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.

Cannabis use has been associated with psychosis through exposure to delta-9-tetrahydrocannabinol (Δ9-THC), its key psychoactive ingredient. Although preclinical and human evidence suggests that Δ9-THC acutely modulates glial function and hypothalamic-pituitary-adrenal (HPA) axis activity, whether differential sensitivity to the acute psychotomimetic effects of Δ9-THC is associated with differential effects of Δ9-THC on glial function and HPA-axis response has never been tested.

A double-blind, randomized, placebo-controlled, crossover study investigated whether sensitivity to the psychotomimetic effects of Δ9-THC moderates the acute effects of a single Δ9-THC dose (1.19 mg/2 ml) on myo-inositol levels, a surrogate marker of glia, in the Anterior Cingulate Cortex (ACC), and circadian cortisol levels, the key neuroendocrine marker of the HPA-axis, in a set of 16 healthy participants (seven males) with modest previous cannabis exposure.

The Δ9-THC-induced change in ACC myo-inositol levels differed significantly between those sensitive to (Δ9-THC minus placebo; M = −0.251, s.d. = 1.242) and those not sensitive (M = 1.615, s.d. = 1.753) to the psychotomimetic effects of the drug (t(14) = 2.459, p = 0.028). Further, the Δ9-THC-induced change in cortisol levels over the study period (baseline minus 2.5 h post-drug injection) differed significantly between those sensitive to (Δ9-THC minus placebo; M = −275.4, s.d. = 207.519) and those not sensitive (M = 74.2, s.d. = 209.281) to the psychotomimetic effects of the drug (t(13) = 3.068, p = 0.009). Specifically, Δ9-THC exposure lowered ACC myo-inositol levels and disrupted the physiological diurnal cortisol decrease only in those subjects developing transient psychosis-like symptoms.

The interindividual differences in transient psychosis-like effects of Δ9-THC are the result of its differential impact on glial function and stress response.

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.

Previous studies support Beck's cognitive model of vulnerability to depression. However, the relationship between his cognitive triad and other clinical features and risk factors among those with major depression (MD) has rarely been systematically studied.

The three key cognitive symptoms of worthlessness, hopelessness and helplessness were assessed during their lifetime worst episode in 1970 Han Chinese women with recurrent MD. Diagnostic and other risk factor information was assessed at personal interview. Odds ratios (ORs) were calculated by logistic regression.

Compared to patients who did not endorse the cognitive trio, those who did had a greater number of DSM-IV A criteria, more individual depressive symptoms, an earlier age at onset, a greater number of episodes, and were more likely to meet diagnostic criteria for melancholia, postnatal depression, dysthymia and anxiety disorders. Hopelessness was highly related to all the suicidal symptomatology, with ORs ranging from 5.92 to 6.51. Neuroticism, stressful life events (SLEs) and a protective parental rearing style were associated with these cognitive symptoms.

During the worst episode of MD in Han Chinese women, the endorsement of the cognitive trio was associated with a worse course of depression and an increased risk of suicide. Individuals with high levels of neuroticism, many SLEs and high parental protectiveness were at increased risk for these cognitive depressive symptoms. As in Western populations, symptoms of the cognitive trio appear to play a central role in the psychopathology of MD in Chinese women.

Cognitive processing therapy (CPT) and prolonged exposure (PE) delivered in an individual setting are efficacious and effective treatments for veterans with posttraumatic stress disorder (PTSD). Group CPT has been shown to be less efficacious than individual CPT, however, evidence regarding real-world effectiveness is limited.

We conducted a retrospective, observational, comparative effectiveness study including veterans that received at least eight sessions of group CPT, individual CPT, or individual PE, and were discharged from PTSD residential treatment at the Department of Veterans Affairs between 1 October 2015, and 30 September 2020. PTSD symptom severity was assessed with the PTSD Checklist for DSM-5 (PCL-5) and treatments delivered in a group (CPT) or individual (CPT or PE) setting were compared at discharge and 4-month post-discharge follow-up.

Of 6735 veterans, 3888 [653 women (17%), median (IQR) age 45 (35–55) years] received individual and 2847 [206 women (7.2%), median (IQR) age 42 (34–54)] received group therapy. At discharge, improvement in PTSD severity was statistically greater among those treated individually (mean difference on the PCL-5, 2.55 (95% CI 1.61–3.49); p = <0.001]. However, the difference was smaller than the minimal clinically important difference of 7.9 points. The groups did not differ significantly at 4-month follow-up [mean difference on the PCL-5, 0.37 (95% CI −0.86 to 1.60); p = 0.551].

Group CPT was associated with a slightly smaller reduction of PTSD symptom severity than individual CPT or PE in veterans at the end of residential treatment. There were no differences at 4-month follow-up.

