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Cited by 288Neurotransmitter Receptor Influence on BehaviorTryptophan and brain disordersTreatment of Major Depression

The DOI matches its Crossref record; 46 of the 46 references it cites were found in a registry or an index.

Covariation of activity in habenula and dorsal raphe nuclei following tryptophan depletion

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Morris, J.S., Smith, K.A., Cowen, P.J., Friston, K.J., Dolan, R.J.·1999·NeuroImage
DOI 10.1006/nimg.1999.0455
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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 (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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Metadata

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.
ORCID
Venue
NeuroImage
Publisher
Elsevier BV
Published
1999-08
Volume
10
Issue
2
Pages
163-172
ISSN
1053-8119 (ISSN-L)
DOI
10.1006/nimg.1999.0455
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
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 (medical) › 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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