Psychiatry Res [JOURNAL]
Sun
200 papers
Global burden of bipolar disorder in 204 countries and territories, 1990-2021: a systematic analysis of temporal trends, demographic disparities, and SDI associations for the Global Burden of Disease Study 2021.
Wu Y, Yang G, Shen H … +6 more , Fan F, Sun Y, Xu JE, Wu Y, Wang W, Zhang L
Psychiatry Res · 2026 Jun · PMID 42335719 · Publisher ↗
BACKGROUND: Bipolar disorder is a chronic psychiatric disorder with recurrent manic/hypomanic and depressive episodes, posing substantial individual, family, and societal burdens as a critical global public health concer...
BACKGROUND: Bipolar disorder is a chronic psychiatric disorder with recurrent manic/hypomanic and depressive episodes, posing substantial individual, family, and societal burdens as a critical global public health concern. METHODS: We extracted bipolar disorder data (incidence, prevalence, and Disability-Adjusted Life Years (DALYs)) from the Global Burden of Disease Study 2021 (1990-2021). R software was used for analyses (trend quantification, Socio-Demographic Index (SDI) correlation), and the Autoregressive Integrated Moving Average (ARIMA) model forecasted 2022-2040 incidence in males/females. RESULTS: From 1990 to 2021, total incident cases, prevalent cases, and DALYs increased across genders and the overall population, while DALYs and prevalence rates decreased. Male and total incidence rates rose (female incidence stabilized); females consistently had higher age-standardized incidence and prevalence rates than males. Oceania and Brazil had a high burden, while Asia and North America had a lower burden. SDI correlated positively with age-standardized incidence. ARIMA projected decreasing male but increasing female incidence post-2021. CONCLUSION: This study provides the first integrated analysis of long-term trends, socioeconomic disparities, and gender-specific forecasts for bipolar disorder burden, offering evidence-based targets for precision public health interventions. The global bipolar disorder burden remains notable, with gender and regional disparities. Targeted interventions for high-risk groups (e.g., females) and under-resourced regions are vital to reduce their impact.
Risk factors associated with fever after modified electroconvulsive therapy: A session-level study.
Liu C, Cong W, Huang J … +1 more , Wang W
Psychiatry Res · 2026 Jun · PMID 42335718 · Publisher ↗
OBJECTIVE: To characterize fever within 24 h after modified electroconvulsive therapy (MECT) and to identify risk factors for post-MECT fever. METHODS: We retrospectively enrolled 451 patients with psychiatric disorders...
OBJECTIVE: To characterize fever within 24 h after modified electroconvulsive therapy (MECT) and to identify risk factors for post-MECT fever. METHODS: We retrospectively enrolled 451 patients with psychiatric disorders who underwent MECT at a single center between August 2021 and August 2022, comprising 3006 treatment sessions. Fever was defined as an axillary temperature ≥37.3 °C within 24 h after each session. Fever incidence and characteristics were summarized. Because multiple treatment sessions were nested within the same patient, a mixed-effects logistic regression model was used to evaluate associations of treatment session order, anesthetic regimen, demographic characteristics, and EEG seizure duration with post-MECT fever. RESULTS: The patient-level incidence of fever was 20.18% (91/451), and the session-level incidence was 3.89% (117/3006). Fever episodes clustered within the first three sessions and were predominantly low-grade (65.8%). Mixed-effects logistic regression analysis showed higher fever risk during the first (OR 2.185, 95% CI 1.416-3.371, P < 0.001) and second (OR 3.113, 95% CI 2.080-4.659, P < 0.001) treatment sessions compared with sessions after the third MECT. Additionally, longer EEG seizure duration was independently associated with post-MECT fever (OR 1.011, 95% CI 1.001-1.020; P = 0.032). CONCLUSIONS: Post-MECT fever was typically low-grade and more likely to occur during the early treatment sessions. Both treatment session order and EEG seizure duration were independently associated with post-MECT fever, highlighting the importance of balancing treatment adequacy with peri‑procedural safety, particularly during the early phase of MECT.
Temporal trends in the prevalence of psychiatric diagnoses among aging veterans in the U.S. Department of Veterans Affairs healthcare system: An analysis by sex, age, period, and cohort.
Beydoun HA, Beydoun MA, Nixdorff N … +2 more , Wallace R, Tsai J
Psychiatry Res · 2026 Jun · PMID 42330865 · Full text
Women and older adults represent rapidly growing segments of the US veteran population. Understanding sex-specific patterns in psychiatric diagnoses among aging veterans is essential for anticipating future healthcare se...
