22q11.2 deletion syndrome (22q11.2DS) is associated with cognitive impairments and an increased risk of psychopathology. Most of the research has been conducted in children and adolescents, although the majority of affected individuals live well into adulthood. Hence, limited data are available on functional outcomes in adults.

To provide more insight in cognitive and adaptive abilities, and daily life functioning (marital status, living situation and work situation) in adults with 22q11.2DS.

This retrospective study included 250 Dutch-speaking adults (16–69 years) with 22q11.2DS from three sites in The Netherlands and Belgium. Data on full-scale IQ (FSIQ) scores (assessed with the Wechsler Adult Intelligence Scale), adaptive functioning (assessed with the Vineland Adaptive Behavior Scale II), and functional outcomes including marital status, living and work situation were systematically collected from clinical files. In addition, we examined predictors of adaptive functioning.

The majority of individuals in our adult sample demonstrated a low level of adaptive functioning (65%). In contrast to previous findings in children and adolescents, the majority functioned at an intellectual disability level (56%). Male sex, lower FSIQ and autism spectrum disorder were predictors of lower adaptive functioning (P = 0.016, P < 0.001 and P = 0.16, respectively).

These results suggest that low levels of cognitive and adaptive functioning are common in adults with 22q11.2DS. Future longitudinal and multicentre studies including older patients (>40 years) are needed to further investigate cognitive and adaptive trajectories and their interactions with physical and psychiatric comorbidities.

Highly accessible youth initiatives worldwide aim to prevent worsening of mental health problems, but research into outcomes over time is scarce.

This study aimed to evaluate outcomes and support use in 12- to 25-year-old visitors of the @ease mental health walk-in centres, a Dutch initiative offering free counselling by trained and supervised peers.

Data of 754 visitors, collected 2018–2022, included psychological distress (Clinical Outcomes in Routine Evaluation 10 (CORE-10)), social and occupational functioning (Social and Occupational Functioning Assessment Scale (SOFAS)), school absenteeism and support use, analysed with change indicators (first to last visit), and mixed models (first three visits).

Among return visitors, 50.5% were female, 79.4% were in tertiary education and 36.9% were born outside of The Netherlands (one-time visitors: 64.7%, 72.9% and 41.3%, respectively). Moreover, 29.9% of return visitors presented with suicidal ideations, 97.1% had clinical psychological distress levels, and 64.1% of the latter had no support in the previous 3 months (one-time visitors: 27.2%, 90.7% and 71.1%, respectively). From visit 1 to 3, psychological distress decreased (β = −3.79, 95% CI −5.41 to −2.18; P < 0.001) and social and occupational functioning improved (β = 3.93, 95% CI 0.51–7.36; P = 0.025). Over an average 3.9 visits, 39.6% improved reliably and 28.0% improved clinically significantly on the SOFAS, which was 28.4% and 8.8%, respectively, on the CORE-10, where 43.2% improved in clinical category. Counselling satisfaction was rated 4.5/5.

Reductions in psychological distress, improvements in functioning and high counselling satisfaction were found among @ease visitors, forming a basis for future research with a control group.

Worldwide, the division between Child and Adolescent Mental Health Services (CAMHS) and Adult Mental Health Services (AMHS) has frequently resulted in fragmented care with an unprepared, non-gradual transition. To improve continuity of care and other service transition experiences, service user input is essential. However, such previous qualitative studies are from a decade ago or focused on one mental disorder or country. The aim of the present study was to learn from service users’ transition experiences and suggested improvements.

Semi-structured interviews were held with young people aged 18–24 and/or parents/caregivers in the United Kingdom, Ireland, the Netherlands and Croatia. Inclusion was based on the experience of specialist mental health care before and after turning 18. Thematic analysis of transcribed and translated interview transcripts was performed using ATLAS.ti 9.

Main themes of service user experiences included abrupt changes in responsibilities, various barriers and a lack of preparation, communication and ongoing care. Young people expressed a great need for continuity of care. Their suggestions to improve transitional care included early and adequate preparation, joint working, improved communication from and between services, overlapping services, staying at CAMHS for longer and designated youth mental health teams.

Young people who experienced care before and after turning 18 suggested either altering the age limits of services or ensuring early preparation and communication regarding the transition and finding AHMS. This communication should include general changes when turning 18. Further considerations include increasing collaboration and overlap between CAMHS and AMHS.

