Early-life stress effects on BDNF DNA methylation in first-episode psychosis and in rats reared in isolation
| Autor: | Camila Marcelino Loureiro, Helene A Fachim, Rosana Shuhama, Caroline F. Dalton, Sri-arun Iamjan, Gavin P. Reynolds, Adrian H. Heald, Cristina Marta Del-Ben, Paulo Rossi Menezes, Samia R. L. Joca, Fabiana Corsi-Zuelli, Paulo Louzada-Junior |
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| Rok vydání: | 2021 |
| Předmět: |
Adult
Male medicine.medical_specialty Psychosis Genotyping Techniques Polymorphism Single Nucleotide 03 medical and health sciences 0302 clinical medicine Adverse Childhood Experiences Neurotrophic factors Surveys and Questionnaires Internal medicine Genotype medicine PSICOSE DA PRIMEIRA INFÂNCIA Animals Humans Hippocampus (mythology) Child Abuse Rats Wistar Child Prefrontal cortex Biological Psychiatry Pharmacology business.industry Brain-Derived Neurotrophic Factor High-Throughput Nucleotide Sequencing Methylation DNA Methylation medicine.disease Rats 030227 psychiatry Endocrinology Psychotic Disorders Social Isolation CpG site DNA methylation Gene-Environment Interaction business |
| Zdroj: | Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual) Universidade de São Paulo (USP) instacron:USP |
| ISSN: | 0278-5846 |
| Popis: | © 2020 Stressful events during early-life are risk factors for psychiatric disorders. Brain-derived neurotrophic factor (BDNF) is implicated in psychosis pathophysiology and deficits in BDNF mRNA in animal models of psychiatric disease are reported. DNA methylation can control gene expression and may be influenced by environmental factors such as early-life stress. We investigated BDNF methylation in first-episode psychosis (FEP) patients (n = 58), their unaffected siblings (n = 29) and community-based controls (n = 59), each of whom completed the Childhood Trauma Questionnaire (CTQ); BDNF methylation was also tested in male Wistar rats housed isolated or grouped from weaning. DNA was extracted from human blood and rat brain (prefrontal cortex and hippocampus), bisulphite-converted and the methylation of equivalent sequences within BDNF exon IV determined by pyrosequencing. BDNF methylation did not differ significantly between diagnostic groups; however, individuals who had experienced trauma presented higher levels of methylation. We found association between the mean BDNF methylation and total CTQ score in FEP, as well as between individual CpG sites and subtypes of trauma. No significant correlations were found for controls or siblings with child trauma. These results were independent of age, gender, body mass index, BDNF genotype or LINE-1, a measure of global methylation, which showed no significant association with trauma. Isolation rearing resulted in increased BDNF methylation in both brain regions compared to group-housed animals, a correlate of previously reported changes in gene expression. Our results suggest that childhood maltreatment may result in increased BDNF methylation, providing a mechanism underlying the association between early-life stress and psychosis. |
| Databáze: | OpenAIRE |
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