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

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Santoro, Marcos Leite ^{[1, 2]} ; Ota, Vanessa ^{[1, 2]} ; de Jong, Simone ^[3] ; Noto, Cristiano ^{[4, 5]} ; Spindola, Leticia M. ^{[4, 2]} ; Talarico, Fernanda ^{[4, 2]} ; Gouyea, Eduardo ^{[4, 5]} ; Lee, Sang Hyuck ^{[3, 6, 7]} ; Moretti, Patricia ^{[4, 2]} ; Curtis, Charles ^{[3, 6, 7]} ; Patel, Hamel ^{[3, 6, 7]} ; Newhouse, Stephen ^{[3, 6, 7]} ; Caryalho, Carolina Muniz ^{[4, 2]} ; Gadelha, Ary ^{[4, 2]} ; Cordeire, Quirino ^{[4, 5]} ; Bressan, Rodrigo Affonseca ^{[4, 2]} ; Belangero, Sintia Iole ^{[4, 1, 2]} ; Breen, Gerome ^{[3, 6, 7]}

Afiliação do(s) autor(es)

^[1] Fed Univ Sao Paulo UNIFESP, Genet Div, Sao Paulo, SP - Brazil

^[2] Fed Univ Sao Paulo UNIFESP, Interdisciplinary Lab Clin Neurosci, Sao Paulo, SP - Brazil

^[3] Kings Coll London, Inst Psychiat Psychol & Neurosci, Social Genet & Dev Psychiat Ctr SGDP, London - England

^[4] Fed Univ Sao Paulo UNIFESP, Dept Psychiat, Sao Paulo, SP - Brazil

^[5] Santa Casa de Misericordia sao Paulo, CAISM, Sao Paulo, SP - Brazil

^[6] South London & Maudsley NHS Trust, NIHR Maudsley Biomed Res Ctr, London SE5 8AF - England

^[7] Kings Coll London, London SE5 8AF - England

• Tipo de documento: Artigo Científico
• Fonte: TRANSLATIONAL PSYCHIATRY; v. 8, AUG 31 2018.
• Citações Web of Science: 6

Resumo

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. (AU)

• Processo FAPESP: 14/50830-2 - Biomarcadores genéticos em pacientes com psicose virgens de tratamento
• Beneficiário: Rodrigo Affonseca Bressan
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 14/07280-1 - Busca por marcadores genéticos de risco, de progressão e de reposta ao tratamento na esquizofrenia
• Beneficiário: Síntia Iole Nogueira Belangero
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 14/22223-4 - Análise de expressão gênica e metilação de DNA em pacientes em primeiro episódio psicótico virgens de tratamento com antipsicótico
• Beneficiário: Marcos Leite Santoro
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Doutorado
• Processo FAPESP: 12/12686-1 - Busca por potenciais marcadores genéticos nas fases iniciais da esquizofrenia
• Beneficiário: Marcos Leite Santoro
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 10/08968-6 - Investigação de marcadores genéticos e epigenéticos: uma abordagem translacional para o tratamento de esquizofrenia
• Beneficiário: Síntia Iole Nogueira Belangero
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 16/13737-0 - Análise do escore poligênico e caracterização do perfil de expressão gênica em crianças e adolescentes em risco para transtornos psiquiátricos
• Beneficiário: Marcos Leite Santoro
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 16/04983-7 - Neuroimagem, genômica, transcriptômica e epigenômica: conduzindo análises em larga escala em direção a um modelo integrativo de transtornos mentais
• Beneficiário: Jair de Jesus Mari
• Modalidade de apoio: Auxílio à Pesquisa - Programa eScience e Data Science - Regular
• Processo FAPESP: 11/50740-5 - Prevenção na esquizofrenia e no transtorno bipolar da neurociência à comunidade: uma plataforma multifásica, multimodal e translacional para investigação e intervenção
• Beneficiário: Rodrigo Affonseca Bressan
• Modalidade de apoio: Auxílio à Pesquisa - Temático