Body weight variability and mortality in older adults: a nationwide population-based cohort study.

Schizophrenia is a highly prevalent and severe mental disorder that typically onset during late adolescence to early adulthood. Its primary manifestations include disturbances in thinking, perceptual abnormalities (e.g., auditory and visual hallucinations), delusions, and behavioral disorganization, often accompanied by significant cognitive impairment. In addition to core psychotic symptoms, sleep disturbances, particularly insomnia, are extremely prevalent among individuals with schizophrenia. Multiple epidemiological studies have reported that approximately 8% to 80% of patients with schizophrenia experience insomnia of varying severity; this wide range likely reflects differences in assessment tools, sample characteristics, and diagnostic criteria. Notably, in the clinical management of schizophrenia, prominent psychotic symptoms such as hallucinations and delusions often dominate diagnostic and therapeutic priorities, leading to inadequate recognition and delayed intervention for sleep disturbances. However, accumulating evidence indicates that comorbid insomnia not only exacerbates the severity of both positive and negative symptoms but also significantly impairs attention, working memory, and executive function, thereby markedly reducing social functioning and subjective quality of life. Furthermore, a systematic review has identified insomnia symptoms as an important early warning sign of schizophrenia relapse. Given the substantial impact of insomnia on prognosis and quality of life in individuals with schizophrenia, a comprehensive understanding of its epidemiological characteristics and modifiable risk factors is critically important. Previous research has robustly demonstrated that a range of psychopathological symptoms is associated with insomnia in individuals with schizophrenia. First, psychotic symptoms themselves may directly disrupt sleep homeostasis. For instance, auditory hallucinations occurring at night can fragment sleep continuity, while persecutory delusions may sustain a state of heightened vigilance. A cross-sectional study conducted in China further confirmed that the severity of psychotic symptoms is an independent risk factor for insomnia in patients with schizophrenia. Moreover, depressive symptoms also play a significant role in insomnia among patients with schizophrenia. A study of outpatients with schizophrenia found that insomnia is significantly associated with depressive symptoms and serves as an independent predictor of reduced quality of life. Aggressive behaviors, a highly disabling comorbid feature in schizophrenia, may also be associated with insomnia. Razki et al. reported that patients with schizophrenia who exhibit aggressive behaviors have a significantly elevated risk of sleep disturbances. Further studies suggest that psychosocial factors including emotional dysregulation and cognitive distortions as well as dysfunction of the prefrontal glutamatergic system may underlie this comorbidity. Therefore, in clinical assessment and intervention, it is essential to recognize the critical role that psychopathological symptoms play in the onset and progression of insomnia in schizophrenia. At the biological level, the neuroimmune and metabolic perspectives are progressively reshaping our understanding of schizophrenia and its comorbid conditions. Growing evidence suggests that chronic low-grade inflammation may serve as a potential pathogenic driver in the onset and progression of schizophrenia. For instance, Barlattani et al. posited that glymphatic clearance dysfunction, leading to the accumulation of neuroinflammation, constitutes a critical pathway in the pathogenesis of psychiatric disorders such as schizophrenia, a process that is intricately linked to sleep-wake rhythms. Under inflammatory or other physiological stressors, leukocytes undergo characteristic shifts including neutrophilia and lymphopenia. Based on these changes, ratios such as the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and monocyte-to-lymphocyte ratio (MLR) have emerged as widely adopted, clinically accessible, and biologically informative peripheral markers of systemic inflammation. A cross-sectional study demonstrated that insomnia severity is positively correlated with NLR, PLR, and MLR. Furthermore, circulating metabolic biomarkers also appear to play a non-negligible role in the manifestation of insomnia. A case-control study found that individuals with schizophrenia and dyslipidemia exhibited significantly more severe sleep disturbances particularly in subjective sleep quality, sleep latency, and total sleep time. Green et al. further reported a robust association between thyroid dysfunction and sleep disturbances. Nonetheless, current research on insomnia in schizophrenia faces several key limitations. First, although the volume of relevant studies is substantial, findings regarding the associations between insomnia and psychopathology remain inconsistent a