DOES POLYGENIC RISK SCORE FOR SCHIZOPHRENIA IMPACT ON JUMPING TO CONCLUSIONS? PRELIMINARY FINDINGS FROM THE EU-GEI CASE-CONTROL STUDY

Abstract

Background: Jumping to conclusions (JTC) is a reasoning and data gathering bias that results in the tendency to require less evidence and make hasty decisions. Preliminary work on reasoning bias focused primarily on the association with delusions, although jumping to conclusions has also been found in non-deluded schizophrenia (SZ) patients. Literature to date has shown JTC as a well-established bias in psychosis even at First Episode Psychosis (FEP), after remission, and in individuals with at risk mental state. Furthermore, JTC has been found to be associated with proneness to psychotic-like experiences in the general population. In teresting findings showed also an association with lower cognitive functioning in psychotic patients, and some degree of stability of JTC over the course of illness. Overall, findings to date could suggest a shared genetic liability between the occurrence of JTC and psychosis. The present study aims to investigate in a sample of FEP and healthy controls: 1) environment, cognitive, and clinical factors associated with JTC bias 2) whether the addition of SZ Polygenic Risk Score (PRS) explains any further variance in the model. Methods: We analyzed data on JTC (Beads task 60:40) in a sample of 503 FEP and 959 population controls for which genetic information was available, recruited as part as the EU-GEI study across UK, Netherlands, France, Spain, Italy and Brazil. In the first step, logistic regressions have been performed to predict JTC respectively in cases and controls considering as covariates: age, gender, level of education, IQ, country, frequency of cannabis use, population density, positive symptoms, and 20 principal components (PCs) for population stratification. In the second step, we estimated a model adding SZ PRS to the aforementioned terms. Results: Individuals coming from Brazil were about 6 times more likely to jump to conclusions in case group (OR=6.69; CI 95%=2.23-20.06; p=0.001) and around 5 times among controls (OR=4.76; CI 95%=2.28-9.93; p<0.001). Likewise, age and low IQ were found to be associated with JTC in both cases (age: OR=1.04; CI 95%=1.02-1.06; p<0.001. IQ: OR=0.98; CI 95%=0.94-0.98; p<0.001) and controls (age: OR=1.04; CI 95%=1.02-1.05; p<0.001. IQ: OR=0.96; CI 95%=0.95-0.97; p<0.001), although a small effect size was observed. A similar trend was detected regarding the association with increased positive symptoms in cases (OR=1.27; CI 95%=1.02-1.57; p=0.02), whereas controls presenting higher level of psychotic-like experiences showed about a 3-fold risk to jump to conclusions (OR=2.6; CI 95%=1.12- 6.02; p=0.02). In addition, being female resulted as significant predictor in cases only (OR=1.87; CI 95%=1.16-3.01; p=0.009). Finally, PRS for schizophrenia seemed not to be associated with jumping to conclusions in both groups, therefore it does not add any variance explained in the abovementioned model (Cases: R2=0.27; Controls: R2=0.22). Discussion: This study suggests that the occurrence of jumping to conclusions cannot be explained by schizophrenia genetic underpinnings using polygenic risk score strategy. However, these preliminary results identified interesting environment, cognitive, and clinical factors associated with JTC bias.