Although non-suicidal self-injury (NSSI) is known typically to begin in adolescence, longitudinal information is lacking about patterns, predictors, and clinical outcomes of NSSI persistence among emerging adults. The present study was designed to (1) estimate NSSI persistence during the college period, (2) identify risk factors and high-risk students for NSSI persistence patterns, and (3) evaluate the association with future mental disorders and suicidal thoughts and behaviors (STB).

Using prospective cohorts from the Leuven College Surveys (n = 5915), part of the World Mental Health International College Student Initiative, web-based surveys assessed mental health and psychosocial problems at college entrance and three annual follow-up assessments.

Approximately one in five (20.4%) students reported lifetime NSSI at college entrance. NSSI persistence was estimated at 56.4%, with 15.6% reporting a high-frequency repetitive pattern (≥five times yearly). Many hypothesized risk factors were associated with repetitive NSSI persistence, with the most potent effects observed for pre-college NSSI characteristics. Multivariate models suggest that an intervention focusing on the 10–20% at the highest predicted risk could effectively reach 34.9–56.7% of students with high-frequency repetitive NSSI persistence (PPV = 81.8–93.4, AUC = 0.88–0.91). Repetitive NSSI persistence during the first two college years predicted 12-month mental disorders, role impairment, and STB during the third college year, including suicide attempts.

Most emerging adults with a history of NSSI report persistent self-injury during their college years. Web-based screening may be a promising approach for detecting students at risk for a highly persistent NSSI pattern characterized by subsequent adverse outcomes.

There is evidence for a polygenic contribution to psychosis. One targetable mechanism through which polygenic variation may impact on individuals and interact with the social environment is stress sensitization, characterized by elevated reactivity to minor stressors in daily life. The current study aimed to investigate whether stress reactivity is modified by polygenic risk score for schizophrenia (PRS) in cases with enduring non-affective psychotic disorder, first-degree relatives of cases, and controls.

We used the experience sampling method to assess minor stressors, negative affect, positive affect and psychotic experiences in 96 cases, 79 first-degree relatives, i.e. siblings, and 73 controls at wave 3 of the Dutch Genetic Risk and Outcome of Psychosis (GROUP) study. Genome-wide data were collected at baseline to calculate PRS.

We found that associations of momentary stress with psychotic experiences, but not with negative and positive affect, were modified by PRS and group (all pFWE<0.001). In contrast to our hypotheses, siblings with high PRS reported less intense psychotic experiences in response to momentary stress compared to siblings with low PRS. No differences in magnitude of these associations were observed in cases with high v. low level of PRS. By contrast, controls with high PRS showed more intense psychotic experiences in response to stress compared to those with low PRS.

This tentatively suggests that polygenic risk may operate in different ways than previously assumed and amplify reactivity to stress in unaffected individuals but operate as a resilience factor in relatives by attenuating their stress reactivity.

One putative psychological mechanism through which momentary stress impacts on psychosis in individuals with increased liability to the disorder is via affective disturbance. However, to date, this has not been systematically tested. We aimed to investigate whether (i) cross-sectional and temporal effects of momentary stress on psychotic experiences via affective disturbance, and (ii) the reverse pathway of psychotic experiences on stress via affective disturbance were modified by familial liability to psychosis.

The Experience Sampling Method was used in a pooled data set of six studies with three groups of 245 individuals with psychotic disorder, 165 unaffected first-degree relatives, and 244 healthy control individuals to index familial liability. Multilevel moderated mediation models were fitted to investigate indirect effects across groups cross-sectionally and multilevel cross-lagged panel models to investigate temporal effects in the proposed pathways across two measurement occasions.

Evidence on indirect effects from cross-sectional models indicated that, in all three groups, effects of stress on psychotic experiences were mediated by negative affect and, vice versa, effects of psychotic experiences on stress were mediated by negative affect, with all indirect effects being weakest in relatives. Longitudinal modelling of data provided no evidence of temporal priority of stress in exerting its indirect effects on psychotic experiences via affective disturbance or, vice versa.

