitoring only). The primary outcome was the severity of depressive symptoms (Patient Health Questionnaire-9 without sleep item; PHQ-WS). Secondary outcomes were insomnia severity, sleep diary parameters, fatigue, daytime consequences of insomnia, anxiety, and perseverative thinking.

At post-test, participants in the i-Sleep condition reported significantly less depressive symptoms (PHQ-WS) compared with participants in the sleep-diary condition (d = 0.76). Large significant effects were also observed for insomnia severity (d = 2.36), most sleep diary parameters, daytime consequences of insomnia, anxiety, and perseverative thinking. Effects were maintained at 3 and 6 month follow-up. We did not find significant post-test effects on fatigue or total sleep time.

Findings indicate that guided online CBT-I is not only effective for insomnia complaints but also for depressive symptoms. The effects are large and comparable with those of depression therapy. Clinical trial registration number: NTR6049 (Netherlands Trial Register).

Social aggression is a form of antisocial behavior in which social relationships and social status are used to damage reputations and inflict emotional harm on others. Despite extensive research examining the prevalence and consequences of social aggression, only a few studies have examined its genetic–environmental etiology, with markedly inconsistent results.

We estimated the etiology of social aggression using the nuclear twin family (NTF) model. Maternal-report, paternal-report, and teacher-report data were collected for twin social aggression (N = 1030 pairs). We also examined the data using the classical twin (CT) model to evaluate whether its strict assumptions may have biased previous heritability estimates.

The best-fitting NTF model for all informants was the ASFE model, indicating that additive genetic, sibling environmental, familial environmental, and non-shared environmental influences significantly contribute to the etiology of social aggression in middle childhood. However, the best-fitting CT model varied across informants, ranging from AE and ACE to CE. Specific heritability estimates for both NTF and CT models also varied across informants such that teacher reports indicated greater genetic influences and father reports indicated greater shared environmental influences.

Although the specific NTF parameter estimates varied across informants, social aggression generally emerged as largely additive genetic (A = 0.15–0.77) and sibling environmental (S = 0.42–0.72) in origin. Such findings not only highlight an important role for individual genetic risk in the etiology of social aggression, but also raise important questions regarding the role of the environment.

The Research Domain Criteria initiative was launched by the US National Institute of Mental Health to establish a multi-level framework for understanding psychological constructs relevant to human psychiatric disorders, and identified ‘effort valuation/willingness to work’ as a clinically useful construct worthy of further study. This construct encompasses the processes by which the cost(s) of obtaining an outcome are calculated, and the tendency to overcome response costs to obtain a reinforcer. The current study aims to examine effort valuation as a correlate of psychopathology in children and adults, and the moderating effects of sex on this relationship.

Participants were 1215 children aged 6–12 and their parents (n = 1044). All participants completed the Effort Expenditure for Rewards Task as a measure of effort expenditure. Child psychopathology was measured via the Child Behavior Checklist, while adult psychopathology was measured via the Adult Self Report. Additionally, the Social Adjustment Inventory for Children and Adolescents and Injury Behavior Checklist were used to examine child social impairments/problem behaviors.

In children, significant interactions between reward sensitivity and sex were observed in association with anxiety and thought problems, specifically at low reward sensitivity levels. In adults, main effects of effort expenditure were seen in drug and alcohol abuse, where higher effort was associated with higher degrees of abuse.

These results establish effort valuation as a relevant psychological construct for understanding psychopathology, but with different profiles of associated psychopathology across sex in children and adults.

Traumatic stressors during childhood and adolescence are associated with psychopathology, mostly studied in the context of post-traumatic stress disorder (PTSD) and depression. We investigated broader associations of traumatic stress exposure with psychopathology and cognition in a youth community sample.

The Philadelphia Neurodevelopmental Cohort (N = 9498) is an investigation of clinical and neurobehavioral phenotypes in a diverse (56% Caucasian, 33% African American, 11% other) US youth community population (aged 8–21). Participants were ascertained through children's hospital pediatric (not psychiatric) healthcare network in 2009–2011. Structured psychiatric evaluation included screening for lifetime exposure to traumatic stressors, and a neurocognitive battery was administered.

Exposure rate to traumatic stressful events was high (none, N = 5204; one, N = 2182; two, N = 1092; three or more, N = 830). Higher stress load was associated with increased psychopathology across all clinical domains evaluated: mood/anxiety (standardized β = .378); psychosis spectrum (β = .360); externalizing behaviors (β = .311); and fear (β = .256) (controlling for covariates, all p < 0.001). Associations remained significant controlling for lifetime PTSD and depression. Exposure to high-stress load was robustly associated with suicidal ideation and cannabis use (odds ratio compared with non-exposed 5.3 and 3.2, respectively, both p < 0.001). Among youths who experienced traumatic stress (N = 4104), history of assaultive trauma was associated with greater psychopathology and, in males, vulnerability to psychosis and externalizing symptoms. Stress load was negatively associated with performance on executive functioning, complex reasoning, and social cognition.

