Coping to move again: the psychological dimension of tele-supported rehabilitation after knee arthroplasty-A randomized controlled trial.

Anxiety disorders and depressive disorders are among the most prevalent mental disorders worldwide (–). In the United States, approximately 9% of adults experience major depressive disorder annually, with a lifetime prevalence of approximately 17% in males and 30% in females (). However, the diagnosis of anxiety and depression has long relied on clinical symptom assessment, lacking objective blood-based biomarkers, which results in low early recognition rates and high misdiagnosis rates (, ). In recent years, peripheral blood biomarkers have garnered considerable attention owing to their non-invasive nature and reproducibility. Lipids have demonstrated potential diagnostic utility in major depressive disorder and anxiety disorders. Triglycerides, total cholesterol, low-density lipoprotein cholesterol, and other lipid markers exhibit significant alterations in affected patients; however, further investigation is warranted to delineate disease-specific biomarker profiles (). Researchers conducted a systematic review and meta-analysis examining neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) in mood and anxiety disorders, finding no significant elevation of NfL or GFAP in patients with depression, whereas NfL levels were elevated in bipolar disorder (). Building on these observations, multi-marker screening strategies grounded in proteomics and metabolomics are progressively being applied to the discovery of biomarkers for psychiatric disorders (–). Nevertheless, the biomarkers examined and the analytical platforms employed in these studies are associated with relatively high costs, limiting their accessibility in many primary healthcare settings (, –). Sex is a critical risk factor in the epidemiology of anxiety and depression (–). Substantial epidemiological evidence demonstrates that the prevalence of anxiety and depression is higher in females than in males (, , ). A comprehensive umbrella review confirmed that the prevalence of internalizing disorders, including anxiety and depression, is significantly higher in females, whereas externalizing disorders are more prevalent in males (, ). Researchers () systematically delineated the role of sex in the environmental risk factors, symptom onset, genetic susceptibility, and disease progression of major depressive disorder, generalized anxiety disorder, and post-traumatic stress disorder, highlighting that the elevated prevalence of internalizing disorders in females involves multiple interactions between sex hormones and psychosocial factors. Furthermore, previous study () comprehensively examined sex differences in the immune system in the context of mood disorders, reporting that females not only exhibit a higher prevalence of autoimmune diseases but also mount stronger immune responses to stress, suggesting that sex may influence the susceptibility and clinical manifestations of psychiatric disorders through immuno-inflammatory mechanisms. The influence of sex on blood biomarkers in patients with anxiety and depression represents a prominent focus of precision psychiatry research in recent years. Researchers () utilized a multiplex immunoassay platform to quantify 171 serum molecules, identifying pronounced sex-specific associations between major depressive disorder (MDD) and immune response-related proteins: MDD in males was specifically associated with elevations in inflammatory markers including C-reactive protein (CRP), cystatin C, and β2-microglobulin, whereas a comparably broad immune activation pattern was not observed in females. An analysis of 144,890 participants from the UK Biobank demonstrated that the association between CRP concentrations and depressive and anxiety symptoms was more pronounced in females than in males, while Mendelian randomization analyses suggested that altered activity of the IL-6/IL-6R pathway may constitute a risk factor for depression (). Notably, some researchers () reported in the Netherlands Study of Depression and Anxiety (NESDA) that elevated CRP was present only in males with current anxiety disorders, not in females, indicating potential sex-specific heterogeneity in the direction of the association between inflammatory markers and anxiety. Previous study () further corroborated that inflammatory, neurotrophic, and serotonergic marker levels are more markedly elevated in females with depression, and that the correlations between these markers and symptom severity are also stronger in females. Collectively, the existing evidence indicates that blood biomarkers of anxiety and depression exhibit pronounced sexual dimorphism, potentially involving immuno-inflammatory, neuroendocrine, and metabolic pathways, thereby underscoring the clinical importance of developing sex-stratified diagnostic and therapeutic strategies.