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Depression Is Still a Mystery - We Need a New Model
By Deepak Chopra, M.D., FACP, Murali Doraiswamy, MD, Professor of Psychiatry, Duke University Medical Center, Durham, North Carolina and 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).


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. Alternatively, it may just be very difficult to find genes for a condition that is so pervasive in society today regardless of genetic composition. What follows 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 overactivity or underactivity in certain areas of the brain whose cause isn’t understood. But depression isn’t localized just in 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. Of course, we must also remember that finding genes for depression is much more difficult than trying to find genes for other more obvious disorders, like heart disease. This is because a depressed family member who may actually have genetic predisposition to depression may increase the odds that other family members also become depressed, even if they are not genetically predisposed. Depression can spread among family and close friends! In carrying out a genetic study to find “depression genes”, one must tell the computer program who in the family is suspected of carrying a depression gene.

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% 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 which 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 focusing on individual depression symptoms (e.g. poor appetite) rather than on people with clinically diagnosed depression. This wasn’t necessarily better, only different. Relying solely on symptoms reported by people (without a doctor verifying the cause) can result in a lower number of those who would be considered clinically depressed if some people are in denial or don’t know the difference between depression and ordinary sadness. But more importantly, symptoms change not just over a lifetime but often on a daily or weekly basis; 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 produce remission of symptoms in only about a third of individuals, and in most recent studies, this is about the same as the placebo effect. Some symptoms of severe depression remain intractable, and yet in other cases, the chronically or more severely 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 its due importance while connecting its responses to secondary mechanisms in the brain.

Deepak Chopra, MD is the author of more than 70 books with twenty-one 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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The new model that is coming through is that the MIND/ PSYCHE is the primary mechanism for the craetion and proliferation of all dis-ease. Sorry folks - this is not new however it is confronting for many. It will be realised soon enough. What we refer to as genetic or physical manifestations of illness are merely secondary bi-products of a source of internal conflict within our minds. In response to Bipolar Advantage, there is a plethora of documented evidence out there to support this - you need not look very hard at all, unless you wish to look in the opposing direction. What we are learning from depression as well as many other perceived illnesses is that the mind is the source of the issue. Chasing down physiological or genetic roads will simply produce the same lack luster results that lead us towards making more and more pharmaceutical companies rich without achieving any results greater than what has already been suggested is the success rate of a placebo. It is a complete change in our way of thinking that is required - the mind/psyche is the source of all dis-ease - it is the link we have been missing all along as we continue to stick our heads in the sand. Science complicates and misses what is an obvious and very simple starting point to our solution
Change the paradigm change the result - February 11, 2013
Excellent article! \n It`s important to note, relying on drugs means suffering physically and otherwise, the various side effects such as synthetic mood enhancers or anti-depressants cause hardening of arteries for instance. So clearly, you`d only want to take drugs for a short time. \n Further, in my experience with many patients, friends and family members that have fought depression over the years, some on and off, some regularly, including myself, ACTION, more than drugs, have long lasting benefits, as well as deeper and more profound benefits: and what I mean by action is, Exercise DAILY & Meditation DAILY,\n (daily because, like food, water, sleep, breath, our Minds need Nourishment!!! and in the West, we aren`t taught how to nourish the mind, heart and soul, not even in religion. \"religious folks suffer depression too)~ \n Art/Creativity of some kind, whether writing, gardening, sculpting, etc; doesn`t need to be great art in any way, simply Creation as part of Who We Are inherently cannot be denied.\n Also essential, positive human interaction and interaction with nature regularly. \n Modern life separates us from much of this, in fact looks down on much that isn`t \"work\" and \"adult\" ~ in a westernized capitalist paradigm. \nControlling our Mind means Controlling our Life; this is becoming more and more apparent in all aspects of neuroscience, psychology etc.\nGood Luck!
Jonathan - January 31, 2013
It is worth noting that depression often co-occurs with other diseases that are not clearly understood- Chronic Fatigue Syndrome, fibromyalgia, IBS, IC, Circadian Rhythm and other sleep disorders, lupus, etc etc. I think it is correct to conclude that there are probably multiple causes- viruses, prenatal events, etc. I agree very much that etiology needs to be an important focus, rather than just inventing more drugs to mask the symptoms.
Christy Begley - January 29, 2013
\"But serotonin is directly regulated by genes\" - really?? I am not a biologist, but I find this very difficult to believe. I would have thought that the factors controlling the amount of serotonin and where it is in the body are controlled by many different factors, including diet, sunlight, various hormones and activity of both the body and brain and the mind.\n\n\"Is there any doubt that this spiral originates in the mind, not the brain?\" - if you ask people who suffer depression due to Seasonal Affective Disorder, or pre-menstrual syndrome they would have many doubts about the lack of a biological, chemical trigger.\n\nI agree that the mind plays a large part in the development (and healing) of depression. And yes, in some cases the mind might be completely responsible for the depression. But you can`t rule out a biochemical cause just because there is no obvious genetic correlation. To do so runs the risk of making people feel like they are to blame for their condition, which just makes things worse.\n\nThis article says we need a new model for depression - I agree - understanding and treatment options are appalling. But I can`t tell if the article is suggesting a new model (if so, it seems to be saying we need to focus on the mind, not the biology, which I think is wrong) or just saying \"we need a new model\" without presenting one. If the latter, where do you see as a good platform to start a discussion on the new model?
Mahina - January 29, 2013
I am not student of science hence I do not know about the role of genes in case of depression. I have my personal experience that I was in deep depression before three years for almost two years. I was having frequent suicidal thoughts as well in my mind. However I came out of it without any medication only by practicing meditation and yoga. Now I can analyse my thought process very well. I can see that though there was trauma that was leading me to depression however deep inside me there were different things. I was having very low self esteem and was dependent on other for my feeling. After practicing meditation and yoga I can see myself as a totally different person. There is sense of being inner fulfilment which is leading me towards totally different perspective of life. I don’t know what the role of my genes is in the entire process. Can anybody explain it?
Deeps - January 29, 2013
A very telling statistic you share in this article is that only 1/3 of the people on anti-depressants experience remission symptoms, which is about the same as a placebo effect. This points to depression being a mental issue, not a genetic one.\nThank you for sharing this.
Simone - January 28, 2013
Depression is a gut problem, isn`t it? Ask anyone who has cured their depression through nutrient dense and fermented foods.
Daisy - January 28, 2013
I really think it\'s the food, the environment, medication is not always the answer.....i tried a little walking over the weekend
Sheki Williams - January 28, 2013
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