Early-life stress effects on BDNF DNA methylation in first-episode psychosis and in rats reared in isolation

Author(s):Show less -

Fachim, Helene A. ^{[1, 2, 3]} ; Corsi-Zuelli, Fabiana ^[1] ; Loureiro, Camila M. ^{[2, 4]} ; Iamjan, Sri-arun ^{[2, 5, 6]} ; Shuhama, Rosana ^[1] ; Joca, Samia ^{[7, 8]} ; Menezes, Paulo Rossi ^[9] ; Heald, Adrian ^[3] ; Louzada-Junior, Paulo ^[4] ; Dalton, Caroline F. ^[2] ; Del-Ben, Cristina Marta ^[1] ; Reynolds, Gavin P. ^[2]

Affiliation

^[1] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Neurosci & Behav, Sao Paulo - Brazil

^[2] Sheffield Hallam Univ, Biomol Sci Res Ctr, Sheffield, S Yorkshire - England

^[3] Salford Royal NHS Fdn Trust, Dept Endocrinol & Metab, Salford, Lancs - England

^[4] Univ Sao Paulo, Ribeirao Preto Med Sch, Div Clin Immunol, Dept Internal Med, Sao Paulo - Brazil

^[5] Burapha Univ, Fac Allied Hlth Sci, Div Anat, Dept Biomed Sci, Saen Suk, Chonburi - Thailand

^[6] Naresuan Univ, Ctr Excellence Med Biotechnol, Fac Med Sci, Phitsanulok - Thailand

^[7] Aarhus Univ, Aarhus Inst Adv Studies AIAS, Aarhus - Denmark

^[8] Univ Sao Paulo, Sch Pharmaceut Sci, Dept Biomol Sci, Ribeirao Preto - Brazil

^[9] Univ Sao Paulo, Dept Prevent Med, Fac Med, Sao Paulo - Brazil

• Document type: Journal article
• Source: PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY; v. 108, JUN 8 2021.
• Web of Science Citations: 1

Abstract

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. (AU)

• FAPESP's process: 12/05178-0 - Schizophrenia and other psychotic disorders: social and biological determinants
• Grantee: Paulo Rossi Menezes
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 12/17626-7 - Cellular and molecular mechanisms involved in the role of atypical neurotransmitters in neuropsychiatric disorders
• Grantee: Francisco Silveira Guimaraes
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 13/11167-3 - Gene-environment interactions in Schizophrenia and other psychotic disorders
• Grantee: Rosana Shuhama
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 17/00624-5 - DNA methylation investigation in first episode of psychosis and in rats undergoing isolation rearing from weaning in the two major excitatory and inhibitory systems
• Grantee: Helene Aparecida Fachim
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• FAPESP's process: 13/08216-2 - CRID - Center for Research in Inflammatory Diseases
• Grantee: Fernando de Queiroz Cunha
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• FAPESP's process: 19/13229-2 - Inflammatory profile in the general population: transdiagnostic dimensions in the context of the psychosis continuum
• Grantee: Fabiana Maria das Graças Corsi Zuelli
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 17/17480-6 - Impact of early life stress in the inflammatory profile of first episode of psychosis (FEP) patients and in the animal model of post-weaning social isolation
• Grantee: Fabiana Maria das Graças Corsi Zuelli
• Support Opportunities: Scholarships abroad - Research Internship - Master's degree
• FAPESP's process: 15/02948-7 - Study of epigenetic alterations in GABAergic neurotransmission in schizophrenia and other psychoses and in animals undergoing social isolation from weaning
• Grantee: Helene Aparecida Fachim
• Support Opportunities: Scholarships in Brazil - Post-Doctoral