Women and older adults represent rapidly growing segments of the US veteran population. Understanding sex-specific patterns in psychiatric diagnoses among aging veterans is essential for anticipating future healthcare service needs within the Department of Veterans Affairs (VA). The purpose of this retrospective study was to estimate prevalence and evaluate age-period-cohort trends in overall and broadly defined psychiatric disorders among women and men veterans aged ≥50 years. Using VA Corporate Data Warehouse data, 254,138 women veterans ≥50 years were 1:1 matched to 254,138 men veterans ≥50 years who used VA healthcare between 2000 and 2023. Twelve-month prevalence of overall psychiatric diagnoses and major diagnostic categories, including substance use disorders (SUDs) (alcohol, drug) and mental health disorders (mood, anxiety, and psychotic), were examined by sex across age, period, and cohort axes using descriptive and age-period-cohort interaction analyses. In the overall population, psychiatric diagnoses were identified in 9.0% of women and 10.6% of men veterans. Women had lower SUDs prevalence than men, with SUD rates declining with age in both sexes. Mental health disorders, particularly mood and anxiety disorders, increased during 2015-2023. Psychotic disorders increased with age but declined across calendar periods. Cohort effects were observed for several diagnostic categories, though less pronounced for alcohol use and mood disorders in both sexes and for psychotic disorders among women. In conclusion, psychiatric disorders are increasingly prevalent among more recent cohorts of aging US veterans, with distinct sex-specific age-period-cohort patterns, underscoring the need for tailored strategies for older women and men veterans.
Long-term antipsychotic use and cardiometabolic adverse effects in adults with non-psychotic disorders: A systematic review.
Radha Krishnan RP, Dzidowska M, Zheng D … +6 more , Russell DJ, Rhaman A, Quintrell E, Chan CH, Buckley NA, Raubenheimer JE
Psychiatry Res · 2026 Jun · PMID 42330864 · Publisher ↗
BACKGROUND: Off-label antipsychotic prescribing for non-psychotic disorders is increasing, often at low doses and over extended periods. While cardiometabolic adverse effects are documented among individuals treated with...
BACKGROUND: Off-label antipsychotic prescribing for non-psychotic disorders is increasing, often at low doses and over extended periods. While cardiometabolic adverse effects are documented among individuals treated with antipsychotics for psychotic disorders, the consequences of long-term off-label antipsychotic use are not well-known. This systematic review synthesises evidence for cardiometabolic adverse effects of long-term antipsychotic therapy in adults and the elderly with non-psychotic disorders. METHODS: We searched electronic databases for randomised controlled trials or observational studies of ≥1 year duration. Adverse events included weight gain, hyperglycaemia, dyslipidaemia, hypertension, metabolic syndrome, ischaemic heart disease, thrombosis and cardiometabolic mortality. RESULTS: We found 13 observational studies with high heterogeneity. Among adults, antipsychotic-treated individuals displayed increased prevalence of weight gain (28.8-77.9%), hyperglycaemia (4.8-23.2%) and dyslipidaemia (15.8-47.5%) compared with untreated patients. Second-generation antipsychotics had a larger effect than first-generation agents. A weak association was observed for cardiometabolic mortality. Results were sparse for the elderly, with one study indicating increased prevalence of metabolic syndrome and its components, and an inverse correlation of treatment duration with the risk for myocardial infarction. Studies were judged to have moderate-high methodological quality using suitable standardised risk of bias assessment tools. CONCLUSIONS: Despite heterogeneity in included studies, this review highlights adverse cardiometabolic outcomes associated with long-term antipsychotic use in adults with non-psychotic disorders, which is concerning given the high proportion of off-label use. Clinicians should exercise caution when prescribing antipsychotics off-label, especially where alternative options are available, and support even low-dose use with regular metabolic monitoring.
Menopausal status-specific association between the triglyceride-glucose index and a body shape index (TyG-ABSI) and depression in U.S. women.
Li G, Bai X, Wang S … +1 more , Feng X
Psychiatry Res · 2026 Jun · PMID 42330863 · Publisher ↗
BACKGROUND: Depression disproportionately affects women, particularly during the menopausal transition, a period of significant endocrine and metabolic changes. The triglyceride-glucose index and a body shape index (TyG-...
BACKGROUND: Depression disproportionately affects women, particularly during the menopausal transition, a period of significant endocrine and metabolic changes. The triglyceride-glucose index and a body shape index (TyG-ABSI), a novel metabolic indicator, has been associated with depressive symptoms. However, its role across different menopausal statuses requires further characterization. METHODS: This cross-sectional study included 2707 premenopausal and 3119 postmenopausal women from the National Health and Nutrition Examination Survey (NHANES) 2007-2020. Depressive symptoms were defined as a Patient Health Questionnaire-9 (PHQ-9) score ≥10. Multivariable logistic regression analyses and restricted cubic spline (RCS) were applied to evaluate the associations between TyG-ABSI and depression. Subgroup and sensitivity analyses were conducted to assess potential effect modification and verify robustness. RESULTS: Significantly positive associations between TyG-ABSI and depression were observed exclusively among postmenopausal women (OR = 1.29, 95%CI: 1.09-1.52), whereas no such relationship existed in premenopausal women. Within the postmenopausal group, participants in the lowest quartile exhibited reduced odds of depression compared with the highest quartile (OR = 0.44, 95%CI: 0.27-0.73). RCS analysis confirmed a linear dose-response relationship in postmenopausal women. Subgroup analyses identified a significant interaction with LTPA, with the association remaining significant only among physically inactive individuals. Sensitivity analyses further validated the robustness of the association. CONCLUSION: This study highlights a menopausal status-specific association between TyG-ABSI and depression. Elevated TyG-ABSI is independently associated with higher odds of depression among postmenopausal women, with the association varying according to LTPA levels. Our findings extend current understanding of the relationship between metabolic dysfunction and depression in women.
