BACKGROUND: Mosaic chromosomal alterations (mCAs) are implicated in neuropsychiatric disorders, yet the contribution to schizophrenia (SCZ) risk for somatic copy number variations (sCNVs) emerging in early developmental stages is not fully established.
METHODS: We analyzed blood-derived genotype arrays from 9,715 SCZ patients and 28,822 controls of Chinese descent using a computational tool (MoChA) based on long-range chromosomal information to detect mCAs. We focused on probable early developmental sCNVs through stringent filtering. We assessed the sCNVs\' burden across varying cell fraction (CF) cutoffs, as well as the frequency with which genes were involved in sCNVs. We integrated this data with the Psychiatric Genomics Consortium (PGC) dataset, which comprises 12,834 SCZ cases and 11,648 controls of European descent, and complemented it with genotyping data from postmortem brain tissue of 936 subjects (449 cases and 487 controls).
RESULTS: Patients with SCZ had a significantly higher somatic losses detection rate than control subjects (1.00% vs 0.52%; odds ratio (OR) = 1.91; 95% CI, 1.47-2.49; two-sided Fisher\'s exact test, p=1.49×10-6). Further analysis indicated that the ORs escalated proportionately (from 1.91 to 2.78) with the increment in CF cutoffs. Recurrent sCNVs associated with SCZ (OR>8; Fisher\'s exact test, p<0.05) were identified, including notable regions at 10q21.1 (ZWINT), 3q26.1 (SLITRK3), 1q31.1 (BRINP3) and 12q21.31-21.32 (MGAT4C and NTS) in the Chinese cohort, some regions validated with PGC data. Cross-tissue validation pinpointed somatic losses at loci like 1p35.3-35.2 and 19p13.3-13.2.
CONCLUSIONS: The study highlights mCAs\' significant impact on SCZ, suggesting their pivotal role in the disorder\'s genetic etiology.

Schizophrenia (SPR) is the most devastating mental illness that causes severe deterioration in social and occupational functioning, but, the etiology remains unknown. The objective of this study is to explore the genetic underpinnings of novelty seeking behavior in schizophrenic family within the Korean population. By conducting a family-based genome-wide association study, we aim to identify potential genetic markers and variations associated with novelty seeking traits in the context of SPR. We have recruited 27 probands (with SPR) with their parents and siblings whenever possible. DNA was extracted from blood sampling of 58 individuals in 27 families and analyzed in an Illumina core exome single nucleotide polymorphism (SNP) array. A family-based association test (qFAM) was used to derive SNP association values across all chromosomes. Although none of the final 800,000 SNPs reached the genome-wide significant threshold of 8.45 × 10-7, the most significant 4 SNPs were within the 10-5 to 10-7. This study identifies genetic associations between novelty seeking behavior and SPR within families. RAPGEF5 emerges as a significant gene, along with other neuropsychiatric-related genes. Noteworthy genes like DRD4 and COMT did not show associations, possibly due to the focus on schizophrenic family. While shedding light on this complex relationship, larger studies are needed for robust conclusions and deeper mechanistic insights.

Observational studies have reported a relationship between multiple common dermatoses and mental illness. To assess the potential bidirectional causality between 3 skin disorders (psoriasis, eczema, and urticaria) and 4 psychiatric disorders (bipolar disorder, schizophrenia, major depressive disorder, and anxiety) in the European population, we used Mendelian randomization (MR) analysis, which provides definitive evidence for causal inference. Eligible single nucleotide polymorphisms were screened for dermatological and psychiatric disorders using a genome-wide association study database. We conducted bidirectional, 2-sample MR analysis using instrumental variables related to psoriasis, eczema, and urticaria as exposure factors, and bipolar disorder, schizophrenia, major depression, and anxiety as outcomes. Reverse MR analysis with bipolar disorder, schizophrenia, major depression, and anxiety as exposure and psoriasis, eczema, and urticaria as outcomes were also performed, and the causality was analyzed using inverse-variance weighting (IVW), MR-Egger, and weighted median methods. To thoroughly assess causality, sensitivity analyses were conducted using the IVW, MR-PRESSO, and MR-Egger methods. The results showed that bipolar disorder increased the incidence of psoriasis (odds ratio = 1.271, 95% confidence interval = 1.003-1.612, P = .047), heterogeneity test with Cochran Q test in the IVW showed P value > .05, (P = .302), the MR-Pleiotropy and MR-PRESSO (outlier methods) in the multiplicity test showed P value > .05, (P = .694; P = .441), and MR-Pleiotropy evidence showed no apparent intercept (intercept = -0.060; SE = 0.139; P = .694). Major depression increased the risk of eczema (odds ratio = 1.002, 95% confidence interval = 1.000-1.004, P = .024), heterogeneity test showed P value > .05, (P = .328), multiplicity detection showed P value > .05, (P = .572; P = .340), and MR-Pleiotropy evidence showed no apparent intercept (intercept = -0.099; SE = 0.162; P = .572). Sensitivity analyses of the above results were reliable, and no heterogeneity or multiplicity was found. This study demonstrated a statistically significant causality between bipolar disorder and psoriasis, major depression, and eczema in a European population, which could provide important information for physicians in the clinical management of common skin conditions.

