Does Depression Shrink Your Brain?

Laura, whose name was changed for confidentiality, said she knew she needed help when she started thinking that death would be preferable to living with the kind of misery and pain she felt, even though she had two young sons whom she loved dearly.

So she went to see a psychiatrist, and he diagnosed major depression and prescribed an antidepressant medication, along with weekly psychotherapy. She took the prescription, and returned the following week, reporting that she had filled it, but could not bring herself to take the pills. She felt that needing to rely on pills reflected a kind of weakness, and she wanted to be strong enough to fight this on her own.

Laura is not alone. Only 25 percent to 50 percent of patients take antidepressants consistently for the length of time recommended by their doctors.

While this is an important issue for short-term health, it may also be important for the longer term, because there is some evidence that depression shrinks the brain — no, it is not the psychiatrists who are the "head shrinkers!" — and that antidepressants might put the brakes on this process.

While much remains to be sorted out, one of the key players in this story might be "neurogenesis," or growth of new brain cells.

Just two weeks ago researchers reported in the journal Science that they had devised a method, based on an imaging technique called magnetic resonance spectroscopy, that could detect new cell growth in the brains of living people. This raises the possibility of being able to monitor effects of antidepressant treatment on neurogenesis in patients.

Hitting on the Hippocampus

The hippocampus is a seahorse-shaped region of the brain found on both the left and right sides, buried a few inches in from the ears. It has a critical role in memory and is part of the connected circuit of brain regions called the limbic system that generate and regulate our emotional lives.

The results of more than 20 studies now strongly suggest that the hippocampus is smaller in patients with major depression than in people without illness. The average difference is about 10 percent.

So the hippocampus is smaller in depression. But does a small hippocampus cause depression or does depression shrink your hippocampus? Some evidence suggests shrinkage occurs.

Scientists began pursuing this line of research after Robert Sapolsky, a Stanford neuroscientist, suggested that chronic stress might unleash a cascade of stress hormones, which over time might kill hippocampal cells. There have since been several studies that have shown that hippocampal size in depression correlates with the length of time a person has been depressed.

Another study has shown that hippocampal size correlates with the amount of time a patient has had untreated depression. Consistent with this, the good news is that evidence suggests depression treatments can block the pernicious effects of chronic stress on neurogenesis, reactivating growth of new brain cells.

Two studies have in fact reported that antidepressants can increase hippocampal size, though both of these were in patients with post-traumatic stress disorder. This has not been observed in a couple of studies of major depression.

Growing Your Brain

The size of the hippocampus varies from one person to another regardless of depression, much like height and foot size vary. Several studies indicate that genetics determines about half of the size variation in the hippocampus.

We have some clues as to which genes determine this variation. One gene in particular, called brain-derived neurotrophic factor, or BDNF, has a variant that has been associated with a smaller hippocampus in at least four studies.

BDNF belongs to a family of genes that influence brain growth, stimulating it like fertilizer in a garden. Antidepressants may act in part by increasing BDNF fertilization in the hippocampus.

Other genes in the BDNF family are currently under study for their potential role in depression. This family of genes might influence how stress impacts the hippocampus, exacerbating the effects in some cases, while warding them off in others.

So what is the message for Laura and others like her? The decision to take an antidepressant can be a complex one, and each patient's unique situation needs to be considered. However, one consideration is that depression is associated with a smaller hippocampus, delayed treatment might be associated with further shrinkage, and antidepressants may have a positive impact on this brain region.

Dr. James Potash is an associate professor of psychiatry and co-director of the Mood Disorders Program (http://www.hopkinsmedicine.org/moods) at the Johns Hopkins School of Medicine in Baltimore. If you have questions or comments, please e-mail at moods@jhu.edu. To participate in our genetic and clinical studies, call 1-877-MOODS-JH.

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