A comparative study of theory of mind in taxon-like clusters of psychometric schizotypes and individuals at genetic risk for schizophrenia.

Introduction: Clinical and family studies suggest that alterations of theory of mind (ToM) represent a marker of genetic liability to schizophrenia. Findings regarding ToM in schizotypy are less consistent. The study aimed to explore whether this might be due to an insufficient account of the heterogeneity of schizotypy in prior research and/or the fact that in psychometric schizotypy ToM alterations could manifest as subtle peculiarities rather than overt errors of mentalising.Methods: Individuals without a family history of psychosis (n = 150) were assigned to low, positive, negative, and high mixed schizotypy classes based on a cluster analysis of 1322 subjects who completed the Schizotypal Personality Questionnaire. The classes were compared on their performance of faux pas tasks with 77 adult first-degree relatives of schizophrenia patients, who represent individuals at genetic risk for schizophrenia. Besides overt errors, subtle alterations in ToM were analysed using expert judgment.Results: The relatives tended to make overt errors and demonstrated specific features of intentional reasoning. None of the schizotypal classes showed similar trends.Conclusions: The results complement the literature on the subjective-objective disjunction in psychometric schizotypes and did not provide evidence that ToM anomalies are a marker of genetic liability to schizophrenia in this cohort.

A study of the association between polymorphisms in the genes for interleukins IL-6 and IL-10 and negative symptoms subdomains in schizophrenia.

Background: Schizophrenia is a severe mental illness manifested by various symptoms. Negative symptoms (NS) are associated with disability and poor function of patients. The study of NS neurobiology is complicated by their heterogeneity. Factor analysis revealed two distinct NS subdomains with different pathophysiological mechanisms: volitional pathology, including avolition and apathy (AA), and diminished expression (DE). Inflammation is one mechanism that may underlie NS, including their heterogeneity. Aims: To search for the association between genes for interleukins (IL-6 -174 G/C, IL-10 -592 C/A, and IL-10 -1082 G/A) and NS subdomains. Materials and Methods: The study included 275 patients with schizophrenia. NS factors were calculated based on the Positive and Negative Syndromes Scale. Results: There was a significant main effect of IL-10 polymorphisms on the AA, but not the DE subdomain. Mean score on the AA subdomain was higher in the IL-10 -592 AA compared to the CC genotype. Differences between IL-10 -1082 G/A genotypes were dose dependent. The lowest score was observed for the IL-10 -1082 GG genotype. The association between the IL-6 -174 G/C polymorphism and AA scores was close to the level of significance. Patients with the IL-6 -174 GG genotype had higher score compared to the AA genotype. Conclusion: The results provide further neurobiological evidence for the validity of the NS factor categorization. An imbalance between pro-inflammatory and anti-inflammatory cytokines because of genetic variations is associated with the AA NS subdomain that is supposed to be a more severe aspect of psychopathology compared to the DE.

A Role of DNA Methylation within the CYP17A1 Gene in the Association of Genetic and Environmental Risk Factors with Stress-Related Manifestations of Schizophrenia.

As genetic and environmental influences on schizophrenia might converge on DNA methylation (DNAm) within loci which are both associated with the disease and implicated in response to environmental stress, we examined whether DNAm within CYP17A1, a hypothalamus-pituitary-adrenal axis gene which is situated within the schizophrenia risk locus 10q24.32, would mediate genetic and environmental effects on stress-related schizophrenia symptoms. DNAm within an exonic-intronic fragment of CYP17A1 was assessed in the blood of 66 schizophrenia patients and 63 controls using single-molecule real-time bisulfite sequencing. Additionally, the VNTR polymorphism of the AS3MT gene, a plausible causal variant within the 10q24.32 locus, was genotyped in extended patient and control samples (n = 700). The effects of local haplotype, VNTR and a polyenviromic risk score (PERS) on DNAm, episodic verbal memory, executive functions, depression, and suicidality of patients were assessed. Haplotype and PERS differentially influenced DNAm at four variably methylated sites identified within the fragment, with stochastic, additive, and allele-specific effects being found. An allele-specific DNAm at CpG-SNP rs3781286 mediated the relationship between the local haplotype and verbal fluency. Our findings do not confirm that the interrogated DNA fragment is a place where genetic and environmental risk factors converge to influence schizophrenia symptoms through DNAm.