Covariation of Activity in Habenula and Dorsal Raphé Nuclei Following Tryptophan Depletion

doi:10.1006/nimg.1999.0455

NeuroImage

Volume 10, Issue 2, August 1999, Pages 163-172

https://doi.org/10.1006/nimg.1999.0455 Get rights and content

Abstract

Abnormal serotonergic function is implicated in the pathogenesis of affective disorders. We induced transient depressive relapses in volunteer patients by rapidly depleting plasma tryptophan, the precursor of serotonin (5-HT), and measured neural activity during different cognitive tasks using positron emission tomography (PET). Neural activity in several 5-HT-related brain areas, e.g., dorsal raphé, habenula, septal region, amygdala, and orbitofrontal cortex, covaried significantly with plasma levels of tryptophan and ratings of depressed mood. Task-specific responses in left amygdala and left anterior cingulate were attenuated by tryptophan depletion. We used these PET data to test the hypothesis that projections from the habenula modulate dorsal raphé activity and that this modulation is enhanced in patients experiencing a profound mood change following serotonergic challenge. A strong linear correlation (r² > 0.5) between habenula and raphé activity was observed in subjects with postdepletion ratings ≥10 on a modified Hamilton depression scale, whereas subjects experiencing milder changes in mood had weaker habenula–raphé coupling (r² < 0.5). These data support a model of the serotonergic system in which the habenula projection to the raphé represents a convergent feedback pathway that controls the release of 5-HT throughout the brain. In our experiment we were able to engage this system in patients who were sensitive to tryptophan depletion.

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Regular ArticleCovariation of Activity in Habenula and Dorsal Raphé Nuclei Following Tryptophan Depletion

Abstract

Brain Res.

Brain Res.

NeuroImage

Neuroscience

Brain Res.

Brain Res.

Brain Res.

Brain Res.

Prog. Neurobiol.

Lancet

Lancet

Neuropharmacology

Neurosci. Biochem. Rev.

The interaction between mood and cognitive function studied with PET

Psychol. Med.

Changes in regional cerebral blood flow on recovery from depression

Psychol. Med.

Positron emission tomography measurement of cerebral metabolic correlates of tryptophan depletion-induced depressive relapse

Arch. Gen. Psychiat.

Cerebral correlates of depressed behaviour in rats, visualised using 14C-2-deoxyglucose autradiography

J. Neurosci.

The biochemistry of affective disorders

Br. J. Psychiat.

Neuroendocrine responses to intravenous tryptophan in major depression

Arch. Gen. Psychiat.

Serotonin function and the mechanism of antidepressent action

Arch. Gen. Psychiat.

Regular Article
Covariation of Activity in Habenula and Dorsal Raphé Nuclei Following Tryptophan Depletion

Cerebral correlates of depressed behaviour in rats, visualised using ¹⁴C-2-deoxyglucose autradiography