Schizophrenia is a longstanding condition and most patients experience multiple relapse in the course of the condition. High expressed emotion (HEE) has been found to be a predictor of relapse. This meta-analysis and meta-regression examined the association of global EE and relapse specifically focusing on timing of relapse and EE domains.

Random-effects model was used to pool the effect estimates. Multiple random-effects meta-regression was used to compute the moderator analysis. Putative effect moderators including culture, EE measurements, age, length of condition and study quality were included.

Thirty-three prospective cohort studies comprising 2284 patients were included in the descriptive review and 30 studies were included for meta-analysis and meta-regression. Findings revealed that global HEE significantly predicted more on early relapse (⩽12 months) [OR 4.87 (95% CI 3.22–7.36)] than that on late relapse (>12 months) [OR 2.13 (95% CI 1.36–3.35)]. Higher level of critical comments (CC) significantly predicted relapse [OR 2.22 (95% CI 1.16–4.26)], whereas higher level of warmth significantly protected patients from relapse [OR 0.35 (95% CI 0.15–0.85)]. None of the moderators included significantly change the results.

These findings indicate that there is a dynamic interaction between EE-relapse association with time, and CC and warmth are the two important EE domains to influence relapse among patients with schizophrenia. Results also confirmed the foci of family interventions on reducing CC and improving warmth in relationship.

Previous literature has extensively investigated the brain activity during response inhibition in adults with addiction. Inconsistent results including both hyper- and hypo-activities in the fronto-parietal network (FPN) and the ventral attention network (VAN) have been found in adults with addictions, compared with healthy controls (HCs).

Voxel-wise meta-analyses of abnormal task-evoked regional activity were conducted for adults with substance dependence (SD) and behavioral addiction during response inhibition tasks to solve previous inconsistencies. Twenty-three functional magnetic resonance imaging studies including 479 substance users, 38 individuals with behavioral addiction and 494 HCs were identified.

Compared with HCs, all addictions showed hypo-activities in regions within FPN (inferior frontal gyrus and supramarginal gyrus) and VAN (inferior frontal gyrus, middle temporal gyrus, temporal pole and insula), and hyper-activities in the cerebellum during response inhibition. SD subgroup showed almost the same activity patterns, with an additional hypoactivation of the precentral gyrus, compared with HCs. Stronger activation of the cerebellum was associated with longer addiction duration for adults with SD. We could not conduct meta-analytic investigations into the behavioral addiction subgroup due to the small number of datasets.

This meta-analysis revealed altered activation of FPN, VAN and the cerebellum in adults with addiction during response inhibition tasks using non-addiction-related stimuli. Although FPN and VAN showed lower activity, the cerebellum exhibited stronger activity. These results may help to understand the neural pathology of response inhibition in addiction.

Poor cognitive abilities and low intellectual quotient (IQ) are associated with an increased risk of suicide attempts and suicide mortality. However, knowledge of how this association develops across the life-course is limited. Our study aims to establish whether individuals who died by suicide by mid-adulthood are distinguishable by their child-to-adolescence cognitive trajectories.

Participants were from the 1958 British Birth Cohort and were assessed for academic performance at ages 7, 11, and 16 and intelligence at 11 years. Suicides occurring by September 2012 were identified from linked national death certificates. We compared mean mathematics and reading abilities and rate of change across 7–16 years for individuals who died by suicide v. those still alive, with and without adjustment for potential early-life confounding factors. Analyses were based on 14 505 participants.

Fifty-five participants (48 males) had died by suicide by age 54 years. While males who died by suicide did not differ from participants still alive in reading scores at age 7 [effect size (g) = −0.04, p = 0.759], their reading scores had a less steep improvement up to age 16 compared to other participants. Adjustments for early-life confounding factors explained these differences. A similar pattern was observed for mathematics scores. There was no difference between individuals who died by suicide v. participants still alive on intelligence at 11 years.

While no differences in tests of academic performance and IQ were observed, individuals who died by suicide had a less steep improvement in reading abilities over time compared to same-age peers.

Several studies have reported diminished learning from non-social outcomes in depressed individuals. However, it is not clear how depression impacts learning from social feedback. Notably, mood disorders are commonly associated with deficits in social functioning, which raises the possibility that potential impairments in social learning may negatively affect real-life social experiences in depressed subjects.

