Little is known about the effects of physical exercise on sleep-dependent consolidation of procedural memory in individuals with schizophrenia. We conducted a randomized controlled trial (RCT) to assess the effectiveness of physical exercise in improving this cognitive function in schizophrenia.

A three-arm parallel open-labeled RCT took place in a university hospital. Participants were randomized and allocated into either the high-intensity-interval-training group (HIIT), aerobic-endurance exercise group (AE), or psychoeducation group for 12 weeks, with three sessions per week. Seventy-nine individuals with schizophrenia spectrum disorder were contacted and screened for their eligibility. A total of 51 were successfully recruited in the study. The primary outcome was sleep-dependent procedural memory consolidation performance as measured by the finger-tapping motor sequence task (MST). Assessments were conducted during baseline and follow-up on week 12.

The MST performance scored significantly higher in the HIIT (n = 17) compared to the psychoeducation group (n = 18) after the week 12 intervention (p < 0.001). The performance differences between the AE (n = 16) and the psychoeducation (p = 0.057), and between the AE and the HIIT (p = 0.999) were not significant. Yet, both HIIT (p < 0.0001) and AE (p < 0.05) showed significant within-group post-intervention improvement.

Our results show that HIIT and AE were effective at reverting the defective sleep-dependent procedural memory consolidation in individuals with schizophrenia. Moreover, HIIT had a more distinctive effect compared to the control group. These findings suggest that HIIT may be a more effective treatment to improve sleep-dependent memory functions in individuals with schizophrenia than AE alone.

Previous studies have reported brain structure abnormalities in conduct disorder (CD), but it is unclear whether these neuroanatomical alterations mediate the effects of familial (genetic and environmental) risk for CD. We investigated brain structure in adolescents with CD and their unaffected relatives (URs) to identify neuroanatomical markers of familial risk for CD.

Forty-one adolescents with CD, 24 URs of CD probands, and 38 healthy controls (aged 12–18), underwent structural magnetic resonance imaging. We performed surface-based morphometry analyses, testing for group differences in cortical volume, thickness, surface area, and folding. We also assessed the volume of key subcortical structures.

The CD and UR groups both displayed structural alterations (lower surface area and folding) in left inferior parietal cortex compared with controls. In contrast, CD participants showed lower insula and pars opercularis volume than controls, and lower surface area and folding in these regions than controls and URs. The URs showed greater folding in rostral anterior cingulate and inferior temporal cortex than controls and greater medial orbitofrontal folding than CD participants. The surface area and volume differences were not significant when controlling for attention-deficit/hyperactivity disorder comorbidity. There were no group differences in subcortical volumes.

These findings suggest that alterations in inferior parietal cortical structure partly mediate the effects of familial risk for CD. These structural changes merit investigation as candidate endophenotypes for CD. Neuroanatomical changes in medial orbitofrontal and anterior cingulate cortex differentiated between URs and the other groups, potentially reflecting neural mechanisms of resilience to CD.

Alcohol use disorder (AUD) is clinically heterogeneous. We examine its potential genetic heterogeneity as a function of sex, age, clinical features and mode of ascertainment.

In the Swedish population born 1932–1995 (n = 5 829 952), we examined the genetic risk profiles for AUD, major depression (MD), anxiety disorders, bipolar disorder, drug use disorder (DUD), attention deficit-hyperactivity disorder (ADHD) and criminal behavior (CB) in 361 124 cases of AUD subdivided by sex, age at onset (AAO), recurrence, mode of ascertainment and medical complications. Family genetic risk scores (FGRS), calculated from 1st to 5th-degree relatives controlling of cohabitation, assesses genetic risk from phenotypes in the family, not from DNA variants.

