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.

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.

Depression as a mental illness is commonly observed to co-occur with various somatic diseases, such as gastrointestinal diseases. However, previous studies have primarily focused on the risk of mental disorders following physical illnesses. Our study took depression as a risk factor, attempting to explore its relationship with gastrointestinal diseases.

A total of 457,940 participants (aged 37–73 years) in the UK Biobank were included. The Cox proportional hazards model was used to assess the relationship between depression and gastrointestinal diseases. Mendelian randomization assessed the causal link between depression and gastrointestinal disorders, and seven machine learning algorithms (including LightGBM, XGBoost, and Random Forest) were trained in the total population to develop predictive models for incident gastrointestinal diseases, with model performance evaluated using the area under the receiver operating characteristic curve (AUC).

During a median follow-up period of 13.7 years, 9563 esophagitis events, 36,420 gastroesophageal reflux disease events, 5469 gastric ulcer events, 3096 duodenal ulcer events, 37,225 gastritis and duodenitis events, and 9153 dyspepsia events were recorded. After adjusting for covariates, depression was associated with increased risk of all six diseases. Two-sample MR analysis supported a causal association. Machine learning models demonstrated good discrimination, with the highest predictive accuracy observed for duodenal ulcer (AUC = 0.76) and gastric ulcer (AUC = 0.75).

Addressing depression as a modifiable risk factor may reduce gastrointestinal disease risk, especially in disadvantaged populations, by integrating mental health care into primary care and using predictive models for early intervention.

Empathy involves communicating and understanding others’ emotion in multisensory contexts, including visual and auditory modalities. Schizophrenia (SCZ) patients have impaired empathy, but whether the impact of visual/auditory context would be altered in SCZ patients and people with high social anhedonia (HSoA) remained unclear.

We administered the modified Chinese version of the Empathic Accuracy Task (EAT) to clinical (50 SCZ patients and 50 healthy controls) and subclinical samples (59 HSoA and 60 low social anhedonia [LSoA] participants). The EAT employed audio-only, audiovisual, and audioavatar visual conditions to assess the impact of multimodal information on empathy during positive and negative emotional events.

In positive-valenced context, SCZ patients performed worse than controls in cognitive and affective empathy. The Modality-by-Group interaction on empathic accuracy was significant, that is, SCZ patients performed worse than controls in both audiovisual and audioavatar visual conditions, but comparable to controls in audio-only condition. In negative-valenced context, SCZ patients performed worse than controls in cognitive empathy. The Modality-by-Group interaction on empathic accuracy was significant, that is, SCZ patients performed worse than controls in audio-only and audiovisual conditions. Moreover, HSoA participants exhibited lower cognitive empathy than controls in positive-valenced context; and lower cognitive empathy and empathic motivation in negative-valenced context. No significant Modality-by-Group interaction was found in the HSoA–LSoA sample.

SCZ patients have generalized impairments of cognitive and affective empathy across positive and negative contexts, particularly in multimodal conditions. HSoA individuals are primarily impaired in cognitive empathy and empathic motivation.

Impaired autophagy has been implicated in the pathophysiology of neurodegenerative disorders, such as Alzheimer’s Disease (AD) and Parkinson’s Disease (PD). Consistent and replicated evidence indicate that Glucagon-like Peptide-1 Receptor Agonists (GLP-1RAs) exert treatment and preventative effects across disparate neurologic and mental disorders, potentially through mechanisms involving autophagy. This systematic review examined the effects of GLP-1RAs on autophagy in cell and animal models of AD and PD, as a proof of concept, to determine if these agents can be repurposed for the prevention and treatment of neurodegenerative and other mental disorders.

A systematic search on PubMed, Web of Science, and OVID (Medline, Embase, and APA PsycInfo databases) was conducted from inception to June 17, 2025. Screening was performed independently by two reviewers (MCS and IH) using predefined inclusion and exclusion criteria. Subsequently, a quality assessment was conducted.

The search yielded 142 studies, of which 14 were included. Across studies, GLP-1RAs (e.g., liraglutide, semaglutide, and exendin-4) autophagy-specific markers, including beclin-1, LC3-II/LC3-I, ATG7, ATG3, and LAMP1, while normalising p62 levels.

In addition to promoting neurogenesis, neuroplasticity, and reducing inflammation, GLP-1RAs appear to modulate molecular and cellular systems contributing to autophagy, potentially mediating their broad therapeutic effects. Collectively, these studies present promising findings of GLP-1RAs for neurodegenerative and mental disorders; however, further studies are required to establish their translatability to human populations.

Hospital-attributable central line-associated bloodstream infections (HA-CLABSI) are associated with severe patient outcomes. Published data on HA-CLABSI epidemiology in hospitals locally remains limited. This study aimed to determine the HA-CLABSI incidence and risk factors to inform targeted infection prevention practices.

Retrospective, nested case-control study was performed at Singapore General Hospital from January 2018 to December 2020, involving 127 cases and 252 controls. HA-CLABSI cases developed CLABSI ≥ 3 calendar days of hospitalization. Controls had central line inserted but did not develop CLABSI. Cases and controls were matched on 1:2 ratio for central line insertion date. Multivariable conditional logistic regression was performed to identify independent risk factors for HA-CLABSI, with adjusted odds ratio (aOR), 95% confidence intervals (CI) and p-values reported. Variables with p-value < 0.05 were statistically significant. HA-CLABSI incidence rate was calculated per 1,000 central line-days.