Antidepressant use and worsening of non-suicidal self-injury and suicidality in bipolar disorder: A multicenter retrospective cohort study.
Deng Y, Xu N, Huang J … +21 more , Hu X, Huang S, Cui Z, Li Y, Wang L, Zhang Y, Sun P, Su Z, Yao Z, An C, Jia Y, Wang Z, Rong H, Lin K, He Z, Hu S, Wang C, Bao J, Xu X, Lv X, Yu X
Psychiatry Res · 2026 Jun · PMID 42330862 · Publisher ↗
The safety of antidepressants in bipolar disorder (BD) remains controversial, particularly regarding the risk of behavioral activation and worsening Non-Suicidal Self-Injury (NSSI). This multi-center retrospective cohort...
The safety of antidepressants in bipolar disorder (BD) remains controversial, particularly regarding the risk of behavioral activation and worsening Non-Suicidal Self-Injury (NSSI). This multi-center retrospective cohort study included 575 patients with BD from 15 medical centers in China to evaluate the association between antidepressant use and NSSI frequency, suicidal ideation (SI), and suicidal behavior (SB) over a one-year period. Multivariable logistic regression revealed that antidepressant use was associated with higher odds of the worsening of NSSI (OR=1.90, p = 0.030), as well as the presence of SI (OR=1.70, p = 0.016) and SB (OR=1.80, p = 0.010). In exploratory subgroup analyses, point estimates were larger in patients with low household income (OR=2.74, p = 0.038) and non-depressive dominant polarity (OR=7.05, p < 0.001), and the association reached significance only in patients not receiving concurrent lithium (OR=2.29, p = 0.032) but not in lithium-treated patients (OR=1.38, p = 0.462); however, none of the formal interaction tests was statistically significant (all interaction p > 0.05). These findings indicate that antidepressant use in BD is associated with higher odds of worsening NSSI and suicidality. The observed subgroup differences did not reach statistical significance on interaction testing and should be regarded as hypothesis-generating.
Characteristics of self-harm in patients with first episode psychosis.
Solberg AC, Ottesen AA, Barrett EA … +3 more , Mork E, Qin P, Melle I
Psychiatry Res · 2026 Jun · PMID 42322928 · Publisher ↗
BACKGROUND: Suicide is a leading cause of premature death in schizophrenia spectrum disorders (SSD). Self-harm (SH)-including suicide attempts (SA) and non-suicidal self-harm (NSSH)-is highly prevalent, especially in fir...
BACKGROUND: Suicide is a leading cause of premature death in schizophrenia spectrum disorders (SSD). Self-harm (SH)-including suicide attempts (SA) and non-suicidal self-harm (NSSH)-is highly prevalent, especially in first-episode psychosis (FEP). Detailed knowledge of SH characteristics before and at treatment start is limited. OBJECTIVES: In a FEP SSD sample, we aimed to: (I) estimate SH prevalence, distinguishing NSSH and SA; (II) describe characteristics of the most recent SH at first treatment, including planning and motives; (III) examine the most recent SA, including violent versus non-violent methods; and (IV) investigate associations between clinical characteristics and current suicidal behavior (SB) at treatment start. METHODS: We included 252 patients aged 18-65 years with DSM-IV SSD from the Thematically Organized Psychosis study, all within their first year of adequate treatment. Assessments included SCID, PANSS, GFS, BIS, PAS, AUDIT/DUDIT, detailed SH interviews, the Scale for Suicidal Ideation, and CGI-SS. Analyses comprised bivariate tests and logistic regressions. RESULTS: Of 251 participants with SH data, 85 (34%) reported lifetime SH and 32 (13%) at least one SA. Multiple SH episodes were associated with younger age, poorer premorbid social adjustment, longer duration of untreated psychosis, fewer negative symptoms, and higher alcohol use. NSSH typically occurred closer to treatment start, with planning under one day and rarely leading to hospitalization. Among SA, 57% used violent methods, more common in men and those with schizophrenia. At baseline, 33% showed current SB, associated with depressive symptoms and higher self-reported insight. CONCLUSIONS: SH and SB are common and often severe in early SSD, with frequent violent SA and short planning times.
Intranasal esketamine in treatment-resistant depression with and without comorbid borderline personality disorder: A multicenter real-world longitudinal study.
Mazzoni F, Raffone F, De Ciechi A … +6 more , Girone N, Macellaro M, Martinotti G, Dell'Osso B, Martiadis V, Olivola M
Psychiatry Res · 2026 Jun · PMID 42322927 · Publisher ↗
BACKGROUND: Borderline personality disorder (BPD) often occurs alongside treatment-resistant depression (TRD), but the impact of BPD on real-world outcomes with intranasal esketamine is unclear. METHODS: Consecutive TRD...
