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      Gender-Specific Association of the Brain-Derived Neurotrophic Factor Gene with Attention-Deficit/Hyperactivity Disorder

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          Abstract

          Objective

          Attention-deficit/hyperactivity disorder (ADHD) is a complex neurodevelopmental disorder with a strong genetic component. Brain-derived neurotrophic factor (BDNF), which participates in the differentiation and survival of dopaminergic and noradrenergic neurons, could play a role in ADHD development. We aimed to explore the relationships between ADHD and BDNF gene polymorphism.

          Methods

          We conducted a case-control analysis of 202 ADHD subjects and 159 controls, performed a transmission disequilibrium test on 151 trios, and compared the results of a continuous performance test (CPT) according to the genotype of the three single nucleotide polymorphisms (rs11030101, rs6265, rs16917204) in the BDNF gene.

          Results

          In the case-control analysis, the AA genotype of the BDNF rs11030101 polymorphism was significantly associated with ADHD only in girls (p=0.024, odds ratio=3.00). The T-G-G haplotype was significantly less frequent (p=0.005) and A-G-G was more frequent (p=0.048) in girls with ADHD than in control girls (global p=0.027). A multivariate analysis of variance for commission errors on the CPT showed a significant main effect for the rs11030101 genotype (p=0.026) and an interaction effect of the rs11030101 genotype and gender (p=0.032) in ADHD probands.

          Conclusion

          These results provide preliminary evidence for a gender-specific association between BDNF and ADHD in the Korean population.

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          Most cited references 34

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          Neurotrophins: roles in neuronal development and function.

          Neurotrophins regulate development, maintenance, and function of vertebrate nervous systems. Neurotrophins activate two different classes of receptors, the Trk family of receptor tyrosine kinases and p75NTR, a member of the TNF receptor superfamily. Through these, neurotrophins activate many signaling pathways, including those mediated by ras and members of the cdc-42/ras/rho G protein families, and the MAP kinase, PI-3 kinase, and Jun kinase cascades. During development, limiting amounts of neurotrophins function as survival factors to ensure a match between the number of surviving neurons and the requirement for appropriate target innervation. They also regulate cell fate decisions, axon growth, dendrite pruning, the patterning of innervation and the expression of proteins crucial for normal neuronal function, such as neurotransmitters and ion channels. These proteins also regulate many aspects of neural function. In the mature nervous system, they control synaptic function and synaptic plasticity, while continuing to modulate neuronal survival.
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            NIMH Diagnostic Interview Schedule for Children Version IV (NIMH DISC-IV): description, differences from previous versions, and reliability of some common diagnoses.

            To describe the National Institute of Mental Health Diagnostic Interview Schedule for Children Version IV (NIMH DISC-IV) and how it differs from earlier versions of the interview. The NIMH DISC-IV is a highly structured diagnostic interview, designed to assess more than 30 psychiatric disorders occurring in children and adolescents, and can be administered by "lay" interviewers after a minimal training period. The interview is available in both English and Spanish versions. An editorial board was established in 1992 to guide DISC development and ensure that a standard version of the instrument is maintained. Preliminary reliability and acceptability results of the NIMH DISC-IV in a clinical sample of 84 parents and 82 children (aged 9-17 years) drawn from outpatient child and adolescent psychiatric clinics at 3 sites are presented. Results of the previous version in a community sample are reviewed. Despite its greater length and complexity, the NIMH DISC-IV compares favorably with earlier versions. Alternative versions of the interview are in development (the Present State DISC, the Teacher DISC, the Quick DISC, the Voice DISC). The NIMH DISC is an acceptable, inexpensive, and convenient instrument for ascertaining a comprehensive range of child and adolescent diagnoses.
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              Sexual dimorphism of brain developmental trajectories during childhood and adolescence.

              Human total brain size is consistently reported to be approximately 8-10% larger in males, although consensus on regionally specific differences is weak. Here, in the largest longitudinal pediatric neuroimaging study reported to date (829 scans from 387 subjects, ages 3 to 27 years), we demonstrate the importance of examining size-by-age trajectories of brain development rather than group averages across broad age ranges when assessing sexual dimorphism. Using magnetic resonance imaging (MRI) we found robust male/female differences in the shapes of trajectories with total cerebral volume peaking at age 10.5 in females and 14.5 in males. White matter increases throughout this 24-year period with males having a steeper rate of increase during adolescence. Both cortical and subcortical gray matter trajectories follow an inverted U shaped path with peak sizes 1 to 2 years earlier in females. These sexually dimorphic trajectories confirm the importance of longitudinal data in studies of brain development and underline the need to consider sex matching in studies of brain development.
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                Author and article information

                Journal
                Psychiatry Investig
                PI
                Psychiatry Investigation
                Korean Neuropsychiatric Association
                1738-3684
                1976-3026
                December 2010
                23 November 2010
                : 7
                : 4
                : 285-290
                10.4306/pi.2010.7.4.285
                3022316
                21253413
                Copyright © 2010 Korean Neuropsychiatric Association

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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