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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

Humby, Trevor, Fisher, Amelia, Allen, Christopher, Reynolds, Meghann, Hartman, Annette, Giegling, Ina, Rujescu, Dan and Davies, William 2017. 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. Brain and Behavior 7 (3) , e00646. 10.1002/brb3.646

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Abstract

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

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Neuroscience and Mental Health Research Institute (NMHRI)
Psychology
Subjects: B Philosophy. Psychology. Religion > BF Psychology
R Medicine > R Medicine (General)
Uncontrolled Keywords: coefficient of variation; intra-individual reaction time variability; RRID: SCR_014794; 5- choice serial reaction time task (5-CSRTT)
Publisher: Wiley Open Access
ISSN: 2162-3279
Funders: MRC, BBSRC, German Research Foundation (DFG) and Cardiff University
Date of First Compliant Deposit: 27 January 2017
Date of Acceptance: 22 December 2016
Last Modified: 02 May 2019 13:10
URI: http://orca-mwe.cf.ac.uk/id/eprint/97837

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