FGRS profiles differed modestly across sex with all scores higher in females. Differences were more pronounced for AAO and recurrence with the FGRS for AUD, DUD, ADHD and CB substantially higher in cases with early AAO or high recurrence rates. Genetic profiles differed considerably by mode of ascertainment, with higher FGRS for AUD and most other disorders in patients seen in hospital v. primary care settings. Cases of AUD with medical complications had higher FGRS for AUD. AUD cases comorbid with MD and DUD had higher FGRS risk for AUD, but this genetic may be less specific given increases in FGRS for multiple other disorders.

From a genetic perspective, AUD differs substantially as a function of AAO, recurrence, mode of ascertainment and patterns of comorbidity, suggesting caution in cross-sample comparisons of AUD cohorts that differ in these features.

Anxiety disorders are the most prevalent mental disorder in children and young people. Developing effective therapy for these children is critical to reduce mental disorders across the lifespan. The study aimed to evaluate the efficacy of combining cognitive behavioural therapy (CBT) and sertraline (SERT) in the treatment of anxiety in youth, using a double-blind randomised control trial design.

Ninety-nine youth (ages 7–15 years) with an anxiety disorder were randomly allocated to either individual (CBT) and SERT or individual CBT and pill placebo and assessed again immediately and 6 months after treatment.

There were no significant differences between conditions in remission of primary anxiety disorder or all anxiety disorders. Furthermore, there were no significant differences in rates of change in diagnostic severity, parent-reported anxiety symptoms, child-reported anxiety symptoms or life interference due to anxiety.

The efficacy of CBT for children and adolescents with anxiety disorders is not significantly enhanced by combination with a short-term course of anti-depressants over and above the combined effects of pill placebo.

Timing of developmental milestones, such as age at first walking, is associated with later diagnoses of neurodevelopmental disorders. However, its relationship to genetic risk for neurodevelopmental disorders in the general population is unknown. Here, we investigate associations between attainment of early-life language and motor development milestones and genetic liability to autism, attention deficit hyperactivity disorder (ADHD), and schizophrenia.

We use data from a genotyped sub-set (N = 25699) of children in the Norwegian Mother, Father and Child Cohort Study (MoBa). We calculate polygenic scores (PGS) for autism, ADHD, and schizophrenia and predict maternal reports of children's age at first walking, first words, and first sentences, motor delays (18 months), and language delays and a generalised measure of concerns about development (3 years). We use linear and probit regression models in a multi-group framework to test for sex differences.

We found that ADHD PGS were associated with earlier walking age (β = −0.033, padj < 0.001) in both males and females. Additionally, autism PGS were associated with later walking (β = 0.039, padj = 0.006) in females only. No robust associations were observed for schizophrenia PGS or between any neurodevelopmental PGS and measures of language developmental milestone attainment.

Genetic liabilities for neurodevelopmental disorders show some specific associations with the age at which children first walk unsupported. Associations are small but robust and, in the case of autism PGS, differentiated by sex. These findings suggest that early-life motor developmental milestone attainment is associated with genetic liability to ADHD and autism in the general population.

It has not yet been determined if the commonly reported cannabis–psychosis association is limited to individuals with pre-existing genetic risk for psychotic disorders.

We examined whether the relationship between polygenic risk score for schizophrenia (PRS-Sz) and psychotic-like experiences (PLEs), as measured by the Community Assessment of Psychic Experiences-42 (CAPE-42) questionnaire, is mediated or moderated by lifetime cannabis use at 16 years of age in 1740 of the individuals of the European IMAGEN cohort. Secondary analysis examined the relationships between lifetime cannabis use, PRS-Sz and the various sub-scales of the CAPE-42. Sensitivity analyses including covariates, including a PRS for cannabis use, were conducted and results were replicated using data from 1223 individuals in the Dutch Utrecht cannabis cohort.

PRS-Sz significantly predicted cannabis use (p = 0.027) and PLE (p = 0.004) in the IMAGEN cohort. In the full model, considering PRS-Sz and covariates, cannabis use was also significantly associated with PLE in IMAGEN (p = 0.007). Results remained consistent in the Utrecht cohort and through sensitivity analyses. Nevertheless, there was no evidence of a mediation or moderation effects.

