Earlier studies have shown that candidate gene risk polymorphisms and psychoactive substance abuse influence the frequency and severity of psychosis.

In this study we examined whether the most studied schizophrenia risk polymorphisms and psychoactive substance abuse interact in their influence on symptom severity and neurocognition.

We analyzed the clinical data of 280 schizophrenia patients, including genotyping data of the candidate genes NRG1, DTNBP1, RGS4, G72/G30 and PIP5K2A. Patients were assessed clinically by the Positive and Negative Symptom Scale (PANSS) and information about substance abuse was based on self-report and reviewing patient charts. We tested for possible interactional effects using the General Linear Model (GLM) analysis.

15,8% of patients reported episodic or regular substance abuse, the vast majority (92%) used cannabis or the combination of cannabis and another drug. Substance abuse was associated with higher scores of the PANSS hostility/excitement factor, independent of sex, age, or genetic results (F = 4,02;p = 0,04). We found significant interactional effects of the DTNBP1 gene risk polymorphisms and substance abuse on different PANSS factors: rs2619528 and positive substance abuse interaction were associated with higher scores on the PANSS negative factor (F = 4,6;p = 0,03), and the PANSS depression factor (F = 4,75;p = 0,03). Moreover the rs3213207 - substance abuse interaction was associated with higher scores on the PANSS cognitive factor (F = 7,55;p = 0,006). Carriers of the Val allele of the COMT Val158Met polymorphism demonstrated significantly higher scores on the PANSS depression factor (F = 5,53;p = 0,02).

Our results underscore the importance of gene-environment interactions in the phenotypic heterogeneity of schizophrenia.