Format

Send to

Choose Destination
  • Filters activated: Field: Title Word. Clear all
Transl Psychiatry. 2018 Aug 31;8(1):174. doi: 10.1038/s41398-018-0230-7.

Polygenic risk score analyses of symptoms and treatment response in an antipsychotic-naive first episode of psychosis cohort.

Author information

1
Genetics Division, Federal University of São Paulo (UNIFESP), São Paulo, SP, Brazil.
2
Interdisciplinary Laboratory of Clinical Neurosciences, Federal University of São Paulo (UNIFESP), São Paulo, SP, Brazil.
3
Social, Genetics & Developmental Psychiatry Centre (SGDP), Institute of Psychiatry, Psychology and Neuroscience at King's College London, London, UK.
4
Department of Psychiatry, Federal University of São Paulo (UNIFESP), São Paulo, SP, Brazil.
5
Centro de Atendimento Integrado em Saúde Mental (CAISM), Santa Casa de Misericórdia de São Paulo, São Paulo, SP, Brazil.
6
NIHR Maudsley Biomedical Research Centre, South London and Maudsley NHS Trust & King's College London, London, SE5 8AF, UK.
7
Social, Genetics & Developmental Psychiatry Centre (SGDP), Institute of Psychiatry, Psychology and Neuroscience at King's College London, London, UK. gerome.breen@gmail.com.
8
NIHR Maudsley Biomedical Research Centre, South London and Maudsley NHS Trust & King's College London, London, SE5 8AF, UK. gerome.breen@gmail.com.

Abstract

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.

PMID:
30171181
PMCID:
PMC6119191
DOI:
10.1038/s41398-018-0230-7
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center