Psychiatry Res [JOURNAL]
Sun
200 papers
Machine learning-based prediction of suicide risk: A long-term OCD cohort follow-up.
Tubío-Fungueiriño M, Puialto M, Cernadas E … +6 more , Fernández-Delgado M, Real E, Alonso P, Carracedo A, Segalàs C, Fernández-Prieto M
Psychiatry Res · 2026 Jun · PMID 42314448 · Publisher ↗
BACKGROUND: Obsessive Compulsive Disorder (OCD) is associated with an increased suicide risk in comparison with general population. Among the suicide risk factors we can highlight psychiatric comorbidities, childhood tra...
BACKGROUND: Obsessive Compulsive Disorder (OCD) is associated with an increased suicide risk in comparison with general population. Among the suicide risk factors we can highlight psychiatric comorbidities, childhood trauma, obsessive-compulsive severity and a combination of other risk factors related to social and family environment. This study aims to develop and validate a reliable machine learning algorithm to predict suicide risk in OCD patients, based on a combination of clinical and sociodemographic variables. METHOD: A cohort of 199 OCD patients was followed for an average of 17.8 years (follow-up time range of between 2-28 years) in an OCD-specialized unit. Suicide-related behaviors were documented in the medical records of each participant at the time of occurrence. For the present study, a specialized psychiatrist systematically reviewed all clinical records to extract detailed information on the type of suicide-related behaviors experienced by each participant. Clinical data, including comorbidities, Y-BOCS and CTQ, were collected and used to train supervised machine learning models. RESULTS: The best-performing model included three predictive variables: family history of suicide, affective comorbidities, and substance use. This model achieved a sensitivity of 71.4%, specificity of 74.4%, F1-score=62.7% and area under ROC curve of 0.80, demonstrating moderate predictive capability. OCD severity and childhood trauma did not significantly enhance prediction performance. CONCLUSION: This study highlights the potential of supervised machine learning in identifying suicide risk in OCD patients based on commonly-collected clinical variables. The presence of any of the three predictors that conform the best-performing model (family history of suicide, affective comorbidities, and substance use) is sufficient to detect the presence of suicide-behavior risk. Those predictors are routinely assessed in clinical practice, making this model a feasible instrument for early risk detection. Further research with larger and more diverse cohorts is needed to refine predictive accuracy and integrate additional biomarkers for improved suicide risk stratification.
Anhedonia in patients with major depressive disorder (MDD): State-of-the-art consensus review.
Cutler AJ, Clayton AH, Krystal AD … +3 more , Maletic V, McIntyre RS, Nemeroff CB
Psychiatry Res · 2026 May · PMID 42314447 · Publisher ↗
Anhedonia is a highly prevalent core pathognomonic symptom of a major depressive episode seen in major depressive disorder (MDD) and bipolar disorder. The symptom is associated with functional impairment, increased suici...
Anhedonia is a highly prevalent core pathognomonic symptom of a major depressive episode seen in major depressive disorder (MDD) and bipolar disorder. The symptom is associated with functional impairment, increased suicidality, psychiatric and somatic comorbidity, and poor therapeutic outcomes. It is an understudied and undertreated symptom, without clinically practical scales to measure its different aspects, and there are no therapies specifically designed to target anhedonia. This expert consensus aims to increase the awareness and understanding of anhedonia among healthcare professionals (HCPs) and provide consensus recommendations on the assessment, management, and treatment of anhedonia in patients with MDD. A group (N=6) of psychiatrists formed an expert consensus group that convened in a teleconference meeting in January 2024 to develop 14 consensus statements that provide an overview of the assessment, management, and treatment of anhedonia in patients with MDD. Anhedonia is a highly prevalent symptom of MDD, and it includes anticipatory, consummatory, and cognitive aspects. Several tools exist to assess the specific components of anhedonia, and the neural circuitry mediating anhedonia continues to be elucidated. The expert opinions provided by the authors aim to increase HCP awareness and understanding of anhedonia, and improve the evaluation, management, and treatment of anhedonia in patients with MDD. HCPs should routinely evaluate all aspects of anhedonia using clinical scales and welcome novel treatments that meaningfully target anhedonia. Future studies should assess the effectiveness of treatments for anhedonia and improve measurement-based initial assessment and monitoring of outcomes with comprehensive tools.
Adjunctive intermittent theta-burst stimulation for first-episode schizophrenia: A randomized clinical trial.
Zhang K, Xue H, Wang C … +3 more , Li N, Sun M, Cui J
Psychiatry Res · 2026 May · PMID 42308997 · Publisher ↗
BACKGROUND: The efficacy of intermittent theta-burst stimulation (iTBS) combined with pharmacotherapy and psychotherapy in first-episode schizophrenia remains unclear. This study evaluated adjunctive iTBS with risperidon...
