In this study, we aimed to test if the schizophrenia (SCZ) polygenic risk score (PRS) was associated with clinical symptoms in (a) the first episode of psychosis pre-treatment (FEP), (b) at nine weeks after initiation of risperidone treatment (FEP-9W) and (c) with the response to risperidone. We performed a detailed clinical assessment of 60 FEP patients who were antipsychotic-naive and, again, after nine weeks of standardized treatment with risperidone. After blood collection and DNA isolation, the samples were genotyped using the Illumina PsychArrayChip and then imputed. To calculate PRS, we used the latest available GWAS summary statistics from the Psychiatric Genomics Consortium wave-2 SCZ group as a training set. We used Poisson regression to test association between PRS and clinical measurements correcting for the four principal components (genotyping). We considered a p-value < 0.0014 (Bonferroni correction) as significant. First, we verified that the schizophrenia PRS was also able to distinguish cases from controls in this south-eastern Brazilian sample, with a similar variance explained to that seen in Northern European populations. In addition, within-cases analyses, we found that PRS is significantly correlated with baseline (pre-treatment) symptoms, as measured by lower clinical global assessment of functioning (−GAF), higher depressive symptoms and higher scores on a derived excitement factor. After standardized treatment for nine weeks, the correlation with GAF and the excitement factor disappeared while depressive symptoms became negatively associated with PRS. We conclude that drug (and other treatments) may confound attempts to understand the aetiological influence on symptomatology of polygenic risk scores. These results highlight the importance of studying schizophrenia, and other disorders, pre-treatment to understand the relationship between polygenic risk and phenotypic features.
The Carleton University Responsiveness to Suggestion Scale (CURSS) yields scores on three suggestibility dimensions. Objective (CURSS:0) scores and subjective (CURSS:S) scores reflect overt and experiential response to suggestion, respectively. Objective-Involuntariness (CURSS:OI) scores indicate the number of objective responses rated as feeling involuntary. Study 1 indicated that all three suggestibility dimensions correlated significantly with the Harvard Group Scale of Hypnotic Susceptibility, and Study 2 showed the three Catleton suggestibility dimensions correlated significantly with Form C of the Stanford Hypnotic Susceptibility Scale. The majority of subjects who obtained high scores on the Stanford:C also scored high on the Carleton suggestibility dimensions. Like the Harvard:A and Stanford:C the three Carleton suggestibility dimensions also correlated significantly with attitude/expectancy measures, absorption, and Field's (1965) “hypnotic experiences” inventory. CURSS:VC (voluntary-cooperation) scores reflect the number of objective responses rated as feeling primarily voluntary rather than involuntary. CURSS:VC scores did not correlate significantly with attitude/expectancy variables, absorption or “hypnotic experiences.” Theoretical implications are discussed.
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