Individuals with schizophrenia spectrum and related psychotic disorders (SSD) experience significant impairments in social cognition that impede functioning. Social cognition is a multidimensional construct consisting of four domains: 1. theory of mind, 2. emotion processing, 3. attributional style and 4. social perception. Metacognitive training (MCT) is an intervention designed to target cognitive biases in psychosis containing two modules addressing social cognition.

A systematic review and meta-analysis was conducted to investigate the effects of MCT on social cognition and two of its domains: theory of mind and emotion processing. Ten electronic databases were scoured from 2007 to 1 February 2022 for MCT studies reporting social cognition outcomes for people with SSD (1050 identified, 282 assessed). Effect sizes were calculated using Cohen's d in R.

Nine studies were included in the meta-analysis (nMCT = 212, ncontrol = 194). MCT had a small but positive effect on global social cognition (d = 0.28 [95% CI 0.07–0.49]) and theory of mind (d = 0.27 [95% CI 0.01–0.52]). MCT showed no evidence of an effect on emotion processing (d = 0.03 [95% CI –0.26 to 0.32]).

MCT has a small but significant effect on social cognition for people with SSD. Our results add to other recent meta-analyses showing significant effects of MCT on clinically relevant outcomes such as positive symptoms, cognitive biases and cognitive insight. We recommend that future studies on MCT report outcomes on all four domains of social cognition.

PROSPERO (in the process of registration) available at https://www.crd.york.ac.uk/prospero/#recordDetails

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.

Dietary interventions did not prevent depression onset nor reduced depressive symptoms in a large multi-center randomized controlled depression prevention study (MooDFOOD) involving overweight adults with subsyndromal depressive symptoms. We conducted follow-up analyses to investigate whether dietary interventions differ in their effects on depressive symptom profiles (mood/cognition; somatic; atypical, energy-related).

Baseline, 3-, 6-, and 12-month follow-up data from MooDFOOD were used (n = 933). Participants received (1) placebo supplements, (2) food-related behavioral activation (F-BA) therapy with placebo supplements, (3) multi-nutrient supplements (omega-3 fatty acids and a multi-vitamin), or (4) F-BA therapy with multi-nutrient supplements. Depressive symptom profiles were based on the Inventory of Depressive Symptomatology.

F-BA therapy was significantly associated with decreased severity of the somatic (B = −0.03, p = 0.014, d = −0.10) and energy-related (B = −0.08, p = 0.001, d = −0.13), but not with the mood/cognition symptom profile, whereas multi-nutrient supplementation was significantly associated with increased severity of the mood/cognition (B = 0.05, p = 0.022, d = 0.09) and the energy-related (B = 0.07, p = 0.002, d = 0.12) but not with the somatic symptom profile.

Differentiating depressive symptom profiles indicated that food-related behavioral interventions are most beneficial to alleviate somatic symptoms and symptoms of the atypical, energy-related profile linked to an immuno-metabolic form of depression, although effect sizes were small. Multi-nutrient supplements are not indicated to reduce depressive symptom profiles. These findings show that attention to clinical heterogeneity in depression is of importance when studying dietary interventions.

– Comorbidity between psychiatric disorders is extensive but, from a genetic perspective, still poorly understood. Modern molecular genetic approaches to this problem are limited by a reliance on case–control designs.

– In 5 828 760 individuals born in Sweden from 1932–1995 with a mean (s.d.) age at follow-up of 54.4 (18.1), we examined family genetic risk score (FGRS) profiles including internalizing, psychotic, substance use and developmental disorders in 10 pairs of psychiatric and substance use disorders diagnosed from population registries. We examined these profiles in three groups of patients: disorder A only, disorder B only and comorbid cases with both disorders.

– The most common pattern of findings, seen in five pairings, was simple and quantitative. Comorbid cases had higher FGRS than both non-comorbid cases for all (or nearly all) disorders. However, the pattern was more complex in the remaining five pairings and included qualitative changes where the comorbid cases showed no increases in FGRS for certain disorders and in a few cases significant decreases. Several comparisons showed an asymmetric pattern of findings with increases, in comorbidity compared to single disorder cases, of the FGRS for only one of the two disorders.

– The examination of FGRS profiles in general population samples where all disorders are assessed in all subjects provides a fruitful line of inquiry to understand the origins of psychiatric comorbidity. Further work will be needed, with an expansion of analytic approaches, to gain deeper insights into the complex mechanisms likely involved.

Binge-eating disorder (BED) co-occurs with neurobehavioral alterations in the processing of disorder-relevant content such as visual food stimuli. Whether neurofeedback (NF) directly targeting them is suited for treatment remains unclear. This study sought to determine feasibility and estimate effects of individualized, functional near-infrared spectroscopy-based real-time NF (rtfNIRS-NF) and high-beta electroencephalography-based NF (EEG-NF), assuming superiority over waitlist (WL).

