Depression and “Chemical Imbalance”

(imported from my other blog)

The main aetiological explanation for depression in the public consciousness is undoubtedly the “serotonin hypothesis”. This probably manifests more popularly as the idea that depression is somehow the result of a “chemical imbalance” in the brain, and therefore that sufferers of depression (whose suffering is not in question) are somehow the passive victims of an organic condition, like victims of diabetes, for example, and that this can be righted with medication. It’s a neat explanation, which, I guess, is why it’s so appealing. However, the evidence, as it so often does, suggests that depression is nowhere near this simple.

The serotonin hypothesis was the product of two papers, both published in the mid 1960s. Basically, the authors of these papers suggested that a deficit in a certain group of neurotransmitters (the monoamines, which include serotonin) could be a cause of depressive illness. Their suggestion was based on an observation that inhibiting a (entirely natural) process which breaks down these chemicals, while feeding patients a diet which includes their precursors, seemed to alleviate depression. This was a perfectly reasonable mechanism to suggest, on the evidence available, but that’s all it was: a suggestion. And the logic of this hypothetical mechanism is not without its critics:

“Some have argued that depression may be due to a deficiency of [noradrenaline] or serotonin because the enhancement of the enhancement of noradrenergic or serotonergic neurotransmission improves the symptoms of depression. However, this is akin to saying that because a rash on one’s arm improves with steroid cream, that the rash is due to steroid deficiency.” – Pedro Delagado and Francisco Moreno, writing in the Journal of Clinical Psychiatry

So, how does the evidence for the “Serotonin Hypothesis” stack up? The answer, it seems, is not very well. To this day there exists no roundly accepted evidence demonstrating reduced serotonin levels in the depressed. Indeed, attempts to demonstrate a link in even the most severely depressed patients have been regarded as fraught with problems and therefore inconclusive. It has also been demonstrated that depression cannot be induced in the healthy by depleting serotonin – an observation which, if accurate, would fatally falsify the serotonin hypothesis. This patchy and inconsistent evidence does much to raise doubt over whether a condition such as depression can be explained by a mechanism as simple as that proposed in the serotonin hypothesis.

All of this is compounded by the fact that, contrary to its popular image, serotonin can’t rightly be described as a “mood improving” chemical. Like all neurotransmitters its effects are highly context dependent, different parts of the nervous system will respond to serotonin in different ways; responses which are modulated by the different ways in which different cells respond to serotonin, all of which is subject to modulation by the local chemical and anatomical environment. Serotonin is no more a “happy drug” than metal’s to be feared because it’s what swords are made of.

But if the drugs are helping people what does this matter?

The problem here is that we’re no longer entirely sure that the drugs are helping people. Recent studies have provided evidence that selective serotonin re-uptake inhibitors (SSRIs, such as as citalopram (cipramil), paroxetine (seroxat), fluoxetine (prozac), sertraline (zoloft), and many others) – drugs which purport to “rebalance” the “imbalance” of serotonin – perform little better in alleviating reported symptoms of depression than identical pills containing no drug (link). On top of this, a simple programme of cardiovascular exercise has been shown to be no less effective than a programme of anti-depressants.

Is it really what we want to have ineffective drugs based on hypotheses that are, at best, dubious? Especially considering that this model of understanding lends credibility to the idea that depression is an inescapable biological phenomenon, the manifestation of a malfunctioning brain. This view can only be hugely disempowering for the depressed.

Clearly, the causes of depression need to be better understood if we’re to develop an effective model for caring for those who suffer from the condition. Resigning people to the conclusion that they are the sufferers of some organic malfunction which can be corrected but not cured by chemical intervention is, quite simply, telling them something which hasn’t stood up to scrutiny. This is not to say that there’s no neurochemical contribution (one or more siblings with depression is a significant risk factor, for example, although I’d imagine the line between genetic and environmental input in most of these cases will be irrecoverably blurred), it’s simply to say that we currently have scant idea of what that contribution might be. And, as for a simple explanation such as “chemical imbalance”, the facts are that science has no idea what the correct balance of brain chemistry is, or if there even is something that could be described as a “correct” balance. The mind is far too complex.

That neurochemistry only modulates our potential response to multitudinous psychosocial and environmental factors needs to be considered – and it is very possible that a cure, not simply a treatment, lies in the consideration of these external factors and situations that the depressed individual finds themselves exposed to. Of course, unless we want to entertain concepts such as “the soul”, we have to accept that behaviour is, at its very root, a chemical event. But the trend for this biological reductionism in depressive illness is, I feel, misguided. Just as we can’t learn much about aerobatics from studying the chemical properties of the polymers in a stunt-plane’s fuselage, neither can we learn much about complex social behaviours from studying the chemistry of the brain.