BACKGROUND: The efficacy of intermittent theta-burst stimulation (iTBS) combined with pharmacotherapy and psychotherapy in first-episode schizophrenia remains unclear. This study evaluated adjunctive iTBS with risperidone and cognitive behavioral therapy (CBT) and explored serum biomarkers indicating treatment response. METHODS: In this randomized, assessor-blind trial, 100 first-episode schizophrenia patients received either iTBS plus risperidone and CBT (iTBS group, n = 50) or risperidone and CBT alone (control, n = 50) for 3 months. The primary outcome was change in PANSS total score at 4 weeks and 3 months. Response was defined as a ≥ 50 % PANSS reduction. Secondary outcomes included cognitive function (MCCB subtests) and serum GDNF, cortisol, and dehydroepiandrosterone sulfate (DHEA-S) levels. RESULTS: The iTBS group showed significantly greater reduction in PANSS total scores than controls at both 4 weeks and 3 months (mean difference at 3 months: -13.3, 95 % CI: -16.8 to -9.8; P < 0.001), with a higher responder rate (76 % vs. 48 %). Significant improvements across all cognitive domains were observed in the iTBS group (all P < 0.001). Post-treatment, the iTBS group exhibited higher GDNF and lower cortisol and DHEA-S levels (all P < 0.001). A combined biomarker panel demonstrated superior discriminative performance for treatment efficacy (AUC=0.865 after cross-validation). Adverse events were comparable between groups. CONCLUSIONS: Adding iTBS to risperidone and CBT significantly improves clinical symptoms and cognitive function in first-episode schizophrenia. The combination of GDNF, cortisol, and DHEA-S shows promise as a composite biomarker for treatment response, though sham-controlled validation is warranted.
Pilot randomized trial of intermittent theta-burst stimulation versus H-Coil transcranial magnetic stimulation for treatment-resistant depression.
Desbeaumes Jodoin V, Bousseau E, Trottier-Duclos F … +10 more , Jutras-Aswad D, Lespérance F, Assi ÉB, Nguyen DK, Blumberger DM, Baker TE, Arns M, Daskalakis ZJ, Lespérance P, Miron JP
Psychiatry Res · 2026 Jun · PMID 42302659 · Publisher ↗
BACKGROUND: Intermittent theta burst stimulation (figure-8-coil iTBS) and H7-coil repetitive transcranial magnetic stimulation (rTMS) are FDA-cleared treatments for major depression; yet their comparative effectiveness i...
BACKGROUND: Intermittent theta burst stimulation (figure-8-coil iTBS) and H7-coil repetitive transcranial magnetic stimulation (rTMS) are FDA-cleared treatments for major depression; yet their comparative effectiveness in treatment-resistant depression (TRD) has not been evaluated in randomized trials. This pilot randomized trial was designed to obtain preliminary comparative estimates and to explore whether baseline cognitive functioning relates to early remission. METHODS: Twenty-eight adults with TRD were randomized to six weeks of figure-8-coil iTBS delivered to the dorsolateral prefrontal cortex (DLPFC) (n = 15) or H7-coil rTMS delivered to the dorsomedial prefrontal cortex (DMPFC) (n = 13). The primary outcome was change in 17-item Hamilton Depression Rating Scale (HRSD-17) score from baseline to week 6, analyzed with ANCOVA. Additional outcomes included response, remission, and symptom trajectories through week 18. Exploratory analyses examined the association between baseline cognitive functioning, such as executive functions and memory, and remission. RESULTS: Twenty-five participants completed all 30 sessions. Adjusted week-6 HRSD-17 scores did not differ between groups (mean difference -0.40, 95% CI -5.23 to 4.43; p=.865). Response rates were 40.0% for figure-8-coil iTBS and 50.0% for H7-coil rTMS (p>.60), and remission rates were identical across groups (20.0%). Remitters showed higher baseline executive functioning than non-remitters in exploratory analyses, although these associations were not confirmed in adjusted models. CONCLUSION: In this pilot trial, figure-8-coil iTBS and H7-coil rTMS showed symptom improvement, with no clear between-group differences. Exploratory findings suggest a potential signal involving executive functioning that warrants further investigation. These results inform the feasibility and design of larger comparative trials. TRIAL REGISTRATION: ClinicalTrials.gov (NCT05902312).
Suicide attempt-related gray matter volume alterations in major depressive disorder and its associations with childhood trauma.
Jung M, Park J, Kang Y … +5 more , Shin D, Kang JC, Tae WS, Ham BJ, Han KM
Psychiatry Res · 2026 Jun · PMID 42296874 · Publisher ↗
BACKGROUND: Suicide is a major cause of premature mortality in major depressive disorder (MDD), yet its neurobiological substrates remain unclear. Suicide attempters represent a distinct phenotype characterized by impair...
BACKGROUND: Suicide is a major cause of premature mortality in major depressive disorder (MDD), yet its neurobiological substrates remain unclear. Suicide attempters represent a distinct phenotype characterized by impaired affect regulation and fronto-limbic structural alterations. Early-life adversity may further sensitize stress-responsive circuits. This study examined gray matter volume (GMV) alterations associated with suicide attempts in MDD and their relationships with childhood trauma and suicidal ideation. METHODS: T1-weighted magnetic resonance imaging data were obtained from 204 adults (61 suicidal depression [SD], 62 non-suicidal depression [NSD], 81 healthy controls [HC]). Whole-brain voxel-based morphometry (VBM) identified regions differentiating SD from NSD. The cluster showing a significant SD-NSD GMV difference was defined as the region of interest (ROI), and its GMV was correlated with Childhood Trauma Questionnaire (CTQ) and Suicidal Ideation Scale (SSI) scores. Exploratory voxel-wise regression assessed childhood trauma-related GMV patterns across groups. RESULTS: VBM revealed reduced GMV in the septal nucleus, distinguishing SD from NSD. ROI analyses confirmed lower septal GMV in SD than in NSD and HC, and smaller volume correlated with greater suicidal ideation in patients with MDD. Within the SD group, voxel-wise regression showed negative associations between CTQ scores and GMV in the cerebellar vermis. CONCLUSION: Distinct gray matter alterations emerged in MDD, with septal atrophy appearing as a potential suicide-related feature, while cerebellar vermis reductions showed a tentative association with early adversity that warrants cautious interpretation. These findings suggest that interrelated limbic, cerebellar, and septal regions may contribute to stress regulation and suicidality in depression.
