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Depression and the Birth and Death of Brain Cells

The turnover of neurons in the hippocampus might help to explain the onset of and recovery from clinical depression

Henriette van Praag, Barry Jacobs, Fred Gage

No one knows the precise mechanism that triggers clinical depression, but people have speculated about it for centuries. From the time of the ancient Greeks until well into the Renaissance, philosophers and scientists believed that bodily fluids called humors were responsible for our moods and personality. Specifically, they thought that one called black bile controlled depression. By the 17th century, dualism—the separation of mind and body—was the dominant dogma. Consequently, it was believed that depression, a disease of the "mind," arose from something gone awry in your physical or social environment. But eventually, by the early 20th century, even Sigmund Freud—the father of psychoanalysis—had come to believe that brain dysfunction would ultimately explain mental illness. Today, neuroscientists know that, in many cases, psychopathology arises because of dysfunctions in particular brain structures or particular brain chemicals. As described in this article, recent evidence suggests that clinical depression might arise from the brain failing to grow new neurons in a specific area.

Figure 1. Theories of the etiology . . .Click to Enlarge ImageFigure 2. Hippocampus . . .Click to Enlarge Image

Neurobiologists long believed that adult brains did not make new neurons, but now we know otherwise. In the early 1960s, Joseph Altman at MIT reported that new neurons were being produced in the brains of adult rats. Those findings were somewhat forgotten for the next 30 years. Recently, this work has been revived and advanced. Elizabeth Gould of Princeton University, one of this article's authors (Gage) and others have reported the birth of new neurons—neurogenesis—in the hippocampus of adult rats, monkeys and humans. This region of the brain lies beneath the cortex in the temporal lobe (see Figure 2)—basically the part of your brain behind your ear—and it appears to play a crucial role in forming new memories. Preventing depression might depend in part on proper control of this ongoing neurogenesis.

Currently available antipsychotic medications usually fall short of the desired therapeutic efficacy and invariably produce unwanted side effects, such as dry mouth or sleep disturbances. These treatments typically act by globally altering the chemical communication between neurons throughout the brain. More recently, cell and molecular biology have begun to exert a strong impact on our understanding and treatment of mental illness. By targeting specific molecular sites in neurons, these techniques can provide precise, powerful and effective means of influencing brain function. One of these approaches—controlling neurogenesis in the adult brain—might have a significant impact on the treatment of mental illness.

Let us first examine the current state of knowledge regarding adult brain neurogenesis. Then we shall focus specifically on the role of neurogenesis in chronic clinical depression. As we shall see, controlling neurogenesis might also be used to treat or prevent a variety of other forms of neuro- and psychopathology.

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