The Neurobiology of Depression

Nemeroff, C.B. (June 1998). The neurobiology of depression. Scientific American, vol. 278, no. 6, 42(7).

This article by Nemeroff is about depression and the search for its biological underpinnings. Depression is a psychiatric disorder characterized by an inability to concentrate, insomnia, loss of appetite, general absence of pleasure, feelings of extreme sadness, guilt, helplessness and hopelessness, and perseverant thoughts of death. However, understanding the neurobiology of depression is a daunting task and still ongoing, as is the goal of identifying simple biological markers (endophenotypes) for the disorder.

The prevalence of depression is surprisingly high, and should get more publicity in my opinion. 5-12% of men and 10-20% of women in the US will experience a major depressive episode at least once in their life, with half of these individuals becoming depressed more than once. As many as 15% of those who suffer from depression will commit suicide each year; in fact, the CDC has ranked depression as the 9th leading cause of death in the US. Further, depression takes its toll economically as well, with an estimated productivity hit of $43 billion each year. Clearly, the need for improved methods of diagnosing, treating, and preventing the disease is becoming more and more critical.

Several neurobiological theories of depression were mentioned in this article. Neurotransmitter hypotheses focus on disturbances in brain circuits that convey signals through monoamine neurotransmitters. For example, Joseph Schildkraut proposed that depression stems from a deficiency in norepinephrine whose circuits originate in the brain stem’s pigmented locus coeruleus and project to many cortical and subcortical regions throughout the brain. Arthur J. Prange, Jr. implicated serotonin-producing neurons which project from the brain stem’s raphe nuclei. Still others point to the dysregulation of the hypothalamicpituitary-adrenal (HPA) axis, which mediates the body’s response to stress. Studies have revealed that chronic hyperactivity in this region is well correlated with depressive symptomatology. In particular, studies show an increased number of corticotrophin releasing factor (CRF) producing neurons in the hypothalamus as well as increased synthesis of CRF in depressed patients as compared with controls, increasing the likelihood of these patients to enter states of hyperarousal (i.e. low stress tolerance) and inevitably lowering their threshold for depression.