Traumatic stress exposure in community non-psychiatric help-seeking youth is substantial, and is associated with more severe psychopathology and neurocognitive deficits across domains, beyond PTSD and depression.

Depression is a common post-stroke complication. Pre-stroke depression may be an important contributor, however the epidemiology of pre-stroke depression is poorly understood. Using systematic review and meta-analysis, we described the prevalence of pre-stroke depression and its association with post-stroke depression.

We searched multiple cross-disciplinary databases from inception to July 2017 and extracted data on the prevalence of pre-stroke depression and its association with post-stroke depression. We assessed the risk of bias (RoB) using validated tools. We described summary estimates of prevalence and summary odds ratio (OR) for association with post-stroke depression, using random-effects models. We performed subgroup analysis describing the effect of depression assessment method. We used a funnel plot to describe potential publication bias. The strength of evidence presented in this review was summarised via ‘GRADE’.

Of 11 884 studies identified, 29 were included (total participants n = 164 993). Pre-stroke depression pooled prevalence was 11.6% [95% confidence interval (CI) 9.2–14.7]; range: 0.4–24% (I2 95.8). Prevalence of pre-stroke depression varied by assessment method (p = 0.02) with clinical interview suggesting greater pre-stroke depression prevalence (~17%) than case-note review (9%) or self-report (11%). Pre-stroke depression was associated with increased odds of post-stroke depression; summary OR 3.0 (95% CI 2.3–4.0). All studies were judged to be at RoB: 59% of included studies had an uncertain RoB in stroke assessment; 83% had high or uncertain RoB for pre-stroke depression assessment. Funnel plot indicated no risk of publication bias. The strength of evidence based on GRADE was ‘very low’.

One in six stroke patients have had pre-stroke depression. Reported rates may be routinely underestimated due to limitations around assessment. Pre-stroke depression significantly increases odds of post-stroke depression.

PROSPERO identifier: CRD42017065544

Early-life adversity (ELA) is a risk factor for internalizing psychopathology (IP). ELA is also linked to alterations in neural phenotypes of emotion processing and maladaptive emotion regulatory strategies, such as ruminative brooding, in adulthood. We therefore expected that ELA would predict cortical brain activation to emotional faces in transdiagnostic IP and in turn, mediate the extent of rumination amongst patients with IPs and ELA (IP + ELA).

One hundred and thirty-two individuals, including 102 treatment-seeking adults with heterogeneous IPs and 30 healthy controls (HCs) performed an Emotional Face-Matching Task during functional magnetic resonance imaging. Whole-brain analyses compared HC (n = 30), IP (n = 52), and IP + ELA (n = 50) neural responses to emotional (angry, fearful, happy, and sad) faces v. shapes, controlling for depression and anxiety symptoms. Parameter estimates of activation were extracted for significant between-group differences and tested as a mediator of ruminative brooding in IP + ELA.

IP + ELA demonstrated increased activation in the superior frontal gyrus and anterior cingulate cortex (fear), superior parietal lobule, precuneus, posterior cingulate, and inferior temporal gyrus (fear only), and cuneus (fear and angry). These regions were preferentially correlated with ruminative brooding in IP + ELA, many of which mediated the link between IP + ELA and ruminative brooding.

Results provide evidence that ELA history amongst IP patients augments engagement of brain regions involved in emotion processing, above and beyond what is accounted for by current symptoms. Though longitudinal designs are needed, alterations in the neural correlates of maladaptive processing of socio-emotional information may be a common pathway by which ELA poses risk for psychopathology.

While studies suggest that nutritional supplementation may reduce aggressive behavior in children, few have examined their effects on specific forms of aggression. This study tests the primary hypothesis that omega-3 (ω-3), both alone and in conjunction with social skills training, will have particular post-treatment efficacy for reducing childhood reactive aggression relative to baseline.

In this randomized, double-blind, stratified, placebo-controlled, factorial trial, a clinical sample of 282 children with externalizing behavior aged 7–16 years was randomized into ω-3 only, social skills only, ω-3 + social skills, and placebo control groups. Treatment duration was 6 months. The primary outcome measure was reactive aggression collected at 0, 3, 6, 9, and 12 months, with antisocial behavior as a secondary outcome.

Children in the ω-3-only group showed a short-term reduction (at 3 and 6 months) in self-report reactive aggression, and also a short-term reduction in overall antisocial behavior. Sensitivity analyses and a robustness check replicated significant interaction effects. Effect sizes (d) were small, ranging from 0.17 to 0.31.

Findings provide some initial support for the efficacy of ω-3 in reducing reactive aggression over and above standard care (medication and parent training), but yield only preliminary and limited support for the efficacy of ω-3 in reducing overall externalizing behavior in children. Future studies could test further whether ω-3 shows promise in reducing more reactive, impulsive forms of aggression.