Decoding psychotic and other psychiatric disorders through placental organ: From cytoarchitecture to stress-responsive signaling networks.
García-Montero C, Fraile-Martinez O, Álvarez-Mon MÁ … +13 more , Lahera G, Ibañez Á, Presa M, Sáez MA, Bujan J, García-Honduvilla N, Barrena-Blázquez S, De León-Luis JA, Bravo C, Lopez-Gonzalez L, Díaz-Pedrero R, Álvarez-Mon M, Ortega MA
Psychiatry Res · 2026 Jun · PMID 42296873 · Publisher ↗
Psychosis-defined as a profound disconnection between objective external reality and internal mental representations-represents a critical mental health condition, especially when it emerges for the first time during pre...
Psychosis-defined as a profound disconnection between objective external reality and internal mental representations-represents a critical mental health condition, especially when it emerges for the first time during pregnancy. First-episode psychosis (FEP) in pregnant women (FEP-PW), though rare, presents severe risks for both maternal and fetal health. Despite its clinical significance, the biological mechanisms underlying FEP-PW remain poorly understood. This narrative review investigates the human placenta as a valuable and dynamic organ for decoding psychiatric and psychological disorders, particularly FEP-PW, but also encompassing conditions such as psychological stress, metabolic stress, post-traumatic stress disorder (PTSD), affective disorders, anxiety, schizophrenia, and broader psychotic syndromes. We define FEP and its unique presentation during pregnancy, highlighting clinical aspects and current diagnostic challenges. Central to this review is the evolving recognition of the placenta, not as a mere byproduct of parturition, but as a biologically active interface that influences both maternal mental health and fetal neurodevelopment. We argue for the importance of studying the human placenta directly, given the species-specific nature of genomic imprinting and stress-responsive signaling, which limits the translational power of animal models. Accumulating evidence reveals that maternal psychological and metabolic stressors can alter placental structure and function, with implications for both maternal psychiatric vulnerability and the long-term mental health of the offspring. These findings support the Developmental Origins of Health and Disease (DOHaD) framework and suggest that placental molecular dysregulation may contribute to the intergenerational transmission of psychiatric risk. By integrating diverse biological and clinical perspectives, this review positions the placenta as a critical organ for future research in perinatal psychiatry and mental health. Emerging strategies such as the analysis of placenta-derived extracellular vesicles (EVs) offer a promising, non-invasive avenue to monitor placental molecular activity in real time. By integrating EV-based transcriptomic and proteomic profiling from maternal blood, future research may identify biomarkers of stress-related placental dysfunction linked to maternal psychiatric conditions. This approach holds strong potential to bridge current gaps in perinatal mental health research, aligning with the DOHaD framework to inform early detection and intervention strategies.
Adverse childhood experiences, family functioning, and duration of untreated illness among adolescents with anxiety and depressive disorders: A nationwide study in China.
Xiang L, Jian Y, Li JJ … +6 more , Zhang D, Meng W, Chen J, Xie B, Cai Y, Li L
Psychiatry Res · 2026 Jun · PMID 42288072 · Publisher ↗
OBJECTIVE: Treatment delay in adolescents with anxiety and depressive disorders may adversely affect outcomes. Although adverse childhood experiences (ACEs) are established risk factors, the family-level mechanisms linki...
OBJECTIVE: Treatment delay in adolescents with anxiety and depressive disorders may adversely affect outcomes. Although adverse childhood experiences (ACEs) are established risk factors, the family-level mechanisms linking ACEs to duration of untreated illness (DUI) remain unclear. This study examined whether family functioning statistically accounted for associations between specific ACEs and delayed help-seeking. METHODS: This nationwide cross-sectional study recruited 1,051 adolescents with first-episode anxiety and depressive disorders from eight Chinese clinical centers. Participants completed the ACE questionnaire and the FACES II-CV; DUI was ascertained through structured clinical interviews. Mediation analyses using PROCESS examined indirect associations of family adaptability and cohesion in the ACE-DUI association. RESULTS: The median DUI was 6.0 months (IQR: 1.0-21.0). ACEs were positively associated with longer DUI. Mediation analyses indicated that family functioning may partly account for statistical associations between specific ACEs and DUI. Indirect-only association patterns were observed for physical neglect, physical abuse, parental separation/death, household substance abuse, and household mental illness (B = 0.02-0.04, all 95% CIs excluding zero), suggesting that these ACEs were associated with treatment delay mainly through lower family adaptability and cohesion. In contrast, emotional neglect, domestic violence, and household incarceration showed significant direct associations with prolonged DUI (B = 0.13-0.36, all 95% CIs excluding zero), with household incarceration also showing an additional indirect association through cohesion. CONCLUSIONS: Family dysfunction may be a potentially modifiable factor linking ACEs to treatment delay. Indirect association patterns indicate that lower family adaptability and cohesion may partly explain why certain ACE domains are associated with longer DUI, supporting family-focused early identification strategies while causal interpretations require confirmation in longitudinal studies.
