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

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Humby, Trevor ; Fisher, Amelia ; Allen, Christopher ; Reynolds, Meghann ; Hartman, Annette ; Giegling, Ina ; Rujescu, Dan ; Davies, William (2017)
  • Publisher: John Wiley and Sons Inc.
  • Journal: Brain and Behavior (vol: 7)
  • Related identifiers: doi: 10.1002/brb3.646, pmc: PMC5346528
  • Subject: 5‐choice serial reaction time task | BF | intra‐individual reaction time variability | RRID: SCR_014794 | Original Research | R1 | coefficient of variation

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