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Influence of serotonin transporter promoter region polymorphisms on hippocampal volumes in late-life depression.

Publication ,  Journal Article
Taylor, WD; Steffens, DC; Payne, ME; MacFall, JR; Marchuk, DA; Svenson, IK; Krishnan, KRR
Published in: Arch Gen Psychiatry
May 2005

CONTEXT: Polymorphisms in the promoter region of the serotonin transporter gene (5-HTTLPR) influence transcription and may play a role in the pathogenesis and course of depression. Recent research demonstrates that specific polymorphisms may be associated with differences in hippocampal volumes in subjects with depression. OBJECTIVE: To examine associations between 5-HTTLPR genotype and hippocampal volumes in elderly control subjects and elderly subjects classified as having early or late onset of depression. DESIGN: Cohort study examining baseline characteristics. PARTICIPANTS: Subjects were community dwelling and 60 years or older. Using a definition of early-onset depression as depression first occurring at 50 years or younger, we examined 72 subjects with early-onset depression, 63 subjects with late-onset depression, and 83 healthy control subjects. MAIN OUTCOME MEASURES: All subjects underwent genotyping for the 5-HTTLPR and underwent brain magnetic resonance imaging. Analyses of hippocampal volumes were controlled for total cerebral volume, age, and sex. RESULTS: The interaction between diagnosis and 5-HTTLPR genotype was statistically significant for the right hippocampus (P = .04). Subjects with late-onset depression who were homozygous for the long (L) allele (L /L genotype) had significantly smaller right hippocampal volumes than did L /L subjects with early-onset depression (P = .046) or L /L control subjects (P = .01). Post hoc analyses showed that later age of depression onset was associated with smaller hippocampal volumes in subjects with the L /L genotype, but earlier age of onset was associated with smaller hippocampal volumes in subjects who were homozygous for the short (S) allele (S/S genotype). CONCLUSIONS: Subjects with late-onset depression who were homozygous for the L allele exhibited smaller hippocampal volumes than other groups. Genotype also mediated the effect of age of onset on hippocampal volumes. Our findings differ from previous work; however, we examined an older and larger cohort of subjects than previous studies. Possible explanations for these findings include interactions between the serotonergic system and neurotrophic factors or cortisol response to stresses, each of which may affect hippocampal volumes.

Duke Scholars

Published In

Arch Gen Psychiatry

DOI

ISSN

0003-990X

Publication Date

May 2005

Volume

62

Issue

5

Start / End Page

537 / 544

Location

United States

Related Subject Headings

  • Serotonin Plasma Membrane Transport Proteins
  • Risk Factors
  • Psychiatry
  • Psychiatric Status Rating Scales
  • Promoter Regions, Genetic
  • Polymorphism, Genetic
  • Nerve Tissue Proteins
  • Models, Genetic
  • Middle Aged
  • Membrane Transport Proteins
 

Citation

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ICMJE
MLA
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Taylor, W. D., Steffens, D. C., Payne, M. E., MacFall, J. R., Marchuk, D. A., Svenson, I. K., & Krishnan, K. R. R. (2005). Influence of serotonin transporter promoter region polymorphisms on hippocampal volumes in late-life depression. Arch Gen Psychiatry, 62(5), 537–544. https://doi.org/10.1001/archpsyc.62.5.537
Taylor, Warren D., David C. Steffens, Martha E. Payne, James R. MacFall, Douglas A. Marchuk, Ingrid K. Svenson, and K Ranga R. Krishnan. “Influence of serotonin transporter promoter region polymorphisms on hippocampal volumes in late-life depression.Arch Gen Psychiatry 62, no. 5 (May 2005): 537–44. https://doi.org/10.1001/archpsyc.62.5.537.
Taylor WD, Steffens DC, Payne ME, MacFall JR, Marchuk DA, Svenson IK, et al. Influence of serotonin transporter promoter region polymorphisms on hippocampal volumes in late-life depression. Arch Gen Psychiatry. 2005 May;62(5):537–44.
Taylor, Warren D., et al. “Influence of serotonin transporter promoter region polymorphisms on hippocampal volumes in late-life depression.Arch Gen Psychiatry, vol. 62, no. 5, May 2005, pp. 537–44. Pubmed, doi:10.1001/archpsyc.62.5.537.
Taylor WD, Steffens DC, Payne ME, MacFall JR, Marchuk DA, Svenson IK, Krishnan KRR. Influence of serotonin transporter promoter region polymorphisms on hippocampal volumes in late-life depression. Arch Gen Psychiatry. 2005 May;62(5):537–544.

Published In

Arch Gen Psychiatry

DOI

ISSN

0003-990X

Publication Date

May 2005

Volume

62

Issue

5

Start / End Page

537 / 544

Location

United States

Related Subject Headings

  • Serotonin Plasma Membrane Transport Proteins
  • Risk Factors
  • Psychiatry
  • Psychiatric Status Rating Scales
  • Promoter Regions, Genetic
  • Polymorphism, Genetic
  • Nerve Tissue Proteins
  • Models, Genetic
  • Middle Aged
  • Membrane Transport Proteins