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

Morey, Rajendra A

Hariri, Ahmad R

Gold, Andrea L

Hauser, Michael A

Munger, Heidi J

Dolcos, Florin

McCarthy, Gregory

England

2015-12-03T15:13:44Z

2011-05-05

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.

http://www.ncbi.nlm.nih.gov/pubmed/21545724

1471-244X-11-76

1471-244X

https://hdl.handle.net/10161/10971

eng

Springer Science and Business Media LLC

BMC Psychiatry

10.1186/1471-244X-11-76

Amygdala

Case-Control Studies

Cognition

Emotions

Functional Neuroimaging

Humans

Magnetic Resonance Imaging

Memory, Short-Term

Polymorphism, Single Nucleotide

Prefrontal Cortex

Promoter Regions, Genetic

Psychomotor Performance

September 11 Terrorist Attacks

Serotonin Plasma Membrane Transport Proteins

Stress Disorders, Post-Traumatic

Veterans

Wounds and Injuries

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

Journal article

http://www.ncbi.nlm.nih.gov/pubmed/21545724

76

Basic Science Departments

Center for Child and Family Policy

Clinical Science Departments

Duke

Duke Institute for Brain Sciences

Duke Molecular Physiology Institute

Duke Science & Society

Duke-UNC Center for Brain Imaging and Analysis

Initiatives

Institutes and Centers

Institutes and Provost's Academic Units

Medicine

Medicine, Medical Genetics

Molecular Genetics and Microbiology

Psychiatry & Behavioral Sciences

Psychiatry & Behavioral Sciences, Translational Neuroscience

Psychology and Neuroscience

Sanford School of Public Policy

School of Medicine

Trinity College of Arts & Sciences

University Institutes and Centers

Published online

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