Interactions between the endocannabinoid system (ECS) and neurotransmitter systems might mediate the risk of developing a schizophrenia spectrum disorder (SSD). Consequently, we investigated in patients with SSD and healthy controls (HC) the relations between (1) plasma concentrations of two prototypical endocannabinoids (N-arachidonoylethanolamine [anandamide] and 2-arachidonoylglycerol [2-AG]) and (2) striatal dopamine synthesis capacity (DSC), and glutamate and y-aminobutyric acid (GABA) levels in the anterior cingulate cortex (ACC). As anandamide and 2-AG might reduce the activity of these neurotransmitters, we hypothesized negative correlations between their plasma levels and the abovementioned neurotransmitters in both groups.

Blood samples were obtained from 18 patients and 16 HC to measure anandamide and 2-AG plasma concentrations. For all subjects, we acquired proton magnetic resonance spectroscopy scans to assess Glx (i.e. glutamate plus glutamine) and GABA + (i.e. GABA plus macromolecules) concentrations in the ACC. Ten patients and 14 HC also underwent [18F]F-DOPA positron emission tomography for assessment of striatal DSC. Multiple linear regression analyses were used to investigate the relations between the outcome measures.

A negative association between 2-AG plasma concentration and ACC Glx concentration was found in patients (p = 0.008). We found no evidence of other significant relationships between 2-AG or anandamide plasma concentrations and dopaminergic, glutamatergic, or GABAergic measures in either group.

Our preliminary results suggest an association between peripheral 2-AG and ACC Glx levels in patients.

Psychotic experiences (PEs) and social isolation (SI) seem related during early stages of psychosis, but the temporal dynamics between the two are not clear. Literature so far suggests a self-perpetuating cycle wherein momentary increases in PEs lead to social withdrawal, which, subsequently, triggers PEs at a next point in time, especially when SI is associated with increased distress. The current study investigated the daily-life temporal associations between SI and PEs, as well as the role of SI-related and general affective distress in individuals at clinical high risk (CHR) for psychosis.

We used experience sampling methodology in a sample of 137 CHR participants. We analyzed the association between SI, PEs, and distress using time-lagged linear mixed-effects models.

SI did not predict next-moment fluctuations in PEs, or vice versa. Furthermore, although SI-related distress was not predictive of subsequent PEs, general affective distress during SI was a robust predictor of next-moment PEs.

Our results suggest that SI and PEs are not directly related on a moment-to-moment level, but a negative emotional state when alone does contribute to the risk of PEs. These findings highlight the role of affective wellbeing during early-stage psychosis development.

Previous meta-analyses have shown that almost all antipsychotics are associated with weight gain. However, mean weight gain is not informative about clinically relevant weight gain or weight loss.

To provide further insight into the more severe body weight changes associated with antipsychotic use, we assessed the proportion of patients with clinically relevant weight gain (CRWG) and clinically relevant weight loss (CRWL), defined as ≥7% weight gain and ≥7% weight loss.

We searched PubMed, Embase and PsycInfo for randomised controlled trials of antipsychotics that reported CRWG and CRWL in study populations aged 15 years or older. We conducted meta-analyses stratified by antipsychotic and study duration using a random-effects model. We performed meta-regression analyses to assess antipsychotic-naive status and psychiatric diagnosis as modifiers for CRWG. PROSPERO: CRD42020204734.

We included 202 articles (201 studies). Almost all included antipsychotics were associated with CRWG. For CRWL, available data were too limited to draw firm conclusions. For some antipsychotics, CRWG was more pronounced in individuals who were antipsychotic-naive than in individuals switching to another antipsychotic. Moreover, a longer duration of antipsychotic use was associated with more CRWG, but not CRWL. For some antipsychotics, CRWG was higher in people diagnosed with schizophrenia, but this was inconsistent.

Switching antipsychotic medication is associated with both weight gain and weight loss, but the level of CRWG is higher than CRWL in antipsychotic-switch studies. CRWG was more pronounced in antipsychotic-naive patients, highlighting their vulnerability to weight gain. The impact of diagnosis on CRWG remains inconclusive.

