Objective. To assess associations between polymorphic sites in the TAAR1–9 gene cluster on chromosome 6 and cognitive functions in patients with schizophrenia spectrum disorders and healthy controls. Materials and methods. Patients with schizophrenia spectrum disorders (n = 216) and healthy controls without any family history of mental disorders (n = 240) completed a battery of cognitive tests, which were used to calculate individual indexes of cognitive functioning. Associations between the cognitive index and 22 polymorphic sites in the TAAR genes were assessed by analysis of covariance, controlling for gender, age, the genetic structure of the sample, and polygenic risk scores for schizophrenia and intelligence. Results. A group/genotype interaction at the rs3813355 site in the TAAR5 gene was found to influence the cognitive index (F = 6.68; p = 0.010; <InlineEquation ID="IEq1"> <InlineMediaObject> <ImageObject Color="BlackWhite" FileRef="11055_2025_1798_Article_IEq1.gif" Format="GIF" Height="22" Rendition="HTML" Resolution="72" Type="Linedraw" Width="18" /> </InlineMediaObject> <EquationSource Format="TEX">${\eta }_{\text{p}}^{2}$</EquationSource> <EquationSource Format="MATHML"><math> <msubsup> <mi>η</mi> <mrow> <mtext>p</mtext> </mrow> <mn>2</mn> </msubsup> </math></EquationSource> </InlineEquation> = 0.02). Post hoc analysis revealed genotype-related differences in the patients group. Homozygotes for the common A allele had less 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 the cognitive index remained significant when additionally controlling for disease duration and negative symptoms (F = 7.99; p = 0.005; <InlineEquation ID="IEq2"> <InlineMediaObject> <ImageObject Color="BlackWhite" FileRef="11055_2025_1798_Article_IEq1.gif" Format="GIF" Height="22" Rendition="HTML" Resolution="72" Type="Linedraw" Width="18" /> </InlineMediaObject> <EquationSource Format="TEX">${\eta }_{\text{p}}^{2}$</EquationSource> <EquationSource Format="MATHML"><math> <msubsup> <mi>η</mi> <mrow> <mtext>p</mtext> </mrow> <mn>2</mn> </msubsup> </math></EquationSource> </InlineEquation> = 0.04). Of the individual cognitive indexes, associations with genotype were found for working memory and attention (F = 8.25; p = 0.005; <InlineEquation ID="IEq3"> <InlineMediaObject> <ImageObject Color="BlackWhite" FileRef="11055_2025_1798_Article_IEq1.gif" Format="GIF" Height="22" Rendition="HTML" Resolution="72" Type="Linedraw" Width="18" /> </InlineMediaObject> <EquationSource Format="TEX">${\eta }_{\text{p}}^{2}$</EquationSource> <EquationSource Format="MATHML"><math> <msubsup> <mi>η</mi> <mrow> <mtext>p</mtext> </mrow> <mn>2</mn> </msubsup> </math></EquationSource> </InlineEquation> = 0.05), cognitive flexibility (F = 5.82; p = 0.017; <InlineEquation ID="IEq4"> <InlineMediaObject> <ImageObject Color="BlackWhite" FileRef="11055_2025_1798_Article_IEq1.gif" Format="GIF" Height="22" Rendition="HTML" Resolution="72" Type="Linedraw" Width="18" /> </InlineMediaObject> <EquationSource Format="TEX">${\eta }_{\text{p}}^{2}$</EquationSource> <EquationSource Format="MATHML"><math> <msubsup> <mi>η</mi> <mrow> <mtext>p</mtext> </mrow> <mn>2</mn> </msubsup> </math></EquationSource> </InlineEquation> = 0.05), and auditory verbal episodic memory (F = 6.75; p = 0.011; <InlineEquation ID="IEq5"> <InlineMediaObject> <ImageObject Color="BlackWhite" FileRef="11055_2025_1798_Article_IEq1.gif" Format="GIF" Height="22" Rendition="HTML" Resolution="72" Type="Linedraw" Width="18" /> </InlineMediaObject> <EquationSource Format="TEX">${\eta }_{\text{p}}^{2}$</EquationSource> <EquationSource Format="MATHML"><math> <msubsup> <mi>η</mi> <mrow> <mtext>p</mtext> </mrow> <mn>2</mn> </msubsup> </math></EquationSource> </InlineEquation> = 0.05). Conclusions. The results obtained here are consistent with the hypothesis that genetic polymorphism of the TAAR5 gene has a role in the variability of cognitive deficit in patients with schizophrenia.

Polymorphic Variants in the Cluster of Genes Encoding Trace Amine Receptors and Cognitive Functioning in Patients with Schizophrenia Spectrum Disorders and Healthy Controls

期刊论文
发表日期：

2025年3月1日

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M. V. Alfimova,
V. V. Plakunova,
T. V. Lezheiko,
V. E. Golimbet

摘要

Objective. To assess associations between polymorphic sites in the TAAR1–9 gene cluster on chromosome 6 and cognitive functions in patients with schizophrenia spectrum disorders and healthy controls. Materials and methods. Patients with schizophrenia spectrum disorders (n = 216) and healthy controls without any family history of mental disorders (n = 240) completed a battery of cognitive tests, which were used to calculate individual indexes of cognitive functioning. Associations between the cognitive index and 22 polymorphic sites in the TAAR genes were assessed by analysis of covariance, controlling for gender, age, the genetic structure of the sample, and polygenic risk scores for schizophrenia and intelligence. Results. A group/genotype interaction at the rs3813355 site in the TAAR5 gene was found to influence the cognitive index (F = 6.68; p = 0.010; ${\eta }_{\text{p}}^{2}$ $η_{p}^{2}$ = 0.02). Post hoc analysis revealed genotype-related differences in the patients group. Homozygotes for the common A allele had less 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 the cognitive index remained significant when additionally controlling for disease duration and negative symptoms (F = 7.99; p = 0.005; ${\eta }_{\text{p}}^{2}$ $η_{p}^{2}$ = 0.04). Of the individual cognitive indexes, associations with genotype were found for working memory and attention (F = 8.25; p = 0.005; ${\eta }_{\text{p}}^{2}$ $η_{p}^{2}$ = 0.05), cognitive flexibility (F = 5.82; p = 0.017; ${\eta }_{\text{p}}^{2}$ $η_{p}^{2}$ = 0.05), and auditory verbal episodic memory (F = 6.75; p = 0.011; ${\eta }_{\text{p}}^{2}$ $η_{p}^{2}$ = 0.05). Conclusions. The results obtained here are consistent with the hypothesis that genetic polymorphism of the TAAR5 gene has a role in the variability of cognitive deficit in patients with schizophrenia.