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The co-occurrence of a copy number variant (CNV) and a functional variant on the other allele may be a relevant genetic mechanism in schizophrenia. We hypothesized that the cumulative burden of such double hits-in particular those composed of a deletion and a coding single-nucleotide variation (SNV)-is increased in patients with schizophrenia. We combined CNV data with coding variants data in 795 patients with schizophrenia and 474 controls. To limit false CNV-detection, only CNVs called by two algorithms were included. CNV-affected genes were subsequently examined for coding SNVs, which we termed "CNV-SNVs." Correcting for total queried sequence, we assessed the CNV-SNV-burden and the combined predicted deleterious effect. We estimated P-values by permutation of the phenotype. We detected 105 CNV-SNVs; 67 in duplicated and 38 in deleted genic sequence. Although the difference in CNV-SNVs rates was not significant, the combined deleteriousness inferred by CNV-SNVs in deleted sequence was almost 4-fold higher in cases compared with controls (nominal P = 0.009). This effect may be driven by a higher number of CNV-SNVs and/or by a higher degree of predicted deleteriousness of CNV-SNVs. No such effect was observed for duplications. We provide early evidence that deletions co-occurring with a functional variant may be relevant, albeit of modest impact, for the genetic etiology of schizophrenia. Large-scale consortium studies are required to validate our findings. Sequence-based analyses would provide the best resolution for detection of CNVs as well as coding variants genome-wide.

Background: Pre-diagnostic stages of psychotic illnesses, including 'clinical high risk' (CHR), are marked by sleep disturbances. These sleep disturbances appear to represent a key aspect in the etiology and maintenance of psychotic disorders. We aimed to examine the relationship between self-reported sleep dysfunction and attenuated psychotic symptoms (APS) on a day-to-day basis. Methods: Seventy-six CHR young people completed the Experience Sampling Methodology (ESM) component of the European Union Gene-Environment Interaction Study, collected through PsyMate® devices, prompting sleep and symptom questionnaires 10 times daily for 6 days. Bayesian multilevel mixed linear regression analyses were performed on time-variant ESM data using the brms package in R. We investigated the day-to-day associations between sleep and psychotic experiences bidirectionally on an item level. Sleep items included sleep onset latency, fragmentation, and quality. Psychosis items assessed a range of perceptual, cognitive, and bizarre thought content common in the CHR population. Results: Two of the seven psychosis variables were unidirectionally predicted by previous night's number of awakenings: every unit increase in number of nightly awakenings predicted a 0.27 and 0.28 unit increase in feeling unreal or paranoid the next day, respectively. No other sleep variables credibly predicted next-day psychotic symptoms or vice-versa. Conclusion: In this study, the relationship between sleep disturbance and APS appears specific to the item in question. However, some APS, including perceptual disturbances, had low levels of endorsement amongst this sample. Nonetheless, these results provide evidence for a unidirectional relationship between sleep and some APS in this population. [ABSTRACT FROM AUTHOR]