Our findings tentatively suggest a rapid vicious cycle of stress impacting psychotic experiences via affective disturbances, which does, however, not seem to be consistently modified by familial liability to psychosis.

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.

It remains poorly understood how negative symptoms are experienced in the daily lives of individuals in the early stages of psychosis. We aimed to investigate whether altered affective experience, anhedonia, social anhedonia, and asociality were more pronounced in individuals with an at-risk mental state for psychosis (ARMS) and individuals with first-episode psychosis (FEP) than in controls.

We used the experience sampling methodology (ESM) to assess negative symptoms, as they occurred in the daily life of 51 individuals with FEP and 46 ARMS, compared with 53 controls.

Multilevel linear regression analyses showed no overall evidence for a blunting of affective experience. There was some evidence for anhedonia in FEP but not in ARMS, as shown by a smaller increase of positive affect (BΔat−risk v. FEP = 0.08, p = 0.006) as the pleasantness of activities increased. Against our expectations, no evidence was found for greater social anhedonia in any group. FEP were more often alone (57%) than ARMS (38%) and controls (35%) but appraisals of the social situation did not point to asociality.

Overall, altered affective experience, anhedonia, social anhedonia and asociality seem to play less of a role in the daily life of individuals in the early stages of psychosis than previously assumed. With the experience of affect and pleasure in daily life being largely intact, changing social situations and appraisals thereof should be further investigated to prevent development or deterioration of negative symptoms.

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.

A dominant idea is that impaired capacities for theory of mind (ToM) are the reasons for impairments in social functioning in several conditions, including autism and schizophrenia. In this paper, we present empirical evidence that challenges this influential assumption.

We conducted three studies examining the association between ToM and social functioning in participants diagnosed with a non-affective psychotic disorder and healthy individuals. We used both the experience sampling method, a structured diary technique collecting information in daily-life, and a standardised questionnaire to assess social functioning. Analysed data are part of Wave 1 and Wave 3 of the Genetic Risk and Outcome of Psychosis (GROUP) study.

Results were highly consistent across studies and showed no significant association between the two constructs.

These findings question the leading assumption that social cognition is a prerequisite for social functioning, but rather suggest that social cognition is possibly a result of basic social interactive capacities.

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.

FK506 binding protein 5 (FKBP5) has repeatedly been shown to be a critical determinant of post-traumatic stress disorder (PTSD) and depression following childhood trauma.

To examine the role of FKBP5-trauma interactions in the partly stress-related psychosis phenotype.

In 401 general population twins, four functional polymorphisms were examined in models of psychosis and Cortisol, and followed up in models of psychosis in three samples at different familial liability (175 controls, 200 unaffected siblings and 195 patients with a psychotic disorder).

The most consistent finding was an interaction between childhood trauma and rs9296158/rs4713916 on psychotic symptoms and Cortisol in the twin sample, combined with a directionally similar interaction in siblings (rs4713916) and patients (rs9296158), A-allele carriers at both polymorphisms being most vulnerable to trauma.

Trauma may increase the risk of psychosis through enduring changes in the Cortisol feedback loop, similar to that for PTSD, suggesting comparable biological mechanisms for psychosis across diagnostic boundaries.

Little is known about the experiential dynamics of the interaction between cannabis and vulnerability to psychosis.

To examine the effects of cannabis on psychotic symptoms and mood in patients with psychosis and healthy controls.

Patients with a psychotic disorder (η = 42) and healthy controls (η = 38) were followed in their daily lives using a structured time-sampling technique.

Daily life cannabis use predicted subsequent increases in positive affect and in patients, but not in controls, decreases in negative affect. In patients, but not in controls, cannabis use predicted increased levels of hallucinatory experiences. Mood-enhancing properties of cannabis were acute, whereas psychosis-inducing effects were sub-acute. There was no direct evidence for self-medication effects in daily life.

Patients with psychosis are more sensitive to both the psychosis-inducing and mood-enhancing effects of cannabis. The temporal dissociation between acute rewarding effects and sub-acute toxic influences may be instrumental in explaining the vicious circle of deleterious use in these patients.

