Brain Circuits in Major Depressive Disorder and Bipolar Disorder

The lifetime prevalence rates of unipolar depression (UPD) in males and females of first-world countries are approximately 15 and 25 percent, respectively. The figures appear to be equally disheartening in developing countries: The 12-month prevalence of major depressive disorder in South Africa is roughly 5 percent. It is therefore not surprising that 25 percent of all visits to health care providers around the world are estimated by the World Health Organization (WHO) to be depression related. Bipolar disorder (BD) has equally serious implications for public health with the WHO listing the disorder as the sixth leading cause of disability in the world among people in the 15 to 44 year-old category in 1990. Recently, the National Comorbidity Survey Replication found that on average 27.2 and 65.5 workdays are lost in the United States each year among people with UPD and BD, respectively. Tragically, up to 30 percent of BD patients attempt suicide, approximately half of them successfully, with an odds ratio for attempts of about six compared to three for UPD. These figures are perhaps partly explained by the modest efficacy of treatment. Only about half of all patients respond to a first-line trial of antidepressant therapy, and the mean drug–placebo difference in response rate is only 10 percent in the average randomized, controlled trial. The picture is even less sanguine for psychotherapy with most data showing psychotherapy to be equivalent to or less effective than pharmacotherapy despite the fact that clinical trials suffer from a selection bias for milder cases. Clearly understanding the etiological and pathophysiological basis of affective illness is an imperative. Unfortunately, progress has been retarded by the sheer complexity of the neural systems involved in mood regulation, and thus current nosological systems are based on symptomatology rather than etiology. Despite these setbacks, advances in neuroimaging and genetics provide reasons for cautious optimism as psychiatry resolves to place itself on an equal footing with medical disciplines such as neurology. Here, the neuroimaging correlates of depression in the guise of both UPD and BD are reviewed and interpreted with reference to developmental and degenerative pathophysiological mechanisms.