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

Author(s):Show less -

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]}

Affiliation:Show less -

^[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

• Document type: Journal article
• Source: TRANSLATIONAL PSYCHIATRY; v. 10, n. 1 MAR 17 2020.
• Web of Science Citations: 0

Abstract

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)

• FAPESP's process: 16/04983-7 - Neuroimaging, genomics, transcriptomics and epigenomics: dealing with big data toward an integrative model of mental disorders
• Grantee: Jair de Jesus Mari
• Support type: Research Grants - eScience and Data Science Program - Regular Program Grants
• FAPESP's process: 08/57896-8 - National Institute for Developmental Psychiatry
• Grantee: Eurípedes Constantino Miguel Filho
• Support type: Research Projects - Thematic Grants
• FAPESP's process: 14/50917-0 - INCT 2014: developmental psychiatry for children and adolescents
• Grantee: Eurípedes Constantino Miguel Filho
• Support type: Research Projects - Thematic Grants
• FAPESP's process: 14/07280-1 - Search for genetic markers of risk, progression and response to treatment
• Grantee: Síntia Iole Nogueira Belangero
• Support type: Regular Research Grants
• FAPESP's process: 17/05339-7 - Characterization of gene expression profiles in children and adolescents at risk for mental disorders
• Grantee: Vanessa Kiyomi Ota Kuniyoshi
• Support type: Regular Research Grants