Suicide ideation among young people in outpatient alcohol and other drug treatment.
Campbell G, Glasgow S, Catakovic A … +3 more , Pocuca N, Dignan J, Hides L
Psychiatry Res · 2026 Jun · PMID 42288071 · Publisher ↗
BACKGROUND: Suicide-related behaviours are common in people with substance use disorders. However, there has been limited research focused on young people (25 years and younger) and among people presenting to alcohol and...
BACKGROUND: Suicide-related behaviours are common in people with substance use disorders. However, there has been limited research focused on young people (25 years and younger) and among people presenting to alcohol and other drug (AOD) outpatient treatment. OBJECTIVES: The study aims to examine the prevalence and correlates associated with recent suicide ideation in young people presenting to outpatient AOD treatment. Factors associated with greater treatment attendance in young people with recent suicide ideation were also explored. METHODS: The study utilises routinely collected administrative, treatment, and service data, as well as baseline patient-reported outcome measures, from a large Australian non-government organisation AOD treatment provider from November 2, 2020, to April 30, 2024. Item nine of the Patient Health Questionnaire was used to identify any recent suicide ideation. RESULTS: Among young people enrolling in treatment (N = 3461), the prevalence of recent suicide ideation was 37.1% (95% CI 35.5-38.7%). Young people with recent suicide ideation had greater alcohol use severity, depression, anxiety and PTSD, and other psychosocial factors such as loneliness and chronic pain. Young people with recent suicide ideation had greater treatment engagement, although they were also more likely to have an unplanned exit from treatment. An unplanned exit was more likely among older clients and those engaged in recent violent behaviour, and less likely among those studying/working. CONCLUSIONS: It is important to screen and monitor for suicide-related behaviours in young people attending outpatient AOD treatment. Future research focused on designing interventions for substance use and suicide-related behaviours in young people, delivered in the fewest possible sessions, is warranted.
The time Collapse-Entrapment model of depersonalization severity.
Madden SP, Serper MR
Psychiatry Res · 2026 Jun · PMID 42288070 · Publisher ↗
BACKGROUND: Depersonalization is a disruption in self-awareness marked by a sense of detachment from one's own thoughts, body, sensory experiences, actions, and emotions. While psychological distress and temporal disturb...
BACKGROUND: Depersonalization is a disruption in self-awareness marked by a sense of detachment from one's own thoughts, body, sensory experiences, actions, and emotions. While psychological distress and temporal disturbances are known correlates, the mechanisms through which these factors contribute to symptom severity remain poorly understood. The present study proposed and tested the Time Collapse-Entrapment Model of Depersonalization Severity, in which temporal blurring (i.e., a subjective blurring of boundaries between the past, present, and future) and a diminished ability to vividly imagine one's future self contribute to increased perceived entrapment, which in turn predicts greater depersonalization symptom severity. METHODS: A total of 433 adults (79 with clinically significant depersonalization severity) completed self-report measures of psychological distress, absorption, future self-continuity, time perspective, cognitive fusion, entrapment, temporal blurring, and depersonalization. RESULTS: Individuals with clinically significant depersonalization reported significantly higher psychological distress, absorption, cognitive fusion, entrapment, and temporal blurring, and significantly lower future self-continuity. Discriminant function analysis correctly classified 75.6% of cases, with psychological distress, temporal blurring, absorption, and entrapment emerging as the strongest contributors to classification. Mediation analyses indicated that temporal blurring and reduced vividness of the future self predicted depersonalization severity via perceived entrapment. CONCLUSIONS: These findings highlight a novel mechanism through which disruptions in temporal continuity and future self-representation may amplify depersonalization symptoms. More broadly, the results highlight the role of multiple cognitive and experiential processes in depersonalization severity beyond general affective distress. Targeting temporal and self-continuity disturbances may represent a clinically relevant intervention target for individuals with severe depersonalization.
Post-marketing safety surveillance of the novel muscarinic antipsychotic Xanomeline-Trospium for schizophrenia: A comparative disproportionality analysis against olanzapine based on FAERS data.
Zeng Y, Wang X, Wu H … +4 more , Tan X, Wang R, Liu Y, Duan J
Psychiatry Res · 2026 Jun · PMID 42288069 · Publisher ↗
OBJECTIVE: To characterize the real-world post-marketing safety reporting profile and adverse event (AE) signals of Xanomeline-Trospium, a novel dual M1/M4 muscarinic antipsychotic for schizophrenia. METHODS: FAERS data...
OBJECTIVE: To characterize the real-world post-marketing safety reporting profile and adverse event (AE) signals of Xanomeline-Trospium, a novel dual M1/M4 muscarinic antipsychotic for schizophrenia. METHODS: FAERS data from 2024Q4 to 2025Q4 were retrospectively analyzed. Reports listing Xanomeline-Trospium as the primary suspected drug were extracted. Signals were detected using four algorithms: ROR, PRR, BCPNN, and MGPS. Additional analyses included Weibull time-to-onset modeling, exploratory comparison with olanzapine, sex- and age-stratified subgroup analyses, and sensitivity analysis excluding concomitant medications. RESULTS: A total of 1410 valid reports were identified. After excluding underlying disease-related confounders, 42 clinically meaningful Preferred Terms showed positive signals. The reporting profile was dominated by gastrointestinal events, including nausea and projectile vomiting; renal and urinary events, especially urinary retention; and acute psychiatric activation, including intrusive thoughts and anger. Compared with olanzapine, Xanomeline-Trospium showed lower reporting odds for metabolic and extrapyramidal events but higher reporting odds for autonomic, gastrointestinal, and acute neurobehavioral signals. Sex subgroup analysis suggested potential divergent autonomic reporting patterns, with females showing more cholinergic signals and males showing more anticholinergic signals. Weibull analysis indicated an "early failure" pattern, with 86.8% of AEs occurring within 30 days of treatment initiation and a median onset of 6.4 days. CONCLUSION: Xanomeline-Trospium showed a distinct FAERS reporting profile characterized by gastrointestinal, urological, and acute psychiatric signals. These findings are hypothesis-generating associations rather than causal risks and support intensive monitoring during treatment initiation.
