Prefrontal activation and connectivity during verbal fluency in autism Spectrum disorder: an fNIRS study.

Post-stroke depression (PSD) represents a prevalent neuropsychiatric sequela of acute ischemic stroke (AIS), affecting approximately 30–50% of patients within three months of onset, with symptoms ranging in severity (, ). Beyond severely impairing patients’ neurological recovery and functional status, PSD also significantly increases the likelihood of recurrent stroke and mortality, emerging as a critical barrier to stroke rehabilitation and secondary prevention (, ). Despite its substantial clinical significance, the pathogenesis of PSD remains incompletely elucidated, and reliable early predictive markers are lacking in clinical practice (). Emerging evidence suggests that metabolic dysregulation, particularly insulin resistance (IR), may play an important role in the development of both cerebrovascular disease and depressive disorders, making it a potential mechanistic link underlying PSD. In recent years, insulin resistance (IR) and the metabolic disturbances it mediates have attracted increasing attention as a potential “pathophysiological bridge” linking cerebrovascular disease and affective disorders (, ). IR has emerged as an independent determinant of AIS, contributing to stroke onset and progression by exacerbating endothelial dysfunction and accelerating atherosclerotic processes (, ). Concurrently, the central nervous system metabolic imbalance, excessive activation of oxidative stress, and neuroinflammatory cascade reactions induced by IR may directly interfere with cerebral mood regulation pathways, thereby participating in the pathophysiological process of post-stroke depression (–). Accordingly, the identification of accessible biomarkers that reliably reflect IR status may enable early recognition of high-risk PSD patients. Among the various surrogate markers proposed for assessing IR, the triglyceride-to-high-density lipoprotein cholesterol ratio (TG/HDL) has attracted considerable attention. Owing to its simplicity, accessibility, and low cost, TG/HDL has been widely validated as a practical surrogate marker of IR in both cardiovascular and metabolic research settings (–). Existing evidence indicates that a higher TG/HDL is linked to poor prognoses in various cardiovascular and metabolic conditions, including coronary heart disease, type 2 diabetes, and metabolic syndrome (–). More importantly, the pathophysiological implications of this ratio may extend beyond the metabolic domain to the field of mental health (). Epidemiological studies have provided preliminary evidence linking dyslipidemia to depressive symptoms: a large-scale cross-sectional study revealed a J-shaped dose-response association between TG/HDL ratio levels and depressive symptoms, suggesting a pathophysiological basis for their non-linear association ().