Post-stroke depression (PSD) is a frequent and debilitating complication of acute ischemic stroke (AIS), yet its underlying biochemical predictors remain insufficiently characterized. The non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) has recently emerged as a robust composite metric for assessing the homeostatic imbalance of lipid metabolism and systemic inflammation. This study aimed to evaluate the longitudinal association between admission NHHR levels and the risk of developing PSD at three months post-stroke in patients with AIS. We consecutively enrolled 408 patients with AIS from the Department of Neurology at Lixin County People’s Hospital between February 2023 and January 2026. Admission NHHR was calculated from fasting lipid panels. Depressive symptoms were evaluated at a 3-month follow-up using the 17-item Hamilton Depression Rating Scale (HAMD-17), with PSD diagnosis confirmed via DSM-V criteria. Participants were stratified into tertiles based on admission NHHR (Q1 ≤7.68; Q2 7.69–10.50; Q3 ≥10.52). Multivariate logistic regression and restricted cubic splines (RCS) were employed to analyze the association between NHHR and PSD risk. Among the 408 participants, 93 (22.79%) were diagnosed with PSD. Patients in the PSD group exhibited significantly higher admission NHHR levels compared to the non-PSD group ( P < 0.001). The prevalence of PSD increased progressively across NHHR tertiles: 10.75% in Q1, 25.81% in Q2, and 63.44% in Q3. After adjusting for age, sex, vascular risk factors, stroke severity (NIHSS), and functional impairment (mRS), the highest NHHR tertile remained a potent independent predictor of PSD (OR 3.240, 95% CI 1.850–5.680, P < 0.001). The admission NHHR level exhibited a robust predictive capacity for PSD, with an AUC of 0.738 (95% CI: 0.681–0.790, P < 0.001). RCS analysis further revealed a statistically significant non-linear relationship ( P for non-linearity < 0.001), identifying a vulnerability window between NHHR values of 10 and 15 where the risk of depression escalated most sharply. This association persisted in various subgroup analyses. Elevated admission NHHR is independently and non-linearly associated with an increased risk of PSD at three months in AIS patients. As an easily accessible biomarker of lipid-driven systemic inflammation, NHHR may serve as a valuable prognostic tool for early risk stratification and targeted psychological intervention in clinical practice.
Xing Xu, Zhaoying Yu, Lei Gao, Yaping Chen, Yu Liu
Social isolation and loneliness are increasingly recognized as important determinants of cognitive decline and dementia risk in older adults. However, the strength and nature of these associations vary substantially across populations, cognitive outcomes, and stages of ageing. This review examines the sources of such heterogeneity by distinguishing objective social isolation from subjective loneliness and exploring their different psychological, behavioural, and biological pathways. Using a systematic multi-database search and thematic synthesis, we integrated evidence from longitudinal studies, neuroimaging research, and intervention trials to identify factors that increase vulnerability and promote resilience. The review highlights how psychosocial, behavioural, neuroendocrine, and neurostructural mechanisms contribute to differences in cognitive outcomes and discusses implications for targeted and context-sensitive interventions. Remaining challenges include measurement heterogeneity, limited causal evidence, and underrepresentation of low- and middle-income countries. Future research should prioritize harmonized assessments, stratified intervention trials, and culturally adapted implementation approaches. Early identification and prevention of social disconnection may provide greater benefits than attempts to reverse established isolation.
Naturalistic repetitive transcranial magnetic stimulation (rTMS) outcome data for treatment-resistant depression remain limited in Southeast Asia. This retrospective study describes such outcomes from a general hospital in Singapore. 28 outpatients received rTMS (10Hz high-frequency or intermittent theta-burst) targeting the left dorsolateral prefrontal cortex (F3 scalp position) between May 2022 and May 2025. Treatment-resistant depression was defined as failing ≥2 antidepressant classes for ≥6 weeks each. The primary outcome was change in the Montgomery-Åsberg Depression Rating Scale (MADRS) score; secondary outcomes included the Quick Inventory of Depressive Symptomatology-Self Report (QIDS-SR16), the Depression, Anxiety and Stress Scale-21 (DASS-21), the Quality of Life, Enjoyment and Satisfaction Questionnaire-Short Form (Q-LES-Q-SF), the Clinical Global Impression-Severity (CGI-S), and the Global Assessment of Functioning (GAF). Despite 85.7% of patients having failed ≥3 antidepressant classes, the mean MADRS score decreased by 15.8 (SD 9.1), from 29.6 (SD 7.6) to 13.9 (SD 11.1, p<0.001). This corresponded to a 67.9% response rate and a 57.1% remission rate. All secondary measures (QIDS-SR16, DASS-21, Q-LES-Q-SF, CGI-S, and GAF) showed significant improvements (all p<0.001). Shorter episode duration and higher baseline quality of life were significantly associated with remission. We report favourable response (67.9%) and remission (57.1%) rates within a general hospital cohort in Singapore following standardised rTMS targeting the left dorsolateral prefrontal cortex (approximated by the F3 position), despite extensive prior antidepressant medication failure. These findings contribute real-world data to the limited Southeast Asian literature on standardised rTMS protocols for treatment-resistant depression in general hospital and similar clinical settings.