Long-term stability of suicidal ideation among young adults residential care leavers: a prospective 10-year study.
Weedage D, d'Huart D, Bürgin D … +5 more , Seker S, In-Albon T, Vermeiren R, Boonmann C, Schmid M
Psychiatry Res · 2026 Jun · PMID 42284936 · Publisher ↗
BACKGROUND: Juveniles in residential care systems have high rates of suicidal ideation (SI). This study aims to expand knowledge of the prevalence and stability of SI, as well its associated factors among young adult car...
BACKGROUND: Juveniles in residential care systems have high rates of suicidal ideation (SI). This study aims to expand knowledge of the prevalence and stability of SI, as well its associated factors among young adult care leavers. METHODS: Swiss juveniles in residential care (N = 179; non-Swiss origin: 12,29%; N = 22) were followed up into young adulthood (34% female/66% males; Age (16.41, 2.86, 11-16); Age (26.64, 3.22, 20-38 years)). SI was assessed at baseline and 10-year follow-up. Statistics included descriptives, proportion of enduring cases (categorical mean-level stability), tetrachoric correlation (Rtet; categorical rank-order stability), χ²- and Kruskal-Wallis tests (to test differences between SI pathways), and multinomial logistic regression analyses (RRR; to investigate risk and protective factors for SI pathways). RESULTS: SI prevalence was 45.25% (baseline) and 31.84% (follow-up). Females showed higher rates. SI appeared moderately stable (43.2%) with higher estimates in females. Participants with remitted and persistent SI experienced more NSSI, internalizing/ externalizing symptoms, lower self-directedness, and lower quality of life than those without SI. Higher self-directedness, cooperativeness and quality of life predicted a lower likelihood of persistent SI. CONCLUSIONS: Results suggest a higher risk and moderate stability of SI for young adult care leavers. Residential care practitioners should watch for risk factors, especially among females, and encourage self-directedness and cooperativeness.
Physical exercise interventions for health outcomes in children and adolescents with attention deficit hyperactivity disorder: An umbrella review with meta-analysis.
Zhu F, Zhang X, Wu Y … +3 more , Li Y, Ren Y, Zhang M
Psychiatry Res · 2026 Jun · PMID 42284935 · Publisher ↗
BACKGROUND: Physical exercise is a promising adjunctive intervention for attention deficit hyperactivity disorder (ADHD), but conclusions from previous meta-analyses remain inconsistent. OBJECTIVES: This umbrella review...
BACKGROUND: Physical exercise is a promising adjunctive intervention for attention deficit hyperactivity disorder (ADHD), but conclusions from previous meta-analyses remain inconsistent. OBJECTIVES: This umbrella review synthesized meta-analytic evidence on the effects of physical exercise interventions on ADHD-related and broader functional outcomes in children and adolescents with ADHD. METHODS: Six databases were searched from inception to March 5, 2026. Eligible meta-analyses evaluating structured physical exercise interventions in children and adolescents with ADHD were included. Random-effects models were used to calculate standardized mean differences (SMDs) with 95% confidence intervals (CIs). Methodological quality and certainty of evidence were assessed using AMSTAR-2 and GRADE, respectively. RESULTS: Forty-five meta-analyses were included. Physical exercise showed significant beneficial effects on ADHD core symptoms (SMD = 0.50, 95% CI: 0.39 to 0.61) and executive functions (SMD = 0.77, 95% CI: 0.62 to 0.93). Benefits were also observed for mental health, motor skills, and social problems, whereas no significant effects were found for sleep quality, body mass index, or academic achievement. Cognitively engaging exercise and interventions delivered at least three times per week showed significantly larger effects in executive functions. Certainty of evidence was low for ADHD core symptoms, executive functions, mental health, motor skills, and social problems, and very low for other outcomes. CONCLUSIONS: Structured physical exercise may be a useful adjunctive component of multimodal ADHD management, but should not replace established treatments. Given the low to very low certainty of evidence across outcomes, these findings should be interpreted cautiously and require confirmation in further high-quality studies.
Choroidal vascularity index in schizophrenia and bipolar disorder.
Yıldız FBP, Çalış AK, Dokuz G … +4 more , Kılıçarslan T, Kırpınar İ, Özdemir MH, Elbay A
Psychiatry Res · 2026 Jun · PMID 42269287 · Publisher ↗
BACKGROUND: This study examined differences in choroidal structural parameters, including the choroidal vascularity index, among patients with schizophrenia, bipolar disorder, and healthy controls. METHODS: This cross-se...