This randomized clinical trial investigates the efficacy of a transdiagnostic ecological momentary intervention for improving self-esteem in youth with low self-esteem and exposure to childhood adversity. Key Points: Question: Can a transdiagnostic, blended ecological momentary intervention improve self-esteem in youth with low self-esteem and prior exposure to childhood adversity? Findings: This randomized clinical trial of 174 youth with low self-esteem and exposure to childhood adversity demonstrated that a novel transdiagnostic ecological momentary intervention improved the primary outcome of self-esteem at postintervention and 6-month follow-up. Small to moderate effect sizes signaled beneficial effects on general psychopathology, quality of life, and other secondary outcomes. Meaning: This trial demonstrated efficacy of a novel transdiagnostic ecological momentary intervention on self-esteem and signaled beneficial effects on secondary outcomes, which needs to be followed by investigating implementation in routine public mental health provision. Importance: Targeting low self-esteem in youth exposed to childhood adversity is a promising strategy for preventing adult mental disorders. Ecological momentary interventions (EMIs) allow for the delivery of youth-friendly, adaptive interventions for improving self-esteem, but robust trial-based evidence is pending. Objective: To examine the efficacy of SELFIE, a novel transdiagnostic, blended EMI for improving self-esteem plus care as usual (CAU) compared with CAU only. Design, Setting, and Participants: This was a 2-arm, parallel-group, assessor-blinded, randomized clinical trial conducted from December 2018 to December 2022. The study took place at Dutch secondary mental health services and within the general population and included youth (aged 12-26 years) with low self-esteem (Rosenberg Self-Esteem Scale [RSES] <26) exposed to childhood adversity. Interventions: A novel blended EMI (3 face-to-face sessions, email contacts, app-based, adaptive EMI) plus CAU or CAU only. Main Outcomes and Measures: The primary outcome was RSES self-esteem at postintervention and 6-month follow-up. Secondary outcomes included positive and negative self-esteem, schematic self-beliefs, momentary self-esteem and affect, general psychopathology, quality of life, observer-rated symptoms, and functioning. Results: A total of 174 participants (mean [SD] age, 20.7 [3.1] years; 154 female [89%]) were included in the intention-to-treat sample, who were primarily exposed to childhood emotional abuse or neglect, verbal or indirect bullying, and/or parental conflict. At postintervention, 153 participants (87.9%) and, at follow-up, 140 participants (80.5%), provided primary outcome data. RSES self-esteem was, on average, higher in the experimental condition (blended EMI + CAU) than in the control condition (CAU) across both postintervention and follow-up as a primary outcome (B = 2.32; 95% CI, 1.14-3.50; P <.001; Cohen d-type effect size [hereafter, Cohen d] = 0.54). Small to moderate effect sizes were observed suggestive of beneficial effects on positive (B = 3.85; 95% CI, 1.83-5.88; P <.001; Cohen d = 0.53) and negative (B = −3.78; 95% CI, −6.59 to −0.98; P =.008; Cohen d = −0.38) self-esteem, positive (B = 1.58; 95% CI, 0.41-2.75; P =.008; Cohen d = 0.38) and negative (B = −1.71; 95% CI, −2.93 to −0.48; P =.006; Cohen d = −0.39) schematic self-beliefs, momentary self-esteem (B = 0.29; 95% CI, 0.01-0.57; P =.04; Cohen d = 0.24), momentary positive affect (B = 0.23; 95% CI, 0.01-0.45; P =.04; Cohen d = 0.20), momentary negative affect (B = −0.33; 95% CI, −0.59 to −0.03, P =.01, Cohen d = −0.27), general psychopathology (B = −17.62; 95% CI, −33.03 to −2.21; P =.03; Cohen d = −0.34), and quality of life (B = 1.16; 95% CI, 0.18-2.13; P =.02; Cohen d = 0.33) across postintervention and follow-up. No beneficial effects on symptoms and functioning were observed. Conclusions and Relevance: A transdiagnostic, blended EMI demonstrated efficacy on the primary outcome of self-esteem and signaled beneficial effects on several secondary outcomes. Further work should focus on implementing this novel EMI in routine public mental health provision. Trial Registration: Dutch Trial Register Identifier:NL7129(NTR7475) [ABSTRACT FROM AUTHOR]

There is an expanding interest to study psychosis in the realm of daily life. The study of the person in the context of daily life may provide a powerful addition to more conventional and cross-sectional research strategies in the study of psychosis. This article first discusses the nature of experience sampling research in psychosis and demonstrates the feasibility and validity of studies using the experience sampling method (ESM) in this patient group. Second, the article presents a review of all ESM research in psychosis with a special focus on (a) the phenomenology, (b) the etiology, and (c) psychological models of psychosis. Variability over time and the dynamic interplay with the environment were found to be essential features of the positive symptoms of psychosis, whereas behavioral patterns as well as self-reported affect in daily life reality might be essential when studying negative symptomatology. ESM contributes to a better understanding of the interplay between psychotic experiences and environmental features, such as stress or cannabis exposure. Finally, the study of symptomatic variability may fuel new research into psychological models and treatment of psychosis and the study of the person-environment interplay may foster new Gene x Environment interaction studies.

How can we enhance activation? Studying should be a challenging, yet rewarding activity for students who intend to graduate. The Flow theory (Csikszentmihalyi, 1990, 1997) predicts that differential levels of perceived challenge and skill (flow) are related to optimized mental states and increased activation. However, the influence of concurrent mental states and specific environmental cues for this state of optimal experience is unknown. In this study we explore the contextual and subjective determinants of flow in relation to activation in studying, and compare this with sports and watching TV or listening to the radio. Method: 43 undergraduate students at the University of Maastricht were assessed with the Experience Sampling Method for one week (Delespaul, 1995). At random moments 10 times each day subjects evaluated the social context, activities, and mood states. Analyses were done with multilevel random regression techniques. Results: We replicated the predicted flow-related patterns in activation and emotions. While overall activation was increased in high challenging moments ([beta] = 0.51; 95% CI: 0.36, 0.19), this effect was less pronounced during study ([beta] = -0.16; 95% CI: -0.25, -0.07). Skills levels did not affect activation ([beta] = -0.01; 95% CI: -0.06, 0.05). Concurrent emotions were independently and additionally related to activation ([delta][[chi square].sub.(4)] = 117.12, p is less than 0.0001). Unexpectedly, activation increased with demotivation ([beta] = -0.12; 95% CI: 0.16, 0.07). We found highly significant and additional effects of context for all the activities (study: [chi square] = 732.63; p is less than 0.0001; [R.sup.2] = 0.30; active leisure: [chi square] = 753.40; p is less than 0.0001; [R.sup.2] = 0.31; and passive leisure: [chi square] = 555.86; p is less than 0.0001; [R.sup.2] = 0.24). Conclusions. The Flow theory is a valuable model leading to predictions of optimal experience as well as activation. However, the dynamics of activity engagement are more complex and related to concurrent emotions and context. In the Dutch student culture, escaping boredom or compulsory duties seems to drive individuals more than pursuing flow.