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.
journal_name
Biol Psychiatryjournal_title
Biological psychiatryauthors
Davies W,Humby T,Kong W,Otter T,Burgoyne PS,Wilkinson LSdoi
10.1016/j.biopsych.2009.01.001subject
Has Abstractpub_date
2009-08-15 00:00:00pages
360-7issue
4eissn
0006-3223issn
1873-2402pii
S0006-3223(09)00026-2journal_volume
66pub_type
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pub_type: 临床试验,杂志文章
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更新日期:2015-12-01 00:00:00
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pub_type: 临床试验,杂志文章
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pub_type: 杂志文章
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pub_type: 杂志文章
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journal_title:Biological psychiatry
pub_type: 杂志文章
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pub_type: 杂志文章
doi:
更新日期:1979-06-01 00:00:00
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pub_type: 杂志文章
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更新日期:2013-06-01 00:00:00
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