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5-HTTLPR polymorphism impacts human cingulate-amygdala interactions: a genetic susceptibility mechanism for depression.

Publication ,  Journal Article
Pezawas, L; Meyer-Lindenberg, A; Drabant, EM; Verchinski, BA; Munoz, KE; Kolachana, BS; Egan, MF; Mattay, VS; Hariri, AR; Weinberger, DR
Published in: Nature neuroscience
June 2005

Carriers of the short allele of a functional 5' promoter polymorphism of the serotonin transporter gene have increased anxiety-related temperamental traits, increased amygdala reactivity and elevated risk of depression. Here, we used multimodal neuroimaging in a large sample of healthy human subjects to elucidate neural mechanisms underlying this complex genetic association. Morphometrical analyses showed reduced gray matter volume in short-allele carriers in limbic regions critical for processing of negative emotion, particularly perigenual cingulate and amygdala. Functional analysis of those regions during perceptual processing of fearful stimuli demonstrated tight coupling as a feedback circuit implicated in the extinction of negative affect. Short-allele carriers showed relative uncoupling of this circuit. Furthermore, the magnitude of coupling inversely predicted almost 30% of variation in temperamental anxiety. These genotype-related alterations in anatomy and function of an amygdala-cingulate feedback circuit critical for emotion regulation implicate a developmental, systems-level mechanism underlying normal emotional reactivity and genetic susceptibility for depression.

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Published In

Nature neuroscience

DOI

EISSN

1546-1726

ISSN

1097-6256

Publication Date

June 2005

Volume

8

Issue

6

Start / End Page

828 / 834

Related Subject Headings

  • Surveys and Questionnaires
  • Serotonin Plasma Membrane Transport Proteins
  • Serotonin
  • Polymorphism, Genetic
  • Neuropsychological Tests
  • Neurology & Neurosurgery
  • Neural Pathways
  • Nerve Tissue Proteins
  • Mutation
  • Membrane Transport Proteins
 

Citation

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Pezawas, L., Meyer-Lindenberg, A., Drabant, E. M., Verchinski, B. A., Munoz, K. E., Kolachana, B. S., … Weinberger, D. R. (2005). 5-HTTLPR polymorphism impacts human cingulate-amygdala interactions: a genetic susceptibility mechanism for depression. Nature Neuroscience, 8(6), 828–834. https://doi.org/10.1038/nn1463
Pezawas, Lukas, Andreas Meyer-Lindenberg, Emily M. Drabant, Beth A. Verchinski, Karen E. Munoz, Bhaskar S. Kolachana, Michael F. Egan, Venkata S. Mattay, Ahmad R. Hariri, and Daniel R. Weinberger. “5-HTTLPR polymorphism impacts human cingulate-amygdala interactions: a genetic susceptibility mechanism for depression.Nature Neuroscience 8, no. 6 (June 2005): 828–34. https://doi.org/10.1038/nn1463.
Pezawas L, Meyer-Lindenberg A, Drabant EM, Verchinski BA, Munoz KE, Kolachana BS, et al. 5-HTTLPR polymorphism impacts human cingulate-amygdala interactions: a genetic susceptibility mechanism for depression. Nature neuroscience. 2005 Jun;8(6):828–34.
Pezawas, Lukas, et al. “5-HTTLPR polymorphism impacts human cingulate-amygdala interactions: a genetic susceptibility mechanism for depression.Nature Neuroscience, vol. 8, no. 6, June 2005, pp. 828–34. Epmc, doi:10.1038/nn1463.
Pezawas L, Meyer-Lindenberg A, Drabant EM, Verchinski BA, Munoz KE, Kolachana BS, Egan MF, Mattay VS, Hariri AR, Weinberger DR. 5-HTTLPR polymorphism impacts human cingulate-amygdala interactions: a genetic susceptibility mechanism for depression. Nature neuroscience. 2005 Jun;8(6):828–834.

Published In

Nature neuroscience

DOI

EISSN

1546-1726

ISSN

1097-6256

Publication Date

June 2005

Volume

8

Issue

6

Start / End Page

828 / 834

Related Subject Headings

  • Surveys and Questionnaires
  • Serotonin Plasma Membrane Transport Proteins
  • Serotonin
  • Polymorphism, Genetic
  • Neuropsychological Tests
  • Neurology & Neurosurgery
  • Neural Pathways
  • Nerve Tissue Proteins
  • Mutation
  • Membrane Transport Proteins