A few years ago, I was fascinated by the surprising news that Prozac patients were growing new braincells. This goes against the traditional medical notion that there is no generation of such neurons in adulthood (after about age 25). Recent research has shown that this regeneration — called poetically neurogenesis — is very likely why Prozac and similar drugs actually help about 60% of depressed people to feel better.
It has long been the view that Prozac works by allowing the re-use of the messenger chemical serotonin. In fact, Prozac and other selective serotonin reuptake inhibitors (SSRIs), cause changes in serotonin uptake within hours of the first dose, but depression does not usually lift for three or four weeks into treatment. Recent studies show that this is when new cells begin to grow in the hippocampus region of the brain.
Since its introduction over 25 years ago, I have been suspicious of Prozac. There is some evidence that it may lead to a higher incidence of suicide and outbursts of aggression in some users. But it is also true that people who found no benefit from earlier tricyclic anti-depressants have sometimes benefitted from an SSRI or a drug that acts upon other monamines or neurotransmitters. However, this recent insight into the mechanism of action of such drugs should lead to more effective treatments. It also opens the debate that depression is in fact a form of brain damage — not simply an inability to produce, or a too abundant release of, neurotransmitters, but a failure to generate new cells.
Depression seems generally to be initiated by a stressful event — or series of events — that inhibits the ability to make new cells in the hippocampus. This part of the brain is associated with access to memory. One of the bizarre effects of depression is an inability to remember happy events. In studies, depressed people really can be stumped when asked to think of even a few happy times, yet when such people are in a happier frame of mind they have no such difficulty.
Other areas of the brain also seem to be affected in depressed people, including the prefrontal cortex, which is involved in reasoning, and the amygdala, which is the fast-reaction part of the brain. Both of these areas are involved in mood changes. The amygdala is part of the old brain — common to all vertebrates, including lizards. It is responsible in part for fear and aggression, priming the fight-or-flight response before there is time for a reasoned estimation of circumstances. It may be that the release of the hormone cortisol brings about an oversized amygdala, which in turn is an aspect of the anxious responses that lead to depression.
This research also warrants a new look at non-chemical means of changing mood, for if psychological stress can cause inhibition of neurogenesis then overcoming that stress would probably be a safer and more effective way of dealing with depression. This has long been the view of Aaron Beck and his many co-workers in cognitive behavioural psychotherapy.
The Prozac generation heightens fears of a Brave New World society in which orderly automatons dose themselves on soma to maintain their euphoric, uncritical view of the vacuous, uncreative society in which they exist. Surely a chemical intervention should be a last resort, as it will never do more than to mask the initiating cause of depression.
Over the last decade there has been increasing criticism of analytical and traumatic-memory based forms of counselling. In the late 1960s Beck’s pioneering work questioned the view that a person suffering from depression — or any other affective disorder — did not know what was wrong. The Freudian school and its derivatives have long insisted that repressed memories which are not available to conscious thought are responsible in all such disorders. Many other forms of psychotherapy have followed the same route, digging for unrembered traumata.
Beck, a professor at the University of Philadelphia, was trained as an analyst, but came to disbelieve the gospel. It is certainly alarming that over a hundred years after the notion of repressed memory was put forward there is as yet no clear scientifically testable evidence for it. It is also quite possible that probing endlessly into supposed early-life traumata can actually create false memories, and the work of experts such as Elizabeth Loftus and Richard Ofshe strongly supports this view. In my own specialized work, I saw many people who believed themselves able to remember numerous former incarnations in great detail, but often showed a very sketchy memory of their last few weeks or months. This can only lead to the suspicion that false memories are easily generated.
Because of their effect on cellular regeneration in the brain — neurogenesis — drugs developed for the treatment of Alzheimer’s may well be more directly effective than current anti-depressants. It seems likely that neurogenesis may also be induced in some people by a very simple method, which is uncontentious and available to all — exercise. It has been shown that depressed people respond well to physical exercise. Excuse me while I pop out for a stroll.
May 2004
