title: Converging pharmacological and genetic evidence indicates a role for steroid sulfatase in attention.
abstract: BACKGROUND
  Attention-deficit/hyperactivity disorder (ADHD) is a complex neurodevelopmental disorder characterized by deficits in attention, increased motor impulsivity, and hyperactivity. Preliminary work in mice and humans has suggested the X-linked gene STS (which encodes the enzyme steroid sulfatase) as a mediator of attentional functioning and as a candidate gene for ADHD.
  
  
  METHODS
  The effects of modulating the murine steroid sulfatase axis pharmacologically (through administration of the substrate dehydroepiandrosterone sulfate [DHEAS], 0-40 mg/kg, or acute inhibition of the enzyme by COUMATE, 10mg/kg) or genetically (through loss of the gene in 39,X(Y)*O mice) were assayed using the 5-choice serial reaction time task (5-CSRTT) a test of visuospatial attention and response control, and a locomotor activity paradigm.
  
  
  RESULTS
  DHEAS administration improved 5-CSRTT performance under attentionally demanding conditions, whereas steroid sulfatase inhibition impaired accuracy under the same conditions. Loss of Sts expression constitutively throughout development in 39,X(Y)*O mice resulted in deficits in 5-CSRTT performance at short stimulus durations and reduced anticipatory responding. Neither the pharmacologic nor the genetic manipulations affected basic locomotor activity.
  
  
  CONCLUSIONS
  These data provide converging evidence indicating a role for steroid sulfatase in discrete aspects of attentional functioning and are suggestive of a role in motor impulsivity. The findings provide novel insights into the neurobiology of attention and strengthen the notion of STS as a candidate gene for the attentional component of ADHD.
authors.affiliation: Behavioural Genetics Group, School of Psychology and Department of Psychological Medicine, School of Medicine, University of Cardiff, London, United Kingdom. daviesw4@cardiff.ac.uk
authors.forename: William
authors.initials: W
authors.lastname: Davies
authors.forename: Trevor
authors.initials: T
authors.lastname: Humby
authors.forename: Wendy
authors.initials: W
authors.lastname: Kong
authors.forename: Tamara
authors.initials: T
authors.lastname: Otter
authors.forename: Paul S
authors.initials: PS
authors.lastname: Burgoyne
authors.forename: Lawrence S
authors.initials: LS
authors.lastname: Wilkinson
mesh_terms: D000818:Animals; D001288:Attention / Q000187:drug effects* / Q000502:physiology*; D001289:Attention Deficit Disorder with Hyperactivity / Q000235:genetics; D002755:Choice Behavior / Q000187:drug effects / Q000502:physiology; D003374:Coumarins / Q000494:pharmacology*; D019314:Dehydroepiandrosterone Sulfate / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D009043:Motor Activity / Q000187:drug effects / Q000235:genetics; D011930:Reaction Time / Q000187:drug effects / Q000235:genetics; D043266:Steryl-Sulfatase / Q000037:antagonists & inhibitors* / Q000235:genetics*; D013449:Sulfonamides / Q000494:pharmacology*
chemical_list: C100463:4-methylcoumarin 7-O-sulfamate; D003374:Coumarins; D013449:Sulfonamides; D019314:Dehydroepiandrosterone Sulfate; D043266:Steryl-Sulfatase