BACKGROUND: This study examined differences in choroidal structural parameters, including the choroidal vascularity index, among patients with schizophrenia, bipolar disorder, and healthy controls. METHODS: This cross-sectional study included 40 patients with bipolar disorder type I in remission, 40 clinically stable patients with schizophrenia, and 40 age- and sex-matched healthy controls. Enhanced depth imaging optical coherence tomography was used to obtain subfoveal choroidal images. Total choroidal area (TCA) and luminal area (LA) were measured by image binarization using ImageJ software, and the choroidal vascularity index (CVI), as the ratio of LA to TCA, was calculated. Group comparisons, correlation analyses, and analyses of covariance were performed. RESULTS: TCA was found higher in schizophrenia (2.52 ± 0.47 mm²) and bipolar disorder (2.45 ± 0.36 mm²) compared with healthy controls (2.07 ± 0.24 mm²) (p < 0.001). LA indicated a similar pattern (schizophrenia: 1.65 ± 0.29 mm²; bipolar disorder: 1.57 ± 0.24 mm²; healthy controls: 1.36 ± 0.14 mm²; p < 0.001). CVI was lower in bipolar disorder (0.64 ± 0.02) compared with healthy controls (0.66 ± 0.03) (p = 0.009), and no significant difference was observed between schizophrenia and controls (p > 0.05). CONCLUSIONS: Increased TCA and LA were observed in both schizophrenia and bipolar disorder, whereas CVI values were lower in bipolar disorder. Findings were independent of metabolic parameters and symptom severity. Choroidal structural measurements may provide additional information about microvascular characteristics in severe mental illnesses.
Symptom trajectories and treatment outcomes following a five-day accelerated intermittent-theta burst stimulation protocol for treatment-resistant depression: A naturalistic study in a real-world setting.
Janssen-Aguilar R, Joseph J, Al-Shamali HF … +12 more , Menzies P, Dunlop K, Jha M, Lin Q, Lou W, Adamsahib F, Mulsant BH, Tang VM, Voineskos D, Blumberger DM, Kaster TS, Bhat V
Psychiatry Res · 2026 Jun · PMID 42263622 · Publisher ↗
BACKGROUND: Accelerated intermittent theta burst stimulation (aiTBS) is a time-efficient treatment for treatment-resistant depression (TRD), but highly intensive protocols like SNT are difficult to implement due to MRI-g...
BACKGROUND: Accelerated intermittent theta burst stimulation (aiTBS) is a time-efficient treatment for treatment-resistant depression (TRD), but highly intensive protocols like SNT are difficult to implement due to MRI-guided targeting and high session frequency. This study evaluated the feasibility and clinical outcomes of a five-day, intermediate-session frequency aiTBS protocol delivered without neuronavigation and characterized response heterogeneity using group-based trajectory modelling. METHODS: This retrospective analysis included 48 adult patients with TRD who received 7 sessions per day of aiTBS for 5 days (35 sessions) targeting the left dorsolateral prefrontal cortex using the modified Beam F3 approach without neuronavigation as part of clinical care. The primary outcome was change in the Patient Health Questionnaire-9 (PHQ-9) score at Day 5 as assessed with a linear mixed-effects model with Holm-Bonferroni correction. RESULTS: Most patients completed the five-day treatment course (89.6%), and symptom data were available for 91% at Day 5. The Day-5 response rate (≥50% PHQ-9 reduction) was 16.7%. PHQ-9 scores decreased significantly from baseline at Day 5 (LSMD = -2.97), with further reductions at two weeks (LSMD = -6.81) and stability at one month (LSMD = -6.50), although follow-up data were incomplete. Trajectory modelling identified four distinct symptom patterns, underscoring variability in response. CONCLUSIONS: This intermediate-session frequency aiTBS protocol was feasible to implement in a real-world clinical setting. While modest symptom reduction was observed, substantial missing data after Day 5 limit confidence in longer-term outcomes. Individual trajectories varied, highlighting the need for personalized approaches and improved follow-up strategies.
Depressive disorders burden attributable to childhood sexual abuse in China and India from 1990 to 2023 and prediction for 2040: Analysis of data from the global burden of disease study 2023.
Yang Q, Wu M, Wang X … +5 more , Qin X, Tang Y, Yu J, Gao LN, Li M
Psychiatry Res · 2026 Jun · PMID 42263621 · Publisher ↗
AIM: This study endeavors to explore the temporal alterations in the disability-adjusted life years (DALYs) of depressive disorders (DD) attributable to childhood sexual abuse (CSA) in China and India, and to predict the...
AIM: This study endeavors to explore the temporal alterations in the disability-adjusted life years (DALYs) of depressive disorders (DD) attributable to childhood sexual abuse (CSA) in China and India, and to predict the future trends of DALYs from 2024 to 2040. METHODS: Using the Global Burden of Disease (GBD) Study 2023, we evaluated the impact of CSA on DD, scrutinizing DALYs per 100,000 population. Our analysis incorporated age, sex, and temporal trends in age-standardized rates (ASR), and an age-period-cohort (APC) analysis was conducted to differentiate the effects of age, period, and cohort on the observed temporal trends. BAPC analysis was employed to forecast the DALYs rates and numbers for different sexes from 2024 to 2040. RESULTS: The number of DALYs for DD attributable to CSA increased by 50.7% in China and by 122% in India from 1990 to 2023. Notable gender disparities emerged, with females demonstrating higher ASR of DALYs in both countries. The highest burden was observed in the 40-44 age group for both sexes in India, and for males in China, while females in China peaked at 35-39 age group. The ASR of DALYs attributable to CSA is projected to increase moderately for both sexes in China, while it will increase sharply in India, especially among females. CONCLUSIONS: CSA-attributable DD burden remains stable in China but rises significantly in India. Targeted interventions for ages 40-44 and full-cycle strategies covering children/adolescents and adult survivors are essential. Our study will help the government formulate more targeted and effective preventive and intervention strategies for CSA-attributable DD.
