Endocrine psychiatric comorbidity in metabolic disorders: Integrative mechanisms and traditional Chinese medicine

Figure 1 Shared pathophysiology underlying endocrine-psychiatric comorbidity in metabolic disorders. Upstream metabolic, behavioral, and treatment-related triggers engage a self-reinforcing loop linking stress/circadian disruption, metabolic inflammation, insulin resistance/metabolic toxicity, gut barrier-microbiome dysbiosis, neuroimmune activation, and altered neural circuitry, generating depressive/anxious symptoms, sleep disturbance, cognitive dysfunction, disordered eating, and reduced adherence that further feed back to worsen metabolic control and cardiometabolic risk. Central hub targets (autonomic-inflammatory reflex, tryptophan-kynurenine pathway, mitochondrial dysfunction/oxidative stress, and glucagon-like peptide-1-related neuropeptides) highlight key leverage points for integrated interventions. BBB: Blood–brain barrier; GLP-1: Glucagon-like peptide-1; HPA: Hypothalamic–pituitary–adrenal axis; HRV: Heart rate variability; IR: Insulin resistance; LPS: Lipopolysaccharide; SCFAs: Short-chain fatty acids; SNS: Sympathetic nervous system.

Figure 2 Proposed integrative clinical pathway for endocrine-psychiatric comorbidity in metabolic-endocrine disorders. Patients undergo a minimal screening set (Patient Health Questionnaire 9, Generalized Anxiety Disorder 7, and Insomnia Severity Index/Pittsburgh Sleep Quality Index) followed by risk stratification to guide tiered, dual-endpoint intervention packages; traditional Chinese medicine pattern assessment and options are incorporated when appropriate with safety monitoring, and outcomes are reassessed using metabolic and mental health endpoints to iteratively adjust care intensity. PHQ-9: Patient Health Questionnaire 9; GAD-7: Generalized Anxiety Disorder 7; ISI: Insomnia Severity Index; PSQI: Pittsburgh Sleep Quality Index; T2DM: Type 2 diabetes mellitus; MAFLD: Metabolic dysfunction-associated fatty liver disease; PCOS: Polycystic ovary syndrome; TCM: Traditional Chinese medicine; HbA1C: Glycated hemoglobin; CRP: C-reactive protein; IL-6: Interleukin-6; HRV: Heart rate variability.

Figure 3 Conceptual framework of endocrine-psychiatric comorbidity in metabolic-endocrine disorders. Major metabolic-endocrine conditions are linked to psychiatric and behavioral phenotypes through bidirectional pathways. Metabolic disease may worsen mental health via metabolic inflammation, endocrine-autonomic dysregulation (hypothalamic-pituitary-adrenal/sympathetic nervous system), and gut-brain signaling, whereas psychiatric illness and its management may aggravate metabolic status through behavioral changes, chronic stress biology, and psychotropic metabolic liability. These overlapping patterns (disease-driven, behavior-driven, and treatment-emergent) contribute to poorer metabolic control, higher cardiometabolic risk, reduced adherence, and lower quality of life, underscoring unmet needs for integrated screening and dual-endpoint interventions targeting both metabolic and mental health outcomes. PCOS: Polycystic ovary syndrome; HPA: Hypothalamic-pituitary-adrenal; SNS: Sympathetic nervous system; OSA: Obstructive sleep apnea; MAFLD: Metabolic dysfunction-associated fatty liver disease.