BACKGROUND: Borderline personality disorder (BPD) often occurs alongside treatment-resistant depression (TRD), but the impact of BPD on real-world outcomes with intranasal esketamine is unclear. METHODS: Consecutive TRD outpatients initiating intranasal esketamine treatment at four Italian centres between 1 September 2024 and 30 September 2025 were enrolled in the study (n = 90): 45 with comorbid BPD and 45 without any personality disorder. The primary outcome was the trajectory of depressive symptoms on the Montgomery-Åsberg Depression Rating Scale (MADRS) from baseline (T0) to 2 weeks (T1), 1 month (T2), 3 months (T3) and 6 months (T4). A response was defined as a ≥ 50% reduction in MADRS score, and remission as a MADRS score of ≤10 at T4. Secondary outcomes (exploratory) included anxiety (HAM-A), impulsivity (BIS-11) and cognitive function (MoCA). RESULTS: MADRS scores decreased over time (F(2.45, 215.50)=365.10, p < 0.001, ηp²=0.81), with a significant time × BPD interaction (F(2.45, 215.50)=17.31, p < 0.001), indicating faster early improvement in the BPD group. Remission at six months was 53.3%, with no difference by BPD status (48.9%vs. 57.8%, p = 0.398). However, response rates were higher in the BPD group from month one onwards (T4 OR=12.57, p = 0.004). Sensitivity analyses adjusting for baseline psychotherapy/medications and excluding patients with a history of hypomanic episodes yielded consistent results. Across the whole sample, anxiety and impulsivity decreased, and there was no evidence of worsening of the MoCA score over six months, supporting cognitive safety. No serious adverse events occurred and no patients dropped out. CONCLUSIONS: In routine care, intranasal esketamine was associated with sustained improvement in TRD over six months, and comorbid BPD did not affect remission outcomes.
Psychiatric readmissions following Soteria versus traditional inpatient care: a propensity score-matched cohort study.
Friedlander A, Oren S, Sinai D … +4 more , Bitan DT, Yoffe R, Eitan R, Lichtenberg P
Psychiatry Res · 2026 Jun · PMID 42322926 · Publisher ↗
The Soteria model offers a community-based, recovery-oriented alternative to traditional psychiatric hospitalization, yet long-term evidence regarding its association with readmission remains limited. This study evaluate...
The Soteria model offers a community-based, recovery-oriented alternative to traditional psychiatric hospitalization, yet long-term evidence regarding its association with readmission remains limited. This study evaluated whether treatment in a Soteria home is associated with lower psychiatric readmission rates compared to traditional hospital care. A retrospective analysis was conducted using Israel Ministry of Health records for patients admitted to Soteria or traditional wards in 2018, with follow-up through May 2021 (N = 164). Outcomes included readmission proportion, frequency, time-to-first readmission, and length of stay. Analysis employed propensity score matching (PSM), logistic regression, and Cox proportional hazards modelling. Soteria patients were significantly less likely to be readmitted at 24 months (41.5%vs. 61.0%) and 30 months (45.1%vs. 63.4%). They also experienced longer times to first readmission. Moderation analyses suggested that the association between Soteria care and delayed readmission was more pronounced among younger patients (≤30 years). To address diagnostic imbalances, a stratified PSM sensitivity analysis was conducted; the reduction in readmission hazard remained statistically significant (HR=0.65, 95% CI: 0.43-1.00, p = 0.048), providing partial support for the primary time-to-readmission findings. Treatment in a Soteria home was associated with lower long-term psychiatric rehospitalization, particularly among younger individuals. While the observational design precludes causal conclusions, these findings suggest that Soteria-based residential alternatives may be associated with reduced long-term psychiatric readmission compared with traditional inpatient treatment.
Depressive symptoms and pornography use: A census-matched longitudinal study.
Engelhardt R, Geppert R, Trommer D … +3 more , Grubbs JB, Maes J, Kraus SW
Psychiatry Res · 2026 Jun · PMID 42322925 · Publisher ↗
BACKGROUND: Depressive symptoms and pornography use are both common in the United States. Prior cross-sectional research has consistently reported positive associations between these variables, while longitudinal evidenc...
BACKGROUND: Depressive symptoms and pornography use are both common in the United States. Prior cross-sectional research has consistently reported positive associations between these variables, while longitudinal evidence remains limited and often relies on only two measurement waves. METHOD: We conducted a five-wave longitudinal study based on a census-matched sample of American adults (N = 2806, 53% women, M = 51, SD = 16). Associations between depressive symptoms and frequency of pornography use were examined via partial correlations and a random-intercept cross-lagged panel model (RI-CLPM). All analyses were adjusted for age, gender, and moral disapproval of pornography use. RESULTS: Across all five waves, depressive symptoms were positively associated with frequency of pornography use, independently of age, gender, and moral disapproval. The RI-CLPM indicated that these associations were stable over time and reflected between-person differences rather than reciprocal effects across six-month intervals. CONCLUSION: Among American adults, depressive symptoms and frequency of pornography use are positively related at the population level. This association appears to reflect a stable between-person link that is not accounted for by demographics, moral attitudes or interactions across waves. Future research should use ecological momentary assessment and multi-wave longitudinal designs with varying intervals to further examine temporal dynamics of depressive symptoms and frequency of pornography use.
Predicting relapse risk from patients' perceptions of family functioning in early psychosis: A three-year longitudinal study.
