General Medical Conditions

Our appreciation and understanding of the interrelationships between disrupted metabolic function and psychiatric disease, depression in particular, have increased significantly over the last few decades. Several broad-scale pathophysiologic mechanisms implicated in both disease areas include inflammation, cytokine and hypothalamic–pituitary–adrenal (HPA) axis dysregulation, oxidative stress, neurotransmitter disruptions, neurogenesis and neuroplasticity, and the microbiome. This chapter will explore these mechanistic overlaps of depression with metabolic disorders, defined broadly to include obesity, diabetes, and cardiovascular disease. The different components of metabolic syndrome will be discussed within this framework. We will touch briefly on relationships between the numerous yet rare inherited metabolic disorders and depression. We will conclude with a discussion of integrated therapeutic strategies for treating depression comorbid with metabolic disease.