Conceptualizing Major Depression: From Genes to Neuroanatomy to Epidemiology

Because its etiology remains largely unexplained, major depression, like other psychiatric diseases, is understood entirely on the basis of symptomatology. Major depression is the most common mental illness and is responsible for substantial mortality, morbidity, and disability. Arguably we know less about the root causes of major depression than about other major mental illnesses (eg, schizophrenia, bipolar disorder, autism). In the current chapter, we examine the literature on the prevalence, diagnostic heterogeneity, risk factors, neuroanatomy, neurophysiology, heritability, endophenotypes, and genetic architecture of major depressive disorder. In addition, we briefly discuss current treatments. Whereas epidemiological results stress the heterogeneity and complex nature of the illness, neuroimaging-based models typically ignore the diversity of clinical factors, potentially limiting their usefulness. Although certainly influenced by environmental factors, there is ample evidence for a genetic component to major depression. However, to date no specific genomic variant or gene has been implicated for depression.