Morejón AJV, Reyes AV, Muñoz-Caracuel MA … +1 more , Vázquez-Morejón R
Psychiatry Res · 2026 Jun · PMID 42322924 · Publisher ↗
This study examines the predictive capacity of the Spanish adaptation of the Influential Relationships Questionnaire (IRQ) in the clinical course of patients with first-episode psychosis. A total of 119 patients diagnose...
This study examines the predictive capacity of the Spanish adaptation of the Influential Relationships Questionnaire (IRQ) in the clinical course of patients with first-episode psychosis. A total of 119 patients diagnosed with psychotic disorders (ICD-10 F20-F31), aged 18 to 35 years and living with one or both parents, were recruited from a Community Mental Health Unit and followed for three years. During initial evaluations, patients completed the short version of the IRQ, in addition to routine clinical assessments. Outcome variables included the number of relapses, hospital admissions, and time to relapse/admission, obtained from clinical records and follow-up databases. The criticism dimension of the IRQ showed the strongest predictive power, with significant and moderate-to-strong correlations with all outcome measures, particularly when referred to fathers. Care was negatively correlated with relapses and admissions, suggesting a protective effect, although with smaller effect sizes. Overinvolvement showed weak and inconsistent associations, while restriction was not significantly related to outcomes. Regression analyses confirmed the explanatory capacity of criticism, accounting for up to 23% of the variance in admissions in the paternal subgroup. Patients in the highest-criticism tertile showed markedly higher rates of relapse and admission compared to those in the lowest tertile. These findings confirm the predictive validity of the Spanish adaptation of the IRQ and highlight the importance of perceived criticism as a key dimension in the family emotional climate of first-episode psychosis. The results underscore the clinical relevance of incorporating the assessment of perceived criticism into routine practice and of including parents, particularly fathers, in therapeutic interventions.
Cytokine changes during a 12-month pragmatic randomized trial in schizophrenia spectrum disorders comparing amisulpride, aripiprazole and olanzapine.
Kroken RA, Johnsen E, Alisauskiene R … +20 more , Anda LG, Bartz-Johannesen C, Berle JØ, Bjarke J, Bruserud Ø, Fathian F, Fleischhacker WW, Hugdahl K, Joa I, Kjelby E, Larsen TK, Løberg EM, Ratke I, Rettenbacher M, Sinkeviciute I, Skrede S, Stabell L, Steen VM, Torsvik A, Reitan SK
Psychiatry Res · 2026 Jun · PMID 42322923 · Publisher ↗
BACKGROUND: Schizophrenia is associated with inflammation. Antipsychotic drugs have anti-inflammatory properties but few antipsychotics have been compared head-to head. The aim of this study was to evaluate the immunomod...
BACKGROUND: Schizophrenia is associated with inflammation. Antipsychotic drugs have anti-inflammatory properties but few antipsychotics have been compared head-to head. The aim of this study was to evaluate the immunomodulatory effects of three pharmacologically different atypical antipsychotics, amisulpiride, aripiprazole and olanzapine, in patients with schizophrenia-spectrum disorders. METHODS: The study reports a predefined secondary outcome of the BeSt InTro-study, a double blind randomized head-to-head trial comparing amisulpride, aripiprazole and olanzapine. Patients with a schizophrenia-spectrum disorder (N=144) were randomized to the different treatment arms, and serum levels of nine cytokines (interleukin [IL]-1β, IL-2, IL-4, IL-6, IL-10, IL-12p70, IL-17A, interferon [IFN]-γ, and tumor necrosis factor [TNF]-α) were assessed at baseline and weeks 1, 3, 6, 12, 26, 39 and 52. A combined pro-inflammatory variable was constructed from IL1-β and TNF-α. The primary analyses were done in per protocol (PP) data in the drug-naïve sample (n = 56). Changes in cytokine levels between baseline and the end of the study were analyzed in a mixed effects model with amisulpride as the reference drug. RESULTS: Treatment with amisulpride was associated with a reduction in pro-inflammatory IL-1β levels over 12 months, this change was statistically different compared to the change in aripiprazole and olanzapine. A significant difference between the influence of amisulpride compared to aripiprazole on the anti-inflammatory cytokine IL-10 was detected. Aripiprazole reduced IL-12p70 more than amisulpride. The combined pro-inflammatory variable decreased from baseline to week 52 with a magnitude of 0.52 standard deviation (SD) after treatment with amisulpride.. CONCLUSION: Patients treated with amisulpride showed greater anti-inflammatory changes in cytokine serum levels than those treated with aripiprazole or olanzapine. FUNDING: The Research Council of Norway, the Western Norway Regional Health Trust, and Klinbeforsk supported the study.
In vivo associations between anticipatory and consummatory reward responsiveness: A cross lagged panel analysis.
Balkind EG, Lord KA, Fields JS … +2 more , Santiago N, Liverant GI
Psychiatry Res · 2026 Jun · PMID 42320290 · Publisher ↗
Reward system functioning involves a complex set of processes, including motivation to pursue rewards, reward salience, and hedonic capacity. Impairments in these processes are implicated in various forms of psychopathol...