Cognitive impairment is a core feature of schizophrenia and has been observed in both familial (FHR) and clinical high-risk (CHR) samples. Nonetheless, there is a paucity of research directly contrasting cognitive profiles in these two high-risk states and first-episode schizophrenia. This study aimed to compare cognitive functions in patients with first-episode schizophrenia-spectrum disorder (FES), their unaffected siblings (FHR), CHR individuals and healthy controls.

A standardized battery of cognitive assessments was administered to 69 FES patients, 71 help-seeking CHR individuals without family history of psychotic disorder, 50 FHR participants and 68 controls. FES and CHR participants were recruited from territory-wide early intervention service for psychosis in Hong Kong. CHR status was ascertained using Comprehensive Assessment of At-Risk Mental State.

Among four groups, FES patients displayed the largest global cognitive impairment and had medium-to-large deficits across all cognitive tests relative to controls. CHR and FHR participants significantly underperformed in most cognitive tests than controls. Among various cognitive tests, digit symbol coding demonstrated the greatest magnitude of impairment in FES and CHR groups compared with controls. No significant difference between two high-risk groups was observed in global cognition and all individual cognitive tests except digit symbol coding which showed greater deficits in CHR than in FHR participants.

Clinical and familial risk groups experienced largely comparable cognitive impairment that was intermediate between FES and controls. Digit symbol coding may have the greatest discriminant capacity in distinguishing FES and CHR from healthy controls, and between two high-risk samples.

High body mass index (BMI) has been associated with lower risks of suicidal behaviour and being underweight with increased risks. However, evidence is inconsistent and sparse, particularly for women. We aim to study this relationship in a large cohort of UK women.

In total 1.2 million women, mean age 56 (s.d. 5) years, without prior suicide attempts or other major illness, recruited in 1996–2001 were followed by record linkage to national hospital admission and death databases. Cox regression yielded relative risks (RRs) and 95% confidence intervals (CIs) for attempted suicide and suicide by BMI, adjusted for baseline lifestyle factors and self-reported treatment for depression or anxiety.

After 16 (s.d. 3) years of follow-up, 4930 women attempted suicide and 642 died by suicide. The small proportion (4%) with BMI <20 kg/m2 were at clearly greater risk of attempted suicide (RR = 1.38, 95% CI 1.23–1.56) and suicide (RR = 2.10, 1.59–2.78) than women of BMI 20–24.9 kg/m2; p < 0.0001 for both comparisons. Small body size at 10 and 20 years old was also associated with increased risks. Half the cohort had BMIs >25 kg/m2 and, while risks were somewhat lower than for BMI 20–24.9 kg/m2 (attempted suicide RR = 0.91, 0.86–0.96; p = 0.001; suicide RR = 0.79, 0.67–0.93; p = 0.006), the reductions in risk were not strongly related to level of BMI.

Being underweight is associated with a definite increase in the risk of suicidal behaviour, particularly death by suicide. Residual confounding cannot be excluded for the small and inconsistent decreased risk of suicidal behaviour associated with being overweight or obese.

Inflammation and immune activation have been implicated in the pathogenesis of severe mental disorders and cardiovascular disease (CVD). Despite high level of comorbidity, many studies of the immune system in severe mental disorders have not systematically taken cardiometabolic risk factors into account.

We investigated if inflammatory markers were increased in schizophrenia (SCZ) and affective (AFF) disorders independently of comorbid CVD risk factors. Cardiometabolic risk factors (blood lipids, body mass index and glucose) and CVD-related inflammatory markers CXCL16, soluble interleukin-2 receptor (sIL-2R), soluble CD14 (sCD14), macrophage inhibitory factor and activated leukocyte cell adhesion molecule (ALCAM) were measured in n = 992 patients (SCZ, AFF), and n = 647 healthy controls. We analyzed the inflammatory markers before and after controlling for comorbid cardiometabolic risk factors, and tested for association with psychotropic medication and symptom levels.

CXCL16 (p = 0.03) and sIL-2R (p = 7.8 × 10−5) were higher, while sCD14 (p = 0.05) were lower in patients compared to controls after controlling for confounders, with significant differences in SCZ for CXCL16 (p = 0.04) and sIL-2R (p = 1.1 × 10−5). After adjustment for cardiometabolic risk factors higher levels of sIL-2R (p = 0.001) and lower sCD14 (p = 0.002) remained, also in SCZ (sIL-2R, p = 3.0 × 10−4 and sCD14, p = 0.01). The adjustment revealed lower ALCAM levels (p = 0.03) in patients. We found no significant associations with psychotropic medication or symptom levels.

The results indicate that inflammation, in particular enhanced T cell activation and impaired monocyte activation, are associated with severe mental disorders independent of comorbid cardiometabolic risk factors. This suggests a role of novel pathophysiological mechanisms in severe mental disorders, particularly SCZ.