Beyond Blue

Beyond Blue

Does Depression Shrink Your Brain? James Potash, M.D.–How Do You Move Beyond Blue?


Below, I have reprinted a fascinating article by James Potash, associate professor of psychiatry and co-director of the Mood Disorders Program (where I graduated with the help of Dr. Smith) at the Johns Hopkins School of Medicine in Baltimore. More and more research is showing that the brain actually shrinks with severe depression, and that is all the more reason to arrest it as soon as possible. For the ABC special report, click here. I have excerpted most of it below.


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.


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  • Larry Parker

    This gives a whole new meaning to the “shrinkage” episode of Seinfeld …

  • therapydoc

    Just fascinating. I stop by to say hi and you have this great interview. Well done, Therese.

  • therapydoc

    I mean article.

  • Margaret Balyeat

    The whole topic of brain regenerization is crucial to those of us who’ve suffered brain cell loss due to stroke or other brain traumas as well (Though not in the hippocamus) since most medical professionals believe the ‘aswer” is in growing new dendrites to create different pathways to “detour” round the damaged cells which can no longer function properly and then train these new connections to do the job previously done by the “dead” cells” That’s exactly why so many of us are pro “stem cell research and therapy” (although not necessarily using the stem cells from aborted or “frozen” embryos. If MRI’s can now prove shruinkage/growth in the hippocamus, can the same for other areas of the brain be far away?(PLEASE G-d!) Sorry to sound so egocentric, but that issue holds more interest for me than jump-starting my hippocamus does. What a wonderful world it would be if a medication could be prescribed that would encourage that kind of new brain cell growth? Think of children born with paralysis who could maybe walk or throw a ball for the first time! (Or old fa**ts like me who could resume daily living activities for ourselves! Yes, I realize it would mean popping yet another pill, but I DARE someoneto criticize medication for that purpose! As with depression, if you haven’t lived it you can’t possibly relate, but unlike depression, it IS at least recognized as a legitimate health issue so the anti-pharacuetical people would have a real WAR on their hands for fightoing that o.

  • Nancy

    Margaret…what about the effects of lithium on BDNF?

  • lynnemarie1


  • lynnemarie1


  • Larry Parker

    Are you saying I’m like that general in Vietnam — destroying my brain in order to save it?

  • Catatonic Kid

    I’m so glad when I see findings like these being talked about!
    It’s so important because these types of findings can go a long way to reducing the stigma many folks feel when deciding about their own or their family’s health care.
    It sounds simple but I bet it sure packs a punch if you hear a doctor tell you that’s it’s not just about unfamiliar chemicals you know from nothing bouncing around in your brain but the very physical structure of your brain that’s at stake. An ounce of prevention, perhaps? Or at least another tick for the ‘it’s a real illness’ campaign.
    Catatonic Kid

  • Lynne

    Good grief! Now I am “The incredible shrinking brain!” Well I would like to know more about lithium. I think that would be in my comfort zone. Also does it have the same effect on the “bi-polar express”? I’m all about the first do no harm, and not to mention a whopping white coat phobia! Can anyone address that?

  • http://AddaURLtothiscomment Deana

    How might the hippocampus be affected in bi-polar, and is any treatment in studies for specifically treating that area as opposed to the typical route for antidepressants?

  • http://AddaURLtothiscomment Sheryl

    What about those of us who have tried every type of antidepressant with no or little response? I have been on everything except MAOI treatment… Some work for a while but seem to stop after a short period of time usually less then six months. I am also very cyclic and have not found a good treatment for that tried a couple different things that seemed to have no effect except to make me very lethargic. One caused a rash and was life threatening. What do treatment resistant bipolar people do?

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