These results suggest that cannabis use remains a risk factor for PLEs, over and above genetic vulnerability for schizophrenia. This research does not support the notion that the cannabis–psychosis link is limited to individuals who are genetically predisposed to psychosis and suggests a need for research focusing on cannabis-related processes in psychosis that cannot be explained by genetic vulnerability.

Gender has been proposed as a potentially important predictor of bereavement outcomes. The majority of research in the field has explored this issue by examining gender differences in global grief severity. Findings have been mixed. In this study, we explore potential gender differences in grief using network analysis. This approach examines how individual symptoms relate to and reinforce each other, and so offers potential to shed light on novel aspects of grief expression across genders.

Graphical lasso networks were constructed using self-report data from 839 spousally bereaved older participants (584 female, 255 male) collected at 2- and 11- months post-bereavement. Edge strength, node strength and global network strength were compared to identify similarities and differences between gender networks across time.

At both time points, the strongest connection for both genders was from yearning to pangs of grief. Yearning, pangs of grief, acceptance, bitterness and shock were prominent nodes at time 1. Numbness and meaninglessness emerged as prominent nodes at time 2. Males and females differed in the relative importance of shock at time 1, and the female network had greater overall strength than the male network at time 2.

This study identified many similarities and few differences in the relationships between prolonged grief symptoms for males and females. Findings suggest that future studies should examine alternate sources of variation in grief outcomes. Limitations are discussed.

This study investigates the extent to which the GHQ-12 exhibits configural, metric and scalar invariance across six ethnic groups in Britain and Northern Ireland, using the UK Household Longitudinal Study (N = 35 410).

A confirmatory factor analysis was carried out on a white British group in order to establish an adequate measurement model. Secondly, a multi-group confirmatory factor analysis was conducted in order to assess measurement invariance. A sensitivity analysis comparing summated and latent means across groups was carried out. Finally, revised estimates of scale reliability were derived using two different methods.

A one-factor model including correlated error terms on the negatively phrased items showed superior fit in all ethnic groups. Tests for equal factor loadings and intercepts also showed adequate fit demonstrating metric and scalar invariance. Latent and summated scale estimates of mean group differences were similar for all groups. Scale reliability using McDonald's ω is lower than when using the more conventional Cronbach's α. Reliability across groups is reasonably consistent.

We find that the GHQ-12 does not display obvious bias in regard to ethnic groups in the UK and that valid comparisons across these groups can be made for the purposes of population research. Caution is needed when using as a screening tool for individuals.

Psychosis, even in its early stages, ranks highly among the causes of disability worldwide, resulting in an increased focus on improved recovery of social and occupational functioning. This study aimed to provide an estimate of the effectiveness of psychosocial interventions for improving functioning in early psychosis. We also sought evidence of superiority between intervention approaches.

An electronic search was conducted using PubMed and PsycINFO to identify original articles reporting on trials of psychosocial interventions in early-stage psychosis, published up to December 2020 and is reported following PRISMA guidelines. Data were extracted on validated measures of functioning from included studies and pooled standardised mean difference (SMD) was estimated.

In total, 31 studies involving 2811 participants were included, focusing on: cognitive behavioural therapy for psychosis (CBTp), family-based therapy, supported employment, cognitive remediation training (CRT) and multi-component psychosocial interventions. Across interventions, improved function was observed (SMD = 0.239; 95% confidence interval 0.115–0.364, p < 0.001). Effect sizes varied by intervention type, stage of illness, length and duration of treatment and outcome measure used. In particular, interventions based on CRT significantly outperformed symptom-focused CBT interventions, while multi-component interventions were associated with largest gains.

Psychosocial interventions, particularly when provided as part of a multi-component intervention model and delivered in community-based settings are associated with significant improvements in social and occupational function. This review underscores the value of sensitively tracking and targeting psychosocial function as part of the standard provided by early intervention services.

