Thursday, July 16, 2015

The Neuroscience of Despair -- Michael W. Begun









New Atlantis
"Pharmaceutical companies sold the idea of depression as much as the drugs themselves, promoting the belief that depression stems from a chemical imbalance in the brain, with a marketing apparatus rival in scope to national political campaigns. (By 2000, pharmaceutical companies were spending over $2 billion in direct-to-consumer advertising. By comparison, spending by candidates in the 2000 presidential election totaled a mere $343 million.) This marketing effort played no small part in shaping the public’s understanding of depression.
The sales of antidepressant drugs increased in kind. According to a 2002 article in the Journal of the American Medical Association, “patients treated for depression were 4.8 times more likely to receive an antidepressant in 1997 than in 1987.” And a 2005 article in Health Affairs reported that in a period of merely five years, between 1996 and 2001, overall spending on SSRIs and other new antidepressants rose from $3.4 billion to $7.9 billion. Edward Shorter writes in A History of Psychiatry (1997) that antidepressants became so popular that “patients began to view physicians as mere conduits to fabled new products rather than as counselors capable of using the doctor-patient relationship itself therapeutically.” While this description may overstate things, it seems likely that the growing popularity of antidepressants and other psychoactive drugs began to reshape our conventional notions of mental disorders.
A Deficient Theory
"It is really not known how drugs alleviate the symptoms of mental disorders,” wrote neuroscientist Elliot S. Valenstein in his book Blaming the Brain (1998), “and it should not be assumed that they do so by correcting an endogenous chemical deficiency or excess.” Valenstein was referring to chemical deficiency (or chemical imbalance) theories of depression, which postulate that depression results from low concentrations of certain neurotransmitters in the brain. Valenstein’s words remain true today: every time a new neurobiological theory seems like it might explain depression, evidence comes along to demonstrate the theory’s inadequacies. The last half century of attempts to formulate such a theory can be summed up by Kafka’s remark: “Like a path in autumn: no sooner is it cleared than it is once again littered with fallen leaves.”
The original chemical deficiency theory of depression dates back to 1965, when Harvard psychiatrist Joseph J. Schildkraut hypothesized that low levels of catecholamines — a kind of neurotransmitter, or brain chemical — were associated with depressive disorders, with high levels corresponding to feelings of elation. The paper remains one of the most frequently cited in the history of psychiatry. While the hypothesis may appear rudimentary today, it laid the groundwork for current chemical imbalance theories of depression.
Schildkraut inspired the development of the monoamine hypothesis, which postulates that deficiencies in certain neurotransmitters such as serotonin and dopamine cause depression. (Monoamines are a class of neurotransmitters that includes serotonin, dopamine, and catecholamines, such as norepinephrine.) In contrast to early antidepressant drugs, which were discovered serendipitously, the later SSRIs were designed on the basis of the monoamine hypothesis. They were expressly engineered to increase the amount of serotonin available in synapses, the junctions between neurons. While SSRIs have proven to be more effective than most other antidepressant drugs, we know little about how they work beyond their immediate biochemical effects. One particular problem scientists have tried to understand is that while the physical effects of SSRIs and other antidepressant drugs transpire within minutes after consumption, the psychological effects typically take nearly two weeks to manifest. This difficulty has prompted further hypotheses and speculative modifications to the monoamine theory, but no empirically bulletproof explanation has thus far been found.
Evidence suggests that nothing close to the simple chemical deficiency hypothesis can be right. Despite intense efforts to correlate serotonin deficiencies with depression, most studies have been unable to do so. The same goes for other monoamines, too. Only about 25 percent of depressed patients actually have low levels of serotonin or norepinephrine, according to Valenstein, suggesting that other processes are involved.
These shortcomings have not stopped the chemical imbalance theory from shaping popular discourse about depression and mental illness in general. Advertisements for antidepressants and anti-anxiety medications have frequently appealed to the chemical imbalance hypothesis, sometimes cartoonishly depicting the deficiency in neurotransmitters that was supposed to cause depression. A Prozac advertisement that ran in Newsweek, Time, and other popular magazines around 1997 and 1998 explained:
When you’re clinically depressed, one thing that can happen is the level of serotonin (a chemical in your body) may drop. So you may have trouble sleeping. Feel unusually sad or irritable. Find it hard to concentrate. Lose your appetite. Lack energy. Or have trouble feeling pleasure.... To help bring serotonin levels closer to normal, the medicine doctors now prescribe most often is Prozac.®
The advertisement respects FDA regulations against false drug advertising statements by including the qualification “one thing that can happen,” though it presents a seductive explanation of a whole range of woes we experience on a daily basis. The mismatch between the empirical status of the chemical deficiency hypothesis and its portrayal in pharmaceutical advertisements led a 2005 paper published in PLOS Medicine to conclude: “The incongruence between the scientific literature and the claims made in FDA-regulated SSRI advertisements is remarkable, and possibly unparalleled.” This kind of aggressive advertising on the part of the pharmaceutical companies (among other practices like political lobbying, incentivizing doctors to prescribe their products, and promoting screening for depression) has led many authors to lambast the pharmaceutical industry for selling the idea of depression just as much as its treatment.
The chemical deficiency hypothesis may itself be deficient, but it helped make possible a new subdiscipline, biological psychiatry, in which mental disorders are understood as arising from facts about the biology of the person. Most psychiatrists today point to more complex explanations than those offered by Schildkraut in the 1960s. For instance, in a 2011 letter to the New York Review of Books, two psychiatrists wrote of “recent advances in neuroscience research that demonstrate that depression is not a disease of a single neurotransmitter system or brain region but probably a disorder that involves multiple neural circuits and neurotransmitters.” Schildkraut himself stressed that his chemical imbalance hypothesis was “undoubtedly, at best, a reductionistic oversimplification of a very complex biological state,” and that it was properly regarded as a heuristic rather than a sufficient explanation of the neurobiology of depression. Yet the form of explanation, in which a mental disorder is related to a neuronal abnormality, has not changed since Schildkraut’s hypothesis first took hold, and today we seem ever more committed to neurobiological explanations of mental illness. How far can they go?"


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