Reward system functioning involves a complex set of processes, including motivation to pursue rewards, reward salience, and hedonic capacity. Impairments in these processes are implicated in various forms of psychopathology. Among several temporal elements within reward processing, anticipatory reward responsiveness (ARR) refers to the anticipation of an expected reward (i.e., wanting) and consummatory reward responsiveness (CRR) involves response to an experienced reward (i.e., liking). Conceptually, it may be that one's ability to anticipate future reward would facilitate initial response to reward receipt. Yet, little research has examined temporal associations between these two distinct components of reward processing over time. The current study utilized ecological momentary assessment (EMA) to explore the relationship between ARR and CRR in response to rewarding daily activities. 544 undergraduate students completed baseline questionnaires assessing demographic information and depressive symptoms. Participants then completed EMA questionnaires assessing ARR and CRR three times per day for seven days. Multilevel modeling with random intercepts and slopes using maximum likelihood (ML) estimation was conducted to examine lagged associations between average ARR and CRR across timepoints. ARR was found to predict subsequent CRR, and a bidirectional relationship was found between CRR and future ARR. Only associations between ARR and subsequent CRR held when controlling for anhedonia symptoms. Our findings support temporal associations between two distinct aspects of reward responsiveness and point to ARR as a key treatment target with potential downstream impacts on future hedonic capacity in patients with blunted reward responding.
A network analysis of adolescent nonsuicidal self-injury from the perspective of an invalidating family environment.
Jiang Y, Han X, Wang B … +1 more , Yi Z
Psychiatry Res · 2026 Jun · PMID 42320289 · Publisher ↗
This study used network analysis to examine the conditional association structure of psychological and environmental risk factors related to nonsuicidal self-injury (NSSI) among adolescents in different invalidating fami...
This study used network analysis to examine the conditional association structure of psychological and environmental risk factors related to nonsuicidal self-injury (NSSI) among adolescents in different invalidating family environments. Cross-sectional data were collected from adolescents in Northwest China (initial N = 9697). After data quality control, defensive responding screening, family-environment grouping, and propensity score matching, 3652 adolescents were included in the main analyses, with 1826 in each of the low- and high-invalidating family environment groups. We estimated separate 16-node networks including individual psychological factors, environmental risk factors, and NSSI, and conducted sensitivity analyses to examine whether the community assignment of NSSI affected bridge centrality. Network structure and global strength differed significantly between groups. Psychological resilience, impulsiveness, and cyberbullying showed relatively high absolute expected influence in both networks. NSSI had the highest bridge expected influence in the main analysis; when NSSI was assigned to the individual psychological community, its bridge centrality decreased but its relative ranking remained high. An exploratory 15-node network excluding NSSI was estimated among adolescents with NSSI in the unmatched high-invalidating group. Psychological resilience, impulsiveness, and rumination showed high absolute expected influence in this exploratory network. These findings suggest that adolescent NSSI-related risk structures may involve complex conditional associations among invalidating family environments, individual regulatory resources, impulsiveness, rumination, and bullying exposure.
Patterns of onset and progression of psychoses induced by psychoactive substance use.
Ifteni P, Miron AA, Necula R … +2 more , Dima L, Teodorescu A
Psychiatry Res · 2026 Jun · PMID 42320288 · Publisher ↗
INTRODUCTION: Drug use in Europe has increased in recent years, including a marked rise in new psychoactive substances (NPS). Substance use disorders negatively affect physical and mental health. Psychotic disorders are...
INTRODUCTION: Drug use in Europe has increased in recent years, including a marked rise in new psychoactive substances (NPS). Substance use disorders negatively affect physical and mental health. Psychotic disorders are highly prevalent among drug users. Establishing a link between illicit drug use and schizophrenia would help clarify the progression risk after substance-induced psychosis. AIMS: To investigate the onset and evolution of substance-induced psychosis in patients hospitalized in Brașov Clinical Hospital of Psychiatry and Neurology. MATERIALS AND METHODS: A retrospective observational study, analyzing data from all the patients admitted to the hospital between 2014 and 2024, who were diagnosed with substance-induced psychosis other than alcohol, according to DSM-5 criteria. RESULTS: Of all admissions, 2353 (9.6%) were diagnosed with acute psychotic disorders, of which 129 (5.5%) were related to psychoactive substances. THC (cannabis) was the main substance used, being present in 82.95% of cases. Almost half of the patients (44.96%) reported multiple drug use. 48.84% of patients required subsequent psychiatric readmissions after a first episode of substance-induced psychosis. 11.62% of the patients with substance-induced psychosis were subsequently diagnosed with a major psychiatric disorder, schizophrenia (N = 10, 7.8%) or bipolar disorder (N = 5, 3.9%). The mean duration of conversion to a major psychiatric disorder was 3.37±3.38 years. CONCLUSIONS: Substance-induced psychosis carried a meaningful risk of later transition to schizophrenia-spectrum or bipolar disorders, particularly among patients with higher-risk substance patterns and other vulnerability factors. THC was the most frequently used substance and emerged as an important risk marker in this cohort, supporting the need for timely recognition, sustained follow-up, and integrated intervention for high-risk patients.
Bayesian colocalization of psychiatric disorder GWAS signals with molecular quantitative trait loci highlights histone involvement and neuroimmune dysregulation in pathogenesis.
Ryu J, Lee C
Psychiatry Res · 2026 Jun · PMID 42320287 · Publisher ↗
Genome-wide association studies (GWAS) have revolutionized our understanding of the genetic architecture of psychiatric disorders. However, the interpretation of these findings remains challenging, as most risk loci resi...