Despite its efficacy in treating comorbid insomnia and depression, cognitive behavioral therapy for insomnia (CBT-I) is limited in its accessibility and, in many countries, cultural compatibility. Smartphone-based treatment is a low-cost, convenient alternative modality. This study evaluated a self-help smartphone-based CBT-I in alleviating major depression and insomnia.

A parallel-group randomized, waitlist-controlled trial was conducted with 320 adults with major depression and insomnia. Participants were randomized to receive either a 6-week CBT-I via a smartphone application, proACT-S, or waitlist condition. The primary outcomes included depression severity, insomnia severity, and sleep quality. The secondary outcomes included anxiety severity, subjective health, and acceptability of treatment. Assessments were administered at baseline, post-intervention (week 6) follow-up, and week 12 follow-up. The waitlist group received treatment after the week 6 follow-up.

Intention to treat analysis was conducted with multilevel modeling. In all but one model, the interaction between treatment condition and time at week 6 follow-up was significant. Compared with the waitlist group, the treatment group had lower levels of depression [Center for Epidemiologic Studies Depression Scale (CES-D): Cohen's d = 0.86, 95% CI (−10.11 to −5.37)], insomnia [Insomnia Severity Index (ISI): Cohen's d = 1.00, 95% CI (−5.93 to −3.53)], and anxiety [Hospital Anxiety and Depression Scale – Anxiety subscale (HADS-A): Cohen's d = 0.83, 95% CI (−3.75 to −1.96)]. They also had better sleep quality [Pittsburgh Sleep Quality Index (PSQI): Cohen's d = 0.91, 95% CI (−3.34 to −1.83)]. No differences across any measures were found at week 12, after the waitlist control group received the treatment.

proACT-S is an efficacious sleep-focused self-help treatment for major depression and insomnia.

ClinicalTrials.gov, NCT04228146. Retrospectively registered on 14 January 2020. https://clinicaltrials.gov/ct2/show/NCT04228146

The relationship between schizophrenia and violence is complex. The aim of this multicentre case–control study was to examine and compare the characteristics of a group of forensic psychiatric patients with a schizophrenia spectrum disorders and a history of significant interpersonal violence to a group of patients with the same diagnosis but no lifetime history of interpersonal violence.

Overall, 398 patients (221 forensic and 177 non-forensic patients) were recruited across five European Countries (Italy, Germany, Poland, Austria and the United Kingdom) and assessed using a multidimensional standardised process.

The most common primary diagnosis in both groups was schizophrenia (76.4%), but forensic patients more often met criteria for a comorbid personality disorder, almost always antisocial personality disorder (49.1 v. 0%). The forensic patients reported lower levels of disability and better social functioning. Forensic patients were more likely to have been exposed to severe violence in childhood. Education was a protective factor against future violence as well as higher levels of disability, lower social functioning and poorer performances in cognitive processing speed tasks, perhaps as proxy markers of the negative syndrome of schizophrenia. Forensic patients were typically already known to services and in treatment at the time of their index offence, but often poorly compliant.

This study highlights the need for general services to stratify patients under their care for established violence risk factors, to monitor patients for poor compliance and to intervene promptly in order to prevent severe violent incidents in the most clinically vulnerable.

A transdiagnostic and contextual framework of ‘clinical characterization’, combining clinical, psychopathological, sociodemographic, etiological, and other personal contextual data, may add clinical value over and above categorical algorithm-based diagnosis.

Prediction of need for care and health care outcomes was examined prospectively as a function of the contextual clinical characterization diagnostic framework in a prospective general population cohort (n = 6646 at baseline), interviewed four times between 2007 and 2018 (NEMESIS-2). Measures of need, service use, and use of medication were predicted as a function of any of 13 DSM-IV diagnoses, both separately and in combination with clinical characterization across multiple domains: social circumstances/demographics, symptom dimensions, physical health, clinical/etiological factors, staging, and polygenic risk scores (PRS). Effect sizes were expressed as population attributable fractions.