UNASSIGNED: In schizophrenia patients, spontaneous speech production has been hypothesized as correlating with right hemispheric activation, including the inferior frontal and superior temporal gyri as speech-relevant areas. However, robust evidence for this association is still missing. The aim of the present fMRI study is to examine BOLD signal changes during natural, fluent speech production in patients with schizophrenia in the chronic phase of their disease.
UNASSIGNED: Using a case-control design, the study included 15 right-handed patients with schizophrenia spectrum disorders as well as 15 healthy controls. The participants described eight pictures from the Thematic Apperception Test for 1 min each, while BOLD signal changes were measured with 3T fMRI. The occurrence of positive and negative formal thought disorders was determined using standardized psychopathological assessments.
UNASSIGNED: We found significant BOLD signal changes during spontaneous speech production in schizophrenia patients compared to healthy controls, particularly in the right hemispheric network. A post-hoc analysis showed that this right-hemispheric lateralization was mainly driven by activation during experimental rests. Furthermore, the TLI sum value in patients correlated negatively with BOLD signal changes in the right Rolandic operculum.
UNASSIGNED: Possible underlying factors for this inverse right-hemispheric lateralization of speech-associated areas are structural changes and transmitter system alterations, as well as a lack of neural downregulation in schizophrenia patients during rest periods due to dysfunctional executive functions. When examining spontaneous speech as the most natural form of language, other influencing factors, such as social cognition or emotional processing, should be considered. Our results indicate that future studies should consider group differences during rest, which might provide additional information typically covered in differential contrasts.

OBJECTIVE: Substance use is highly prevalent among people with schizophrenia (SCZ) and related disorders, however, there is no broad-spectrum pharmacotherapy that concurrently addresses both addiction and psychotic symptoms. Psychosocial (PS) interventions, which have yielded promising results in treating psychosis and substance dependence separately, demonstrate potential but have not been systematically evaluated when combined.
METHODS: Systematic review and random-effects meta-analyses of randomized controlled trials (RCTs) investigating PS interventions for individuals with comorbid substance use and psychotic disorders, encompassing SCZ and schizophrenia spectrum disorders (SSD). We included relevant studies published from MEDLINE, PsycINFO, and Google Scholar through May 2023.
RESULTS: We included 35 RCTs (5176 participants total; approximately 2840 with SSD). Intervention durations ranged from 30 min to 3 years. Meta-analysis did not identify a statistically significant pooled PS intervention effect on the main primary outcome, substance use (18 studies; 803 intervention, 733 control participants; standardized mean difference, -0.05 standard deviation [SD]; 95% CI, -0.16, 0.07 SD; I2 = 18%). PS intervention effects on other outcomes were also not statistically significant. Overall GRADE certainty of evidence was low.
CONCLUSIONS: At present, the literature lacks sufficient evidence supporting the use of PS interventions as opposed to alternative therapeutic approaches for significantly improving substance use, symptomatology, or functioning in people with SCZ and related disorders. However, firm conclusions were precluded by low certainty of evidence. Further RCTs are needed to determine the efficacy of PS treatments for people with dual-diagnoses (DD), either alone or in combination with pharmacotherapy.

BACKGROUND: There is conflicting evidence on impulsivity and its potential relationship with inhibitory control in schizophrenia. This study therefore aimed to identify differences in impulsivity and cognitive and motor inhibition between patients with deficit (DS) and non-deficit (NDS) schizophrenia and healthy controls (HC). We also explored the relationships between impulsivity and different dimensions of inhibitory control in all studied groups.
METHODS: The sample comprised 28 DS patients, 45 NDS patients, and 39 age-matched HC. A neuropsychological battery was used.
RESULTS: DS patients scored lower in venturesomeness, while those with NDS scored higher in impulsiveness compared to HC. In addition, both groups of patients scored higher on measures of cognitive and motor inhibition, including those relatively independent of information processing speed (although the results were slightly different after adjusting for IQ and/or years of education). Correlations between impulsivity and cognitive inhibition emerged in DS patients, while links between impulsivity and motor inhibition were observed in HC.
CONCLUSIONS: Our results suggest the presence of deficits in experimentally assessed inhibitory control in schizophrenia patients, with predominant impulsivity in the NDS population. In addition, impulsivity may affect the cognitive control of inhibition in deficit schizophrenia. Nevertheless, due to the preliminary nature of these findings, they require further empirical verification in future research.

