Clinical Commentary| Volume 81, ISSUE 4, e27-e28, February 15, 2017

The Habenula: Darkness, Disappointment, and Depression

      In his memoir, Styron (
      • Styron W.
      Darkness Visible: A Memoir of Madness.
      ) describes hopelessness as the subjective core of depression. He introduces his experience of depression on a rainy street in Paris in 1985, where he is on the way to receive a prestigious award. Despite expectations of objective success, his mood is despairing and he feels that he will never return to Paris again. As he identifies his malady and seeks treatment, he laments the lack of progress in the study of depression, which has “yielded its secrets far more reluctantly than any of the other major ills.” Styron is disheartened by the lack of a biological explanation for his disorder and by the limited treatment options available at the time. The first selective serotonin reuptake inhibitor, fluoxetine, was introduced during the years following Styron’s episode, ushering in a new era of pharmacological treatments for depression based on the monoaminergic hypothesis. Yet Styron’s critique remains trenchant to the many patients who will not respond to current treatments and in the lack of a cohesive circuit-based model integrating behavioral and learning perspectives on depression. But at that same moment in time, outside of the spotlight of attention, researchers began to ascribe a role for the activation of a tiny brain region, the lateral habenula, in the symptoms Styron experienced (
      • Caldecott-Hazard S.
      • Mazziotta J.
      • Phelps M.
      Cerebral correlates of depressed behavior in rats, visualized using 14C-2-deoxyglucose autoradiography.
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