Genome-wide association studies (GWAS) have revolutionized our understanding of the genetic architecture of psychiatric disorders. However, the interpretation of these findings remains challenging, as most risk loci reside in non-coding regions, obscuring the underlying molecular mechanisms. To elucidate the functional consequences of psychiatric risk variants, we implemented a multi-omics Bayesian colocalization framework using transcript, protein and metabolite levels for attention-deficit/hyperactivity disorder, autism spectrum disorder, bipolar disorder (BIP), major depressive disorder (MDD), and schizophrenia (SCZ). Sixty-five SCZ, BIP, and MDD GWAS signals colocalized with immune cell-type-specific expression quantitative trait loci (eQTL), targeting 70 genes. Notably, they included 17 histone-encoding genes colocalized from five GWAS signals. These signals subsequently colocalized with protein QTL (pQTL), targeting 310 proteins enriched in various immune-related pathways (P < 5.99 × 10). Further colocalization with metabolite QTL (metabQTL) revealed 23 metabolites, highlighting GABAergic neurotransmission, norepinephrine metabolism, and androgenic neurosteroid pathways. Considering critical histone function as damage-associated molecular patterns, variability in histone expression might have contributed to neuroimmune mechanisms and thus the pathogenesis of the psychiatric disorders. This study underscores the role of common nucleotide variants regulating histone genes in neuroimmune mechanisms contributing to SCZ, BIP, and MDD. These findings enhance our understanding of underlying molecular targets in their pathophysiology, with a potential strategy of precision psychiatry.
Cytomegalovirus-related immune activation and major neuropsychiatric disorders: Mendelian randomization and bulk transcriptomic validation.
Li J, Chen T
Psychiatry Res · 2026 Jun · PMID 42320286 · Publisher ↗
BACKGROUND: Cytomegalovirus (CMV) establishes lifelong latency and induces persistent changes in peripheral immunity. Observational links to neuropsychiatric disorders are difficult to interpret because of confounding an...
BACKGROUND: Cytomegalovirus (CMV) establishes lifelong latency and induces persistent changes in peripheral immunity. Observational links to neuropsychiatric disorders are difficult to interpret because of confounding and reverse causation. METHODS: We performed two-sample, multivariable, and bidirectional Mendelian randomization (MR) on genetically predicted CMV seropositivity and antigen-specific antibody levels for Parkinson's disease (PD), bipolar disorder (BD), schizophrenia (SCZ), major depressive disorder (MDD), and Alzheimer's disease (AD). Instruments were selected at P < 5 × 10 (secondary at P < 5 × 10). Multivariable MR (MVMR) sensitivity analysis accounting for age-related genetic structure, pleiotropy/heterogeneity tests, and reverse MR evaluated robustness. Bulk transcriptomic validation tested whether CMV CD14+ late-response and HCMV reactivation-related host signatures were enriched in public PD and BD whole-blood datasets. RESULTS: Genetically predicted anti-CMV IgG seropositivity was associated with PD (MVMR sensitivity aOR: 1.12, P = 0.020), with directional consistency in a single-instrument secondary analysis (OR: 1.25, P = 0.003). Anti-CMV pp28 antibody levels were associated with BD (aOR: 1.12, P = 0.043). The SCZ signal attenuated after adjustment, and no robust evidence was observed for MDD or AD. Both CMV-related host signatures were significantly enriched among PD-upregulated genes (CMV CD14+ NES = 1.85, FDR = 2.73 × 10; HCMV reactivation NES = 2.03, FDR = 9.11 × 10); BD showed no robust positive enrichment after covariate adjustment. CONCLUSIONS: Integrated genetic and transcriptomic evidence prioritizes CMV-related peripheral immune activation as a plausible contributor to PD risk. The pp28-BD signal is hypothesis-generating and requires validation in datasets with direct CMV serostatus.
Associations between metabolic features and psychotic symptoms in anxious depression across different ages of onset: the mediating role of symptom severity.
Sun QM, Zhang S, Wang C … +1 more , Zhang XY
Psychiatry Res · 2026 Jun · PMID 42320285 · Publisher ↗
BACKGROUND: Anxiety and psychotic symptoms frequently occur in major depressive disorder (MDD) and are associated with metabolic features. Age of onset plays a crucial role in the variability of MDD patients. AIMS: To in...
