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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

Niarchou, Maria, Zammit, Stanley, Escott-Price, Valentina, Owen, Michael John and van den Bree, Marianne Bernadette 2014. 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. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics 165 (5) , pp. 410-420. 10.1002/ajmg.b.32245

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Abstract

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 COMT have been associated with cognitive deficits, and the low activity alleles with higher risk of anxiety disorders, no associations of COMT with PEs have been found. One possible explanation is that the association between COMT and PEs is indirect, through cognitive function and anxiety disorders. We examined whether the association between PEs and COMT (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 COMT 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 COMT on PEs, nor for an indirect effect through anxiety disorders. This is the first study to examine indirect effects of COMT 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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: MRC Centre for Neuropsychiatric Genetics and Genomics
Medicine
Neuroscience and Mental Health Research Institute (NMHRI)
Subjects: R Medicine > R Medicine (General)
R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Publisher: Wiley-Blackwell
ISSN: 1552-4841
Last Modified: 10 Oct 2017 16:28
URI: http://orca-mwe.cf.ac.uk/id/eprint/74898

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