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21-07-2010 | Mental health | Article

Psychosis susceptibility gene linked to patients with spared cognition


Free abstract

MedWire News: A variant of the Zinc Finger Protein 804A gene (ZNF804A) is implicated in schizophrenia susceptibility, but its association may be specific to individuals with relatively spared cognitive ability, study findings show.

"Given the heterogeneity of the schizophrenia syndrome and the fact that it is possible to be schizophrenic and cognitively intact, it is perhaps to be expected that not all identified susceptibility genes will have detrimental effects on broad cognitive abilities," say Gary Donohoe, from St James's Hospital in Dublin, Ireland, and colleagues.

The researchers looked at the association between the identified risk allele at the disease-associated single nucleotide polymorphism rs1344706 of the ZNF804A gene and neuropsycological performance in individuals with and without schizophrenia.

They first studied an Irish population comprising 297 schizophrenia patients and 165 controls, and then tested significant findings in this population in a German replication sample of 251 patients with schizophrenia and 1472 controls.

As expected, the schizophrenic patients performed significantly worse than controls on each of the four cognitive domains - IQ, working memory, episodic memory, and attention.

Comparisons in the Irish sample also showed a significant interaction between ZNF804A genotype and variation in working memory tasks among schizophrenia patients but not controls.

This genotype explained 2.8% of variance in verbal working memory in the patients and 4.4% of variance in spatial working memory.

Notably, patients who were homozygous for the A risk allele performed significantly better on both tasks than patients who were CC homozygous.

There was also a significant association between the ZNF804A genotype and verbal episodic memory in patients but not controls, explaining 2.7% of variance in immediate logical memory scores and 1.1% of variance in delayed verbal memory scores.

These differences were driven by AA and AC risk allele carriers performing significantly better than homozygous non-risk carriers (CC).

Attention, however, was not affected by the ZNF804A genotype.

These findings were replicated in the German sample of patients, and the researchers note that when patients with a low IQ were excluded, the association between ZNF804A and schizophrenia strengthened in both samples.

For example, in the Irish sample, the odds ratio for the allelic association between ZNF804A and schizophrenia increased from 1.37 in all patients to 2.29 in patients whose IQ approached 90 (the range for normal IQ).

"The present data suggest that ZNF804A is indexing a psychosis pathway defined by cognitive rather than diagnostic characteristics," say Donohoe et al in the Archives of General Psychiatry.

"If confirmed, defining the molecular etiology involved in this group may have important diagnostic, prognostic, and therapeutic implications."

MedWire ( is an independent clinical news service provided by Current Medicine Group, a trading division of Springer Healthcare Limited. © Springer Healthcare Ltd; 2010

By Lucy Piper

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