Interplay between stress response genes associated with attention-deficit hyperactivity disorder and brain volume
| Autor: | van der Meer, D., Hoekstra, P.J., Bralten, J., Donkelaar, M.M.J., Heslenfeld, D.J., Oosterlaan, J., Faraone, S.V., Franke, B., Buitelaar, J.K., Hartman, C.A. |
|---|---|
| Přispěvatelé: | Other departments, Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Clinical Cognitive Neuropsychiatry Research Program (CCNP), Cognitive Psychology, Clinical Neuropsychology, IBBA |
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
Male
Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7] Adolescent Genetic Variation Hypothalamo-Hypophyseal System/physiopathology Serotonin Plasma Membrane Transport Proteins/genetics Polymorphism Single Nucleotide Cohort Studies Young Adult Gene Frequency Haplotypes Stress Psychological/genetics mental disorders Receptors Glucocorticoid/genetics Humans Female Gene-Environment Interaction Pituitary-Adrenal System/physiopathology Brain/anatomy & histology Attention Deficit Disorder with Hyperactivity/genetics |
| Zdroj: | Genes, brain, and behavior, 15(7), 627-636. Wiley-Blackwell Genes, Brain and Behavior, 15, 627-36 Genes, Brain and Behavior, 15(7), 627-636. Wiley-Blackwell Genes, Brain and Behavior, 15(7), 627-636. Wiley-Blackwell Publishing Genes, Brain and Behavior, 15, 7, pp. 627-36 van der Meer, D, Hoekstra, P J, Bralten, J, Donkelaar, M M J, Heslenfeld, D J, Oosterlaan, J, Faraone, S V, Franke, B, Buitelaar, J K & Hartman, C A 2016, ' Interplay between stress response genes associated with attention-deficit hyperactivity disorder and brain volume ', Genes, Brain and Behavior, vol. 15, no. 7, pp. 627-636 . https://doi.org/10.1111/gbb.12307 |
| ISSN: | 1601-1848 |
| DOI: | 10.1111/gbb.12307 |
| Popis: | Contains fulltext : 167897.pdf (Publisher’s version ) (Open Access) The glucocorticoid receptor plays a pivotal role in the brain's response to stress; a haplotype of functional polymorphisms in the NR3C1 gene encoding this receptor has been associated with attention-deficit hyperactivity disorder (ADHD). The serotonin transporter (5-HTT) gene polymorphism 5-HTTLPR is known to influence the relation between stress exposure and ADHD severity, which may be partly because of its reported effects on glucocorticoid levels. We therefore investigated if NR3C1 moderates the relation of stress exposure with ADHD severity and brain structure, and the potential role of 5-HTTLPR. Neuroimaging, genetic and stress exposure questionnaire data were available for 539 adolescents and young adults participating in the multicenter ADHD cohort study NeuroIMAGE (average age: 17.2 years). We estimated the effects of genetic variation in NR3C1 and 5-HTT, stress exposure and their interactions on ADHD symptom count and gray matter volume. We found that individuals carrying the ADHD risk haplotype of NR3C1 showed significantly more positive relation between stress exposure and ADHD severity than non-carriers. This gene-environment interaction was significantly stronger for 5-HTTLPR L-allele homozygotes than for S-allele carriers. These two- and three-way interactions were reflected in the gray matter volume of the cerebellum, parahippocampal gyrus, intracalcarine cortex and angular gyrus. Our findings illustrate how genetic variation in the stress response pathway may influence the effects of stress exposure on ADHD severity and brain structure. The reported interplay between NR3C1 and 5-HTT may further explain some of the heterogeneity between studies regarding the role of these genes and hypothalamic-pituitary-adrenal axis activity in ADHD. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|