This study examines acute and delayed adverse reactions reported in naturalistic psychedelic use, focusing on their associations with substance-use patterns, contextual variables, and user motivations. Using an online survey incorporating the Psychedelic Use Scale, data were collected from a large naturalistic sample (N = 1022) to analyze patterns of self-reported adverse reactions. Acute adverse reactions were consistently associated with similar delayed adverse reactions, suggesting continuity between immediate and subsequent self-reported adverse experiences. Furthermore, most acute adverse reactions, with the exception of vomiting, which showed an opposite pattern, were associated with higher current psychopathology and lower well-being. Self-reported lifetime use of individual psychedelics (e.g., DMT, MDMA, and LSD) and combined substances (e.g., alcohol, caffeine, and cannabis) showed participant-level associations with specific self-reported adverse-reaction categories, while MDMA use was also associated with poorer current psychological indicators. Adverse reactions were also associated with contextual variables, including setting, type of companionship, and user motivations. Younger age and higher current frequency of psychedelic consumption were associated with higher odds of reporting adverse reactions. Because the study is cross-sectional and retrospective, and adverse reactions were not linked to specific substances or psychedelic episodes, the findings should be interpreted as correlational, hypothesis-generating co-reporting patterns rather than as substance-specific attribution. Nevertheless, they provide an empirical basis for future prospective, longitudinal, and clinical studies aimed at clarifying temporal relationships and informing harm reduction strategies.

Abnormal sleep duration (ASD) and sarcopenia are highly prevalent. However, their combined effects on dynamic depressive trajectories remain unclear. This study aimed to explore the associations of coexisting ASD and sarcopenia with first-onset depressive symptoms and depressive symptom trajectories in adults aged ≥45 years. Data were derived from the China Health and Retirement Longitudinal Study. A total of 11,295 and 6739 participants were included in cross-sectional, cohort studies and trajectory analysis. Sarcopenia was diagnosed based on the AWGS 2025 criteria, and ASD was defined as sleep duration <6 h or >8 h. Depressive symptoms were assessed using the CES-d-10 scale. Latent class growth model was used to identify depressive trajectories, and multinomial logistic regression was applied to analyze the relationship. ASD combined with sarcopenia was associated with an increased hazard of depressive symptoms based on cross-sectional and cohort study. Three distinct depressive trajectories were identified: persistently low-level normal trajectory (Cluster 1), slowly elevating depressive trajectory (Cluster 2), rapidly elevating depressive trajectory (Cluster 3). After adjusting for covariates (age, gender, education, marital status, smoking, chronic diseases, etc.), ASD combined with sarcopenia group had a significantly higher odds of belonging to cluster 3 (OR=4.130, 95%CI: 2.455-6.948) and cluster 2 (OR=2.436, 95%CI: 1.700-3.941) compared to the reference trajectory. ASD and sarcopenia are jointly associated with first-onset depressive symptoms and adverse depressive trajectories in adults aged ≥45, with a stronger link to rapidly elevating trajectories, which emphasizes the value of integrated psychosomatic screening and intervention targeting ASD and sarcopenia for the management of depressive symptom progression.

This systematic review aimed to synthesize longitudinal evidence on the risk of developing schizophrenia (SCZ) among individuals previously diagnosed with obsessive-compulsive disorder (OCD).

This systematic review and pairwise meta-analysis examined the efficacy of psychological and psychosocial smoking cessation interventions in individuals with schizophrenia spectrum disorders (SSD). Tobacco use is highly prevalent in this population and negatively affects both physical and mental health, potentially interfering with treatment outcomes. A comprehensive search of electronic databases up to January 13, 2025 identified 14 randomized controlled trials (RCTs), of which nine were included in the meta-analysis. Primary outcomes included smoking reduction measured with a) abstinence (number of abstinent participants), b) validated scales and c) cigarettes smoked per day and overall symptoms of schizophrenia. The results showed that interventions demonstrated beneficial effects on smoking-related outcomes. Consistent for all three outcomes on reduction: abstinence (RR = 1.60, 95% CI: 1.07 to 2.38, 9 trials), validated scales (SMD = -0.30, 95% CI: -0.58 to -0.01, 2 trials) and cigarettes smoked per day (MD = -3.09, 95% CI: -5.16 to -1.02, 3 trials). Results showed no improvement in overall symptoms for schizophrenia (SMD = -0.54, 95% CI: -1.43 to 0.35, 3 trials). Tolerability could not be evaluated due to insufficient reporting of adverse events. Overall, psychological and psychosocial interventions appear effective in reducing smoking in individuals with SSD but show limited impact on psychiatric symptoms. The findings are constrained by limited data, highlighting the need for future research using standardized measures, long-term follow-up, quality-of-life outcomes, and improved reporting of adverse effects.

