Prior observational studies have reported conflicting results regarding whether antidepressant treatment reduces long-term dementia risk, likely due to confounding by indication and reverse causation. We aimed to investigate the association between baseline antidepressant use and incident dementia, incorporating cognitive and neuroimaging outcomes.

We conducted a prospective cohort study using UK Biobank participants free of dementia at baseline. Antidepressant use was self-reported at baseline (2006–2010). Incident dementia was identified through linked electronic health records until December 19, 2022. Cox proportional hazards models estimated hazard ratios (HRs) for all-cause dementia, Alzheimer’s disease (AD), and vascular dementia (VD), adjusting for sociodemographic, lifestyle, health-related, antidepressant indication factors, and co-medication of other anticholinergics. In subsamples, cognitive performance (n = 57,330) and structural brain imaging (n = 42,276) were examined as intermediate outcomes.

Among 461,464 participants, 33,721 (7.3%) reported baseline antidepressant use. Over a mean follow-up of 13.4 years, 7,922 (1.7%) developed incident dementia. Baseline antidepressant use was associated with higher risks of all-cause dementia (adjusted HR: 1.47, 95% CI 1.36–1.60), AD (1.53, 1.36–1.73), and VD (1.44, 1.23–1.70). Users performed worse on fluid intelligence and prospective memory tasks and showed lower total and gray matter volume, regional reductions in the hippocampal gray matter and basal nucleus, and greater white matter hyperintensity volume.

Baseline antidepressant use was linked to a higher risk of dementia, poorer cognitive performance, and adverse brain structural changes. These findings underscore the importance of judicious prescribing, regular cognitive monitoring, and consideration of non-pharmacological approaches in clinical care.

Schizophrenia (SCZ) and bipolar disorder (BD) are severe psychiatric conditions with overlapping clinical presentations, genetic risk factors, and brain network dysfunction. Whether alterations in large-scale intrinsic brain networks reflect shared or disorder-specific genetic influences remains poorly understood. Clarifying this distinction is essential for refining etiological models and improving diagnostic precision.

Genome-wide inferred statistics (GWIS) were applied to decompose the genetic architecture of SCZ and BD into shared and unique components. Using resting-state network (RSN) data from the UK Biobank, functional connectivity (FC) and structural connectivity (SC) were extracted as neuroimaging phenotypes. Causal inference approaches were subsequently employed to infer potential directional relationships between brain network connectivity and each disorder.

Analyses revealed both common and distinct patterns of brain network connectivity associated with SCZ and BD. Notably, SC within the default mode network (DMN) exhibited opposing effects across the two disorders, suggesting divergent structural underpinnings despite clinical overlap. Additionally, SC within the limbic network (LN) and frontotemporal control network demonstrated potential causal relationships with both conditions, implicating these circuits astransdiagnostic neural substrates.

These findings illuminate the shared and disorder-specific genetic and neural architecture underlying SCZ and BD. Integrating genome-wide genetic methods with large-scale neuroimaging data offers a powerful framework for disentangling psychiatric comorbidity and may inform more targeted diagnostic criteria and individualized treatment strategies.

Cognitive impairment in first-episode schizophrenia (FES) is a major contributor to functional decline, but antipsychotics provide limited cognitive improvement, and few repetitive transcranial magnetic stimulation (rTMS) studies have targeted the orbitofrontal cortex (OFC). This study investigated whether right OFC rTMS enhances specific cognitive functions in FES and its relationship with symptom reduction.

Ninety drug-naive FES patients were enrolled, with 48 receiving active right OFC rTMS and 42 sham stimulation for 20 sessions over 8 weeks, while all patients took olanzapine (10–20 mg/day). Cognitive function was assessed using the Chinese version of the MATRICS Consensus Cognitive Battery (MCCB) at baseline and week 4, and psychotic symptoms were rated with the Positive and Negative Syndrome Scale (PANSS).

Repeated-measures analysis of variance (RMANOVA) demonstrated a significant Time×Group interaction for visuospatial memory (assessed via the Brief Visuospatial Memory Test-Revised, BVMT; F = 5.079, df = 1, 83, p = 0.027, η2 = 0.058). Post hoc tests revealed significant BVMT improvement in the active group (p < 0.001) but not in the sham group (p = 0.312). In the active group, improvements in BVMT and Neuropsychological Assessment Battery (NAB) scores were significantly correlated with lower PANSS total scores after Bonferroni correction.

