Shirah Vollmer MD

The Musings of Dr. Vollmer

A Gene For Depression?

Posted by Dr. Vollmer on January 20, 2016

 

http://www.nature.com/news/first-robust-genetic-links-to-depression-emerge-1.17979

 

Jonathan Flint MD http://grandchallenges.ucla.edu/depression/team/ presented his work today in which he gave a compelling talk demonstrating that he has found possible two genetic links to depression. He is a recent UCLA hire in which he joins the UCLA Grand Depression Challenge in which there is a multidisciplinary team working on understanding depression. He began with the familiar statistic that women are twice as likely to get depressed as men, and within that, women have a 20 percent chance of having a depression during their lifetime. He did not quite define depression but in the Q and A, he said that he was using the PHQ-9 which are nine questions to determine the diagnosis, which, of course, makes me suspect. Then he said it causes tremendous disability throughout the world and as such costs the world a lot of money in terms of lost labor. So, he summarizes that depression is common, causes disability and is costly and yet research on depression is minimally funded compared to diseases such as cancer or heart disease. He proceeds to show a negative  study by  his colleague Ken Kendler which did not demonstrate a gene for depression and so from that he concluded that depression is a heterogeneous disease. Well, that cannot be new information, I think to myself. He went to China where he studied only women, who apparently do not smoke or drink, and through looking at their DNA in their saliva, he could demonstrate that the women with depression had a different genetic makeup than did the controls. At this point I was beginning to be interested. The gene, he continues, impacts the mitochondrial DNA, which is the engine of the cell. He was a wonderful speaker and he did fascinating work, all as a result of new technology that makes sequencing DNA cheap and easy. Like the internet, UCLA could lead the world in this work. I am proud to be a Bruin today!

 

 

4 Responses to “A Gene For Depression?”

  1. Jon said

    Epidemiology, while important, can be far from definitive. Like you, I worry about a lack of definition of “depression” by a member of the UCLA Grand Depression Challenge team. Apparently, there are nine questions to the PHQ-9. Why nine? Why not 10 or 8? Are the questions that did not make the cut not worthy of being considered for depression? One has to start somewhere, but one should consider alternative starting points and what that means for the journey.

    We come back to epidemiology. There is a correlation between the genetic makeup of some women and depression compared to a control group. How does that correlation look compared to other potentially viable definitions of depression? Assuming there is a true correlation, the much more difficult task is then to find causation.

    Looking at the Nature article to which the link was provided, I see that Dr. Flint was also surprised by his results. Good. In his research he found two sequences that might be linked to depression – a non-fully-understood enzyme and another next to a gene SIRT1. Correlations were again confirmed with another set of men and women as well as controls. Again, good. Now the investigation is on as to why no correlation was found in a previous study of 17,000 people – perhaps it is because of not looking for people with severe depression. Again, we are back to worrying about definitions of depression.

    It is noted by Patrick Sullivan that Flint’s success is energizing a search for proteins to affect certain cellular functions. Correlation to causality. Causality to mechanisms. Mechanisms to treatments. It is a long and royal road. May this one not be set with too many dead ends.

  2. Shelly said

    What about epigenetics, Shirah? This would explain the different DNA found in the subjects’ saliva. What about twin studies? Not so sure that there was anything new in this article, although to tell you the truth, I didn’t read through the article due to time limitations–just your brief summary you posted here. How do you explain depressive episodes in people stemming from causes like loss of a family member, diseases, loss of jobs, etc.? These don’t necessarily have genetic bases.

    • Yes, epigenetics is a big question and I wondered about that as well. Childhood trauma has a large impact on life-long recurrent depression so that we know. In essence, the buzz phrase these days is that depression is a heterogeneous disorder, which is a short-term way of saying that we do not know what depression is. I think we need to come clean about that, but heterogeneous sounds better than “I dunno”. Thanks.

  3. Elie Fabs said

    My business partners were looking for PHQ-9 A2663B yesterday and saw an online platform with an online forms database . If others are interested in PHQ-9 A2663B too , here’s Patient Health Questionnaire

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