Ninety-two participants with high (HD; N = 40) and low (LD; N = 52) depression scores were recruited. Subjects performed a learning task, during which they received monetary outcomes or social feedback which they were told came from other people. Additionally, participants answered questions about their everyday social experiences. Computational models were fit to the data and model parameters were related to social experience measures.

HD subjects reported a reduced quality and quantity of social experiences compared to LD controls, including an increase in the amount of time spent in negative social situations. Moreover, HD participants showed lower learning rates than LD subjects in the social condition of the task. Interestingly, across all participants, reduced social learning rates predicted higher amounts of time spent in negative social situations, even when depression scores were controlled for.

These findings indicate that deficits in social learning may affect the quality of everyday social experiences. Specifically, the impaired ability to use social feedback to appropriately update future actions, which was observed in HD subjects, may lead to suboptimal interpersonal behavior in real life. This, in turn, may evoke negative feedback from others, thus bringing about more unpleasant social encounters.

Subclinical adolescent alcohol use is highly prevalent and may have deleterious effects on important psychosocial and brain outcomes. Prior research has focused on identifying endophenotypes of pathological drinking, and the predictors of normative drinking remain understudied. This study investigated the incremental predictive value of two potential psychophysiological endophenotypes, P3 amplitude (an index of decision making) and midfrontal theta power (a correlate of attentional control), for prospectively predicting the expression and initiation of alcohol use emerging in adolescence.

A large (N = 594) epidemiological sample was prospectively assessed at ages 11/14/17. Alcohol/substance use was assessed at all ages via a computerized self-report inventory. EEG was recorded at age-14 during a visual oddball task to elicit P3 and theta.

Reduced target-related P3 and theta at age-14 prospectively predicted drinking at age-17 independent of one another. Among alcohol-naive individuals at age-14, attenuated P3 and theta increased the odds of new-onset alcohol behaviors 3 years later. Importantly, the endophenotypes provided significant incremental predictive power of future non-clinical alcohol use beyond relevant risk factors (prior alcohol use; tobacco/illicit drug initiation; parental alcohol use disorder).

The current report is the first of our knowledge to demonstrate that deviations in parietal P3 and midfrontal theta prospectively predict the emergence of normative/non-pathological drinking. P3 and theta provide modest yet significant explanatory variance beyond prominent self-report and familial risk measures. Findings offer strong evidence supporting the predictive utility of P3 and theta as candidate endophenotypes for adolescent drinking.

Depression even at the subclinical level is often accompanied by sleep disturbances, but little is known about the dynamics of the sleep stages in relation to depressive symptoms. We examined whether the amount, associations, and transition probabilities of various sleep stages were associated with depressive symptoms in a community sample of adolescents.

The participants (N = 172, 59% girls, mean age 16.9 years) underwent overnight polysomnography and provided data on depressive symptoms (Beck Depression Inventory II). The association between depression status and total duration of each stage type was analyzed using ANOVA and survival analyses. The associations between the number of different sleep stage types were analyzed using graphical Gaussian models, mixed graphical models, and relative importance networks. A Markov chain algorithm was used to estimate the transition probabilities between each state and these probabilities were further compared between depression status groups.

The associations between N1 and N3 were significantly stronger in both directions of the association (p-values for interactions 0.012 and 0.006) in those with more depressive symptoms. Similarly, a stronger association was observed from N1 to wake stage in those with more depressive symptoms (p-value for interaction 0.002). In those with more depressive symptoms, it was more likely to transition from N2 to N3 and from REM to N2 compared to others.

These findings indicate that changes in sleep architecture are not limited to clinical depression and that the transitional dynamics of sleep stages are an important marker of subclinical depression.

Anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis is an immune-mediated disorder which requires multi-disciplinary treatment including immunomodulation therapy. First presentation is most commonly to psychiatric services and continuing psychiatric care is required to treat disabling symptoms, such as behaviour disturbance, psychosis and catatonia. There is minimal available evidence to guide symptomatic treatment and concern for increased sensitivity to antipsychotics complicates traditional approaches.

All cases of cerebrospinal fluid positive anti-NMDAR encephalitis tested in Queensland, Australia were identified. Demographic, clinical and therapeutic data were collected and reviewed by two independent clinicians. Pre-specified variables reflecting possible treatment side effects were compared.

The majority of the 30 cases (83%) had early psychiatric symptoms and were treated with antipsychotics (67%), average daily olanzapine equivalence dose of 11.5 mg, prior to immunomodulation therapy. Although there was an 88% reduction in cases with aggression, there was little improvement in psychosis, affective symptoms or catatonia with antipsychotics alone. In the cases with psychiatric symptoms, there was no significant difference in the rate of occurrence of neurological and autonomic symptoms between cases prescribed and not prescribed antipsychotics.

