Covariation of activity in habenula and dorsal raphe nuclei following tryptophan depletion
Open accessAbstract
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 (r(2) > 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 (r(2) < 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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The lateral habenula is implicated in negative mood states in both animal and human research.
“The LHb is implicated in negative mood states in both animal and human research.”
From Deep brain stimulation for depression. (2022) · cites this paper as [42]
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- Authors
- Morris, J. S., Smith, K. A., Cowen, P. J., Friston, K. J., & Dolan, R. J.
- Affiliations
- National Hospital for Neurology and Neurosurgery (GB)
- Warneford Hospital (GB)
- The Royal Free Hospital (GB)
- Corresponding author
- Dolan, R.J.
- Venue
- NeuroImage
- Publisher
- Elsevier BV
- Published
- 1999-08
- Volume
- 10
- Issue
- 2
- Pages
- 163-172
- ISSN
- 1053-8119 (ISSN-L)
- OpenAlex
- W2030196595
- Cited by
- 288
- References
- 45
- Citations by year
- 2026: 5 · 2025: 6 · 2024: 18 · 2023: 9 · 2022: 14 · 2021: 15 · 2020: 8 · 2019: 16 · 2018: 18 · 2017: 17 · 2016: 16 · 2015: 16 · 2014: 17 · 2013: 21 · 2012: 14
- FWCI
- 1.57
- Type
- journal article
- Language
- en
- Open access
- green
- hdl.handle.net
- Licence
- Locations
- NeuroImage (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Max Planck Digital Library (submittedVersion, other-oa)
- MPG.PuRe (Max Planck Society) (submittedVersion, other-oa)
- Funders
- Wellcome Trust
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Keywords
- tryptophan depletion, serotonin, habenula, dorsal raphe nucleus, serotonergic system, depression, amygdala, anterior cingulate cortex, mood disorders, depressive mood
- MeSH terms
- Adult, Amygdala, Arousal, Attention, Brain Mapping, Major Depressive Disorder, Gyrus Cinguli, Humans, Image Processing, Computer-Assisted, Male, Middle Aged, Raphe Nuclei, Recurrence, Serotonin, Tomography, Emission-Computed, Tryptophan, Verbal Behavior, Habenula
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