Exploring the indirect effects of catechol‐O‐methyltransferase (COMT) genotype on psychotic experiences through cognitive function and anxiety disorders in a large birth cohort of children. Issue 5 (27th May 2014)

• Record Type: Journal Article
• Authors: Niarchou, Maria; Zammit, Stanley; Escott‐Price, Valentina; Owen, Michael J.; van den Bree, Marianne B. M.
• Is Part Of: American journal of medical genetics. Volume 165:Issue 5(2014)
• Page Start: 410
• Page End: 420
• Publication Date: 2014-05-27
• Subjects: Neuropsychiatry -- Periodicals; Medical genetics -- Periodicals; 616.8904205
• DOI: 10.1002/ajmg.b.32245
• Languages: English
• ISSNs: 1552-4841

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="ajmgb32245-sec-0001" sec-type="section"> <p>Children reporting psychotic experiences (PEs) are at increased risk of developing psychosis in adulthood. Cognitive deficits and anxiety disorders often precede psychotic disorders and are associated with higher risk of PEs. While the high activity alleles of variants within <italic>COMT</italic> have been associated with cognitive deficits, and the low activity alleles with higher risk of anxiety disorders, no associations of <italic>COMT</italic> with PEs have been found. One possible explanation is that the association between <italic>COMT</italic> and PEs is indirect, through cognitive function and anxiety disorders. We examined whether the association between PEs and <italic>COMT</italic> (four single nucleotide polymorphisms and three haplotypes) is indirect, through cognition or anxiety disorders. 6, 784 individuals from the Avon Longitudinal Study of Parents and Children (ALSPAC) were genotyped and completed neurocognitive assessments at ages 8 and 11, as well as semi‐structured interviews for anxiety disorders and PEs at ages 10 and 12, respectively. Alleles rs2097603 and rs4680, and two <italic>COMT</italic> haplotypes, all indexing high activity, were indirectly associated with higher risk of PEs through impaired processing speed, IQ and attention. There was no evidence of a total effect of <italic>COMT</italic> on PEs, nor for an indirect effect through anxiety disorders. This is the first study to examine indirect effects of <italic>COMT</italic> on PEs. Evidence of an indirect association suggests a complex developmental pathway underlies the emergence of PEs in children, with possible implications for prevention/intervention strategies. Our findings provide additional support for processing speed and attention as endophenotypes in psychotic disorders. © 2014 Wiley Periodicals, Inc.</p> </sec> </abstract>