Mind Matters -- November 2002
Written by Ron Sterling, M.D. and Published in Northwest Prime Time Magazine

It's All About the Hippocampus!


    Dear Dr. Ron:

      I read your last column about depression and it got me to thinking and doing a little research. I keep reading that exercise benefits the brain and I found several articles on the subject, but nothing that tells me how it really works when it comes to depression. I think everyone knows that there is an "uplifting feeling" that a person gets from exercise, but is there anything else? Signed -- Curious in Kent

    Dear Curious:

      Thank you for writing! My answer is going to be a little more about the brain than about the mind. As you know, the mind depends on the brain, so you can't really feel good unless the brain is functioning well. What follows is very simplified, but true.

      After you read this column you will be able to impress your friends with at least three big words. Those words are corticotropin releasing factor (CRF), brain-derived neurotrophic factor (BDNF), and the hippocampus.

      You probably already know that the latest antidepressants increase certain already existing chemicals in our brains such as serotonin. You might also know that antidepressants can take a long time to work. There is a reason for why it takes a while for them to work and it has to do with the regrowth of nerve cells, not just an increase in certain chemicals in the brain.

      CRF is the main culprit in depression. Stress dramatically increases CRF levels in the human brain. CRF is toxic to nerve cells in the hippocampus.

      "So, Dr. Ron, what is the hippocampus?" Think of the hippocampus as a horseshoe-shaped brain structure that sits inside the brain. It's two ends point forward and it crosses from one side to the other toward the back of the head. It contains most of the norepinephrine and serotonin found in the brain. It is essentially our mood control center.

      By using special MRI imaging techniques, many studies have found a link between a smaller hippocampus and moderate to severe depression. What makes a hippocampus smaller? Right, high CRF levels shrink the hippocampus. You might wonder how people who are always stressed avoid having their hippocampus damaged and ending up depressed. That is where BDNF comes in.

      BDNF is made by nerve cells and it stimulates them to grow and make more connections to other nerve cells. The hippocampus normally has large amounts of BDNF. However, under stress, BDNF in the hippocampus of rats can be dramatically depleted.

      So, the cycle goes like this: Stress increases CRF; high CRF levels damage the hippocampus; stress decreases BDNF; nerve cells lose the ability to produce certain chemicals; depression follows.

      Is there anything that can help? In rats, either Prozac-type antidepressants or exercise alone increase BDNF levels and protect against the bad effects of CRF. "So, Dr. Ron, what does rat research have to do with humans?"

      I forgot to tell you one other thing about the hippocampus. It is one of the "oldest" parts of the brain. Unlike the cerebral cortex, that huge, new, added-on part of the human brain that makes us the thinking animals that we are, the hippocampus exists in almost all mammals, in a similar form and having a similar function as it does in humans.

      No tool yet exists to measure BDNF in the human hippocampus. However, given what we know about human CRF levels and stress, the relationship between a smaller hippocampus and depression, and how antidepressants actually help the hippocampus regrow, it all fits -- CRF bad, BDNF good! Exercise good!

      I hope that helps to answer your question. You can view diagrams and read more about the hippocampus at www.Hippocampus.us. Take care, and here's to a healthy hippocampus. -- Dr. Ron.

        Author Bio:

        Ron Sterling, M.D. is a 64 year-old General and Geriatric Psychiatrist with a private practice in Seattle. He invites you to e-mail him at with any questions about mental wellness or emotional, relationship, or aging concerns. He is the only person who reads e-mail sent to Dr. Ron. Please be assured that your questions and identities are completely confidential and protected. For more information about Dr. Ron and for resources related to senior mental health, please go to SeniorMentalHealth.org. Read our Disclaimer.

        Thank You for Stopping By!

      Have a great day!


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RON STERLING, M.D.
General Psychiatry with Specialization in Adult Attention Deficit Disorder
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Updated October 7, 2007
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