Michelangelo Di Luzio, Maria Pontillo, Barbara D’Aiello, Giulia D’Amario, Ilaria Bertoncini, Roberto Averna, Milena Labonia, Stefano Vicari
Childhood-onset schizophrenia (COS), defined by the onset of psychotic symptoms before the age of 13 years, is a rare and severe form of schizophrenia. Despite growing interest, little is known about how neurodevelopmental comorbidities shape its clinical presentation. This study aimed to examine whether COS with comorbid neurodevelopmental disorders differs in psychopathological profile from COS with psychiatric comorbidities and from COS without comorbidities. Sixty-one children diagnosed with COS and evaluated at symptom onset in a specialized early psychosis service were included and classified into three subgroups: COS with neurodevelopmental comorbidities, COS with psychiatric comorbidities, and COS without comorbidities. Psychopathological dimensions were assessed using the Kiddie Schedule for Affective Disorders and Schizophrenia for School-Aged Children – Present and Lifetime Version and the Structured Interview for Psychosis-Risk Syndromes and the Scale of Prodromal Symptoms (SIPS/SOPS). Group differences were examined using MANOVA and mixed-design repeated-measures ANOVA, repeated with IQ as a covariate, with False Discovery Rate correction across all SIPS measures. A secondary analysis separated intellectual disability from autism spectrum disorder and/or attention-deficit/hyperactivity disorder. Children with COS and neurodevelopmental comorbidities showed an earlier age at onset, lower IQ, greater bizarre thinking and less social anhedonia. In contrast, COS with psychiatric comorbidity and COS without comorbidities exhibited largely overlapping profiles, marked by greater severity of negative symptoms and more organized thought processes. Within the neurodevelopmental group, the symptom pattern did not appear to be driven by specific diagnoses. These preliminary findings are consistent with variation in the configuration of psychopathological features within COS along a continuum, and highlight the relevance of neurodevelopmental trajectories in shaping symptom expression. Accounting for neurodevelopmental comorbidities may be crucial for improving early diagnostic characterization and informing targeted therapeutic strategies in pediatric schizophrenia.
Autism spectrum disorder (ASD) is a complicated neurodevelopmental condition that currently lacks a targeted therapy. Although stem cell-derived extracellular vesicles (EVs) represent a potential therapeutic approach for neurological disorders, their efficacy in ASD remains unclear. The objective of this study was to investigate the efficacy of stem cell-derived EVs on autistic-like behaviors in animal models of ASD and to explore the underlying mechanisms. Relevant studies published up to April 20, 2026 were searched across five databases. Data were pooled using Review Manager 5.4. Outcome measures included behavioral tests and inflammatory cytokine levels. Out of 1,165 initially retrieved articles, five animal studies met the inclusion criteria. Pooled analyses demonstrated that EV treatment improved autistic-like behaviors in the self-grooming test, three-chamber social interaction test, and marble burying test, and decreased levels of proinflammatory cytokines IL-6 and IL-1β (all P < 0.05). No notable enhancements were observed for the open field test, Morris Water Maze, TNF-α or IL-10 (all P > 0.05). Stem cell-derived EV therapy may improve repetitive behaviors and social deficits in ASD animal models, with observed associations with reduced IL-6 and IL-1β levels. These preclinical findings suggest promising translational potential of EV-based therapy for ASD. https://osf.io/c78xm , identifier 10.17605/OSF.IO/C78XM.
