A genetic variant within STS previously associated with inattention in boys with Attention Deficit Hyperactivity Disorder is associated with enhanced cognition in healthy adult males

摘要

Introduction: The enzyme steroid sulfatase converts sulfated steroids to their non-sulfated forms.udDeficiency for this enzyme is associated with inattention but preserved response control. Theudpolymorphism rs17268988 within the X-linked steroid sulfatase gene (STS) is associated withudinattentive, but not other, symptoms in boys with Attention Deficit Hyperactivity Disorder (ADHD).udMethods: We initially tested whether rs17268988 genotype was associated with attention, responseudcontrol and underlying aspects of cognition, using questionnaires and neuropsychological tasks, in twoudindependent cohorts of healthy adult males. In an additional analysis based upon existing data, theudperformance of mice with genetic or pharmacological manipulations of the steroid sulfatase axisudunder attentionally-demanding conditions was investigated.udResults: G-allele carriers at rs17268988 exhibited reduced reaction time, enhanced attention andudreduced reaction time variability relative to C-allele carriers. Mice with genetic or pharmacologicaludmanipulations of the steroid sulfatase axis were shown to have perturbed reaction time variability.udDiscussion: Our findings provide additional support for an association between rs17268988 genotypeudand attention, which may be partially mediated by reaction time variability; they also indicate that, inudcontrast to the situation in boys with ADHD, in healthy men, the G allele at rs17268988 is associatedudwith enhanced cognition. As reaction time variability is a predictor of wellbeing, rs17268988 genotypeudmay represent a biomarker for long-term health.