Psychiatric input is imperative for both acute and longer-term management of anti-NMDAR encephalitis. Primary symptomatic treatment should remain immunotherapy and surgery. Antipsychotic medications have particular value in managing agitation and aggression. Potential side effects from antipsychotic treatment are difficult to differentiate from progression of anti-NMDAR encephalitis but there was no evidence in this cohort of increased antipsychotic sensitivity. Treatment with psychotropic medication should be individualised and adjusted during the course of the illness.

Although maternal depressive symptoms are robustly associated with offspring early-life psychopathology symptoms, it is not clear which potential mechanisms are at play. We aimed to estimate the relative importance of genetic transmission and direct environmental exposure in these associations on three occasions in early childhood.

Biometric modeling of maternal sisters and their offspring from the Norwegian Mother and Child Cohort Study. The analyzed sample comprised 22 316 mothers and 35 589 offspring. Mothers reported their own depressive symptoms using the Symptom checklist, and offspring's concurrent symptoms of psychopathology using the Child Behavior Checklist at 1.5, 3, and 5 years postpartum.

Associations between maternal symptoms of depression and offspring emotional problems were predominantly explained by passive genetic transmission at 1.5 and 3 years postpartum. At age 5, associations were more due to direct environmental exposure. For offspring behavioral problems, there was no net increase in the importance of direct environmental exposure across occasions.

Associations between maternal depressive symptoms and offspring psychopathology symptoms remained after accounting for shared genes, consistent with a small, causal effect. For offspring emotional problems, this effect appeared to increase in importance over time. Our findings imply that treatment of maternal depressive symptoms could also benefit the offspring, and that genetic confounding should be considered in future studies of such mother–offspring associations.

Maternal inflammation in early pregnancy has been identified epidemiologically as a prenatal pathogenic factor for the offspring's later mental illness. Early newborn manifestations of the effects of maternal inflammation on human fetal brain development are largely unknown.

Maternal infection, depression, obesity, and other factors associated with inflammation were assessed at 16 weeks gestation, along with maternal C-reactive protein (CRP), cytokines, and serum choline. Cerebral inhibition was assessed by inhibitory P50 sensory gating at 1 month of age, and infant behavior was assessed by maternal ratings at 3 months of age.

Maternal CRP diminished the development of cerebral inhibition in newborn males but paradoxically increased inhibition in females. Similar sex-dependent effects were seen in mothers' assessment of their infant's self-regulatory behaviors at 3 months of age. Higher maternal choline levels partly mitigated the effect of CRP in male offspring.

The male fetal-placental unit appears to be more sensitive to maternal inflammation than females. Effects are particularly marked on cerebral inhibition. Deficits in cerebral inhibition 1 month after birth, similar to those observed in several mental illnesses, including schizophrenia, indicate fetal developmental pathways that may lead to later mental illness. Deficits in early infant behavior follow. Early intervention before birth, including prenatal vitamins, folate, and choline supplements, may help prevent fetal development of pathophysiological deficits that can have life-long consequences for mental health.

The neurodevelopmental and trauma theories are two widely cited models of psychosis. A third – the developmental risk factor model (DRFM) – recognises the combined role of neurodevelopmental risks and trauma. Our objective was to test these theories using preterm populations as a natural experiment, given the high prevalence of neurodevelopmental deficits and exposure to trauma.

Two population-based preterm birth cohorts, the Bavarian Longitudinal Study (BLS; N = 399) and EPICure Study (N = 184), were included with term-born controls. Peer victimisation in childhood was assessed by parent and child report and psychotic experiences (PE) were assessed in early adulthood. Different models of psychosis were tested using regression and mediation analyses.

There was support for the trauma and DRFM in the BLS. Peer victimisation increased the risk of PE for preterm and term-born participants equally [odds ratio = 4.87, 95% confidence interval (CI) 1.96–12.08]. There was an indirect effect where preterm children were more likely to be victimised, which subsequently increased risk of PE [β = 1.12 (s.e. = 0.61), 95% CI 0.11–2.48]. The results were replicated in EPICure.

Exposure to trauma which is experienced more often by neurodevelopmental risk children rather than neurodevelopmental risk per se increases the risk of PE. The findings are consistent with the trauma model and DRFM. Interventions focused on reducing trauma may reduce the development of PE.

