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Abstract
BackgroundSchizotypal traits are considered as inheritable traits and the endophenotype for schizophrenia. A common variant in the NOTCH4 gene, rs204993, has been linked with schizophrenia, but the neural underpinnings are largely unknown.MethodsIn present study, we compared the differences of brain functions between different genotypes of rs204993 and its relationship with schizotypal traits among 402 Chinese Han healthy volunteers. The brain function was evaluated with functional connectivity strength (FCS) using the resting-state functional magnetic resonance image(rs-fMRI). The schizotypal traits were measured by the schizotypal personality questionnaire (SPQ).ResultsOur results showed that carriers with the AA genotype showed reduced FCS in the left occipital cortex when compared with carriers with the AG and GG genotypes, and the carriers with the AG genotype showed reduced FCS in the left occipital cortex when compared with carriers with the GG genotype. The FCS values in the left occipital lobe were negatively associated with the SPQ scores and its subscale scores within the carriers with the GG genotype, but not within the carriers with AA or AG genotype.ConclusionOur results suggested that the common variant in the NOTCH4 gene, rs204993, modulates the function of the occipital cortex, which may contribute to schizotypal traits. These findings provide insight for genetic effects on schizotypal traits and its potential neural substrate.
Highlights
Schizotypal traits are considered as inheritable traits and the endophenotype for schizophrenia
The AA genotype of rs204993 was associated with a higher risk for schizophrenia in the Chinese Han population [17]. These findings suggested the common variant of the Neurogenic locus notch homolog protein4 (NOTCH4) gene, single nucleotide polymorphisms (SNPs) rs204993 may be a potential genetic basis for schizophrenia in the Chinese population
We aimed to investigate the genetic effect of the schizophrenia-related gene (NOTCH4 rs204993 genotype) on brain function and its relationship with schizotypal traits among healthy volunteers
Summary
Schizotypal traits are considered as inheritable traits and the endophenotype for schizophrenia. A common variant in the NOTCH4 gene, rs204993, has been linked with schizophrenia, but the neural underpinnings are largely unknown. Some individuals present preclinical symptoms of schizophrenia called schizotypal traits [2]. Schizotypal traits refer to a set of traits, continually distributed in the general population, that resemble some of the symptoms of schizophrenia. Schizotypal traits provide important insights into understanding the origins of schizophrenia [3]. Schizotypal traits are more frequent in first-degree relatives of patients with schizophrenia, suggesting a genetic link between schizotypal traits and schizophrenia [5, 6]. The schizophreniarisk gene contributes to the presence of schizotypal traits [7, 8]. The schizophrenia-risk gene may have potential modulatory effects on schizotypal traits
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