Psychotic patients with COMTVal158Met Met alleles were recently found to display more intense psychotic and affective responses to daily life stressors. We aimed to test the hypothesis that the Met allele is implicated in the development of affective and psychotic symptomatology in subjects genetically at risk for schizophrenia, by testing if unaffected first-degree relatives of patients with schizophrenia who share a Met allele have greater concordance of symptomatology than relatives not sharing a Met allele.

Unaffected relatives (n = 38) were arranged in as many genetically related pairs as possible (n = 26), and Met-sharing between Index Unaffected Subject (IUS) and Related Unaffected Subject (RUS) was assessed. Symptomatology was assessed with the Brief Psychiatric Rating Scale (BPRS) total score.

Multilevel regression revealed an interaction between RUS BPRS score and Met-sharing in the model of IUS BPRS score (interaction χ2 = 3.78, p = 0.05). Stratified analyses revealed that IUS–RUS total BPRS scores were significantly associated in the case of Met-sharing (B = 0.57, 95% CI: 0.22–0.93, p = 0.002), but were not when there was no Met-sharing.

These findings support the hypothesis that the Met allele may be involved in the causation of psychopathology, at least in populations with a genetic predisposition to psychosis.

A disorder of self-monitoring may underlie the positive symptoms of psychosis. The cognitive mechanisms associated with these symptoms may also be detectable in individuals at risk of psychosis

To investigate (a) whether patients with psychosis show impaired self-monitoring, (b) to what degree this is associated with positive symptoms, and (c) whether this is associated with liability to psychotic symptoms

The sample included: individuals with a lifetime history of non-affective psychosis (n=37), a genetically defined risk group (n=41), a psychometrically defined risk group (n=40), and control group (n=49). All participants carried out an action-recognition task

Number of action – recognition errors was associated with psychosis risk (OR linear trend over 3 levels: 1.12, 95% CI 1.04–1.20) and differential error rate was associated with the degree of delusional ideation in a dose–response fashion (OR linear trend over 3 levels: 1.13, 95% CI 1.00–1.26)

Alterations in self-monitoring are associated with psychosis with evidence of specificity for delusional ideation. In the risk state, this is expressed more as failure to recognise self-generated actions, whereas in illness failure to recognise alien sources come to the fore

A bias to develop negative affect in response to daily life stressors may be an important depression endophenotype, but remains difficult to assess.

To assess this mood bias endophenotype, uncontaminated by current mood, in the course of daily life.

The experience samping method was used to collect multiple appraisals of daily life event-related stress and negative affect in 279 female twin pairs. Cross-twin, cross-trait associations between daily life mood bias and DSM – IV depression were conducted.

Probands whose co-twins were diagnosed with lifetime depression showed a stronger mood bias to stress than those with co-twins without such a diagnosis, independent of probands' current depressive symptoms and to a greater extent in monozygotic twins than in dizygotic twins.

Genetic liability to depression is in part expressed as the tendency to display negative affect in response to minor stressors in daily life. This trait may represent a true depression endophenotype.

Exposure to stressful life events increases the risk of developing a psychotic disorder. Moreover, increased reactivity to stress seems to represent part of the vulnerability for psychosis. This study aimed to investigate whether a functional polymorphism in the catechol-O-methyltransferase (COMT Val158Met) gene moderates the psychosis-inducing effects of stress.

A semi-experimental stress exposure paradigm was used in a sample of 306 genotyped young men (aged 19–24 years), in whom measures of psychotic symptoms were obtained at recruitment in the Greek army (exposed condition) and again after 18 months of military training (unexposed condition).

Stress exposure at army induction was associated with an increased level of psychotic symptoms. In addition, carriers of the COMT Val158Met Val allele were more susceptible to the effect of stress on the psychosis outcome than those with the Met/Met genotype (test for interaction: χ2=5·02, df=1, p=0·025).

The COMT Val158Met genotype may moderate the effect of stress on psychotic symptoms.