Any prediction of DSM-diagnosis in relation to need and outcome in separate models was entirely reducible to components of contextual clinical characterization in joint models, particularly the component of transdiagnostic symptom dimensions (a simple score of the number of anxiety, depression, mania, and psychosis symptoms) and staging (subthreshold, incidence, persistence), and to a lesser degree clinical factors (early adversity, family history, suicidality, slowness at interview, neuroticism, and extraversion), and sociodemographic factors. Clinical characterization components in combination predicted more than any component in isolation. PRS did not meaningfully contribute to any clinical characterization model.

A transdiagnostic framework of contextual clinical characterization is of more value to patients than a categorical system of algorithmic ordering of psychopathology.

Antisociality across adolescence and young adulthood puts individuals at high risk of developing a variety of problems. Prior research has linked antisociality to autonomic nervous system and endocrinological functioning. However, there is large heterogeneity in antisocial behaviors, and these neurobiological measures are rarely studied conjointly, limited to small specific studies with narrow age ranges, and yield mixed findings due to the type of behavior examined.

We harmonized data from 1489 participants (9–27 years, 67% male), from six heterogeneous samples. In the resulting dataset, we tested relations between distinct dimensions of antisociality and heart rate, pre-ejection period (PEP), respiratory sinus arrhythmia, respiration rate, skin conductance levels, testosterone, basal cortisol, and the cortisol awakening response (CAR), and test the role of age throughout adolescence and young adulthood.

Three dimensions of antisociality were uncovered: ‘callous-unemotional (CU)/manipulative traits’, ‘intentional aggression/conduct’, and ‘reactivity/impulsivity/irritability’. Shorter PEPs and higher testosterone were related to CU/manipulative traits, and a higher CAR is related to both CU/manipulative traits and intentional aggression/conduct. These effects were stable across age.

Across a heterogeneous sample and consistent across development, the CAR may be a valuable measure to link to CU/manipulative traits and intentional aggression, while sympathetic arousal and testosterone are additionally valuable to understand CU/manipulative traits. Together, these findings deepen our understanding of the fundamental mechanisms underlying different components of antisociality. Finally, we illustrate the potential of using current statistical techniques for combining multiple datasets to draw robust conclusions about biobehavioral associations.

Apathy, a disabling and poorly understood neuropsychiatric symptom, is characterised by impaired self-initiated behaviour. It has been hypothesised that the opportunity cost of time (OCT) may be a key computational variable linking self-initiated behaviour with motivational status. OCT represents the amount of reward which is foregone per second if no action is taken. Using a novel behavioural task and computational modelling, we investigated the relationship between OCT, self-initiation and apathy. We predicted that higher OCT would engender shorter action latencies, and that individuals with greater sensitivity to OCT would have higher behavioural apathy.

We modulated the OCT in a novel task called the ‘Fisherman Game’, Participants freely chose when to self-initiate actions to either collect rewards, or on occasion, to complete non-rewarding actions. We measured the relationship between action latencies, OCT and apathy for each participant across two independent non-clinical studies, one under laboratory conditions (n = 21) and one online (n = 90). ‘Average-reward’ reinforcement learning was used to model our data. We replicated our findings across both studies.

We show that the latency of self-initiation is driven by changes in the OCT. Furthermore, we demonstrate, for the first time, that participants with higher apathy showed greater sensitivity to changes in OCT in younger adults. Our model shows that apathetic individuals experienced greatest change in subjective OCT during our task as a consequence of being more sensitive to rewards.

Our results suggest that OCT is an important variable for determining free-operant action initiation and understanding apathy.

