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Drucker-Colin, R; Graff-Guerrero, A; De la Fuente-Sandoval, C; Camarena, B; Gomez-Martin, D; Apiquian, R; Fresan, A; Aguilar, A; Mendez-Nunez, JC; Escalona-Huerta, C; Nicolini, H (2005)

FRONTAL AND LIMBIC METABOLIC DIFFERENCES IN SUBJECTS SELECTED ACCORDING TO GENETIC VARIATION OF THE SLC6A4 GENE POLYMORPHISM

NEUROIMAGE 25(4):1197-1204
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Allelic variants in the promoter region of the scrotonin transporter (5-HTT) gene have been implicated in several psychiatric disorders and personality traits. In particular, two common alleles in a variable repeal: sequence of the promoter region (SLC6A4) have been differentially associated with a display of abnormal levels of anxiety and affective illness in individuals carrying the "s" allele. The aim of this stud, v was to compare the basal cerebral metabolic activity of non-psychiatric subjects in fronto-limbic structures to determine whether differences exist in basal metabolic activity within this functional polymorphism. PET scans with fluorine-18 flurodeoxyglucose as radiotracer were performed in 71 non-psychiatric subjects previously screened for psychopathology and subsequently genotyped for SLC6A4; PET images were compared with SPM12 according to s/s (n = 27), s/I (n = 25), and 1/1 (n = 19) groups considering a significance threshold in a priori selected areas of P < 0.001 and an extent threshold >= 5 voxels. The analysis showed an effect of interest among the three genotype groups in right anterior cingulate gyrus (ACC), left middle frontal gyrus, and left posterior cingulate gyrus (PCC). Comparison between 1/1 vs. s/s showed increased metabolism for 1/1 in left middle Frontal gyrus and an increase for s/s in right ACC and left PCC. Comparison between s/s vs. s/I showed an increase for s/s in left PCC and right ACC. Increased basal metabolism in fronto-limbic structures for the s/s group may be conceived as an "overactive metabolic state" of these structures, possibly related to an increased susceptibility for developing an anxiety-depression spectrum disorder. (c) 2005 Elsevier Inc. All rights reserved.