Celia Maria de Araujo1, Andre Zugman2, Walter Swardfager3, Sintia Iole Nogueira Belangero4, Vanessa Kiyomi Ota5, Leticia Maria Spindola5, Hakon Hakonarson6, Renata Pellegrino6, Ary Gadelha2, Giovanni Abrahão Salum7, Pedro Mario Pan2, Luciana Monteiro de Moura8, Marco Del Aquilla2, Felipe Almeida Picon7, Edson Amaro9, João Ricardo Sato10, Elisa Brietzke11, Rodrigo Grassi-Oliveira12, Luis Augusto P Rohde7, Euripedes Constantino Miguel13, Rodrigo A Bressan2, Andrea Parolin Jackowski2. 1. National Institute of Developmental Psychiatry for Children and Adolescents (INCT-CNPq), São Paulo, Brazil; Department of Psychiatry, Universidade Federal de São Paulo, Brazil. Electronic address: celia.fit@gmail.com. 2. National Institute of Developmental Psychiatry for Children and Adolescents (INCT-CNPq), São Paulo, Brazil; Department of Psychiatry, Universidade Federal de São Paulo, Brazil. 3. Department of Pharmacology & Toxicology, University of Toronto, Toronto, Canada; Hurvitz Brain Sciences Program, Sunnybrook Research Institute, Toronto, Canada. 4. National Institute of Developmental Psychiatry for Children and Adolescents (INCT-CNPq), São Paulo, Brazil; Department of Psychiatry, Universidade Federal de São Paulo, Brazil; Department of Morphology and Genetics, Universidade Federal de São Paulo, São Paulo, Brazil. 5. Department of Psychiatry, Universidade Federal de São Paulo, Brazil; Department of Morphology and Genetics, Universidade Federal de São Paulo, São Paulo, Brazil. 6. Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, PA, United States. 7. National Institute of Developmental Psychiatry for Children and Adolescents (INCT-CNPq), São Paulo, Brazil; Department of Psychiatry, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil. 8. Mathematics & Statistics Institute, Universidade Federal do ABC, Santo André, Brazil. 9. Institute of Radiology (INRAD), Universidade de São Paulo, São Paulo, Brazil. 10. National Institute of Developmental Psychiatry for Children and Adolescents (INCT-CNPq), São Paulo, Brazil; Mathematics & Statistics Institute, Universidade Federal do ABC, Santo André, Brazil. 11. Department of Psychiatry, Universidade Federal de São Paulo, Brazil. 12. Developmental Cognitive Neuroscience Laboratory (DCNL), Pontifical Catholic University of Rio Grande do Sul, Porto Alegre, Brazil. 13. National Institute of Developmental Psychiatry for Children and Adolescents (INCT-CNPq), São Paulo, Brazil; Department & Institute of Psychiatry (IPq), Universidade de São Paulo, São Paulo, Brazil.
Abstract
BACKGROUND: The brain-derived neurotrophic factor (BDNF) Val66Met polymorphism (rs6265) has been associated with several neuropsychiatric disorders and regional structural brain changes in adults, but little is known about Val66Met's effect on brain morphology during typical or atypical neurodevelopment. Windows of vulnerability to psychopathology may be associated with the different alleles of the Val66Met polymorphism during childhood and adolescence. METHODOLOGY: We investigated the effect of Val66Met on cortical thickness in MRI scans of 718 children and adolescents (6-12 years old) with typical development, and in those meeting DSM criteria for a psychiatric disorder. RESULTS: Val66Met had a significant effect on cortical thickness. Considering the typically developing group, Met-carriers presented thicker parietal and occipital lobes and prefrontal cortices compared to Val homozygotes. Met-carriers with psychiatric disorders presented thicker medial and lateral temporal cortices than Val homozygotes. Furthermore, a significant genotype × psychiatric diagnosis interaction was found: Met-carriers with a psychiatric diagnosis presented thinner bilateral prefrontal cortices than Val homozygotes. CONCLUSION: This study provides evidence that Val66Met is associated with cortical maturation in children and adolescents with and without psychiatric disorders.
BACKGROUND: The brain-derived neurotrophic factor (BDNF) Val66Met polymorphism (rs6265) has been associated with several neuropsychiatric disorders and regional structural brain changes in adults, but little is known about Val66Met's effect on brain morphology during typical or atypical neurodevelopment. Windows of vulnerability to psychopathology may be associated with the different alleles of the Val66Met polymorphism during childhood and adolescence. METHODOLOGY: We investigated the effect of Val66Met on cortical thickness in MRI scans of 718 children and adolescents (6-12 years old) with typical development, and in those meeting DSM criteria for a psychiatric disorder. RESULTS: Val66Met had a significant effect on cortical thickness. Considering the typically developing group, Met-carriers presented thicker parietal and occipital lobes and prefrontal cortices compared to Val homozygotes. Met-carriers with psychiatric disorders presented thicker medial and lateral temporal cortices than Val homozygotes. Furthermore, a significant genotype × psychiatric diagnosis interaction was found: Met-carriers with a psychiatric diagnosis presented thinner bilateral prefrontal cortices than Val homozygotes. CONCLUSION: This study provides evidence that Val66Met is associated with cortical maturation in children and adolescents with and without psychiatric disorders.
Authors: Alessandra Cirillo; Elton Diniz; Ary Gadelha; Elson Asevedo; Luiza K Axelrud; Eurípedes C Miguel; Luis Augusto Rohde; Rodrigo A Bressan; Pedro Pan; Jair de J Mari Journal: Braz J Psychiatry Date: 2020-04-03 Impact factor: 2.697