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Neural mechanisms underlying 5-HTTLPR-related sensitivity to acute stress.

Publication ,  Journal Article
Drabant, EM; Ramel, W; Edge, MD; Hyde, LW; Kuo, JR; Goldin, PR; Hariri, AR; Gross, JJ
Published in: The American journal of psychiatry
April 2012

Many studies have shown that 5-HTTLPR genotype interacts with exposure to stress in conferring risk for psychopathology. However, the specific neural mechanisms through which this gene-by-environment interaction confers risk remain largely unknown, and no study to date has directly examined the modulatory effects of 5-HTTLPR on corticolimbic circuit responses during exposure to acute stress.An acute laboratory stressor was administered to 51 healthy women during blood-oxygen-level-dependent functional magnetic resonance imaging. In this task, participants were threatened with electric shocks of uncertain intensity, which were unpredictably delivered to the wrist after a long anticipatory cue period of unpredictable duration.Relative to women carrying the L allele, those with the SS genotype showed enhanced activation during threat anticipation in a network of regions, including the amygdala, hippocampus, anterior insula, thalamus, pulvinar, caudate, precuneus, anterior cingulate cortex, and medial prefrontal cortex. Individuals with the SS genotype also displayed enhanced positive coupling between medial prefrontal cortex activation and anxiety experience, whereas enhanced negative coupling between insula activation and perceived success at regulating anxiety was observed in individuals carrying the L allele.These findings suggest that during stress exposure, neural systems that enhance fear and arousal, modulate attention toward threat, and perseverate on emotional salience of the threat may be engaged preferentially in individuals with the SS genotype. This may be one mechanism underlying the risk for psychopathology conferred by the S allele upon exposure to life stressors.

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Published In

The American journal of psychiatry

DOI

EISSN

1535-7228

ISSN

0002-953X

Publication Date

April 2012

Volume

169

Issue

4

Start / End Page

397 / 405

Related Subject Headings

  • Stress, Psychological
  • Serotonin Plasma Membrane Transport Proteins
  • Psychiatry
  • Polymorphism, Single Nucleotide
  • Neural Pathways
  • Magnetic Resonance Imaging
  • Humans
  • Genotype
  • Functional Neuroimaging
  • Female
 

Citation

APA
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Drabant, E. M., Ramel, W., Edge, M. D., Hyde, L. W., Kuo, J. R., Goldin, P. R., … Gross, J. J. (2012). Neural mechanisms underlying 5-HTTLPR-related sensitivity to acute stress. The American Journal of Psychiatry, 169(4), 397–405. https://doi.org/10.1176/appi.ajp.2011.10111699
Drabant, Emily M., Wiveka Ramel, Michael D. Edge, Luke W. Hyde, Janice R. Kuo, Philippe R. Goldin, Ahmad R. Hariri, and James J. Gross. “Neural mechanisms underlying 5-HTTLPR-related sensitivity to acute stress.The American Journal of Psychiatry 169, no. 4 (April 2012): 397–405. https://doi.org/10.1176/appi.ajp.2011.10111699.
Drabant EM, Ramel W, Edge MD, Hyde LW, Kuo JR, Goldin PR, et al. Neural mechanisms underlying 5-HTTLPR-related sensitivity to acute stress. The American journal of psychiatry. 2012 Apr;169(4):397–405.
Drabant, Emily M., et al. “Neural mechanisms underlying 5-HTTLPR-related sensitivity to acute stress.The American Journal of Psychiatry, vol. 169, no. 4, Apr. 2012, pp. 397–405. Epmc, doi:10.1176/appi.ajp.2011.10111699.
Drabant EM, Ramel W, Edge MD, Hyde LW, Kuo JR, Goldin PR, Hariri AR, Gross JJ. Neural mechanisms underlying 5-HTTLPR-related sensitivity to acute stress. The American journal of psychiatry. 2012 Apr;169(4):397–405.
Journal cover image

Published In

The American journal of psychiatry

DOI

EISSN

1535-7228

ISSN

0002-953X

Publication Date

April 2012

Volume

169

Issue

4

Start / End Page

397 / 405

Related Subject Headings

  • Stress, Psychological
  • Serotonin Plasma Membrane Transport Proteins
  • Psychiatry
  • Polymorphism, Single Nucleotide
  • Neural Pathways
  • Magnetic Resonance Imaging
  • Humans
  • Genotype
  • Functional Neuroimaging
  • Female