The New York Times Magazine (April 22) broadcast on its cover, "All in Our Minds." We might be forgiven for anticipating yet another paean to brain chemistry, à la the slavish dedication the Times consistently shows to Nora Volkow, who maintains that addiction is "all about the dopamine."

But the issue of the magazine was anything but. In a sense, it was the opposite. It reversed the reduction of mental health to neurochemistry, and instead focused on the power of individuals to impact their brain functioning.

The two primary examples (among the five articles comprising the issue) are "Can You Make Yourself Smarter?" and "How Exercise Could Lead to a Better Brain." Both reviewed the evidence that human beings' volitional behavior, à la physical and mental exercise, impacts their brains' blood flow and connections, rather than imagining genetic and chemical efforts to enhance our intellectual capacities.

But we have been these places before. In fact, two of the further remaining articles were reunions of a sort. One—"How Psychedelic Drugs Can Help Patients Face Death"—revisited the quite well-trodden path of the salutory effects of psychedelic drugs (shades of Aldous Huxley, Timothy Leary, and Terence McKenna). Of course, in a sense this is a neurochemcally driven approach, since the drugs are seen as a source of salvation. Yet, this image of psychedelics is so at odds with the Volkow "addiction = chronic-brain-disease" model that dominates America that it actually stands as a reversal of mainstream thinking in this area.

The fourth of the five articles—"The Maniac in Me"—is really a return to W.H. Auden’s 1948 Pulitzer-Award-winning poem The Age of Anxiety. Since we are now in the era of massive Xanax prescription (who doesn't know a host of people on this drug?), and since we certainly have a ton of things to be anxious about, it reminds us that a half-century and more of neurochemistry and pharmaceuticals really can't reverse the fundamental currents of our times. Really, our faith and investment in neurochemistry and medical therapies are more proof that this is true.

Last—but not least—of the articles included in the magazine is Siddharta Mukherjee's provocative "Post-Prozac Nation," which argues, based on the now amply demonstrated failures of anti-depressant drugs, that "we need a more sophisticated theory of depression." Mukherjee's piece marks a significant improvement over Peter Kramer's intellectually dishonest defense of antidepressants in the Times; yet it still falls short of the mark.

We by now have seen repeatedly that there is no reliable evidence that (a) depression can be traced to depreciated serotonin levels, (b) anti-depressants operate to effectively raise such levels to "normal."  As Mukherjee quotes Jonathan Rottenberg in Psychology Today: “As a scientific venture, the theory that low serotonin causes depression appears to be on the verge of collapse. This is as it should be; the nature of science is ultimately to be self-correcting. Ideas must yield before evidence.”

But Mukherjee's best efforts fail to accomplish the rescue of serotonin, antidepressants, and the whole enterprise of finding depression in the brain. Like others, he points to the dismal failures of research to show improvement among antidepressant users, but attributes this to the expanded use of these drugs to mild-to-moderate depressives, while in fact only the severely depressed benefit from them.

But the fundamental epistemological-scientific problems remain with this vision. Why does an effective remedy for a neurochemical problem only kick in at the highest levels of the problem? As Marcia Angell pointed out in the New York Review of Books, that's now how any other medical therapies (think antibiotics) work. If a medication addresses an actual chemical imbalance, it should impact that imbalance up and down the scale. Moreover, the absence of actual measurable discrepancies—or changes—in serotonin levels among the depressed or formerly depressed eliminates any claims of a scientific basis for neurochemical models of depression. Furthermore, per Rottenberg, that placebos work better for more severe sufferers is entirely consistent with the nature of placebos.

But this piece isn't about revisiting the arguments made by Angell, Rottenberg, Kramer, Mukherjee, Irving Kirsch, and Robert Whittaker. It's about the appearance of this particular issue of the Times Magazine at this point in history, one that is unwilling to make—incapable of making—a head-on, full-force claim that we are on the verge of discovering—have in fact discovered—the sources for all that ails us in the human brain and neurochemical systems. Ultimately, what is most significant about the Mukherjee article was that he, and those he speaks for, were required to write it to shore up their flagging effort. (Mukherjee, a physician and popular writer, is actually an oncologist.)

This is a breakthrough.

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