Women with triple X syndrome (TXS) have an extra X chromosome. TXS appeared to be associated with psychiatric disorders in biased or underpowered studies.

This study aims to describe the prevalence of psychiatric disorders in adults with TXS in a relatively large and less biased group of participants.

In this cross-sectional study, data were collected from 34 women with TXS (mean age = 32.9; s.d. = 13.1) and 31 controls (mean age = 34.9; s.d. = 13.7). Psychiatric disorders were assessed using the MINI International Neuropsychiatric Interview (MINI) and the adult behavior checklist (ABCL). Trait and state anxiety were assessed using the State–Trait Anxiety Inventory.

In the TXS group, MINI results showed a higher prevalence of major depressive episodes (43.3%), psychotic disorders (29.4%), and suicidality (23.5%). Only 50% of the TXS group earned a normal score for the total syndrome score using the ABCL. In addition, levels of trait anxiety were higher in the TXS group. Only three women in each group received psychotropic medication. Impaired social functioning appeared to represent a major risk factor in TXS as regards psychotic, affective disorders, trait anxiety, and low self-esteem.

Women with TXS are vulnerable to developing psychiatric disorders, and women with both TXS and impaired social functioning are even more vulnerable.

Cognitive deficits may be characteristic for only a subgroup of first-episode psychosis (FEP) and the link with clinical and functional outcomes is less profound than previously thought. This study aimed to identify cognitive subgroups in a large sample of FEP using a clustering approach with healthy controls as a reference group, subsequently linking cognitive subgroups to clinical and functional outcomes.

204 FEP patients were included. Hierarchical cluster analysis was performed using baseline brief assessment of cognition in schizophrenia (BACS). Cognitive subgroups were compared to 40 controls and linked to longitudinal clinical and functional outcomes (PANSS, GAF, self-reported WHODAS 2.0) up to 12-month follow-up.

Three distinct cognitive clusters emerged: relative to controls, we found one cluster with preserved cognition (n = 76), one moderately impaired cluster (n = 74) and one severely impaired cluster (n = 54). Patients with severely impaired cognition had more severe clinical symptoms at baseline, 6- and 12-month follow-up as compared to patients with preserved cognition. General functioning (GAF) in the severely impaired cluster was significantly lower than in those with preserved cognition at baseline and showed trend-level effects at 6- and 12-month follow-up. No significant differences in self-reported functional outcome (WHODAS 2.0) were present.

Current results demonstrate the existence of three distinct cognitive subgroups, corresponding with clinical outcome at baseline, 6- and 12-month follow-up. Importantly, the cognitively preserved subgroup was larger than the severely impaired group. Early identification of discrete cognitive profiles can offer valuable information about the clinical outcome but may not be relevant in predicting self-reported functional outcomes.

Triple X syndrome (TXS) is caused by aneuploidy of the X chromosome and is associated with impaired social functioning in children; however, its effect on social functioning and emotion recognition in adults is poorly understood.

The aim of this study was to investigate social functioning and emotion recognition in adults with TXS.

This cross-sectional cohort study was designed to compare social functioning and emotion recognition between adults with TXS (n = 34) and an age-matched control group (n = 31). Social functioning was assessed with the Adult Behavior Checklist and Social Responsiveness Scale for Adults. Emotion recognition was assessed with the Emotion Recognition Task in the Cambridge Neuropsychological Test Automated Battery. Differences were analysed by Mann-Whitney U-test.

Compared with controls, women with TXS scored higher on the Adult Behavior Checklist, including the Withdrawn scale (P < 0.001, effect size 0.4) and Thought Problems scale (P < 0.001, effect size 0.4); and higher on the Social Responsiveness Scale for Adults, indicating impaired social functioning (P < 0.001, effect size 0.5). In addition, women with TXS performed worse on the Emotion Recognition Task, particularly with respect to recognising sadness (P < 0.005, effect size 0.4), fear (P < 0.01, effect size 0.4) and disgust (P < 0.02, effect size 0.3).

Our findings indicate that adults with TXS have a higher prevalence of impaired social functioning and emotion recognition. These results highlight the relevance of sex chromosome aneuploidy as a potential model for studying disorders characterised by social impairments such as autism spectrum disorder, particularly among women.

The prevalence of psychotic experiences (PEs) is higher in low-and-middle-income-countries (LAMIC) than in high-income countries (HIC). Here, we examine whether this effect is explicable by measurement bias.