Social anxiety disorder in Canada: sociodemographic and psychosocial correlates.
Chau TN, Oliver SA, Fuller-Thomson E
Psychiatry Res · 2026 Jun · PMID 42259068 · Publisher ↗
This study examines the lifetime prevalence of social anxiety disorder (SAD) in a representative sample of the adult Canadian population, as well as characteristics associated with SAD in this population. Secondary analy...
This study examines the lifetime prevalence of social anxiety disorder (SAD) in a representative sample of the adult Canadian population, as well as characteristics associated with SAD in this population. Secondary analyses were conducted on the nationally representative 2022 Canadian Mental Health and Access to Care Survey (MHACS). The World Health Organization Composite International Diagnostic Interview scale was used to identify individuals with lifetime occurrence of SAD which is based upon Diagnostic and Statistical Manual of Mental Disorders IV (DSM-IV) criteria. The weighted lifetime prevalence of SAD was 13.9% among adults aged 20 and older. There was a negative dose-response relationship between age and SAD. For example, the lifetime prevalence of SAD was 24.2 % among adults aged 20-24 compared to 6.2% among those aged 65 and older. Demographic factors associated with higher odds of lifetime SAD included being female, Canadian-born, and single (compared to never married, widowed, separated, or divorced). Individuals who experienced childhood sexual abuse and/or parental domestic violence had higher odds of SAD, as did those who had one or more chronic health conditions, chronic pain, or those who had lifetime substance or alcohol use disorder. Psychosocial characteristics associated with SAD included lower perceived social support and reporting that spirituality was of limited or no importance in their lives. In contrast to expectations, personal income and childhood physical abuse were not significantly associated with SAD. The 2022 prevalence of lifetime SAD (13.9%) was much higher than was reported in a 2002 Canadian survey (8.1%), highlighting the need for increased awareness of SAD and for targeted support.
Depression stigma, treatment-seeking intentions, and barriers to care among adolescents: demographic factors in a crowdsourced sample.
Markman R, Steier K, Fisch CT … +5 more , Jankowski S, DiGiovanni M, Dixon LB, Martin A, Amsalem D
Psychiatry Res · 2026 Jun · PMID 42250491 · Publisher ↗
OBJECTIVE: To examine the association of age, gender, and race/ethnicity with depression stigma, barriers to care, and treatment-seeking intentions among adolescents. METHODS: 1127 US adolescents (aged 14-18) recruited v...
OBJECTIVE: To examine the association of age, gender, and race/ethnicity with depression stigma, barriers to care, and treatment-seeking intentions among adolescents. METHODS: 1127 US adolescents (aged 14-18) recruited via CloudResearch, a crowdsourcing platform, completed online measures of depression stigma, treatment-seeking intentions and barriers to care. RESULTS: Significant differences were found across gender groups in depression stigma (F(2,1124)=78.05, p < .001), barriers to care (F(2,1124)=5.96, p=.003) and treatment-seeking intentions (F(2,1124)=53.71, p<.001). Boys reported the highest depression stigma and lowest treatment-seeking intentions compared to girls and TGD youth (stigma: boys vs. TGD, t = 13.5, p < .001, d = 1.21; treatment-seeking: boys vs. TGD, t = 10.19, p < .001, d = 1.02). TGD youth endorsed the highest barriers to care (boys vs. TGD, t=-3.07, p = .007, d = 0.37). Significant differences were also found across racial/ethnic groups in depression stigma (F(3,1123)=11.49, p < .001) and treatment-seeking intentions (F(3,1123)=4.11, p = .007). Older adolescents reported higher treatment-seeking intentions (t=-2.99, p=.003) and higher barriers to care (t=-2.92, p=.004) than younger ones. CONCLUSIONS: Depression stigma, barriers to care, and treatment-seeking intentions vary significantly across different demographic groups. Tailored interventions addressing specific subgroup needs are therefore essential. Crowdsourcing offered results comparable to traditional recruitment strategies, alongside large-scale sample recruitment with hard-to-reach populations such as TGD youth. The trial was prospectively registered with clinicaltrials.gov (NCT06222528).
Digital phenotyping using wearable-determined physical behaviours and machine learning to detect depression and anxiety symptoms in a general population.
Sameh A, Nauha L, Seppänen M … +4 more , Niemelä M, Oussalah M, Korpelainen R, Farrahi V
Psychiatry Res · 2026 May · PMID 42247773 · Publisher ↗
BACKGROUND: Depression and anxiety are widespread mental health disorders, yet their diagnosis remains challenging. Digital phenotyping provides a promising approach for detecting depression and anxiety. This study aims...