An increase in reported psychological distress, particularly among adolescent girls, is observed across a range of countries. Whether a similar trend exists among students in higher education remains unknown. The aim of the current study was to describe trends in self-reported psychological distress among Norwegian college and university students from 2010 to 2018.

We employed data from the Students' Health and Wellbeing Study (SHoT), a nationwide survey for higher education in Norway including full-time students aged 18–34. Numbers of participants (participation rates) were n = 6065 (23%) in 2010, n = 13 663 (29%) in 2014 and n = 49 321 (31%) in 2018. Psychological distress was measured using the Hopkins Symptom Checklist-25 (HSCL-25).

Overall, a statistically significant increase in self-reported psychological distress was observed over time across gender and age-groups. HSCL-25 scores were markedly higher for women than for men at all time-points. Effect-size of the mean change was also stronger for women (time-by-gender interaction: χ2 = 70.02, df = 2, p < 0.001): in women, mean HSCL-25 score increased from 1.62 in 2010 to 1.82 in 2018, yielding a mean change effect-size of 0.40. The corresponding change in men was from 1.42 in 2010 to 1.53 in 2018, giving an effect-size of 0.26.

Both the level and increase in self-reported psychological distress among Norwegian students in higher education are potentially worrying. Several mechanisms may contribute to the observed trend, including changes in response style and actual increase in distress. The relative low response rates in SHoT warrant caution when interpreting and generalising the findings.

Cannabis use and cannabis use disorder (CUD) is increased in patients with schizophrenia. It is important to establish if this is explained by non-causal factors, such as shared genetic vulnerability. We aimed to investigate whether the polygenic risk scores (PRS) for schizophrenia and other psychiatric disorders would predict CUD in controls, patients with schizophrenia, and patients with other psychiatric disorders.

We linked nationwide Danish registers and genetic information obtained from dried neonatal bloodspots in an observational analysis. We included people with schizophrenia, other psychiatric disorders, and controls. The exposures of interest were the PRS for schizophrenia, attention-deficit hyperactivity disorder (ADHD) autism spectrum disorder, and anorexia nervosa. The main outcome of interest was the diagnosis of CUD.

The study included 88 637 individuals. PRS for schizophrenia did not predict CUD in controls [hazard ratio (HR) = 1.16, 95% CI 0.95–1.43 per standard-deviation increase in PRS, or HR = 1.47, 95% CI 0.72–3.00 comparing highest v. remaining decile], but PRS for ADHD did (HR = 1.27, 95% CI 1.08–1.50 per standard-deviation increase, or HR = 2.02, 95% CI 1.27–3.22 for the highest decile of PRS). Among cases with schizophrenia, the PRS for schizophrenia was associated with CUD. While CUD was a strong predictor of schizophrenia (HR = 4.91, 95% CI 4.36–5.53), the inclusion of various PRS did not appreciably alter this association.

The PRS for schizophrenia was not associated with CUD in controls or patients with other psychiatric disorders than schizophrenia. This speaks against the hypothesis that shared genetic vulnerability would explain the association between cannabis and schizophrenia.

Functional neurological disorder (FND) is a condition at the intersection of neurology and psychiatry. Individuals with FND exhibit corticolimbic abnormalities, yet little is known about the role of white matter tracts in the pathophysiology of FND. This study characterized between-group differences in microstructural integrity, and correlated fiber bundle integrity with symptom severity, physical disability, and illness duration.

A diffusion tensor imaging (DTI) study was performed in 32 patients with mixed FND compared to 36 healthy controls. Diffusion-weighted magnetic resonance images were collected along with patient-reported symptom severity, physical disability (Short Form Health Survey-36), and illness duration data. Weighted-degree and link-level graph theory and probabilistic tractography analyses characterized fractional anisotropy (FA) values across cortico-subcortical connections. Results were corrected for multiple comparisons.

Compared to controls, FND patients showed reduced FA in the stria terminalis/fornix, medial forebrain bundle, extreme capsule, uncinate fasciculus, cingulum bundle, corpus callosum, and striatal-postcentral gyrus projections. Except for the stria terminalis/fornix, these differences remained significant adjusting for depression and anxiety. In within-group analyses, physical disability inversely correlated with stria terminalis/fornix and medial forebrain bundle FA values; illness duration negatively correlated with stria terminalis/fornix white matter integrity. A FND symptom severity composite score did not correlate with FA in patients.