These findings indicate that right OFC rTMS improves specific cognitive functions in FES, with cognitive benefits associated with symptom alleviation, supporting the right OFC as a promising target for cognitive intervention in FES.

Insomnia is commonly seen in opioid use disorder (OUD) patients receiving methadone maintenance treatment (MMT) and might be related to high heroin relapse risk. This study aims to identify potential mediation pathways among peripheral cytokines, neuroimaging characteristics, and insomnia in MMT patients, and explore diagnostic markers and therapeutic targets for MMT-related insomnia.

A total of 121 OUD individuals (OUDs) and 109 healthy controls were recruited, including MMT individuals (MMT group, N = 53), short-term abstinent (median: 30 days) heroin users at baseline (OUD1, N = 68), and around 10-month follow-up (OUD2, N = 61) without MMT, healthy controls-cohort 1 (HC1, N = 53, age/gender/education match MMT), and healthy controls-cohort 2 (HC2, N = 56, age/gender match OUD1). Multimodal datasets, including cerebral diffusion tensor imaging (DTI), peripheral hematologic indicators, and neuropsychological assessments, were collected from the MMT group and HC1. Within the MMT group, we revealed relationships among cytokines, DTI metrics, and neuropsychological assessments via partial correlation and mediation analyses. Mendelian randomization (MR) analyses between OUD and white matter (WM)-related imaging-derived phenotypes were used to further confirm Tract-Based Spatial Statistics (TBSS) results. Besides, the results of TBSS among OUD1, OUD2, and HC2 hypothetically served as baseline WM alteration before MMT.

Through comparisons among OUD1, OUD2, and HC2, WM aberrances could return to normal after 10-month abstinence, and we used the results as baseline alterations before MMT. MMT patients exhibited a broad imbalance in peripheral immune cells and cytokines, as well as presented insomnia, anxiety, and depression symptoms. After Bonferroni correction, mean diffusivity and radial diffusivity in extensive WM regions were higher in MMT patients than those of HC1. Ultimately, through multimodal correlation analysis, the ‘Interferon-γ (IFN-γ)-WM aberrance-insomnia’ axis was discovered in the MMT group.

Together, these results primarily link cytokines and WM injury for OUDs with MMT to insomnia, implicating pharmacological IFN-γ target as a latent strategy to improve the insomnia of MMT patients.

Inconsistent findings persist across resting-state functional imaging studies of regional brain alterations in postpartum depression (PPD), while connections to transcriptional profiles and neurotransmitter systems remain largely uncharacterized.

We performed a whole-brain voxel-wise meta-analysis of resting-state functional imaging studies comparing PPD patients and healthy controls using SDM-PSI software. JuSpace toolbox analyzed atlas-based nuclear imaging-derived neurotransmitter maps, and transcriptional data were sourced from the Allen Human Brain Atlas.

Our systematic review identified 12 functional imaging studies (475 PPD patients, 504 controls). Patients with PPD displayed increased resting-state functional activity in the left inferior occipital gyrus and left precuneus as well as decreased resting-state functional activity in the right amygdala and left precentral gyrus. These functional alterations spatially overlapped with serotonergic, dopaminergic, and VAChT systems. Transcriptional analysis revealed PPD-related gene enrichments in ion channel function (transmembrane transport, gated/passive channels) and channel complexes.

The meta-analysis revealed functional alterations within the DMN, limbic, and primary sensorimotor systems in PPD patients. These changes were linked to neurotransmitter alterations and genetic modulations underlying brain dysfunction. Collectively, these findings advance mechanistic understanding of PPD pathophysiology.

Increasing evidences show that inflammation might be involved in bipolar disorder (BD), but the association between abnormal brain function and inflammation in BD is still unclear. In this study, we tried to explore the disrupted brain functional network topology, peripheral inflammatory cytokine levels, and their correlations in unmedicated bipolar II depression (BDII-D).

In this study, 65 individuals with unmedicated BDII-D and 50 healthy controls (HCs) underwent resting-state magnetic resonance imaging scans. Graph theory analysis was performed to investigate the topological properties of the whole-brain functional connectome at both global and nodal levels. Besides, serum levels of 17 inflammatory cytokines were measured in both BDII-D and HCs. Correlations between topological properties, clinical variables, and peripheral inflammatory cytokine levels in BDII-D were calculated.

