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Converging pharmacological and genetic evidence indicates a role for steroid sulfatase in attention

Davies, William, Humby, Trevor, Kong, Wendy, Otter, Tamara Leonie, Burgoyne, Paul S. and Wilkinson, Lawrence Stephen 2009. Converging pharmacological and genetic evidence indicates a role for steroid sulfatase in attention. Biological Psychiatry 66 (4) , pp. 360-367. 10.1016/j.biopsych.2009.01.001

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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], 0–40mg/kg, or acute inhibition of the enzyme by COUMATE, 10mg/kg) or genetically (through loss of the gene in 39,XY*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,XY*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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Psychology
Medicine
MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Neuroscience and Mental Health Research Institute (NMHRI)
Subjects: R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Uncontrolled Keywords: Accuracy; attention-deficit/hyperactivity disorder; dehydroepiandrosterone sulfate; 5-choice serial reaction Time task; Turner syndrome; X chromosome
Publisher: Elsevier
ISSN: 0006-3223
Last Modified: 02 May 2019 13:06
URI: http://orca-mwe.cf.ac.uk/id/eprint/11546

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