Chronic oxidative stress (OS) is strongly implicated in the pathobiology of adult-onset schizophrenia, while contributions to childhood- and adolescent-onset schizophrenia (CAOS) have not been extensively investigated. Here we examined abnormalities in peripheral OS markers and associations with symptoms in a large CAOS cohort. Total superoxide dismutase (T-SOD), Mn-SOD, CuZn-SOD, glutathione peroxidase (GSH-Px), thioredoxin peroxidase (TPx), and catalase (CAT) activities as well as the Mn-SOD/T-SOD ratio were measured in plasma samples from 120 CAOS cases and 40 healthy controls (HCs). Psychopathological symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS) and cognitive function using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Marker diagnostic performance was assessed by receiver operating characteristic analysis. Patients exhibited significantly lower T-SOD (Cohen's d = 0.56, P = 0.002), Mn-SOD (Cohen's d = 0.67, P < 0.001), and GSH-Px (Cohen's d = 0.55, P = 0.003), reduced Mn-SOD/T-SOD (Cohen's d = 0.36, P = 0.005), and elevated TPx (Cohen's d = 1.00, P < 0.001) versus HCs. Elevated TPx activity was associated with higher PANSS negative symptom score (β=0.220, P = 0.016) and total PANSS score (β=0.220, P = 0.010); a five-factor PANSS analysis further linked TPx to the thought disturbance/disorganization dimension. Unexpectedly, higher TPx was also associated with improved RBANS attention index (β=0.218, P = 0.013) and total score (β=0.192, P = 0.011). Plasma TPx was the strongest diagnostic marker (AUC=0.711), while a combined antioxidant enzyme index (CAEI) improved diagnostic performance (AUC=0.756, sensitivity 83.3%, specificity 60.0%). CAOS patients demonstrated multiple antioxidant enzyme activity abnormalities; TPx correlated with greater negative symptoms but better attention performance. Future studies are warranted to confirm the diagnostic utility of our CAEI.

Neuroinflammation is a key pathophysiological mechanism underlying treatment-resistant schizophrenia (TRS). Interleukin (IL)-6 is a trait-related biomarker that exhibits consistently elevated levels in schizophrenia. However, studies focusing on TRS and examining the associations of clozapine treatment with inflammatory marker and clinical characteristics remain limited. Therefore, this multicenter cross-sectional study focused on patients with TRS and antipsychotic-responsive schizophrenia (ARS). Plasma IL-6 levels were measured in all participants, while plasma clozapine and N-desmethylclozapine concentrations were quantified in patients with TRS. Psychotic symptoms and cognitive function were assessed using the Positive and Negative Syndrome Scale (PANSS) and the Brief Assessment of Cognition in Schizophrenia-Short Form (BAC-SF), respectively. Multiple regression analysis was conducted to identify clinical factors associated with plasma IL-6 levels in the TRS group. In total, 37 patients with TRS and 22 with ARS were included in this study. Plasma IL-6 levels were significantly higher in the TRS group than in the ARS group (p < 0.001). In the TRS group, clozapine treatment duration was negatively associated with plasma IL-6 levels after adjustment for age, diabetes mellitus, and treatment setting (β = -0.398; p = 0.031). No significant associations were observed between plasma IL-6 levels and psychiatric symptom severity (PANSS total) or cognitive function (BAC-SF) in the TRS group. Overall, these findings suggest that TRS may differ from ARS in terms of peripheral inflammatory profiles and that longer-term clozapine treatment may be associated with lower plasma IL-6 levels in TRS.