Compared with HCs, at the global level, BDII-D showed significantly higher $ \lambda $, decreased $ \gamma $, $ \sigma $, Eglo, and Eloc; at the nodal level, BDII-D showed decreased Enodal in the right olfactory cortex, left pallidum, and vermis. Besides, BDII-D showed higher levels of interleukin-8 (IL-8), interleukin-10 (IL-10), and granulocyte colony-stimulating factor (G-CSF) compared with the HCs. In BDII-D, $ \gamma $ and $ \sigma $ were significantly negatively correlated with the Hamilton Depression Rating Scale (HDRS) scores and number of episodes. Also, IL-8 level showed significant negative correlation with $ \gamma $, $ \sigma $, and Enodal of the left pallidum in BDII-D.

Reduced information segregation and integration, and lower nodal efficiency in the left pallidum were associated with proinflammatory cytokine IL-8 level and might contribute to severe depressive symptoms in unmedicated BDII-D.

To synthesize the available experimental study evidence to estimate the effects of ketamine on suicide ideation (SI) in high-risk individuals.

We conducted a systematic review and meta-analysis following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Double-blind randomized controlled trials and open-label studies investigating the safety and effectiveness of ketamine on SI published up to October 2025 were identified. Data were pooled using random-effects meta-analysis. The main outcome was standardized mean difference on SI in high-risk individuals. Secondary outcomes were the percentage of adverse events and the moderator effects.

We identified 21 studies with a total of 927 participants meeting our inclusion criteria. The pooled effect size for the reduction of SI after ketamine treatment was significant and clinically meaningful (large effect size of −1.40, 95% confidence interval: −2.15 to −0.66, P < 0.001, low–quality evidence). Dissociation (38.8%, P = 0.014), nausea (31.6%, P < 0.001), dizziness (24.7%, P = 0.003), headache (22.0%, P = 0.011) and anxiety (15.8%, P < 0.001) were the frequently reported adverse events. Moderator analyses indicated that the effect was higher in younger individuals and those with severe SI.

Our findings highlight the effectiveness of ketamine in reducing SI in high-risk individuals, especially younger individuals and those with severe ideation. Nonetheless, additional research is required to better understand optimal dosing regimens and the potential long-term effects of ketamine treatment.

Depression among middle-aged and older adults is a critical public health priority. Clarifying the dynamic evolution of depression is essential for establishing prevention and intervention strategies; however, relevant research is limited. The aim of this study was to elucidate the transition patterns underlying different depressive symptoms (DS) states.

Data from the China Health and Retirement Longitudinal Study were utilised in this study, which included participants aged ≥45 years with multiple DS assessments via the Center for Epidemiological Studies Depression Scale. Multi-state Markov models were employed to estimate transition probabilities and intensities between DS states, the total length of stay and mean sojourn time in each state and the hazard ratios (HRs) of factors.

Among 19,991 participants (average follow-up: 7.3 years), the 10-year cumulative probabilities of transition from non-DS to depressive states increased by 19.4% in males and 31.8% in females. Mild DS was the most unstable state, with the highest transition intensities (males: 1.029; females: 0.970) and shortest sojourn time (males: 0.959 years; females: 1.022 years). Sex and age strongly influenced depressive state transitions. Compared to participants without chronic disease, those with ≥3 chronic diseases had a higher risk of developing mild DS (HR = 1.685, 95% Confidence Interval [CI]: 1.530–1.856) and transitioning to death from both the non-DS (HR = 2.905, 95% CI: 2.293–3.681) and severe-DS (HR = 3.429, 95% CI: 1.290–9.112) states, but a lower likelihood of recovery from mild DS (HR = 0.821, 95% CI: 0.749–0.900) and severe DS (HR = 0.730, 95% CI: 0.630–0.847). Compared to no participation in social activities, frequent participation was associated with a lower risk of progression to the mild-DS state (HR = 0.851, 95% CI: 0.785–0.920) and a greater likelihood of recovery from severe DS (HR = 1.169, 95% CI: 1.034–1.322). Being underweight was associated with an increased risk of mild-DS onset (HR = 1.338, 95% CI: 1.129–1.587) and transitioning to death from both the non-DS and mild-DS states, compared with individuals of normal weight.

Our study revealed a continuous population shift towards depressive states and identified the mild-DS state as a critical intervention state owing to its instability. In addition to sex and age, modifiable factors, including chronic disease conditions, social activity participation and weight status, significantly influenced DS-state transitions, offering actionable insights for precision prevention strategies.