Beyond affect: a role for genetic variation of the serotonin transporter in neural activation during a cognitive attention task.
Prior work has highlighted the role of genetic variation within the repetitive sequence in the transcriptional control region of the serotonin (5-HT) transporter gene (5-HTT, SLC6A4) in modulating amygdala and prefrontal activation to negative emotional stimuli. However, these studies have not explicitly tested the assumption that the control condition (neutral baseline) does not itself produce changes in activation as a function of 5-HTT genotype. Using a fixation baseline condition, we show that variation in 5-HTT genotype is associated with differential activation to negative, positive, and neutral stimuli in limbic, striatal, and cortical regions. We replicate earlier reports of increased amygdala activation to negative, relative to neutral, stimuli, but then show that these differences are driven by decreased activation to neutral stimuli, rather than increased activation to negative stimuli, in carriers of the 5-HTT short allele. Using high-resolution structural images and automated processes to test for brain volume and gray matter density, we further report significant differences, as a function of 5-HTT genotype, in frontal cortical regions, anterior cingulate, and cerebellum. These functional and structural differences suggest a much broader role for 5-HT transport efficiency in brain processes than previously thought. 5-HTT genotype affects neural systems controlling affective, cognitive, and motor processes.
Canli
Turhan
T
Department of Psychology and Graduate Program in Genetics, Stony Brook University, Stony Brook, NY 11794-2500, USA. turhan.canli@sunysb.edu
Omura
Kazufumi
K
Haas
Brian W
BW
Fallgatter
Andreas
A
Constable
R Todd
RT
Lesch
Klaus Peter
KP
D000704:Analysis of Variance; D001288:Attention / Q000502:physiology*; D001837:Body Weights and Measures; D001921:Brain / Q000502:physiology* / Q000648:ultrastructure; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D010775:Photic Stimulation; D049268:Positron-Emission Tomography; D021381:Protein Transport / Q000502:physiology; D011597:Psychomotor Performance; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics* / Q000378:metabolism
C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins