Serotonin transporter gene polymorphisms and brain function during emotional distraction from cognitive processing in posttraumatic stress disorder

doi:10.1186/1471-244X-11-76

BMC Psychiatry. 2011; 11: 76.

Published online 2011 May 5. doi: 10.1186/1471-244X-11-76

PMCID: PMC3112079

Serotonin transporter gene polymorphisms and brain function during emotional distraction from cognitive processing in posttraumatic stress disorder

Rajendra A Morey,^1,^2,³ Ahmad R Hariri,^2,⁴ Andrea L Gold,⁵ Michael A Hauser,^3,⁶ Heidi J Munger,^3,⁶ Florin Dolcos,⁷ and Gregory McCarthy^3,⁵

¹Department of Psychiatry and Behavioral Sciences, Duke University, Durham, NC 27710 USA

²Duke-UNC Brain Imaging and Analysis Center, Duke University, Durham, NC 27705 USA

³Mid-Atlantic Mental Illness Research Education and Clinical Center, Durham VA Medical Center, Durham, NC 27705 USA

⁴Department of Psychology & Neuroscience, and Institute for Genome Sciences and Policy, Duke University, Durham, NC 27708 USA

⁵Department of Psychology, Yale University, New Haven, CT 06520 USA

⁶Center for Human Genetics, Duke University, Durham, NC 27710 USA

⁷Department of Psychology, Neuroscience Program, and Beckman Institute for Advanced Science & Technology, University of Illinois, Urbana-Champaign, IL, USA

Corresponding author.

Rajendra A Morey: morey/at/biac.duke.edu; Ahmad R Hariri: ahmad/at/haririlab.com; Andrea L Gold: andrea.gold/at/yale.edu ; Michael A Hauser: mike.hauser/at/duke.edu; Heidi J Munger: Heidi.munger/at/duke.edu; Florin Dolcos: fdolcos/at/cyrus.psych.illinois.edu; Gregory McCarthy: gregory.mccarthy/at/yale.edu

Received December 24, 2010; Accepted May 5, 2011.

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

This article has been cited by other articles in PMC.

Abstract

Background

Serotonergic system dysfunction has been implicated in posttraumatic stress disorder (PTSD). Genetic polymorphisms associated with serotonin signaling may predict differences in brain circuitry involved in emotion processing and deficits associated with PTSD. In healthy individuals, common functional polymorphisms in the serotonin transporter gene (SLC6A4) have been shown to modulate amygdala and prefrontal cortex (PFC) activity in response to salient emotional stimuli. Similar patterns of differential neural responses to emotional stimuli have been demonstrated in PTSD but genetic factors influencing these activations have yet to be examined.

Methods

We investigated whether SLC6A4 promoter polymorphisms (5-HTTLPR, rs25531) and several downstream single nucleotide polymorphisms (SNPs) modulated activity of brain regions involved in the cognitive control of emotion in post-9/11 veterans with PTSD. We used functional MRI to examine neural activity in a PTSD group (n = 22) and a trauma-exposed control group (n = 20) in response to trauma-related images presented as task-irrelevant distractors during the active maintenance period of a delayed-response working memory task. Regions of interest were derived by contrasting activation for the most distracting and least distracting conditions across participants.

Results

In patients with PTSD, when compared to trauma-exposed controls, rs16965628 (associated with serotonin transporter gene expression) modulated task-related ventrolateral PFC activation and 5-HTTLPR tended to modulate left amygdala activation. Subsequent to combat-related trauma, these SLC6A4 polymorphisms may bias serotonin signaling and the neural circuitry mediating cognitive control of emotion in patients with PTSD.

Conclusions

The SLC6A4 SNP rs16965628 and 5-HTTLPR are associated with a bias in neural responses to traumatic reminders and cognitive control of emotions in patients with PTSD. Functional MRI may help identify intermediate phenotypes and dimensions of PTSD that clarify the functional link between genes and disease phenotype, and also highlight features of PTSD that show more proximal influence of susceptibility genes compared to current clinical categorizations.

Keywords: PTSD, imaging genetics, ventrolateral PFC, amygdala, SLC6A4, rs16965628, working memory, emotion processing, cognitive control

Articles from BMC Psychiatry are provided here courtesy of
BioMed Central