Single-center, assessor-blinded feasibility study with randomization to rtfNIRS-NF, EEG-NF, or WL and assessments at baseline (t0), postassessment (t1), and 6-month follow-up (t2). NF comprised 12 60-min food-specific rtfNIRS-NF or EEG-NF sessions over 8 weeks. Primary outcome was the binge-eating frequency at t1 assessed interview-based. Secondary outcomes included feasibility, eating disorder symptoms, mental and physical health, weight management-related behavior, executive functions, and brain activity at t1 and t2.

In 72 patients (intent-to-treat), the results showed feasibility of NF regarding recruitment, attrition, adherence, compliance, acceptance, and assessment completion. Binge eating improved at t1 by −8.0 episodes, without superiority of NF v. WL (−0.8 episodes, 95% CI −2.4 to 4.0), but with improved estimates in NF at t2 relative to t1. NF was better than WL for food craving, anxiety symptoms, and body mass index, but overall effects were mostly small. Brain activity changes were near zero.

The results show feasibility of food-specific rtfNIRS-NF and EEG-NF in BED, and no posttreatment differences v. WL, but possible continued improvement of binge eating. Confirmatory and mechanistic evidence is warranted in a double-blind randomized design with long-term follow-up, considering dose–response relationships and modes of delivery.

To advance knowledge regarding the etiology of eating disorders, we characterized the sequencing of eating disorder symptom emergence for adolescent girls who subsequently developed anorexia nervosa (AN), bulimia nervosa (BN), binge eating disorder (BED), and purging disorder (PD) for community-recruited adolescents and tested whether prodromal symptoms increased risk for future onset of each eating disorder.

Data collected from adolescent girls (N = 496; M age = 13.02, s.d. = 0.73) who completed a diagnostic interview annually over an 8-year period were used to address these aims.

For all four eating disorders, compensatory weight-control behaviors were the first behavioral symptom to emerge and weight/shape overvaluation was the first cognitive symptom to emerge. Moreover, lower-than-expected BMI predicted future AN onset, binge eating and all cognitive symptoms predicted future BN onset, weight/shape overvaluation predicted future BED onset, and compensatory behavior and all cognitive symptoms predicted future PD onset. These predictive effects were small-to-large in magnitude. Collectively, prodromal symptoms predicted an eating disorder onset with 83–87% accuracy.

Results suggest that compensatory weight-control behaviors and weight/shape overvaluation typically emerge before other prodromal symptoms in all eating disorders during adolescence. Moreover, different prodromal symptoms seem to predict future onset of different eating disorders. Screening adolescent girls for these prodromal symptoms and implementing indicated prevention programs designed to reduce these symptoms may prove effective in preventing future onset of eating disorders.

Successful interventions have been developed for smoking cessation although the success of smoking relapse prevention protocols has been limited. Cognitive behavioural therapy (CBT) in particular has been hampered by a high relapse rate. Because relapse can be due to conditions associated with tobacco consumption (such as drinking in bars with friends), virtual reality cue exposure therapy (VRCE) can be a potential tool to generate 3D interactive environments that simulate risk situations for relapse prevention procedures.

To assess the effectiveness of VRCE with CBT, a comparative trial involving 100 smoking abstinent participants was designed with all required virtual environments (VE) created with an inexpensive graphic engine/game level editor.

Outcome measures confirmed the immersive and craving eliciting effect of these VEs. Results demonstrated that more participants in the VRCE group did not experience smoking relapse and that VRCE is at least as efficacious as traditional CBT in terms of craving reduction and decrease in nicotine dependence. Dropout and relapse rate in the VRCE group was noticeably lower than the CBT group. Aside from mood scores, no significant differences were found regarding the other scales.

The present clinical trial provides evidence that VRCE was effective in preventing smoking relapse. Improvement in technology and methodology for future research and applications is delineated.

Anhedonia – a diminished interest or pleasure in activities – is a core self-reported symptom of depression which is poorly understood and often resistant to conventional antidepressants. This symptom may occur due to dysfunction in one or more sub-components of reward processing: motivation, consummatory experience and/or learning. However, the precise impairments remain elusive. Dissociating these components (ideally, using cross-species measures) and relating them to the subjective experience of anhedonia is critical as it may benefit fundamental biology research and novel drug development.

Using a battery of behavioural tasks based on rodent assays, we examined reward motivation (Joystick-Operated Runway Task, JORT; and Effort-Expenditure for Rewards Task, EEfRT) and reward sensitivity (Sweet Taste Test) in a non-clinical population who scored high (N = 32) or low (N = 34) on an anhedonia questionnaire (Snaith–Hamilton Pleasure Scale).

