Cited by 613Neurotransmitter Receptor Influence on BehaviorTreatment of Major DepressionTryptophan and brain disorders

A serotonin transporter gene promoter polymorphism (5-HTTLPR) and prefrontal cortical binding in major depression and suicide

Mann, J. John, Huang, Yung-yu, Underwood, Mark D., Kassir, Suham A., Oppenheim, Sara, Kelly, Thomas M., Dwork, Andrew J., Arango, Victoria·2000·Archives of General Psychiatry

Abstract

BACKGROUND: Major depression and suicide are associated with fewer serotonin transporter (5-HTT) sites. The 5'-flanking promoter region of the 5-HTT gene has a biallelic insertion/deletion (5-HTTLPR). We assayed prefrontal cortical (PFC) 5-HTT binding in major depression and suicide and examine the relationship to the 5-HTTLPR allele. METHODS: Postmortem brain samples from 220 individuals were genotyped for the 5-HTTLPR polymorphism. Binding of 5-HTT was assayed by quantitative autoradiography in the PFC of a subset of subjects (n = 159). Clinical information, including DSM-III-R Axis I diagnoses, was obtained by psychological autopsy and medical chart review. RESULTS: Binding to 5-HTT was lower in the ventral PFC of suicides compared with nonsuicides and was lower throughout the PFC of subjects with a history of major depression. The 5-HTTLPR genotype was associated with major depression but not with suicide or 5-HTT binding. CONCLUSIONS: A diffuse reduction of 5-HTT binding in the PFC of individuals with major depression may reflect a widespread impairment of serotonergic function consistent with the range of psychopathologic features in major depression. The localized reduction in 5-HTT binding in the ventral PFC of suicides may reflect reduced serotonin input to that brain region, underlying the predisposition to act on suicidal thoughts. The 5-HTTLPR genotype was not related to the level of 5-HTT binding and does not explain why 5-HTT binding is lower in major depression or suicide. Arch Gen Psychiatry. 2000;57:729-738

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Crossref · 10.1001/archpsyc.57.8.729

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  • Postmortem and imaging findings show decreased serotonin transporter (SERT) binding in the ventral prefrontal cortex of suicide victims, suggesting region-specific serotonergic deficits linked to behavioral dyscontrol.

    “Postmortem and imaging findings show decreased serotonin transporter (SERT) binding in the ventral PFC of suicide victims, suggesting region-specific serotonergic deficits linked to behavioral dyscontrol (25).”

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Authors
Mann, J. J., Huang, Y.-Y., Underwood, M. D., Kassir, S. A., Oppenheim, S., Kelly, T. M., Dwork, A. J., & Arango, V.
Affiliations
New York State Psychiatric Institute (US)
Venue
Archives of General Psychiatry
Published
2000-08-01
Volume
57
Issue
8
Pages
729
ISSN
0003-990X (ISSN-L)
OpenAlex
W2107995274
Cited by
613
References
123
Citations by year
2026: 5 · 2025: 6 · 2024: 10 · 2023: 8 · 2022: 4 · 2021: 14 · 2020: 9 · 2019: 8 · 2018: 16 · 2017: 13 · 2016: 24 · 2015: 23 · 2014: 30 · 2013: 26 · 2012: 27
FWCI
15.48
Type
journal article
Language
en
Open access
closed
Locations
  • Archives of General Psychiatry (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Institute of Mental Health (R01MH040695, MH46745, MH-40210, R01MH040210, MH 40695)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
  • Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
  • Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
Keywords
serotonin transporter, 5-HTTLPR, promoter polymorphism, major depressive disorder, suicide, prefrontal cortex, serotonin transporter binding, ventral prefrontal cortex, serotonergic function, postmortem brain
MeSH terms
Adult, Autoradiography, Mental Disorders, Carrier Proteins, Depressive Disorder, Female, Genotype, Humans, Male, Membrane Glycoproteins, Middle Aged, Nerve Tissue Proteins, Polymorphism, Genetic, Promoter Regions, Genetic, Serotonin, Sex Factors, Suicide, Gene Expression, Prefrontal Cortex, Membrane Transport Proteins, Serotonin Plasma Membrane Transport Proteins

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