title: Genetic variants within the dopaminergic system interact to modulate endocrine stress reactivity and recovery.
abstract: Catecholamines modulate endocrine stress reactivity by affecting regulatory influences of extra-hypothalamic brain structures on hypothalamus-pituitary-adrenal (HPA)-axis. Therefore, we aimed to investigate combined effects of functional allelic variations that affect dopamine availability in both cortical (COMT Val¹⁵⁸Met polymorphism) and subcortical (DAT1 VNTR) brain regions on HPA-axis reactivity to psychosocial stress. By using a standardized laboratory stress task (public speaking) we obtained saliva cortisol samples during stress exposure and an extended recovery period in 100 healthy male adults. We report for the first time significant epistasis between COMT Val¹⁵⁸Met and DAT1 VNTR on cortisol response patterns. Subjects homozygous for both the Met¹⁵⁸ and the 10-repeat allele of DAT1 VNTR were characterized by markedly elevated cortisol reactivity and impaired stress recovery compared to all other groups. Our results indicate a crucial role of functional genetic variants within the dopaminergic system in the modulation of HPA-axis response patterns and highlight the need to investigate combined effects of specific candidate genes on stress-related endophenotypes.
authors.affiliation: Center for Psychobiology and Behavioral Medicine, University of Giessen, Department of Psychology, Otto-Behaghel-Str. 10, D-35394 Giessen, Germany. nina.alexander@psychol.uni-giessen.de
authors.forename: Nina
authors.initials: N
authors.lastname: Alexander
authors.forename: Roman
authors.initials: R
authors.lastname: Osinsky
authors.forename: Eva
authors.initials: E
authors.lastname: Mueller
authors.forename: Anja
authors.initials: A
authors.lastname: Schmitz
authors.forename: Sarah
authors.initials: S
authors.lastname: Guenthert
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Kuepper
authors.forename: Juergen
authors.initials: J
authors.lastname: Hennig
mesh_terms: D000328:Adult; D000483:Alleles; D000704:Analysis of Variance; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics*; D058068:Endophenotypes; D006801:Humans; D006854:Hydrocortisone / Q000032:analysis*; D007030:Hypothalamo-Hypophyseal System / Q000503:physiopathology; D008297:Male; D010913:Pituitary-Adrenal System / Q000503:physiopathology; D020641:Polymorphism, Single Nucleotide; D012463:Saliva / Q000737:chemistry; D013315:Stress, Psychological / Q000235:genetics* / Q000503:physiopathology; D011795:Surveys and Questionnaires
chemical_list: D050483:Dopamine Plasma Membrane Transport Proteins; C493214:SLC6A3 protein, human; D002394:Catechol O-Methyltransferase; D006854:Hydrocortisone