Introduction Fetal or neonatal hypoxia (FoNH) is a known risk factor for schizophrenia. It has been hypothesized that FoNH induced expression of schizophrenia susceptibility genes (Schmidt-Kastner et al. 2012, Giannopoulou et al. 2018). Objectives To test this hypothesis, we explore the effects of FoNH and some genetic variants on age at onset (AAO) of schizophrenia. Methods The study included 1670 patients (women 1021 (61.1%), mean age 34.6 (SD 13.6), mean age at disease onset 25.4 (10.5) years) with ICD-10 diagnosis of schizophrenia or schizoaffective psychosis. The effects of FoNH in interaction with sex, family history (FH) and genetic variants on AAO of schizophrenia were evaluated. Polymorphisms rs2514218 DRD2 (n=943), Val66Met BDNF (n=820) and VNTR AS3MT (n=804) were genotyped. Results Among all patients studied 179 (10.8%) had experienced FoNH. Regression model showed that FoNH, sex and FH of schizophrenia contribute significantly (p=0.000) to AAO. In the FoNH group, AAO was lower compared to the group without FoNH (20.7 (6.2) vs 25.5 (10.) years). When comparing men and women, there was a difference between FoNH and non- FoNH subgroups only in women (p=0.000). No interaction between FH and FoNH was observed though positive FH had an effect on AAO. There was the interaction effect of VNTR AS3MT and FoNH on AAO. In the FoNH group, carriers of 2 repeats had younger AAO compared to the carriers homozygous for 3 repeat variant (19.6 (4.9) vs 22. (7.6) years). Conclusions We demonstrate the interaction effects of FoNH and VNTR AS3MT polymorphism on AAO of schizophrenia. Disclosure No significant relationships.

Introduction Negative symptoms (NS) are a core feature of schizophrenia. NS show heterogeneity proven by factor analysis, which revealed two distinct negative symptoms subdomains: diminished expression (DE) and avolition/apathy (AA) (Marder et al. 2017, Fleischhacker et al. 2019). Some studies showed the different effects of these subdomains on clinical features of schizophrenia that suggest different pathophysiological mechanisms for their development (Stanculete 2021). It has been also shown that the levels of peripheral interleukins (IL) specifically correlate with NS (Enache et al. 2021), in particular, increased IL levels were determined in patients with deficit syndrome compared to non-deficit schizophrenia (Goldsmith et al. 2018). Objectives To search for the association of genes for IL-4, IL-6, IL-10 and C-reactive protein (CRP) with NS subdomains. Methods The total sample included 551 patients (women 51,4%, aged 18-72 years) with ICD-10 diagnosis of schizophrenia. NS were assessed by PANSS. PANSS-derived factors include AA (items N2, N4, G16) and DE (N1, N3, N6, G5, G7, G13). Genotyping was performed for the following polymorphisms: C-589T IL-4, C-174G IL-6, C-592A IL-10, G-1082A IL-10, CRP (rs2794521). Results There are effects of C-592A IL-10 (p=0.017) and G-1082A IL-10 (p=0.012) on AA subdomain. Post-hoc Bonferroni corrected comparisons show that carriers of the haplotype AA (C-592A)- AA (G-1082A) have the highest AA score. A significant effect of CRP (rs2794521) on AA is identified (p=0.007). There is a trend towards the association of C-589T IL-4 and C-174G IL-6 with AA. No association of these polymorphisms with DE was found. Conclusions AA and DE may have different genetic background. Disclosure No significant relationships.