A community sample from 13 countries (N = 7141) was used to examine the measurement invariance (MI) of a frequently used self-report measure of PEs, the Community Assessment of Psychic Experiences (CAPE), in LAMIC (n = 2472) and HIC (n = 4669). The CAPE measures positive (e.g. hallucinations), negative (e.g. avolition) and depressive symptoms. MI analyses were conducted with multiple-group confirmatory factor analyses.

MI analyses showed similarities in the structure and understanding of the CAPE factors between LAMIC and HIC. Partial scalar invariance was found, allowing for latent score comparisons. Residual invariance was not found, indicating that sum score comparisons are biased. A comparison of latent scores before and after MI adjustment showed both overestimation (e.g. avolition, d = 0.03 into d = −0.42) and underestimation (e.g. magical thinking, d = −0.03 into d = 0.33) of PE in LAMIC relative to HIC. After adjusting the CAPE for MI, participants from LAMIC reported significantly higher levels on most CAPE factors but a significantly lower level of avolition.

Previous studies using sum scores to compare differences across countries are likely to be biased. The direction of the bias involves both over- and underestimation of PEs in LAMIC compared to HIC. Nevertheless, the study confirms the basic finding that PEs are more frequent in LAMIC than in HIC.

Previous studies using resting-state functional neuroimaging have revealed alterations in whole-brain images, connectome-wide functional connectivity and graph-based metrics in groups of patients with schizophrenia relative to groups of healthy controls. However, it is unclear which of these measures best captures the neural correlates of this disorder at the level of the individual patient.

Here we investigated the relative diagnostic value of these measures. A total of 295 patients with schizophrenia and 452 healthy controls were investigated using resting-state functional Magnetic Resonance Imaging at five research centres. Connectome-wide functional networks were constructed by thresholding correlation matrices of 90 brain regions, and their topological properties were analyzed using graph theory-based methods. Single-subject classification was performed using three machine learning (ML) approaches associated with varying degrees of complexity and abstraction, namely logistic regression, support vector machine and deep learning technology.

Connectome-wide functional connectivity allowed single-subject classification of patients and controls with higher accuracy (average: 81%) than both whole-brain images (average: 53%) and graph-based metrics (average: 69%). Classification based on connectome-wide functional connectivity was driven by a distributed bilateral network including the thalamus and temporal regions.

These results were replicated across the three employed ML approaches. Connectome-wide functional connectivity permits differentiation of patients with schizophrenia from healthy controls at single-subject level with greater accuracy; this pattern of results is consistent with the ‘dysconnectivity hypothesis’ of schizophrenia, which states that the neural basis of the disorder is best understood in terms of system-level functional connectivity alterations.

The 22q11.2 deletion syndrome (22q11DS) is caused by a deletion on chromosome 22 locus q11.2. This copy number variant results in haplo-insufficiency of the catechol-O-methyltransferase (COMT) gene, and is associated with a significant increase in the risk for developing cognitive impairments and psychosis. The COMT gene encodes an enzyme that primarily modulates clearance of dopamine (DA) from the synaptic cleft, especially in the prefrontal cortical areas. Consequently, extracellular DA levels may be increased in prefrontal brain areas in 22q11DS, which may underlie the well-documented susceptibility for cognitive impairments and psychosis in affected individuals. This study aims to examine DA D2/3 receptor binding in frontal brain regions in adults with 22q11DS, as a proxy of frontal DA levels.

The study was performed in 14 non-psychotic, relatively high functioning adults with 22q11DS and 16 age- and gender-matched healthy controls (HCs), who underwent DA D2/3 receptor [18F]fallypride PET imaging. Frontal binding potential (BPND) was used as the main outcome measure.

BPND was significantly lower in adults with 22q11DS compared with HCs in the prefrontal cortex and the anterior cingulate gyrus. After Bonferroni correction significance remained for the anterior cingulate gyrus. There were no between-group differences in BPND in the orbitofrontal cortex and anterior cingulate cortex.

This study is the first to demonstrate lower frontal D2/3 receptor binding in adults with 22q11DS. It suggests that a 22q11.2 deletion affects frontal dopaminergic neurotransmission.