Compared to the low anhedonia group, the high anhedonia group displayed marginal impairments in effort-based decision-making (EEfRT) and reduced reward sensitivity (Sweet Taste Test). However, we found no evidence of a difference between groups in physical effort exerted for reward (JORT). Interestingly, whilst the EEfRT and Sweet Taste Test correlated with anhedonia measures, they did not correlate with each other. This poses the question of whether there are subgroups within anhedonia; however, further work is required to directly test this hypothesis.

Our findings suggest that anhedonia is a heterogeneous symptom associated with impairments in reward sensitivity and effort-based decision-making.

Consistent evidence supports the involvement of genetic and environmental factors, and their interactions, in the etiology of psychosis. First-episode psychosis (FEP) comprises a group of disorders that show great clinical and long-term outcome heterogeneity, and the extent to which genetic, familial and environmental factors account for predicting the long-term outcome in FEP patients remains scarcely known.

The SEGPEPs is an inception cohort study of 243 first-admission patients with FEP who were followed-up for a mean of 20.9 years. FEP patients were thoroughly evaluated by standardized instruments, with 164 patients providing DNA. Aggregate scores estimated in large populations for polygenic risk score (PRS-Sz), exposome risk score (ERS-Sz) and familial load score for schizophrenia (FLS-Sz) were ascertained. Long-term functioning was assessed by means of the Social and Occupational Functioning Assessment Scale (SOFAS). The relative excess risk due to interaction (RERI) was used as a standard method to estimate the effect of interaction of risk factors.

Our results showed that a high FLS-Sz gave greater explanatory capacity for long-term outcome, followed by the ERS-Sz and then the PRS-Sz. The PRS-Sz did not discriminate significantly between recovered and non-recovered FEP patients in the long term. No significant interaction between the PRS-Sz, ERS-Sz or FLS-Sz regarding the long-term functioning of FEP patients was found.

Our results support an additive model of familial antecedents of schizophrenia, environmental risk factors and polygenic risk factors as contributors to a poor long-term functional outcome for FEP patients.

Individuals with autism spectrum disorder (ASD) are challenged not only by the defining features of social-communication deficits and restricted repetitive behaviors, but also by a myriad of psychopathology varying in severity. Different cognitive deficits underpin these psychopathologies, which could be subjected to intervention to alter the course of the disorder. Understanding domain-specific mediating effects of cognition is essential for developing targeted intervention strategies. However, the high degree of inter-correlation among different cognitive functions hinders elucidation of individual effects.

In the Philadelphia Neurodevelopmental Cohort, 218 individuals with ASD were matched with 872 non-ASD controls on sex, age, race, and socioeconomic status. Participants of this cohort were deeply and broadly phenotyped on neurocognitive abilities and dimensional psychopathology. Using structural equation modeling, inter-correlation among cognitive domains were adjusted before mediation analysis on outcomes of multi-domain psychopathology and functional level.

While social cognition, complex cognition, and memory each had a unique pattern of mediating effect on psychopathology domains in ASD, none had significant effects on the functional level. In contrast, executive function was the only cognitive domain that exerted a generalized negative impact on every psychopathology domain (p factor, anxious-misery, psychosis, fear, and externalizing), as well as functional level.

Executive function has a unique association with the severity of comorbid psychopathology in ASD, and could be a target of interventions. As executive dysfunction occurs variably in ASD, our result also supports the clinical utility of assessing executive function for prognostic purposes.

Psychotic experiences and negative symptoms (PENS) are common in non-clinical populations. PENS are associated with adverse outcomes, particularly when they persist. Little is known about the trajectories of PENS dimensions in young people, nor about the precursory factors associated with these trajectories.

We conducted growth mixture modelling of paranoia, hallucinations, and negative symptoms across ages 16, 17, and 22 in a community sample (N = 12 049–12 652). We then described the emergent trajectory classes through their associations with genome-wide polygenic scores (GPS) for psychiatric and educational phenotypes, and earlier childhood characteristics.

Three trajectory classes emerged for paranoia, two for hallucinations, and two for negative symptoms. Across PENS, GPS for clinical help-seeking, major depressive disorder, and attention deficit hyperactivity disorder were associated with increased odds of being in the most elevated trajectory class (OR 1.07–1.23). Lower education GPS was associated with the most elevated trajectory class for hallucinations and negative symptoms (OR 0.77–0.91). Conversely for paranoia, higher education GPS was associated with the most elevated trajectory class (OR 1.25). Trajectory class associations were not significant for schizophrenia, obsessive-compulsive disorder, bipolar disorder, or anorexia GPS. Emotional/behaviour problems and life events in childhood were associated with increased odds of being in the most elevated trajectory class across PENS.

Our results suggest latent heterogeneity in the development of paranoia, hallucinations, and negative symptoms in young people that is associated with specific polygenic scores and childhood characteristics.