Relevance of Sex-Specific Metabolic Phenotypes in Diagnosis and Treatment of Mood Disorders and PTSD

Mood disorders and post-traumatic stress disorder (PTSD) are considered brain-based illnesses, but they present with somatic symptoms and are often comorbid with insulin resistance. Peripheral and central mechanisms implicate the hypothalamus as a center for bi-directional communication of stress between the brain and body. The hypothalamic-pituitary-adrenal axis and the hypothalamic-pituitary-gonadal axis regulate glucocorticoid levels, yielding sex differences in stress response in addition to differences in PTSD and mood disorder susceptibility and course in males and females. Glucocorticoids and gonadal hormones modulate inflammatory response via cytokine receptor coupling, yielding multiple mechanisms connecting neuroinflammation and disturbances of mood and metabolism. Reduction of metabolic and psychologic stress via pharmacologic and behavioral interventions should be applied with attention to the commonalities and the heterogeneity in pathophysiology of these comorbid conditions across metabolic and sex-related phenotypes.