22q11.2 deletion syndrome (22q11DS), one of the most common recurrent copy number variant disorders, is associated with dopaminergic abnormalities and increased risk for psychotic disorders.

Given the elevated prevalence of substance use and dopaminergic abnormalities in non-deleted patients with psychosis, we investigated the prevalence of substance use in 22q11DS, compared with that in non-deleted patients with psychosis and matched healthy controls.

This cross-sectional study involved 434 patients with 22q11DS, 265 non-deleted patients with psychosis and 134 healthy controls. Psychiatric diagnosis, full-scale IQ and COMT Val158Met genotype were determined in the 22q11DS group. Substance use data were collected according to the Composite International Diagnostic Interview.

The prevalence of total substance use (36.9%) and substance use disorders (1.2%), and weekly amounts of alcohol and nicotine use, in patients with 22q11DS was significantly lower than in non-deleted patients with psychosis or controls. Compared with patients with 22q11DS, healthy controls were 20 times more likely to use substances in general (P < 0.001); results were also significant for alcohol and nicotine use separately. Within the 22q11DS group, there was no relationship between the prevalence of substance use and psychosis or COMT genotype. Male patients with 22q11DS were more likely to use substances than female patients with 22q11DS.

The results suggest that patients with 22q11DS are at decreased risk for substance use and substance use disorders despite the increased risk of psychotic disorders. Further research into neurobiological and environmental factors involved in substance use in 22q11DS is necessary to elucidate the mechanisms involved.

None.

Depression has been associated with abnormalities in neural underpinnings of Reward Learning (RL). However, inconsistencies have emerged, possibly owing to medication effects. Additionally, it remains unclear how neural RL signals relate to real-life behaviour. The current study, therefore, examined neural RL signals in young, mildly to moderately depressed – but non-help-seeking and unmedicated – individuals and how these signals are associated with depressive symptoms and real-life motivated behaviour.

Individuals with symptoms along the depression continuum (n = 87) were recruited from the community. They performed an RL task during functional Magnetic Resonance Imaging and were assessed with the Experience Sampling Method (ESM), completing short questionnaires on emotions and behaviours up to 10 times/day for 15 days. Q-learning model-derived Reward Prediction Errors (RPEs) were examined in striatal areas, and subsequently associated with depressive symptoms and an ESM measure capturing (non-linearly) how anticipation of reward experience corresponds to actual reward experience later on.

Significant RPE signals were found in the striatum, insula, amygdala, hippocampus, frontal and occipital cortices. Region-of-interest analyses revealed a significant association between RPE signals and (a) self-reported depressive symptoms in the right nucleus accumbens (b = −0.017, p = 0.006) and putamen (b = −0.013, p = .012); and (b) the quadratic ESM variable in the left (b = 0.010, p = .010) and right (b = 0.026, p = 0.011) nucleus accumbens and right putamen (b = 0.047, p < 0.001).

Striatal RPE signals are disrupted along the depression continuum. Moreover, they are associated with reward-related behaviour in real-life, suggesting that real-life coupling of reward anticipation and engagement in rewarding activities might be a relevant target of psychological therapies for depression.

Abnormalities in reward learning in psychotic disorders have been proposed to be linked to dysregulated subcortical dopaminergic (DA) neurotransmission, which in turn is a suspected mechanism for predisposition to psychosis. We therefore explored the striatal dopaminergic modulation of reward processing and its behavioral correlates in individuals at familial risk for psychosis.

We performed a DA D2/3 receptor [18F]fallypride positron emission tomography scan during a probabilistic reinforcement learning task in 16 healthy first-degree relatives of patients with psychosis and 16 healthy volunteers, followed by a 6-day ecological momentary assessment study capturing reward-oriented behavior in the everyday life.

We detected significant reward-induced DA release in bilateral caudate, putamen and ventral striatum of both groups, with no group differences in its magnitude nor spatial extent. In both groups alike, greater extent of reward-induced DA release in all regions of interest was associated with better performance in the task, as well as in greater tendency to be engaged in reward-oriented behavior in the daily life.

These findings suggest intact striatal dopaminergic modulation of reinforcement learning and reward-oriented behavior in individuals with familial predisposition to psychosis. Furthermore, this study points towards a key link between striatal reward-related DA release and pursuit of ecologically relevant rewards.