Objective Endothelial dysfunction and systemic inflammation are increasingly implicated in the pathophysiology of schizophrenia. The Endothelial Activation and Stress Index (EASIX), a composite marker derived from lactate dehydrogenase, creatinine and platelet count, reflects both processes but has not previously been investigated in schizophrenia. We aimed to investigate how EASIX and complete blood count–derived inflammatory indices changed between the acute psychotic and remission phases in the same patients. Methods In this retrospective study, the acute psychotic and remission phases of 83 patients with schizophrenia were evaluated. EASIX, sEASIX, their log₂-transformed values, and the NLR, PLR, MLR, SII and AISI values were compared between the two clinical states using paired-sample t-tests and Wilcoxon signed-rank tests. Results Both EASIX and sEASIX were significantly higher in the acute psychotic episode compared with remission and stayed significant after Bonferroni correction (adjusted p = 0.018 and p = 0.014, respectively). Of the inflammatory indices, NLR remained significant after adjustment (adjusted p = 0.015) while SII was only significant in the unadjusted analysis (p = 0.037). There was no significant difference in PLR, MLR and AISI between the two clinical states. Conclusion EASIX and the selected inflammatory indices were at higher levels during the acute psychotic episode and decreased during the remission phase. EASIX may be a readily obtainable, low-cost candidate biomarker for disease activity in schizophrenia; however, a prospective validation study is required.
Background Inflammation and metabolic dysregulation are closely linked to mental disorders. This study systematically compared three metabolic-inflammatory indices-remnant cholesterol inflammatory index (RCII), neutrophil-to-high-density lipoprotein cholesterol ratio (NHR), and C-reactive protein-triglyceride-glucose index (CTI)-with the risk of severe and common mental disorders. Methods This prospective cohort study included 230,147 participants from the UK Biobank. Kaplan-Meier curves and log-rank tests were used to compare cumulative incidence across quartiles. Cox regression estimated associations between metabolic-inflammatory indices and incident mental disorders. The area under the curve (AUC) and Net Reclassification Index (NRI) were used to evaluate incremental predictive value. Results Over a median follow-up of 14.27 years, 15,485 participants developed mental disorders. All indices were associated with increased risks of depression, anxiety, and overall mental disorders. Schizophrenia risk was elevated only in the highest quartile. Bipolar disorder was associated only with NHR (HR = 1.111, 95% CI: 1.004-1.230, P = 0.041). NHR showed superior predictive ability for depression (AUC: 0.622 to 0.627, P = 0.007) and overall mental disorders (AUC: 0.614 to 0.618, P = 0.004). RCII and CTI showed comparable predictive performance for anxiety and depression, with all indices significantly improving risk reclassification (NRI > 0, P < 0.05). Conclusions All indices exhibited threshold effects for schizophrenia. NHR showed unique predictive value for bipolar disorder and superior predictive ability for depression and overall mental disorders. These findings suggest that distinct metabolic-inflammatory indices may serve as complementary tools for predicting different mental disorders.
Background Sex hormones influence brain circuits that regulate mood, but previous studies in men have focused on few hormones and treated depression as a single condition. In a nationally representative sample of men, we systematically examine 12 serum sex hormones across the adult lifespan in relation to dimensional depressive symptoms. Methods We analyzed cross-sectional data from the National Health and Nutrition Examination Survey (2017–2023). Serum sex hormones were measured, and depressive symptoms were assessed by PHQ-9, with a score ≥5 indicating mild or greater symptoms. Survey-weighted regression models examined associations between hormones and depressive symptoms, total scores, somatic/non-somatic subscales, and nine individual symptoms. Results Among 5668 men (mean age 51.1 years), 1344 (23.7%) had depressive symptoms. Higher anti-Müllerian hormone (AMH, OR=0.86), dehydroepiandrosterone sulfate (DHEAS, OR=0.83), and estrone sulfate (ES1, OR=0.87) were associated with lower odds of depressive symptoms; higher luteinizing hormone (LH, OR=1.11) with increased odds. Age-stratified analyses showed ES1 was inversely associated with depressive symptoms in middle-aged and older men, DHEAS only in older men, and AMH in younger and middle-aged men. Dimensionally, ES1, AMH, and testosterone were associated with lower somatic symptom scores (β=-0.12, -0.16, and -0.17), while AMH was also associated with lower non-somatic scores (β=-0.23). AMH was inversely associated with concentration difficulties; FSH and LH with sleep disturbance. Conclusions Sex hormones show distinct, age and symptom-dimension-specific associations with male depression, challenging unitary diagnostic approaches. These findings support hormone-informed subtyping of male depression and suggest clinical assessment should consider both age and symptom presentation.
Inflammatory bowel disease (IBD) and depression frequently co-occur, and previous studies have suggested temporal associations in both directions. We conducted two complementary matched cohort studies using the Korean National Health Insurance Service database to further characterize these associations in a nationwide Korean population. In Study I, 11,725 patients with ulcerative colitis (UC) and 2918 patients with Crohn’s disease (CD) were matched with 58,572 controls without IBD to assess incident depression. In Study II, 622,131 individuals with depression were matched 1:1 with 622,131 controls without depression to assess incident UC and CD. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using stratified Cox proportional hazards models adjusted for demographic, lifestyle, metabolic, and clinical covariates. UC was associated with an increased risk of subsequent depression (adjusted HR, 1.24; 95% CI, 1.14–1.36), whereas CD was not significantly associated with depression (adjusted HR, 1.14; 95% CI, 0.93–1.39). Conversely, depression was associated with increased risks of subsequent UC (adjusted HR, 1.31; 95% CI, 1.14–1.52) and CD (adjusted HR, 1.62; 95% CI, 1.20–2.18). These findings provide complementary evidence of associations in both temporal directions between depression and IBD, although the pattern was not symmetric across IBD subtypes.
Background Stimulant use disorder (StUD) remains a major public health concern with limited treatment options and high attrition. Deep transcranial magnetic stimulation (dTMS) targeting the medial prefrontal and anterior cingulate cortices may modulate circuits involved in craving and control. This pilot study evaluated the safety, tolerability, and feasibility of accelerated dTMS (adTMS) using the H7 coil in individuals with moderate to severe StUD. Methods In this open-label, single-arm feasibility trial, participants received 30 sessions of high-frequency (20 Hz) adTMS using the H7 coil (three daily sessions delivered over 10 days). Primary outcomes were feasibility and safety. Secondary outcomes included craving (SCQ-B; daily visual analog scale), and stimulant use (Timeline Follow-Back, urine toxicology). Exploratory outcomes, including changes in depression (PHQ-9), anxiety (GAD-7), withdrawal (SSSA), and rumination (RRS) were analyzed with linear mixed-effects models. Results 19 participants enrolled, 16 initiated treatment, and 12 (75% of those who initiated treatment) completed ≥80% of sessions. Among these 12 treatment completers, retention was 67% at 2 and 4 weeks and 58% at 12 weeks. No serious adverse events occurred; the most frequent side effects were mild headache (75%) and fatigue (69%). Depressive symptoms (p=.020) and withdrawal severity (p=.033) improved significantly, while changes in anxiety, rumination, craving, and stimulant use did not (p>.05). Conclusions Our adTMS protocol was safe and well tolerated in individuals with StUD. Retention was similar to what has been observed in other trials in this population, but refining retention strategies may help decrease attrition. Depression and withdrawal scores decreased over time, but not craving or stimulant use. Larger, sham-controlled studies with optimized retention strategies are warranted to determine efficacy.
