Abstract
IntroductionThe enzyme steroid sulfatase (STS) 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 STS gene is associated with inattentive, but not other, symptoms in boys with attention deficit hyperactivity disorder (ADHD).MethodsWe 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 STS axis under attentionally demanding conditions was investigated.ResultsG‐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 STS axis were shown to have perturbed reaction time variability.DiscussionOur 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 well‐being, rs17268988 genotype may represent a biomarker for long‐term health.
Highlights
| INTRODUCTIONThe enzyme steroid sulfatase (STS), encoded by the X-linked gene STS, cleaves sulfate groups from a variety of steroids (e.g., dehydroepiandrosterone sulfate) to convert them to precursors for a variety of estrogens and androgens that can elicit widespread and profound physiological effects (Mueller, Gilligan, Idkowiak, Arlt, & Foster, 2015)
The enzyme steroid sulfatase (STS) converts sulfated steroids to their non-sulfated forms
Two independent genetic association studies examining the STS gene in boys from UK with attention deficit hyperactivity disorder (ADHD) identified the single nucleotide polymorphism (SNP) rs17268988 as being associated with inattentive symptoms, but not hyperactive or impulsive symptoms (Brookes et al, 2008; Stergiakouli et al, 2011); the G-allele at this SNP was associated with a greater number of inattentive symptoms
Summary
The enzyme steroid sulfatase (STS), encoded by the X-linked gene STS, cleaves sulfate groups from a variety of steroids (e.g., dehydroepiandrosterone sulfate) to convert them to precursors for a variety of estrogens and androgens that can elicit widespread and profound physiological effects (Mueller, Gilligan, Idkowiak, Arlt, & Foster, 2015). Mice lacking the Sts gene, or given an inhibitor of the enzyme, display attentional deficits relative to wildtype or vehicle-treated mice manifest as increased omission or commission errors respectively (Davies et al, 2009); interestingly, contrary to expectation, the former groups exhibit enhanced response inhibition relative to wildtype or vehicle-treated mice (Davies et al, 2014) Somewhat consistent with these mouse data, males lacking a functional STS gene are at increased risk of developing attention deficit hyperactivity disorder (ADHD; the inattentive presentation) but seem to exhibit normal levels of motor impulsivity (Chatterjee, Humby, & Davies, 2016; Kent et al, 2008). We subsequently tested whether our human findings were consistent with the previously obtained data from our mouse model studies
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