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Influence of NOS1 on verbal intelligence and working memory in both patients with schizophrenia and healthy control subjects

Donohoe, Gary, Walters, James Tynan Rhys, Morris, Derek W., Quinn, Emma M., Róisín, Judge, Norton, Nadine, Giegling, Ina, Hartmann, Annette M., Möller, Hans-Jürgen, Muglia, Pierandrea, Williams, Hywel John, Escott-Price, Valentina, Peel, Rosemary, O’Donoghue, Theresa, Owen, Michael John, O'Donovan, Michael Conlon, Gill, Michael and Rujescu, Dan 2009. Influence of NOS1 on verbal intelligence and working memory in both patients with schizophrenia and healthy control subjects. Archives of General Psychiatry 66 (10) , pp. 1045-1054. 10.1001/archgenpsychiatry.2009.139

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Abstract

Context: Human and animal studies have implicated the gene NOS1 in both cognition and schizophrenia susceptibility. Objective: To investigate whether a potential schizophrenia risk single-nucleotide polymorphism (rs6490121) identified in a recent genome-wide association study negatively influences cognition in patients with schizophrenia and healthy control subjects. Design: A comparison of both cases and controls grouped according to NOS1 genotype (GG vs AG vs AA) on selected measures of cognition in 2 independent samples. We tested for association between NOS1 rs6490121 and cognitive functions known to be impaired in schizophrenia (IQ, episodic memory, working memory, and attentional control) in an Irish sample. We then sought to replicate the significant results in a German sample. Setting: Unrelated patients from general adult psychiatric inpatient and outpatient services and unrelated healthy volunteers from the general population were ascertained. Participants: Patients with DSM-IV–diagnosed schizophrenia and healthy control subjects from independent samples of Irish (cases, n = 349; controls, n = 230) and German (cases, n = 232; controls, n = 1344) nationality. Results: A main effect of NOS1 genotype on verbal IQ and working memory was observed in the Irish sample where the homozygous carriers of the schizophrenia risk G allele performed poorly compared with the other genotype groups. These findings were replicated in the German sample, again with the GG genotype carriers performing below other genotype groups. Post hoc analysis of additional IQ measures (full-scale and performance IQ) in the German sample revealed that NOS1 GG carriers underperformed on these measures also. Conclusions: NOS1 is associated with clinically significant variation in cognition. Whether this is a mechanism by which schizophrenia risk is increased (eg, via an influence on cognitive reserve) is yet to be confirmed.

Item Type: Article
Date Type: Publication
Status: Published
Schools: 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
Publisher: American Medical Association
ISSN: 0003-990X
Last Modified: 05 Jun 2017 02:43
URI: http://orca.cf.ac.uk/id/eprint/18049

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