BACKGROUND: Depression and anxiety are widespread mental health disorders, yet their diagnosis remains challenging. Digital phenotyping provides a promising approach for detecting depression and anxiety. This study aims to explore the extent to which physical behaviour metrics can be used as digital phenotypes for identifying individuals with and without depression and anxiety symptoms using machine learning (ML) algorithms. METHODS: At age 46 years, participants (n = 2,810) from the Northern Finland Birth Cohort 1966 carried wrist- and waist-worn accelerometers for 14 consecutive days. Physical activity, sedentary and sleep behaviours were measured using data from the waist- and wrist-worn devices. A total of 54 physical behaviour metrics were extracted for each participant. Severity of depression and anxiety were assessed using three validated instruments: the Beck Depression Inventory-II, Generalized Anxiety Disorder-7, and the Hopkins Symptom Checklist-25. Five ML algorithms were applied to identify depression and anxiety symptoms. SHapley Additive exPlanations (SHAP) was used to assess the contribution of metrics. RESULTS: Random forest achieved the best performance with accuracy (66%-72%) and AUC (66%-70%) for all three instruments. Other models showed lower accuracy in predicting depression and anxiety symptoms. In SHAP analysis, wake-up time, time in bed, bedtime, and prolonged sedentary bouts emerged as most important features. CONCLUSIONS: Physical behaviour metrics using ML models can be utilized with reasonable accuracy to differentiate between participants with and without depression and anxiety symptoms. Our findings support the utility of physical behaviour digital phenotypes for predicting depression and anxiety symptoms in a general population.
Investigation of potential associations between four redox-related long non-coding RNAs and glutathione peroxidase in schizophrenia: a combination of bioinformatics and experimental analyses.
Khaki M, Massoudifar A, Davoodian N … +3 more , Mousavi P, Davoodian N, Mahmoudi M
Psychiatry Res · 2026 May · PMID 42247772 · Publisher ↗
BACKGROUND: Glutathione peroxidase (GPx), a key antioxidant enzyme, shows altered activity in individuals with schizophrenia. However, the molecular mechanisms behind this alteration remain incompletely understood. In th...
BACKGROUND: Glutathione peroxidase (GPx), a key antioxidant enzyme, shows altered activity in individuals with schizophrenia. However, the molecular mechanisms behind this alteration remain incompletely understood. In this study, we combined bioinformatics and experimental approaches to explore potential associations between redox-related long non-coding RNAs (lncRNAs) and GPx activity in schizophrenia. METHODS: We selected four redox-related lncRNAs (PVT1, NEAT1, SOX21-AS1, H19), and bioinformatics analyses predicted their potential interactions with GPX-related genes. Subsequently, we measured lncRNA expression levels in peripheral blood mononuclear cells (PBMCs) and assessed serum GPx activity in patients with acute schizophrenia. RESULTS: Bioinformatics analyses identified 16 candidate miRNAs putatively targeted by the selected lncRNAs and differentially expressed in schizophrenia. Further analyses identified 154 transcription factors (TFs) targeted by the candidate miRNAs that regulate GPx expression. Based on these predicted interactions, we constructed a putative RNA regulatory network comprising 3 lncRNAs, 16 miRNAs, and 154 TFs. KEGG pathway enrichment revealed significant involvement of MAPK, mTOR, Hippo, neurotrophin, and TNF signaling pathways within this network. Experimental findings showed significant upregulation of SOX21-AS1 and downregulation of PVT1 and NEAT1 in the PBMCs of patients with acute schizophrenia. Among the examined lncRNAs, PVT1 exhibited the highest potential to distinguish patients from controls. Furthermore, decreased GPx activity was observed in the serum of patients. CONCLUSIONS: The identified GPx‑associated RNA network may contribute to redox imbalance in schizophrenia. Although the interactions are prediction‑based, this network provides a framework for future functional studies and may help identify potential biomarkers and therapeutic targets.
20-year pharmacological treatment trajectories in a cohort of patients with bipolar disorder.
Grabuleda N, Borràs R, Martínez-Arán A … +18 more , Anmella G, Roberto N, Botí MÁ, de Prisco M, Oliva V, Fico G, Valentí M, Murru A, González-Campos M, Pacchiarotti I, Solé B, Sánchez-Moreno J, Del Mar Bonnin C, Mazzei DH, Vieta E, Torrent C, Grande Í, Comes M
Psychiatry Res · 2026 May · PMID 42242171 · Publisher ↗
BACKGROUND: Bipolar disorder (BD) is a prevalent, chronic and severe condition, with a high impact on psychosocial functioning. In the treatment of BD, maintenance therapy is crucial for preventing affective recurrences...
BACKGROUND: Bipolar disorder (BD) is a prevalent, chronic and severe condition, with a high impact on psychosocial functioning. In the treatment of BD, maintenance therapy is crucial for preventing affective recurrences and long-term complications. The goal of this study was to conduct a descriptive analysis of the trajectories of pharmacological treatment along 20 years in a cohort of patients with BD, to better understand the diversity and changes in treatment patterns. METHODS: This study analyses the prescription patterns of psychotropic medications and their association with clinical variables (sex, BD type, predominant polarity and psychotic symptoms) in a sample of 68 outpatients with BD (54.4% female, age of 39.31±12.04 at the start of the study) over a 20-year period. RESULTS: Maintenance therapy was predominantly based on combination strategies (75.8% at baseline). Our findings showed an increase in polypharmacy and benzodiazepines and a decline of mood stabilizers. CONCLUSIONS: This study offers insight into maintenance medication patterns among BD patients in a real-world setting over an extended period, revealing how prescribing tendencies have evolved. The widespread use of polypharmacy and benzodiazepines and the decrease in the prescription of mood stabilizers during the follow-up highlight a noticeable divergence between clinical practice and guideline recommendations.
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