By Deepak Chopra, M.D., Murali Doraiswamy, M.D., and Rudolph E. Tanzi, Ph.D.
The magazine ScienceNews begins a recent article on depression with a blanket judgment: "A massive effort to uncover genes involved in depression has largely failed." A general reader would probably not feel the shock waves that spread from this assessment. Gene research is always going up and down. That doesn't change the public's general sense that depression is being handled pretty well. Billion-dollar antidepressants continue to flourish. Somewhere in the future, better ones will improve the situation even more.
Informed opinion on the subject is very different, however, because the model for depression that has been accepted for decades counts it as a brain disorder, and brain disorders are rooted in genetics. The failure to find the genes involved in depression strongly suggest -- as more than one prominent researcher now concedes -- that the genes of depressed people are not damaged or distorted compared with the genes of people who aren't depressed. What follows from that is another false assumption. The most popular antidepressants supposedly worked by repairing chemical imbalances in the synapses -- the gaps between two nerve endings -- where the culprit seemed to be an imbalance of serotonin. But serotonin is directly regulated by genes, and some key research indicates that drugs aimed at fixing the serotonin problem either don't work that way or that there wasn't a serotonin problem in the first place.
The ScienceNews report doesn't leave much wiggle room for a laissez-faire attitude on this point: "By combing through the DNA of 34,549 volunteers, an international team of 86 scientists hoped to uncover genetic influences that affect a person's vulnerability to depression. But the analysis turned up nothing." Nothing doesn't mean something.
If the chain of explanation running from genes to the synapses and finally to the pharmaceutical lab is broken, a host of doubts arises. Is depression a brain disease in the first place, or is it -- as psychiatry assumed before the arrival of modern drug treatment -- a disorder of the mind? The latest theories haven't gone back to square one. What we know isn't black and white. There are many variables in depression, which leads to some fairly good conclusions:
- There are many kinds of depression.
- Each depressed person displays their own mixture of causes and symptoms.
- The mental component in depression includes upbringing, learned behavior, core beliefs, and judgment about the self.
The brain component includes wired-in neural pathways, with suggested weaknesses in certain areas of the brain whose cause isn't understood. But depression isn't localized in just a single region in the brain. The interaction of multiple regions is involved.
The genetic component may explain why depression runs in families, but no gene or group of genes seems to guarantee that a person will become depressed. We are talking instead about genes that make you susceptible to the disorder. What triggers these (unknown) genes remains a mystery. In any case, genes are not fixed but fluid in their output, so the genetic situation is changeable.
Finally, there is an X factor, or maybe more than one. The X factor could be predisposition in young children that doesn't blossom into depression for years. It could be social interactions that create a sense of helplessness or victimization.
A skeptic could look at this list and say, "so anything and everything can make me depressed." That's not really true. About 20 percent of people will experience a severe depression some time in their lives. At the moment, there is a rash of depression among combat soldiers who served in Afghanistan (this would be directly related to a sudden increase in suicides, which is generally linked to depression) and among laid-off workers who are enduring long-term unemployment. In both cases, an outside event led to the depression, but we do not know why, in the sense that only a proportion of people become depressed under the same stimulus (war and losing your job).
In our opinion, a major issue in the failure to solve this mystery is the difficulty in accurately encoding in the analysis who is clinically depressed and who is not. Depression "spreads" in families and among friends without the need for an inherited gene. One can be sure that there are genes that predispose a person to depression, but finding them requires accurately telling the genetic algorithm which family member is a likely carrier versus not -- this is almost impossible.
The study about the failure to find the genes responsible for depression, which was published in the January 3 issue of Biological Psychiatry, took an unusual approach by ignoring diagnoses of depression and going instead with symptoms. This wasn't necessarily better, only different. Asking people about symptoms results in a lower number of those who would be considered depressed. This could be because some people are in denial or don't know the difference between depression and ordinary sadness. But more importantly, symptoms change over a lifetime; there is a sliding scale for each sufferer and also for the disorder as a whole.
In the end, the situation is too cloudy for anyone to offer either a pessimistic or optimistic prediction about where depression is heading. Drug treatment remains hugely popular, no matter what the basic science says. In cases of mild to moderate depression -- the most common type -- antidepressants sometimes don't work better than 30 percent, about the same as the placebo effect. Some symptoms of severe depression remain intractable, and yet in other cases, the chronically depressed perform the best with drug treatment. Hope is always better than giving up.
Our purpose was simply to underline that depression is joining other mental disorders, particularly schizophrenia, where no simple disease model works. There are too many variables, and patients follow highly individual paths as the disorder sets in. The mind-body connection has yet to be fully understood, but the present impasse suggests that we have to solve it, not rely on drugs that simply mask the underlying disorder by relieving symptoms. Human beings are sensitive creatures. Hearing the words "I don't love you anymore" or "you're fired" can lead to a complex downward spiral. Is there any doubt that this spiral originates in the mind, not the brain? It is time to give the mind is due importance while connecting its responses to secondary mechanisms in the brain.
Deepak Chopra, M.D. is the author of more than 70 books with 21 New York Times bestsellers and co-author with Rudolph Tanzi of Super Brain: Unleashing the Explosive Power of Your Mind to Maximize Health, Happiness, and Spiritual Well-being. (Harmony)
Murali Doraiswamy, M.D., Professor of Psychiatry, Duke University Medical Center, Durham, North Carolina and a leading physician scientist in the area of mental health, cognitive neuroscience and mind-body medicine.
Rudolph E. Tanzi, Ph.D., Joseph P. and Rose F. Kennedy Professor of Neurology at Harvard University, and Director of the Genetics and Aging Research Unit at Massachusetts General Hospital (MGH), co- author with Deepak Chopra of Super Brain: Unleashing the Explosive Power of Your Mind to Maximize Health, Happiness, and Spiritual Well-being. (Harmony)
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