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Effects of HTR1A C(-1019)G on amygdala reactivity and trait anxiety.

Publication ,  Journal Article
Fakra, E; Hyde, LW; Gorka, A; Fisher, PM; Muñoz, KE; Kimak, M; Halder, I; Ferrell, RE; Manuck, SB; Hariri, AR
Published in: Archives of general psychiatry
January 2009

Serotonin 1A (5-hydroxytryptamine 1A [5-HT(1A)]) autoreceptors mediate negative feedback inhibition of serotonergic neurons and play a critical role in regulating serotonin signaling involved in shaping the functional response of major forebrain targets, such as the amygdala, supporting complex behavioral processes. A common functional variation (C[-1019]G) in the human 5-HT(1A) gene (HTR1A) represents 1 potential source of such interindividual variability. Both in vitro and in vivo, -1019G blocks transcriptional repression, leading to increased autoreceptor expression. Thus, -1019G may contribute to relatively decreased serotonin signaling at postsynaptic forebrain target sites via increased negative feedback.To evaluate the effects of HTR1A C(-1019)G on amygdala reactivity and to use path analyses to explore the impact of HTR1A-mediated variability in amygdala reactivity on individual differences in trait anxiety. We hypothesized that -1019G, which potentially results in decreased serotonin signaling, would be associated with relatively decreased amygdala reactivity and related trait anxiety.Imaging genetics in participants from an archival database.Eighty-nine healthy adults.Consistent with prior findings, -1019G was associated with significantly decreased threat-related amygdala reactivity. Importantly, this effect was independent of that associated with another common functional polymorphism that affects serotonin signaling, 5-HTTLPR. While there were no direct genotype effects on trait anxiety, HTR1A C(-1019)G indirectly predicted 9.2% of interindividual variability in trait anxiety through its effects on amygdala reactivity.Our findings further implicate relatively increased serotonin signaling, associated with a genetic variation that mediates increased 5-HT(1A) autoreceptors, in driving amygdala reactivity and trait anxiety. Moreover, they provide empirical documentation of the basic premise that genetic variation indirectly affects emergent behavioral processes related to psychiatric disease risk by biasing the response of underlying neural circuitries.

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Published In

Archives of general psychiatry

DOI

EISSN

1538-3636

ISSN

0003-990X

Publication Date

January 2009

Volume

66

Issue

1

Start / End Page

33 / 40

Related Subject Headings

  • Signal Transduction
  • Receptor, Serotonin, 5-HT1A
  • Psychiatry
  • Pattern Recognition, Visual
  • Oxygen
  • Middle Aged
  • Male
  • Magnetic Resonance Imaging
  • Image Processing, Computer-Assisted
  • Humans
 

Citation

APA
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MLA
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Fakra, E., Hyde, L. W., Gorka, A., Fisher, P. M., Muñoz, K. E., Kimak, M., … Hariri, A. R. (2009). Effects of HTR1A C(-1019)G on amygdala reactivity and trait anxiety. Archives of General Psychiatry, 66(1), 33–40. https://doi.org/10.1001/archpsyc.66.1.33
Fakra, Eric, Luke W. Hyde, Adam Gorka, Patrick M. Fisher, Karen E. Muñoz, Mark Kimak, Indrani Halder, Robert E. Ferrell, Stephen B. Manuck, and Ahmad R. Hariri. “Effects of HTR1A C(-1019)G on amygdala reactivity and trait anxiety.Archives of General Psychiatry 66, no. 1 (January 2009): 33–40. https://doi.org/10.1001/archpsyc.66.1.33.
Fakra E, Hyde LW, Gorka A, Fisher PM, Muñoz KE, Kimak M, et al. Effects of HTR1A C(-1019)G on amygdala reactivity and trait anxiety. Archives of general psychiatry. 2009 Jan;66(1):33–40.
Fakra, Eric, et al. “Effects of HTR1A C(-1019)G on amygdala reactivity and trait anxiety.Archives of General Psychiatry, vol. 66, no. 1, Jan. 2009, pp. 33–40. Epmc, doi:10.1001/archpsyc.66.1.33.
Fakra E, Hyde LW, Gorka A, Fisher PM, Muñoz KE, Kimak M, Halder I, Ferrell RE, Manuck SB, Hariri AR. Effects of HTR1A C(-1019)G on amygdala reactivity and trait anxiety. Archives of general psychiatry. 2009 Jan;66(1):33–40.

Published In

Archives of general psychiatry

DOI

EISSN

1538-3636

ISSN

0003-990X

Publication Date

January 2009

Volume

66

Issue

1

Start / End Page

33 / 40

Related Subject Headings

  • Signal Transduction
  • Receptor, Serotonin, 5-HT1A
  • Psychiatry
  • Pattern Recognition, Visual
  • Oxygen
  • Middle Aged
  • Male
  • Magnetic Resonance Imaging
  • Image Processing, Computer-Assisted
  • Humans