Endocrine Factors in Key Structural and Intracellular Changes in Depression.

Endocrine disturbances play predominant roles in recently discovered, clinically relevant abnormalities in depression. These affect multiple sites in the prefrontal cortex, amygdala, hippocampus, nucleus accumbens, and habenula. Deficits consist of changes in volume, neuroplasticity, neural connectivity, synapse composition, and neurogenesis. Depression is associated with endocrine-related, premature systemic disease, that results in a loss of approximately 7 years of life. CRH, glucocorticoids, somatostatin, gonadal steroids, and thyroid hormones all contribute to the deficits that largely define the pathophysiologic presentation of depression. The World Health Organization ranks depression as the second greatest cause of disability worldwide. The response rate to current antidepressants is below 60%. It is important that new knowledge about the endocrine-mediated pathophysiology of depression be communicated to provide targets for new agents.