Delivering face-to-face psychological interventions for cannabis use disorder (CUD) in early intervention services (EIS) for psychosis is often limited by structural barriers. App-based interventions may help overcome these limitations, though studies in non-psychosis populations report low engagement and retention. This study evaluated the feasibility of conducting an efficacy randomized controlled trial (RCT) of iCanChange (iCC), a novel app-based psychological intervention for CUD, and explored preliminary effects on cannabis use and related outcomes. We conducted a pilot RCT across 6 EIS programs in Canada, with 101 young adults aged 18-35 years with first-episode psychosis and CUD. They were randomized to modified EIS plus iCC (n = 51) or EIS only (n = 50). The intervention lasted 12 weeks with assessments at baseline and weeks 6, 12 (primary endpoint), and 24. Primary feasibility outcomes were intervention acceptability, defined as iCC completion (>50% of participants completing >50% modules), and trial retention, defined as >50% of participants retained at week 12. Secondary outcomes included cannabis use quantity and frequency, participant satisfaction, and app use metrics. Exploratory outcomes included cannabis-related outcomes, psychotic symptoms, and life satisfaction. Retention at week 12 was 84% in the intervention group and 86% in the control group, while iCC completion rate was 49% in intent-to-treat and 54% in per-protocol analyses. Preliminary signals of improvement in the intervention group were observed regarding cannabis use frequency, cannabis-related problems, dependence severity, and coping self-efficacy. Results demonstrate strong retention, supporting the feasibility of an efficacy trial while highlighting the need to enhance app engagement in youth with psychosis.

Gene expression studies have identified multiple dysregulated genes in brains of schizophrenia cases compared with controls. However, many dysregulated genes are not replicated or confirmed in independent cohorts and it remains a major challenge to identify genes whose altered expression have a causal role in schizophrenia. Here we conducted differential expression analysis in three large-scale independent expression datasets, including CommonMind Consortium (CMC, 258 cases and 279 controls), Lieber Institute for Brain Development (LIBD, 155 cases and 196 controls), and a GEO meta-analysis (140 cases and 134 controls), and identified 7 overlapping genes (CA4, SCN1B, IGFBP6, HR, GHR, DCP2, and FAM65B) that showed concordant expression change across all three datasets, strongly suggesting the pivotal role of these genes in schizophrenia. We also conducted Gene Ontology (GO) analysis and found that pathways related to nucleus, protein binding, mitochondria, among others, are dysregulated in schizophrenia cases in at least two independent datasets, indicating the potential causal role of these pathways in schizophrenia. Further we explored the genetic associations between these 7 overlapping genes and schizophrenia in populations of European ancestry, and found that a genetic variant (rs6503945) near CA4 showed association with schizophrenia risk (P = 3.17 × 10[-3]). Finally, integrative analyses supported that CA4 is a risk gene whose genetically regulated downregulation is associated with schizophrenia risk. Collectively, these convergent and consistent results suggest that CA4 is a potential schizophrenia driven gene whose downregulation may have a causal role in schizophrenia pathogenesis.

Understanding short-term risk factors for suicidal ideation (SI) and non-fatal suicide attempts (NFSAs) in at-risk populations is essential for suicide prevention initiatives. The prospective associations between previously identified near-term risk factors for suicidal behavior and SI and NFSAs were examined in a sample of adults with recent suicidal ideation (N = 423; 72.3% female) who completed questionnaires every two weeks for a year (n = 6321 included observations; completion rates ranged from 70-89%). Linear and logistic models examined the prospective associations between the risk factors and SI and NFSAs, adjusting for age, sex, and NFSA history. Overall, 414 (97.9%) participants reported SI on at least one assessment and 32 (7.6%) reported at least one NFSA during this period. Emptiness (adjusted B [aB]=.13), burdensomeness (aB=.11), alcohol quantity (aB=.05), and prior-timepoint SI (aB=.15) had significant prospective associations with SI. Interpersonal negative life events (adjusted odds ratio [aOR]=1.63), emptiness (aOR=1.83), central nervous system stimulant use (aOR=2.65), and SI (aOR=1.20) had significant positive associations with subsequent NFSAs. Burdensomeness (aOR=.77) had a significant negative association with subsequent NFSAs in the adjusted model. These findings highlight constructs that may improve identification of individuals at short-term risk for worsening SI and/or NFSAs.