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.