BACKGROUND: Anxiety and psychotic symptoms frequently occur in major depressive disorder (MDD) and are associated with metabolic features. Age of onset plays a crucial role in the variability of MDD patients. AIMS: To investigate associations between metabolic features and psychotic symptoms in anxious MDD patients categorized by age of onset. METHODS: We conducted a cross-sectional analysis involving 894 anxious MDD patients, utilizing standardized assessments for depression (Hamilton Depression Scale, HAMD), anxiety (Hamilton Anxiety Scale, HAMA), and psychotic symptoms (Positive and Negative Syndrome Scale, PANSS), alongside metabolic features. Patients were categorized into the early adulthood onset (EAO, <45 years old) group and the mid-adulthood onset (MAO, ≥45 years old) group. RESULTS: Our findings revealed that MAO patients exhibited higher prevalence of psychotic symptoms compared to EAO group. In the EAO group, fasting blood glucose (FBG) was independently associated with a higher risk of psychotic symptoms, while in the MAO group, triglyceride (TG) levels and systolic blood pressure (SBP) showed independent associations with increased risk. Exploratory serial mediation analyses indicated that depression/anxiety severity fully statistically mediated the relationship between FBG and psychotic symptoms in EAO patients. Additionally, symptom severity fully statistically mediated the SBP-psychotic symptoms link in MAO patients but only partially statistically mediated the TG-psychotic symptoms relationship. CONCLUSIONS: These results underscore the complex interplay between psychological and physiological factors in anxious MDD, indicating that age of onset group statistically moderated the associations between metabolic features and psychotic symptoms, and depression/anxiety severity showed exploratory indirect associations consistent with statistical mediation between metabolic features and psychotic symptoms.
Machine learning algorithms in jointly developing prediction models for subsequent school bullying victimization in Chinese children and adolescents.
Peng J, Yang H, Lu J … +7 more , Xiang Y, Liu X, Wang X, Gao F, Zheng Y, Yang Z, Xiao Y
Psychiatry Res · 2026 Jun · PMID 42320284 · Publisher ↗
Existing evidence indicates that children and adolescents experiencing bullying victimization (BV) exhibit mental health deterioration, and such effects can persist into adulthood. As current decision-making tools are sc...
Existing evidence indicates that children and adolescents experiencing bullying victimization (BV) exhibit mental health deterioration, and such effects can persist into adulthood. As current decision-making tools are scarce, we aim to develop a tool to predict subsequent BV risk among Chinese youth. Data were retrieved from a three-wave prospective study which incorporated into the Mental Health Survey for Children and Adolescents in Yunnan (MHSCAY). Six common machine learning (ML) algorithms were used. We internally validated the models using 500 times bootstrap approach to assess discrimination, calibration, and utility. A total of 5345 participants aged 10-17 years completed the survey. The internal validation showed the logistic regression (LR) model slightly outperformed other ML algorithms and exhibited more evenly distributed individual-level prediction uncertainty. It was therefore selected as the final model, achieving an AUROC of 0.800 (95% CI: 0.785, 0.815), AUPRC of 0.519 (95% CI: 0.483, 0.553), calibration intercept of -0.001 (95% CI: -0.076, 0.069), calibration slope of 0.990 (95% CI: 0.930, 1.059), and Brier score of 0.122 (95% CI: 0.117, 0.128). Furthermore, the calibration plot indicated excellent precision, and positive net benefits were observed across broad threshold ranges. Fairness analysis revealed no predictive bias in key subpopulations. This novel predictive tool utilizes seven baseline predictors that are readily accessible to generate accurate, individualized predictions of subsequent BV risk in children and adolescents. Upon further validation, the model may facilitate risk stratification, thereby guiding resource allocation and informing targeted interventions for potential BV crises among Chinese children and adolescents.
Multi-omics integration identifies cell-type-specific CISD1 and QDPR as druggable regulators linking hepatocellular carcinoma and major depressive disorder.
Sun L, Bi J, Sun J
Psychiatry Res · 2026 Jun · PMID 42314449 · Publisher ↗
BACKGROUND: Hepatocellular carcinoma (HCC) and major depressive disorder (MDD) often co-occur, but whether this comorbidity reflects shared pharmacologically tractable biology remains unclear. METHODS: We integrated a th...
BACKGROUND: Hepatocellular carcinoma (HCC) and major depressive disorder (MDD) often co-occur, but whether this comorbidity reflects shared pharmacologically tractable biology remains unclear. METHODS: We integrated a three-step mendelian randomization strategy-comprising whole-blood eQTL screening, GTEx eQTL validation, and single-cell immune eQTL refinement-to systematically screen 2,534 druggable genes, to identify targets with consistent causal effects across two diseases. Subsequently, we dissected their potential mediating pathways using 91 circulating inflammatory proteins and 338 cerebrospinal fluid metabolites as mediators, and subsequently validated repurposable compounds via molecular docking. RESULTS: Two genes satisfied all stringent criteria: CISD1and QDPR. Immune-cell-specific expression patterns of CISD1 in CD4 NC, CD8 ET, and NK cells increased shared risk, whereas QDPR transcription in CD4 ET, CD4 NC, CD8 ET, Mono C, and NK R cells reduced risk. Alpha-hydroxyisovalerate mediated 6.98% (HCC) and 8.75% (MDD) of CISD1's causal effect; N-acetyl-β-alanine accounted for 16.15% (HCC) and 8.13% (MDD) of QDPR's protective effect. Dihydroergotamine, an FDA-approved antimigraine agent, exhibited high binding affinity for both proteins (-9.3 and -10.2 kcal mol⁻¹), nominating it as a dual-indication candidate. CONCLUSIONS: CISD1and QDPRconstitute genetically supported, druggable regulators that converge mechanistically on metabolic-inflammatory axes associated with HCC-MDD comorbidity. Repurposing dihydroergotamine warrants immediate preclinical evaluation for simultaneous oncologic and psychiatric benefits.
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