In his memoir, Styron (
) 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 (
2
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References
- Darkness Visible: A Memoir of Madness.Vintage, New York1992
- Cerebral correlates of depressed behavior in rats, visualized using 14C-2-deoxyglucose autoradiography.J Neurosci. 1988; 8: 1951-1961
- Translating the habenula—From rodents to humans.Biol Psychiatry. 2017; 81: 296-305
- Prolonged dopamine signalling in striatum signals proximity and value of distant rewards.Nature. 2013; 500: 575-579
- Lateral habenula as a source of negative reward signals in dopamine neurons.Nature. 2007; 447: 1111-1115
- Mood as representation of momentum.Trends Cogn Sci. 2016; 20: 15-24
- Synaptic potentiation onto habenula neurons in the learned helplessness model of depression.Nature. 2011; 470: 535-539
- Habenula responses to potential and actual loss in major depression: Preliminary evidence for lateralized dysfunction.Soc Cogn Affect Neurosci. 2016; 11: 843-851
- Evidence for structural abnormalities of the human habenular complex in affective disorders but not in schizophrenia.Psychol Med. 2010; 40: 557-567
- Remission of major depression under deep brain stimulation of the lateral habenula in a therapy-refractory patient.Biol Psychiatry. 2010; 67: e9-e11
Article info
Publication history
Accepted:
December 5,
2016
Received:
December 2,
2016
Identification
Copyright
© Society of Biological Psychiatry, 2016.
