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

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.

SUBMITTER: Ota VK

PROVIDER: S-EPMC7078305 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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

Ota Vanessa Kiyomi VK Santoro Marcos Leite ML Spindola Leticia Maria LM Pan Pedro Mario PM Simabucuro Andressa A Xavier Gabriela G Vieira-Fonseca Tamiris T Zanardo Evelin Aline EA Dos Santos Felipe Rodolfo Camargo FRC Schäfer Julia Luiza JL Kulikowski Leslie Domenici LD Galante Pedro A F PAF Asprino Paula Fontes PF Brietzke Elisa E Grassi-Oliveira Rodrigo R Rohde Luis Augusto LA Miguel Euripedes Constantino EC Gadelha Ary A Mari Jair Jesus JJ Bressan Rodrigo Affonseca RA Salum Giovanni Abrahao GA Belangero Sintia Iole SI

Translational psychiatry 20200317 1

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 ( ...[more]

PMID: 32184383

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Project description:Aim: Long-term outcome data in preterm children is often limited to cross-sectional measurement of neurodevelopmental impairment (NDI) at the corrected age of 24-36 months. However, impairments may only become overt during childhood or resolve with time, and individual trajectories in outcome over time may vary. The primary aim of this study was to describe NDI in very preterm born children at three subsequent ages of 2, 5, and 8 years of age. As a secondary aim, a longitudinal analysis was performed on the individual longitudinal trajectories in NDI from 2 to 8 years of age. Methods: Single-center prospective cohort study including children born between 1990 and 2011 below 30 weeks' gestation and followed into 2019. The outcome measurement was NDI assessed at 2, 5, and 8 years of age. NDI is a composite score that includes cognitive, neurological, visual, and auditory functions, in which problems were categorized as none, mild, moderate, or severe. Cognitive function measured as total DQ/IQ score was assessed by standardized psychometric tests. Neurological, visual, and auditory functions were assessed by the neonatologist. Results: In total, 921 children were eligible for follow-up, of whom 726 (79%) children were assessed. No NDI was seen in 54, 54, and 62%, mild NDI was seen in 31, 36, and 30%, and moderate-to-severe NDI was seen in 15, 9.2, and 8.6% of the children at 2, 5, and 8 years, respectively. From 2 to 8 years, 63% of the children remained in the same NDI category, 20% of the children improved to a better NDI category, and 17% deteriorated toward a worse NDI category. No differences were found in baseline characteristics of infants that improved or deteriorated. Extreme prematurity, male gender and low parental education were associated with worse NDI status at all time points. Although we observed considerable individual variation over time in NDI status, the course of the trajectories in NDI were not associated with gestation, gender, and parental education. Conclusions: Continued follow-up until school life is essential in order to provide optimal and individually focused referrals and care when needed.

Dataset Information

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

Publications

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

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