Many people with schizophrenia spectrum disorders (SSDs) experience profound amotivation, which is strongly related to anticipatory anhedonia. Yet, the neuropsychological fundamentals of anticipatory anhedonia and amotivation are barely understood, resulting in a lack of effective treatments for these patients. Aberrancies in positive mental imagery may interfere with the anticipation of pleasure and could thus explain anticipatory anhedonia and amotivation. However, the nature of mental imagery and its relationship with amotivational psychopathology in SSD is largely unknown. In this preregistered study, we therefore examined mental imagery characteristics and their relation to anticipatory anhedonia, amotivation, and daily life activity in SSD. TheN = 86 participants included individuals with SSD (n = 43) and demographically matched healthy controls (n = 43). Mental imagery, anticipatory pleasure, amotivation, and activity engagement were assessed with structured interviews and self-report questionnaires. Ecological momentary assessment was used to measure state anticipatory pleasure and activity engagement in daily life (n = 81). Compared to the control group, the SSD group showed comparable quantity, but less vividness of mental imagery. Reduced vividness of mental imagery in SSD was significantly associated with higher anticipatory anhedonia, amotivation, and low activity engagement in cross-sectional and prospective analyses. Reduced mental imagery vividness may cause a lack of internal incentive to seek pleasurable experiences and could explain amotivation. Interventions aiming to improve mental imagery vividness and related anticipatory pleasure responses in SSD may be effective in targeting amotivation.

OBJECTIVE: For a long time, it was proposed that schizophrenia (SCZ) patients rely more on sensory input and less on prior information, potentially leading to reduced serial dependence-ie, a reduced influence of prior stimuli in perceptual tasks. However, existing evidence is constrained to a few paradigms, and whether reduced serial dependence reflects a general characteristic of the disease remains unclear.
METHODS: We investigated serial dependence in 26 SCZ patients and 27 healthy controls (CNT) to evaluate the influence of prior stimuli in a classic visual orientation adjustment task, a paradigm not previously tested in this context.
RESULTS: As expected, the CNT group exhibited clear serial dependence, with systematic biases toward the orientation of stimuli shown in the preceding trials. Serial dependence in SCZ patients was largely comparable to that in the CNT group.
CONCLUSIONS: These findings challenge the prevailing notion of reduced serial dependence in SCZ, suggesting that observed differences between healthy CNT and patients may depend on aspects of perceptual or cognitive processing that are currently not understood.

BACKGROUND: Schizophrenia is heavily stigmatized among health professionals. Given that health professional students are future members of the workforce and will provide care for people with schizophrenia, it is essential to implement interventions aimed at reducing stigma among this group.
OBJECTIVE: This scoping review aimed to identify and synthesize existing literature on interventions to decrease schizophrenia stigma among health professional students, and to determine the possible gaps in the literature.
METHODS: Nine electronic databases and gray literature were searched, including PubMed, Embase, the Cumulative Index to Nursing and Allied Health Literature, PsycINFO, MEDLINE, Web of Science, Scopus, China National Knowledge Infrastructure, WanFang, and Google on 5 May 2023. Two researchers independently conducted data screening, data extraction, and assessed study risks. A most updated search was also done on 22 May 2024. The Cochrane risk of bias tool version 2 for randomized trials and Risk of Bias in Non-randomized Studies were used to assess the studies\' risk of bias. Data synthesis and analysis were conducted by two reviewers using a narrative approach. Reporting adhered to Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews.
RESULTS: This review included twenty-one studies with 2520 health professional students. The majority of included studies were non-randomized controlled trials (38 %) and pre-post studies (52 %). Most of the included studies were conducted in the United States (24 %). The participants in ten (48 %) studies were medical students. The number of intervention sessions ranged from one to 13, with an average of three. Seven (33 %) studies had an intervention duration of less than four weeks and 16 (76 %) studies had no follow-up. Various scales were used to assess the outcomes of schizophrenia stigma. Only two studies (10 %) indicated the intervention\'s ineffectiveness, with the majority of interventions led by psychiatry department faculty and individuals with schizophrenia.
CONCLUSIONS: Most studies (90 %) utilized various approaches, including face-to-face or online education, direct contact with individuals with schizophrenia, or a combination thereof, to diminish stigma among health professional students. However, none addressed cultural and empathy factors in their intervention designs, and the included studies lacked theoretical guidance. The review only comprised English quantitative studies with significant heterogeneity, with 17 studies (81 %) displaying serious or high risk of bias, limiting comprehensive discussions. These findings offer valuable insights for future systematic review. Tweetable abstract Studies on reducing health professional students\' schizophrenia stigma need to address cultural and empathy factors.

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