Polymorphic variants in the cluster of genes encoding trace amine receptors and cognitive functioning in patients with schizophrenia spectrum disorders and healthy controls

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OBJECTIVE

To evaluate the association of polymorphisms in the TAAR1—9 gene cluster on chromosome 6 with cognitive functions in patients with schizophrenia spectrum disorders and healthy controls.

MATERIAL AND METHODS

Patients with schizophrenia spectrum disorders (n=216) and healthy people without a family history of mental disorders (n=240) completed a battery of cognitive tests, from which individual indices of cognitive functioning were derived. Associations of the cognitive index with 22 polymorphisms in the TAAR genes were assessed using ANCOVA controlling for sex, age, genetic structure of the sample, and polygenic risk scores of schizophrenia and intelligence.

RESULTS

An interaction effect between group and genotype on the cognitive index was found at the rs3813355 site in the TAAR5 gene (F=6.68; p=0.010; η²_p=0.02). A post hoc analysis revealed genotype-related differences in the patient group. Homozygotes for the common A allele had a milder cognitive deficit than carriers of the minor G allele (t=2.75; p=0.032; Cohen’s d=0.38). The effect of genotype on cognitive index remained significant after the inclusion of disease duration and negative symptoms in the model (F=7.99; p=0.005; η²_p=0.04). Of the individual cognitive indicators, associations with genotype were found for working memory and attention (F=8.25; p=0.005; η²p=0.05), cognitive flexibility (F=5.82; p=0.017; η²_p=0.05) and verbal episodic memory (F=6.75; p=0.011; η²_p=0.05).

CONCLUSION

The results are consistent with the assumption of the role of the TAAR5 genetic polymorphism in the variability of cognitive deficits in patients with schizophrenia.

Keywords:

genes

polymorphism

trace amines

TAAR

cognitive deficit

schizophrenia

Authors:

Alfimova M.V.

Mental Health Research Center;
Alexeev Mental Health Clinic No. 1 Moscow Healthcare Department

ORCID: 0000-0003-0155-8412

Plakunova V.V.

Mental Health Research Center

ORCID: 0000-0001-8690-5422

Lezheiko T.V.

Mental Health Research Center

ORCID: 0000-0002-7873-2039

Golimbet V.E.

Mental Health Research Center;
Alexeev Mental Health Clinic No. 1 Moscow Healthcare Department

ORCID: 0000-0002-9960-7114

Received:

09.01.2024

Accepted:

04.06.2024

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