Gene-environment interactions - seminal studies
Professor Helen Mayberg discusses several recent studies that have changed how we understand depression - how different gene-environment interactions can predict depression onset.
So one of the very interesting and seminal studies in the last few years in depression has been the characterization and the role of the serotonin transporter polymorphism. The SERT transporter as itâ€™s called comes in two forms, and if you have the SS form, it seems to convey risk in the situation of a stressful environment. In a fabulous study published by Caspi and replicated more recently by Kellner, itâ€™s been shown that if you have the SS form of the allele, and you have a history of early trauma or traumatic life events, those act in an additive way to put you at risk for later depression, whereas if you have the same amount of environmental stress, but have the LL form of the gene, it actually seems to protect you. Weâ€™ve always known that people are at risk if they have early trauma; it affects the stress axis, the stress hormones, it changes in early development the way your brain will respond chemically to a stressful life experience. But it seems now that if you are dealt the hand of this particular allele, and are exposed to early life events, itâ€™s a double whammy and that may change your brain and make you more vulnerable for later stress that leads to depression. Thatâ€™s an incredibly important observation, and it turns out that many of those patients may in fact do best with therapy. That drug can attenuate the chemical system but it doesnâ€™t get them all the way well, but actually changing the way they frame the environment, actually teaching them to use their brain differently, may be more effective for those patients than patients who donâ€™t have that combination of gene and environment. Thatâ€™s something thatâ€™s now a source of interest and a source of testing. Because itâ€™s very clear: it isnâ€™t just a continuum of severity that you start with therapy, and then if that doesnâ€™t work you add a drug, and if that doesnâ€™t work you add another drug. It has totally turned this upside down to think about that there actually may be a type of depression where drugs isnâ€™t the answer. In fact that patients that havenâ€™t done well on drugs, it isnâ€™t sort of unlucky, itâ€™s that that isnâ€™t the proper treatment for them. I think that the next few years with research on that is going to be quite interesting. On the other hand, there are certainly patients that are comparably ill, intractably ill, where you canâ€™t trace it to an obvious â€˜this particular geneâ€™ or to the environment. Equally there are patients who have the SS allele and have no stress and are depressed, so they are all combinations; it doesnâ€™t explain all the variance. Like many things nothing is as simple as we all would hope. But itâ€™s a very interesting way to start segregating different subtypes of depression, different biologies, in the same way we do that for heart disease. Someone can have a heart attack and it can be due to a spasm in an artery. You treat that very differently from someone who has blockage of just one vessel, and you treat both of those very differently from someone who has blockage of all the vessels. So again, we want to define the biology of the problem, knowing that the symptoms may look very, very similar, but whatâ€™s causing the symptoms is very different and that we match the treatment for whatâ€™s best for the patientâ€™s brain.
depression, gene, environment, interaction, stress, serotonin, sert, transporter, allele, caspi, kellner, helen, mayberg
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