Insight in schizophrenia shows a genetic signature: evidence from SOX2-OT and PTPRZ1 polymorphisms

Background

Insight in schizophrenia is a multidimensional construct associated with treatment adherence, clinical outcomes, and prognosis. There is limited evidence suggesting that insight may have a genetic basis. However, the contribution of specific genetic polymorphisms to insight and related clinical features remains unclear. This study aimed to investigate the relationship between SOX2-OT rs1479165 and PTPRZ1 rs1206353 polymorphisms and insight, as well as their associations with treatment adherence and clinical symptoms in patients with schizophrenia.

Methods

This cross-sectional study included 150 clinically stable outpatients with schizophrenia (DSM-5; age 18–65 years; CGI-Severity score <4) recruited from a university psychiatry clinic. Patients with neurological disorders, intellectual disability, active mood episodes, substance intoxication, or antipsychotic-related hyperkinetic movement disorders were excluded. Insight was evaluated using the Schedule for Assessing Insight (SAI), the Scale to Assess Unawareness of Mental Disorder (SUMD), and the Beck Cognitive Insight Scale (BCIS). Treatment adherence was assessed with the Drug Attitude Inventory (DAI-10). Clinical symptoms were assessed using the Scale for the Assessment of Positive Symptoms (SAPS) and the Scale for the Assessment of Negative Symptoms (SANS). Clinical variables, including compulsory hospitalizations and time since last exacerbation, were also recorded. Gene polymorphisms were genotyped using polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP) and PCR-based sequencing methods. Genotype groups (T/T, T/C, C/C for SOX2-OT and A/A, A/T, T/T for PTPRZ1) were analyzed individually and as wild-type vs non–wild-type groups. Group comparisons were performed using appropriate parametric or non-parametric tests, followed by correlation and multiple linear regression analyses to examine associations and identify independent predictors of insight.

Results

Significant differences were observed according to SOX2-OT rs1479165 genotype. Patients with the wild-type (T/T) genotype showed poorer clinical insight, with lower SAI and higher SUMD scores (p < 0.05). The T/T group also showed poorer treatment adherence (lower DAI-10 scores, p = 0.041) and more severe disorganization (higher SAPS bizarre behavior scores, p = 0.018) compared to C allele carriers (T/C and C/C combined). Correlation analyses revealed that better clinical insight was associated with better treatment adherence, lower positive and negative symptom severity, fewer compulsory hospitalizations, and longer time since last exacerbation (all p < 0.05). In multiple regression analyses, SOX2-OT rs1479165 polymorphism remained an independent predictor of clinical insight (model p < 0.001). Overall, C allele carriers (T/C and C/C) demonstrated a more favorable clinical profile, including better insight compared to the wild-type (T/T) genotype, suggesting a potential protective effect of C allele carriage. In contrast, PTPRZ1 rs1206353 polymorphism was not associated with clinical or cognitive insight measures.

Conclusions

The findings indicate that the SOX2-OT rs1479165 polymorphism is associated with variation in clinical insight among patients with schizophrenia. The T/T genotype was linked to poorer insight, whereas C allele carriage was associated with better insight, suggesting a potential protective effect of the C allele. Notably, this association was specific to clinical insight and was not observed for cognitive insight. In contrast, PTPRZ1 rs1206353 polymorphism was not associated with insight. These results suggest that insight in schizophrenia may be influenced by genetic mechanisms.

References

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