Sex hormone influence and neuroimmune interplay in mental disorders. The HPA and hypothalamic-pituitary-gonadal (HPG) axes interact with each other and shape the downstream inflammatory responses, neurotransmitters, synaptic plasticity, and behavioral deficits observed in mental disorders. During psychosocial environmental stressors, microglia are stimulated through activation of immune receptors (TLRs, CRH receptors, and cytokine and chemokine receptors). Subsequent cytokine and chemokine secretion attracts activated myeloid cells to the brain via the cellular route. Once in the brain, infiltrating macrophages can drive central inflammatory responses. During psychosocial stress, catecholamines (e.g., noradrenaline released by activated SNS fibers) stimulate increases in myeloid cells (e.g., monocytes) in the periphery. Through induction of inflammatory signaling pathways (such as NF-κB and NLRP3 inflammasome), more proinflammatory cytokines and chemokines are produced that contribute to glucocorticoid resistance through glucocorticoid receptor cleavage. Proinflammatory cytokines and chemokines can access CNS through humoral and neural routes. Monocytes then infiltrate CNS through a compromised blood-brain barrier and differentiate to activated macrophages. Sex hormones affect risk for mental disorders by modulating these pathways at several levels: they 1) influence the perception, processing, and regulation of threat and fear; 2) modulate SNS/HPA reactivity to psychosocial stressors; and importantly 3) alter microglial and macrophage signal transduction through post-translational modifications and epigenetic changes. FSH, follicle stimulating hormone; GnRH, gonadotropin releasing hormone; LH, luteinizing hormone.