The relationship of childhood trauma and DNA methylation of NMDA receptor genes in first-episode schizophrenia

Author(s)

Loureiro, Camila M. ^{[1, 2, 3, 4]} ; Fachim, Helene A. ^[5] ; Corsi-Zuelli, Fabiana ^{[6, 3]} ; Shuhama, Rosana ^{[6, 4]} ; Menezes, Paulo R. ^{[7, 4]} ; Dalton, Caroline F. ^[2] ; Del-Ben, Cristina M. ^{[6, 4]} ; Reynolds, Gavin P. ^[2] ; Louzada-Junior, Paulo ^{[1, 3]}

Affiliation

^[1] Univ Sao Paulo, Ribeirao Preto Med Sch, Div Clin Immunol, Dept Internal Med, BR-14049900 Sao Paulo - Brazil

^[2] Sheffield Hallam Univ, Biomol Sci Res Ctr, Sheffield S1 1WB3, S Yorkshire - England

^[3] Univ Sao Paulo, Ribeirao Preto Med Sch, Ctr Res Inflammatory Dis, BR-14049900 Sao Paulo - Brazil

^[4] Univ Sao Paulo, NAP SaMP, Populat Mental Hlth Ctr, BR-01246903 Sao Paulo - Brazil

^[5] Salford Royal Fdn Trust, Dept Endocrinol & Metab, Salford M6 8HD6, Lancs - England

^[6] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Neurosci & Behav, BR-14049900 Sao Paulo - Brazil

^[7] Univ Sao Paulo, Fac Med, Dept Prevent Med, BR-01246903 Sao Paulo - Brazil

• Document type: Journal article
• Source: Epigenomics; v. 13, n. 12, p. 927-937, JUN 2021.
• Web of Science Citations: 0

Abstract

Aim: We investigated GRIN1, GRIN2A, GRIN2B and LINE-1 DNA methylation in first-episode schizophrenia patients, their nonaffected siblings and age- and sex-matched controls testing for associations between DNA methylation and exposition to childhood trauma. Materials \& methods: The Childhood Trauma Questionnaire evaluated the history of childhood trauma. Genomic DNA was bisulfite converted and pyrosequencing was employed to quantify DNA methylation. Results: GRIN2A, GRIN2B and LINE-1 DNA methylation was not associated with childhood trauma in patients, siblings and controls. Siblings with childhood trauma had hypermethylation at CpG1 of GRIN1 compared with siblings without trauma. Conclusion: Childhood trauma may influence GRIN1 methylation in subjects with liability to psychosis, but not in frank schizophrenia or controls. Lay abstract Schizophrenia results from a combination of genetic and environmental influences. We investigated how some changes in genes can be silenced by a process named DNA methylation and may be linked to schizophrenia. For this reason, we hypothesized that childhood trauma, an environmental risk factor, would be associated with DNA methylation in schizophrenia patients compared with their unaffected siblings and controls. Our research has shown that altered blood DNA methylation of one candidate gene for psychiatric disorders may be associated with childhood trauma in the unaffected siblings of schizophrenia patients, but not in frank schizophrenia or controls. We believe that this gene plays an important role in helping identify vulnerable as well as resilient individuals to schizophrenia disorder. (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: 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: 16/12195-9 - 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 in Brazil - Master
• 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: 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
• 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