期刊
BIOLOGICAL PSYCHIATRY
卷 74, 期 8, 页码 607-614出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.biopsych.2013.03.027
关键词
Attention-deficit/hyperactivity disorder; genetics; inferior frontal gyrus; monoamine oxidase A; neuroimaging; ventral striatum
资金
- European Union [LSHM-CT-2007-037286]
- FP7 projects ADAMS (Genomic Variations Underlying Common Neuropsychiatric Diseases and Disease Related Cognitive Traits in Different Human Populations) [242257]
- Innovative Medicine Initiative Project EU-AIMS [115300-2]
- United Kingdom National Institute for Health Research Biomedical Research Centre Mental Health
- Medical Research Council Programme Grant Developmental Pathways into Adolescent Substance Abuse [93558]
- Swedish Research Council
- Medical Research Council [G0801418B, G0901858] Funding Source: researchfish
- MRC [G0901858] Funding Source: UKRI
Background: Attention-deficit/hyperactivity disorder (ADHD) is characterized by deficits in reward sensitivity and response inhibition. The relative contribution of these frontostriatal mechanisms to ADHD symptoms and their genetic determinants is largely unexplored. Methods: Using functional magnetic resonance imaging and genetic analysis of the monoamine oxidase A (MAOA) gene, we investigated how striatal and inferior frontal activation patterns contribute to ADHD symptoms depending on MAOA genotype in a sample of adolescent boys (n = 190). Results: We demonstrate an association of ADHD symptoms with distinct blood oxygen level-dependent (BOLD) responses depending on MAOA genotype. In A hemizygotes of the expression single nucleotide polymorphism rs12843268, which express lower levels of MAOA, ADHD symptoms are associated with lower ventral striatal BOLD response during the monetary incentive delay task and lower inferior frontal gyrus BOLD response during the stop signal task. In G hemizygotes, ADHD symptoms are associated with increased inferior frontal gyrus BOLD response during the stop signal task in the presence of increased ventral striatal BOLD response during the monetary incentive delay task. Conclusions: Depending on MAOA genotype, ADHD symptoms in adolescent boys are associated with either reward deficiency or insufficient response inhibition. Apart from its mechanistic interest, our finding may aid in developing pharmacogenetic markers for ADHD.
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