Polygenic Risk Score associated with specific symptom dimensions in first-episode psychosis

Recent Genome-Wide Association Studies (GWAS) have provided evidence for the involvement of a number of genetic variants in schizophrenia (SCZ). The objective of the current study was to examine the association between these variants and symptom dimensions, evaluated prospectively over a period of 24months, in a clinically well-characterized sample of individuals (n=241) with first-episode psychosis (FEP). The genetic variants were analyzed collectively as captured through a Polygenic Risk Score (PRS), calculated for each individual. At each evaluation time point (baseline, 1, 2, 6 and 24months), correlation analysis was conducted with PRS and symptom dimension scores assessed by the Positive and Negative Syndrome Scale (PANSS). We also examined the association of PRS with global symptom rating, depression, anxiety, social and occupational functioning as measured by widely used and well validated scales. At baseline, significant positive correlation was observed between PRS and the general psychopathology dimension of the PANSS but no associations were observed with the positive or negative symptom dimensions. Anxiety, assessed using the Hamilton Anxiety Rating Scale, was also significantly correlated with the PRS. No significant correlation was observed with other symptom dimensions or with the PANSS score at the later evaluations. These results provide novel evidence of an association between general psychopathology and PRS in young people with first episode psychosis. They also demonstrate that it is important to note the dynamic changes of symptoms over time when trying to refine the relationship between genetic factors and phenotypes.