When patients are prescribed antidepressants, they are usually told that their depression was due to their brain’s diminished capacity to “uptake [properly process] serotonin.” Despite the articles in professional psychiatric journals that have regularly appeared for years—and more recently in the media—this is what most people are told. And yet, in the words of the song from Porgy and Bess, it “ain’t necessarily so.”
Ever since Peter Kramer published his book Listening to Prozac in 1987, it has been accepted in lay and psychiatric circles that depression is caused by the brain’s failure to uptake the neurochemical serotonin. Provide a pill, the conventional wisdom had it, that prevents neurons from “reuptaking” (that is, refusing to allow serotonin in) and all would be well. Prozac was but the first of a long line of selective serotonin reuptake inhibitors (SSRIs) designed to do just that. And it’s probably true that the brains of depressed people don’t process serotonin very well.
However, recent research—particularly studies using powerful brain-imaging equipment—have shown that brain chemistry (serotonin in particular) is by no means the whole story, and may not even be a very important part of it. In terms of the brain, long-term depression seems to be the result of misdevelopment in a number of crucial areas of the brain.
If you’re depressed, and a scan is taken of your brain, you’ll find some interesting structural anomalies when compared with the brain of a nondepressed person. These anomalies, which are most pronounced in victims of childhood abuse, have a dramatic effect on how the brain functions. This recent discovery has forced the experts to change most of what they thought they knew about depression. Probably the most significant of these abnormalities involve the hippocampus and amygdala in the limbic system, and the frontal lobe of the cerebral cortex.
If a person suffers from long-term depression, the hippocampus, a crescent shaped part of the brain that deals with learning and forming new memories, is smaller than in people without the illness. It has fewer neurons. The hippocampus allows a rat, for example, to remember where it was when it got an electric shock and what was going on around it at the time. Such contextual learning helps the poor rodent avoid dangerous places in the future. A depressed or anxious person may not be so good at remembering, and thus avoiding, the circumstances that trigger depressive or anxiety-provoking episodes.
The walnut-sized amygdala is a key area of the limbic system and helps process emotions. Its job is to alert you to signs of stress or danger. It does this by passing almost instantaneous messages to the hippocampus, the frontal lobe (part of the command and control center of the brain), and the central nervous system. It activates the automatic flight, fight, or freeze reactions. The amygdala is not designed to be accurate—just fast. If you suffer from anxiety or depression, this area of the brain is more active and enlarged—sending out more emotionally charged messages—than that of someone not afflicted with depression or anxiety.
Finally, there’s a problem with the frontal lobe, the brain’s decision-making area. Recent studies using Functional Magnetic Resource Imaging (fMRI) have shown that if it doesn’t work as it should, then making decisions—even simple ones, like getting up in the morning—may be difficult. In a depression sufferer, this area remains undeveloped and it works more slowly than it should. In particular, it is slow to switch off the alarm signals coming from the amygdala, leaving the sufferer stuck in the “down,” low-self-esteem, submissive mode typical of depression or the tense state of anxiety.
Like Prof. Nemeroff ’s CRF imbalance, these structural problems are directly related to early trauma or abuse. Apparently, these experiences abort proper brain development in the frontal lobe, prevent neurogenesis (brain cell growth) at a critical time in the hippocampus, and enlarge the amygdala. The effects of this damage are elegantly summed up by neurobiologist Martin Teicher, writing in the journal Cerebrum:
“Whether abuse of a child is physical, psychological, or sexual, it sets off a ripple of hormonal changes that wire the child’s brain to cope with a malevolent world. It predisposes the child to have a biological basis for fear, though he may act and pretend otherwise. Early abuse molds the brain to be more irritable, impulsive, suspicious, and prone to be swamped by fight-or-flight reactions that the rational mind may be unable to control. The brain is programmed to a state of defensive adaptation, enhancing survival in a world of constant danger, but at a terrible price. To a brain so tuned, Eden itself would seem to hold its share of dangers; building a secure, stable relationship may later require virtually superhuman personal growth and transformation.”
In light of all this, we believe that the inability of the brain to uptake serotonin is a side issue, one of the symptoms of the structural problem of the depressed brain. Taking an SSRI antidepressant is rather like taking aspirin when you’ve got the flu—it may make you feel a bit better, but it doesn’t cure the disease. In fact, a number of researchers, including David Burns, M.D., are adamant that serotonin deficiency may not be the problem at all. In an article published in 2000, the Psychiatric Times reviewed recent studies, and Burns and others wrote: “There is no persuasive or consistent evidence that a deficiency of brain serotonin causes depression or that an increase in brain serotonin relieves depression.”
Another problem for the Listening to Prozac lobby is that antidepressants, according to a 2002 Royal College of Psychiatrists report, only work for about 60 percent of people at best, and that placebos (sugar pills) work just about as well. Furthermore, research indicates that the drugs’ effect wears off quickly. According to a study by Prof. Giovanni A. Fava of the University of Bologna and others, which was done with long-term antidepressant users who were slipping back into depression (as most do), four of five patients responded to a larger dose of the drugs, but all relapsed again within a year.
Many studies (few of which have found their way into the mainstream press) have shown that even the so-called “safe” SSRIs, such as Prozac, have some very nasty side effects ranging from sexual dysfunction and heart disease to suicide.
Despite all this, we are not saying that no one should take antidepressants. We sometimes encourage clients to get a medical opinion regarding going on antidepressants (and always to get medical supervision when coming off them, which can be problematic). Some of our clients have received short-term benefits from taking antidepressants. Whether their relief is due to the placebo effect is neither here nor there when someone is in pain.
Some “natural” antidepressants, such as St. John’s Wort and SAM-e, have been shown to work, but only in cases of mild depression. Even then, their efficacy is no greater than SSRIs.
Like many drugs that went through awkward development stages, in the future antidepressants may provide safe and more focused answers to at least some of the most difficult symptoms of depression. If so, we’ll encourage our clients to look into them, as well as working on underlying issues.
(extracted from) Creating Optimism: A Proven, 7-Step Program for Overcoming Depression, Based on the popular Uplift program, written by Bob Murray Ph. D., and Alicia Fortinberry, published by Mcgraw-Hill