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

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.

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Citation

Published Version (Please cite this version)

10.1186/1471-244X-11-76

Publication Info

Morey, Rajendra A, Ahmad R Hariri, Andrea L Gold, Michael A Hauser, Heidi J Munger, Florin Dolcos and Gregory McCarthy (2011). Serotonin transporter gene polymorphisms and brain function during emotional distraction from cognitive processing in posttraumatic stress disorder. BMC Psychiatry, 11. p. 76. 10.1186/1471-244X-11-76 Retrieved from https://hdl.handle.net/10161/10971.

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Scholars@Duke

Morey

Rajendra A. Morey

Professor of Psychiatry and Behavioral Sciences

Research in my lab is focused on brain changes associated with posttraumatic stress disorder (PTSD), traumatic brain injury (TBI), and other neuropsychiatric disorders. We apply several advanced methods for understanding brain function including functional MRI, structural MRI, diffusion tensor imaging, and genetic effects.

Hariri

Ahmad Hariri

Professor of Psychology and Neuroscience

Integrating psychology, neuroimaging, pharmacology and molecular genetics in the search for biological pathways mediating individual differences in behavior and related risk for psychopathology.

Hauser

Michael Arthur Hauser

Professor in Medicine

Dr. Hauser has a strong interest in ocular genetics. Genomic studies at the Center for Human Genetics have identified multiple linkage peaks and susceptibility genes in primary open angle glaucoma (POAG) and age related macular degeneration (AMD). Dr. Hauser has recently accepted a 20% appointment at the Singapore Eye Research INstitute and the Duke/National University of Singapore.  In collaboration with multiple collaborators in Singapore, and Dr. Rand Allingham at the Duke Eye Center, Dr. Hauser is currently conducting a genome wide association study for glaucoma in individuals of African ancestry. These investigations include large datasets collected in Ghana, Nigeria, and South Africa.  
 
Dr. Hauser is also involved in collaborative investigations into the genetics of post-tramatic stress disorder in US veterans from Iraq and Afghanistan.   Major collaborators include Dr. Allison Ashley Koch, Dr. Jean Beckham, Dr. Christine Marx and the MIRECC Collaborative group at the Durham Veteran's Administration.  We have published a genome wide association study, as well as numerous investigations into candidate genes.  Epigenomic DNA methylation analysis and gene expression analysis of 3500 individuals is currently ongoing. 


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