Gene expression changes associated with trajectories of psychopathology in a longitudinal cohort of children and adolescents

Autor(es):Mostrar menos -

Ota, Vanessa Kiyomi ^{[1, 2, 3, 4]} ; Santoro, Marcos Leite ^{[1, 2, 3, 4]} ; Spindola, Leticia Maria ^{[1, 2, 3]} ; Pan, Pedro Mario ^{[1, 2, 3]} ; Simabucuro, Andressa ^{[1, 2, 4]} ; Xavier, Gabriela ^{[1, 2, 4]} ; Vieira-Fonseca, Tamiris ^{[2, 3, 4]} ; Zanardo, Evelin Aline ^[5] ; Camargo dos Santos, Felipe Rodolfo ^{[6, 7]} ; Schafer, Julia Luiza ^{[1, 8]} ; Kulikowski, Leslie Domenici ^[5] ; Galante, Pedro A. F. ^[7] ; Asprino, Paula Fontes ^[7] ; Brietzke, Elisa ^{[3, 9, 10, 11]} ; Grassi-Oliveira, Rodrigo ^[12] ; Rohde, Luis Augusto ^{[1, 13, 14]} ; Constantino Miguel, Euripedes ^{[1, 15]} ; Gadelha, Ary ^{[1, 2, 3]} ; Mari, Jair Jesus ^{[1, 3]} ; Bressan, Rodrigo Affonseca ^{[1, 2, 3]} ; Salum, Giovanni Abrahao ^{[1, 8]} ; Belangero, Sintia Iole ^{[1, 2, 3, 4]}

Afiliação do(s) autor(es):Mostrar menos -

^[1] Natl Inst Dev Psychiat Children & Adolescents INP, Sao Paulo - Brazil

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

^[3] Univ Fed Sao Paulo, Postgrad Program Psychiat & Med Psychol, Sao Paulo - Brazil

^[4] Univ Fed Sao Paulo, Genet Div, Dept Morphol & Genet, Sao Paulo - Brazil

^[5] Univ Sao Paulo, Fac Med, Dept Patol, Lab Citogenom, Sao Paulo - Brazil

^[6] Univ Sao Paulo, Sao Paulo - Brazil

^[7] Hosp Sirio Libanes, Ctr Oncol Mol, Sao Paulo - Brazil

^[8] Univ Fed Rio Grande do Sul, Hosp Clin Porto Alegre, Dept Psychiat, Porto Alegre, RS - Brazil

^[9] Queens Univ, Kingston Gen Hosp, Kingston, ON - Canada

^[10] Queens Univ, Providence Care Hosp, Sch Med, Dept Psychiat, Kingston, ON - Canada

^[11] Queens Univ, CNS, Kingston, ON - Canada

^[12] Pontificia Univ Catolica Rio Grande do Sul, Sch Med, Brain Inst InsCer, Med & Med Sci Grad Program, Porto Alegre, RS - Brazil

^[13] Univ Fed Rio Grande do Sul, Hosp Clin Porto Alegre, Lab TDAH, Porto Alegre, RS - Brazil

^[14] Univ Fed Rio Grande do Sul, Hosp Clin Porto Alegre, Lab Psiquiatria Desenvolvimento, Porto Alegre, RS - Brazil

^[15] FMUSP, Dept Psychiat, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: TRANSLATIONAL PSYCHIATRY; v. 10, n. 1 MAR 17 2020.
• Citações Web of Science: 0

Resumo

We aimed to identify blood gene expression patterns associated to psychopathological trajectories retrieved from a large community, focusing on the emergence and remission of general psychiatric symptoms. Hundred and three individuals from the Brazilian High-Risk Cohort Study (BHRCS) for mental disorders were classified in four groups according to Child Behavior Checklist (CBCL) total score at the baseline (w0) and after 3 years (w1): low-high (L-H) (N = 27), high-low (H-L) (N = 12), high-high (H-H) (N = 34) and low-low (L-L) groups (N = 30). Blood gene expression profile was measured using Illumina HT-12 Beadchips, and paired analyses comparing w0 and w1 were performed for each group. Results: 98 transcripts were differentially expressed comparing w0 and w1 in the L-H, 33 in the H-L, 177 in the H-H and 273 in the L-L. Of these, 66 transcripts were differentially expressed exclusively in the L-H; and 6 only in the H-L. Cross-Lagged Panel Models analyses revealed that RPRD2 gene expression at w1 might be influenced by the CBCL score at w0. Moreover, COX5B, SEC62, and NDUFA2 were validated with another technique and were also differentially regulated in postmortem brain of subjects with mental disorders, indicating that they might be important not only to specific disorders, but also to general psychopathology and symptoms trajectories. Whereas genes related to metabolic pathways seem to be associated with the emergence of psychiatric symptoms, mitochondrial inner membrane genes might be important over the course of normal development. These results suggest that changes in gene expression can be detected in blood in different psychopathological trajectories. (AU)

• 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: 08/57896-8 - O Instituto Nacional da Psiquiatria do Desenvolvimento: uma nova abordagem para a psiquiatria tendo como foco as nossas crianças e o seu futuro
• Beneficiário: Eurípedes Constantino Miguel Filho
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 14/50917-0 - INCT 2014: psiquiatria do desenvolvimento para crianças e adolescentes
• Beneficiário: Eurípedes Constantino Miguel Filho
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• 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: 17/05339-7 - Caracterização do perfil de expressão gênica em crianças e adolescentes em risco para transtornos mentais
• Beneficiário: Vanessa Kiyomi Ota Kuniyoshi
• Modalidade de apoio: Auxílio à Pesquisa - Regular