In this first DTI study of mixed FND, microstructural differences were observed in limbic and associative tracts implicated in salience, defensive behaviors, and emotion regulation. These findings advance our understanding of neurocircuit pathways in the pathophysiology of FND.

Disturbed sleep and activity are prominent features of bipolar disorder type I (BP-I). However, the relationship of sleep and activity characteristics to brain structure and behavior in euthymic BP-I patients and their non-BP-I relatives is unknown. Additionally, underlying genetic relationships between these traits have not been investigated.

Relationships between sleep and activity phenotypes, assessed using actigraphy, with structural neuroimaging (brain) and cognitive and temperament (behavior) phenotypes were investigated in 558 euthymic individuals from multi-generational pedigrees including at least one member with BP-I. Genetic correlations between actigraphy-brain and actigraphy-behavior associations were assessed, and bivariate linkage analysis was conducted for trait pairs with evidence of shared genetic influences.

More physical activity and longer awake time were significantly associated with increased brain volumes and cortical thickness, better performance on neurocognitive measures of long-term memory and executive function, and less extreme scores on measures of temperament (impulsivity, cyclothymia). These associations did not differ between BP-I patients and their non-BP-I relatives. For nine activity-brain or activity-behavior pairs there was evidence for shared genetic influence (genetic correlations); of these pairs, a suggestive bivariate quantitative trait locus on chromosome 7 for wake duration and verbal working memory was identified.

Our findings indicate that increased physical activity and more adequate sleep are associated with increased brain size, better cognitive function and more stable temperament in BP-I patients and their non-BP-I relatives. Additionally, we found evidence for pleiotropy of several actigraphy-behavior and actigraphy-brain phenotypes, suggesting a shared genetic basis for these traits.

Change in the experience of oneself may lay the groundwork for the development of additional hallucinations and delusions in individuals with schizophrenia. However, to date, the course and symptom and functioning correlates of passivity symptoms (cf. thought insertion, thought withdrawal) have not been measured consistently over long periods of time. Information on the course and correlates of passivity symptoms is essential for developing models of their contribution to schizophrenic illness.

Eighty-two individuals diagnosed with schizophrenia or schizoaffective disorder were recruited at an index hospitalization and reassessed at three or more follow-ups over the following 18 years.

The results indicate that a small group of participants report passivity symptoms at all follow-ups, many reported passivity symptoms at some follow-ups, and the majority of individuals never reported passivity symptoms. The prevalence of passivity symptoms was similar to that for delusions of reference and persecutory delusions. Notably, when individuals did experience passivity symptoms, they also had a greater number of additional psychotic symptoms than individuals without passivity symptoms. Further, the presence of passivity symptoms was associated with work impairment at some assessments.

Passivity symptoms present episodically, at a similar rate as delusions of reference and persecutory delusions, and when present, they are associated with having a higher number of additional psychotic symptoms, as well as having some impact on work functioning. These results suggest that passivity symptoms may increase vulnerability to additional psychotic symptoms and greater work impairment.

Transcutaneous vagus nerve stimulation (tVNS) is a promising therapeutic option for major depressive disorder (MDD) in adults. Alternative third-line treatments for MDD in adolescents are scarce. Here we aimed to assess the effects of acute tVNS on emotion recognition in adolescents with MDD.

Adolescents (14–17 years) with MDD (n = 33) and non-depressed controls (n = 30) received tVNS or sham-stimulation in a cross-sectional, case–control, within-subject cross-randomized controlled trial, while performing different tasks assessing emotion recognition. Correct responses, response times, and errors of omission and commission on three different computerized emotion recognition tasks were assessed as main outcomes. Simultaneous recordings of electrocardiography and electro dermal activity, as well as sampling of saliva for the determination of α-amylase, were used to quantify the effects on autonomic nervous system function.

tVNS had no effect on the recognition of gradually or static expressed emotions but altered response inhibition on the emotional Go/NoGo-task. Specifically, tVNS increased the likelihood of omitting a response toward sad target-stimuli in adolescents with MDD, while decreasing errors (independent of the target emotion) in controls. Effects of acute tVNS on autonomic nervous system function were found in non-depressed controls only.

Acute tVNS alters the recognition of briefly presented facial expressions of negative valence in adolescents with MDD while generally increasing emotion recognition in controls. tVNS seems to specifically alter early visual processing of stimuli of negative emotional valence in MDD. These findings suggest a potential therapeutic benefit of tVNS in adolescent MDD that requires further evaluation within clinical trials.