HA-CLABSI incidence rate during the study period was 8.4/1,000 central line-days. Independent risk factors for HA-CLABSI were transfer to high-risk areas (aOR: 2.03, 95% CI: 1.05–3.92), immunocompromised health status (aOR: 4.62, 95% CI: 2.20–9.69), antibiotic administration (aOR: 7.41, 95% CI: 3.24–16.92), and total parenteral nutrition (aOR: 3.61, 95% CI: 1.49–8.77) being included as indications for central line insertion, insertion of PICC (aOR: 13.61, 95% CI: 3.12–55.53), presence of non-tunneled central lines (aOR: 2.95, 95% CI: 1.48–5.87) and prior MRSA acquisition (aOR: 3.41, 95% CI: 1.83–6.35).

HA-CLABSI remains a significant concern despite on-going infection prevention efforts. Risk factors identified facilitate development of targeted, evidence-based interventions.

Antidepressants are the primary treatment for major depressive disorder (MDD), yet their precise neurobiological mechanisms remain incompletely understood. This study aimed to elucidate neural differences between medicated and unmedicated MDD patients by analyzing resting-state functional magnetic resonance imaging data.

We conducted a coordinate-based meta-analysis, complemented by behavioral, genetic, and neurotransmitter-level evaluations to identify potential therapeutic targets and diagnostic biomarkers. Using seed-based d-mapping with permutation of subject images (SDM-PSI), we assessed brain activation changes associated with antidepressant treatment. The identified regions were further characterized using large-scale molecular and functional brain databases.

A total of 59 studies on unmedicated MDD (2,618 patients, 2,486 controls) and 15 studies on medicated MDD (541 patients, 483 controls) were included. The meta-analysis revealed significantly increased activation in the left striatum among medicated patients, a region linked to cognitive functions such as memory and perception. Gene expression analysis highlighted SLC5A7 and prolactin (PRL) as key genes in this region, while neurotransmitter mapping showed associations with serotonin (5-HT1a, 5-HT2a) and dopamine (D1, D2) receptors. Additionally, reduced activation in the left middle occipital gyrus (MOG) was observed across both medicated and unmedicated groups. This region, implicated in recognition and face processing, showed high expression of TFAP2B and PRL and was associated with serotonin and norepinephrine transporter distributions.

These findings suggest that the left striatum may represent a core neurofunctional target of antidepressant treatment, while the left MOG may serve as a stable neurobiological marker for MDD diagnosis, independent of pharmacological status.

Euthymic bipolar disorder (euBD) patients exhibit deficits in neurocognitive and social cognitive functioning compared to healthy controls (HCs). Our prior research has shown that the excitatory/inhibitory (E/I) imbalance in the default mode network (DMN) is linked to executive function in euBD. Neurocognitive impairments are associated with social cognition deficits in individuals with mental disorders. Given this connection, this study posits E/I imbalance within the DMN is associated with social cognition, with executive function as a mediator.

Seventy-five HCs and 49 euBD individuals were recruited. Using the emotion recognition task, Diagnostic Analysis of Nonverbal Accuracy 2-Taiwan version (DANVA-2-TW) and cognitive flexibility task, Wisconsin Card Sorting Test (WCST), we assessed emotion recognition and prefrontal function. Proton magnetic resonance spectroscopy (1H-MRS) measured metabolites in the posterior cingulate cortex (PCC) and medial prefrontal cortex/anterior cingulate cortex (mPFC/ACC), quantifying excitatory glutamate+glutamine (Glx) and inhibitory GABA to calculate the E/I ratio.

euBD patients showed poorer emotion recognition (p = 0.020) and poorer cognitive flexibility (fewer WCST categories completed, p = 0.002). A negative association was found between emotion recognition and the E/I ratio in the mPFC/ACC of the BD patients (r = −0.30, p = 0.034), which was significantly mediated by cognitive flexibility (Z = −2.657, p = 0.007).

The BD patients demonstrate deficits in emotion recognition, linked to an altered E/I balance in the prefrontal cortex, and the cognitive flexibility, a key aspect of executive function, mediates the impact of the E/I ratio on emotion recognition accuracy in euBD patients.

Adolescence is a period marked by high vulnerability to onset of depression. Neuroimaging studies have revealed considerableatrophy of brain structure in patients with major depressive disorder (MDD). However, the causal structural networks underpinning gray matter atrophies in depressed adolescents remain unclear. This study aimed to examine the initial gray matter alterations in MDD adolescents and investigate their causal relationships of abnormalities within brain structural networks.

First-episode adolescent patients with MDD (n = 80, age = 15.57 ± 1.78) and age- and sex-matched healthy controls (n = 82, age = 16.11 ± 2.76) were included. We analyzed T1-weighted structural images using voxel-based morphometry to identify gray matter alterations in patients and the disease stage-specific abnormalities. Granger causality analysis was then conducted to construct causal structural covariance networks. We also identified potential pathways between the causal source and target.

Compared to controls, MDD patients with shorter illness duration showed gray matter atrophy in localized brain regions such as ventral medial prefrontal cortex (vmPFC), anterior cingulate cortex, and insula. With a prolonged course of MDD, gray matter atrophy extended to widespread brain areas. Causal network results demonstrated that early abnormalities had positive effects on the default mode, frontoparietal networks, and reward circuits. Moreover, vmPFC demonstrated the highest out-degree value, possibly representing the initial source of brain abnormality in adolescent depression.

These findings revealed the progression of gray matter atrophy in adolescent depression and demonstrated the directional influences between initial localized alterations and subsequent deterioration in widespread brain networks.