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06-10-2009 | Mental health | Article

NOS1 gene link to worse cognitive performance unaffected by schizophrenia


Free abstract

MedWire News: Variations in the nitric oxide synthase 1 gene (NOS1) are associated with poor performance on cognitive tests in both schizophrenia patients and healthy individuals, although patients perform significantly worse, say European researchers.

Recent studies have identified the rs6490121 single nucleotide polymorphism (SNP) in the NOS1 gene as being potentially associated with schizophrenia, although the evidence is not conclusive.

To investigate further, Gary Donohue, from St James’s Hospital in Dublin, and colleagues genotyped 349 schizophrenia patients and 230 healthy controls from an Irish sample and 232 patients and 1344 controls from a German sample.

The Irish participants underwent a comprehensive cognitive assessment examining general cognitive functioning, episodic memory, working memory, and attentional control, with the findings correlated with the genotyping analysis, and the procedure repeated in the German sample for comparison.

NOS1 genotypes were not associated with age, gender, years of education, symptom severity ratings, or medication dosage in either the Irish or German samples, the team notes in the Archives of General Psychiatry.

However, analysis showed that carriers of the risk GG allele performed an average of 5–6 standard verbal IQ points below AG and AA carriers. Although patients performed significantly worse than controls, there was no significant interaction between genotype and diagnostic group in either the Irish or German samples. Similar results were seen for performance and full-scale IQ.

Genotype was also found to be significantly associated with verbal working memory, with GG carriers performing an average of 3 scaled score points worse than AA carriers, with the findings replicated for spatial working memory. Again, there was no significant interaction with diagnosis, although patients performed worse than controls.

Interestingly, the results demonstrated that there was no association between NOS1 genotype and either verbal or nonverbal memory, or between genotype and attentional control, and the associations were consequently not tested in the German sample.

The team writes: “The present data do not provide evidence one way or another for association between NOS1 and schizophrenia.”

They add: “One interpretation of these findings is in terms of cognitive reserve – the idea that individuals with lower IQ are more vulnerable to or more likely to express the features of neurodevelopmental, neurodegenerative, or acquired brain injury.”

MedWire ( is an independent clinical news service provided by Current Medicine Group, a trading division of Springer Healthcare Limited. © Springer Healthcare Ltd; 2009

By Liam Davenport

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