title: Serotonin transporter polymorphism predicts waking cortisol in young girls.
abstract: Major Depressive Disorder (MDD) is one of the most prevalent and costly of all psychiatric disorders. The hypothalamic pituitary adrenal (HPA)-axis, which regulates the hormonal response to stress, has been found to be disrupted in depression. HPA dysregulation may represent an important risk factor for depression. To examine a possible genetic underpinning of this risk factor without the confound of current or lifetime depression, we genotyped 84 never-disordered young girls, over a third of whom were at elevated risk for depression, to assess the association between a polymorphism in the promoter region of the serotonin transporter (5-HTT) gene and diurnal variation in HPA-axis activity. This 5-HTT-linked polymorphic region (5-HTTLPR) has been previously found to interact with stress to increase risk for depression. We found 5-HTTLPR to be significantly associated with diurnal cortisol levels: girls who were homozygous for the short-allele had higher levels of waking (but not afternoon or evening) cortisol than did their long-allele counterparts. This finding suggests that genetic susceptibility to HPA-axis dysregulation, especially apparent in levels of waking cortisol, is detectable in individuals as young as 9 years of age.
authors.affiliation: Stanford University, Department of Psychology, United States. mcchen@stanford.edu
authors.forename: Michael C
authors.initials: MC
authors.lastname: Chen
authors.forename: Jutta
authors.initials: J
authors.lastname: Joormann
authors.forename: Joachim
authors.initials: J
authors.lastname: Hallmayer
authors.forename: Ian H
authors.initials: IH
authors.lastname: Gotlib
mesh_terms: D000293:Adolescent; D001143:Arousal / Q000235:genetics* / Q000502:physiology; D002648:Child; D002940:Circadian Rhythm / Q000235:genetics / Q000502:physiology; D003865:Major Depressive Disorder / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D005260:Female; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D006854:Hydrocortisone / Q000235:genetics / Q000378:metabolism*; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism / Q000503:physiopathology; D010913:Pituitary-Adrenal System / Q000378:metabolism / Q000503:physiopathology; D011110:Polymorphism, Genetic; D011379:Prognosis; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*
chemical_list: D050486:Serotonin Plasma Membrane Transport Proteins; D006854:Hydrocortisone