Psychosis expression in the general population may reflect a behavioral manifestation of the risk for psychotic disorder. It can be conceptualized as an interconnected system of psychotic and affective experiences; a so-called ‘symptom network’. Differences in demographics, as well as exposure to adversities and risk factors, may produce substantial heterogeneity in symptom networks, highlighting potential etiological divergence in psychosis risk.

To explore this idea in a data-driven way, we employed a novel recursive partitioning approach in the 2007 English National Survey of Psychiatric Morbidity (N = 7242). We sought to identify ‘network phenotypes’ by explaining heterogeneity in symptom networks through potential moderators, including age, sex, ethnicity, deprivation, childhood abuse, separation from parents, bullying, domestic violence, cannabis use, and alcohol.

Sex was the primary source of heterogeneity in symptom networks. Additional heterogeneity was explained by interpersonal trauma (childhood abuse and domestic violence) in women and domestic violence, cannabis use, ethnicity in men. Among women, especially those exposed to early interpersonal trauma, an affective loading within psychosis may have distinct relevance. Men, particularly those from minority ethnic groups, demonstrated a strong network connection between hallucinatory experiences and persecutory ideation.

Symptom networks of psychosis expression in the general population are highly heterogeneous. The structure of symptom networks seems to reflect distinct sex-related adversities, etiologies, and mechanisms of symptom-expression. Disentangling the complex interplay of sex, minority ethnic group status, and other risk factors may help optimize early intervention and prevention strategies in psychosis.

Conduct disorder (CD) has been associated with dysfunction in reinforcement-based decision-making. Two forms of affective traits that reflect the components of CD severity are callous-unemotional (CU; reduced guilt/empathy) traits and irritability. The form of the reinforcement-based decision-making dysfunction with respect to CD and CU traits remains debated and has not been examined with respect to irritability in cases with CD. The goals of the current study were to determine the extent of dysfunction in differential (reward v. punishment) responsiveness in CD, and CU traits and irritability in participants with CD.

The study involved 178 adolescents [typically developing (TD; N = 77) and cases with CD (N = 101)]. Participants were scanned with fMRI during a passive avoidance task that required participants to learn to respond to (i.e. approach) stimuli that engender reward and refrain from responding to (i.e. passively avoid) stimuli that engender punishment.

Adolescents with CD showed reduced differential reward-punishment responsiveness within the striatum relative to TD adolescents. CU traits, but not irritability, were associated with reduced differential reward-punishment responsiveness within the striatum, rostromedial, and lateral frontal cortices.

The results suggest CD is associated with reduced differential reward-punishment responsiveness and the extent of this dysfunction in participants with CD is associated with the severity of CU traits but not irritability.

Difficulties in the ability to adapt beliefs in the face of new information are associated with psychosis and its central symptom – paranoia. As cognitive processes and psychotic symptoms are both known to be sensitive to stress, the present study investigated the exact associations between stress, adapting of beliefs [reversal learning (RL), bias against disconfirmatory evidence (BADE), and jumping to conclusions (JTC)] and paranoia. We hypothesized that paranoia would increase under stress and that difficulties in adapting of beliefs would mediate or moderate the link between stress and paranoia. Furthermore, we hypothesized that the investigated effects would be strongest in the group of individuals diagnosed with a psychotic disorder.

We exposed 155 participants (38 diagnosed with a psychotic disorder, 40 individuals with attenuated psychotic symptoms, 39 clinical controls diagnosed with an obsessive-compulsive disorder, and 38 healthy controls) to a control condition and a stress condition, in which we assessed their levels of paranoia and their ability to adapt beliefs. We applied multilevel models to analyze the data.

Paranoia was higher in the stress condition than in the control condition, b = 1.142, s.e. = 0.338, t(150) = 3.381, p < 0.001. RL, BADE, and JTC did not differ between conditions and did not mediate or moderate the association between stress and paranoia (all ps > 0.05).

The results support the assumption that stress triggers paranoia. However, the link between stress and paranoia does not seem to be affected by the ability to adapt beliefs.