Article

Anatomic Brain Abnormalities in Monozygotic Twins Discordant for Attention Deficit Hyperactivity Disorder

Child Psychiatry Branch, National Institute of Mental Health (NIMH), 베서스다, Maryland, United States
American Journal of Psychiatry (Impact Factor: 13.56). 10/2003; 160(9):1693-6. DOI: 10.1176/appi.ajp.160.9.1693
Source: PubMed

ABSTRACT To examine brain-behavior relationships in attention deficit hyperactivity disorder (ADHD), the authors obtained magnetic resonance imaging (MRI) scans of monozygotic twins discordant for ADHD.
National recruitment was followed by in-person assessment. MRI scans were measured algorithmically for nine pairs of monozygotic twins discordant for ADHD.
The affected twins had significantly smaller caudate volumes (mean difference=-0.56 ml, CI=-0.92 to -0.21) than their unaffected co-twins.
These results provide further support for striatal models of ADHD pathophysiology.

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    • "However, only a limited number of studies have been published on ADHD discordant MZ twin pairs to date (Castellanos et al., 2003; Lehn et al., 2007; Pearsall- Jones et al., 2008, 2009; Sharp et al., 2003; Van't Ent et al., 2009). Results from these studies report differences in brain anatomy, i.e. reduced caudate nucleus and prefrontal lobe volumes in cases (Castellanos et al., 2003), and the identification of environmental risk factors such as low birth weight, delayed motor development, and being born the second twin in the pair (Lehn et al., 2007). Furthermore, results from functional Magnetic Resonance Imaging (fMRI) in twins pairs discordant and concordant for ADHD indicate that attention problems caused by genetic versus non-shared environmental factors, affect the brain in different ways. "
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    ABSTRACT: Introduction: The study of differences between monozygotic (MZ) twin pairs with respect to ADHD may provide novel leads to disentangle the environmental contribution driving its phenotypes. Objectives: To examine non-shared environmental influences on executive function in dimensionally defined ADHD. Methods: This study included 27 MZ twin pairs (7 female) aged 11–20 years being moderately to substantially discordant for ADHD traits as assessed by the Attention Problem (AP) scale of the Child Behavior Checklist/Adult Behavior Checklist. The twins completed the Wisconsin Card Sorting Test (WCST) for cognitive flexibility and the Tower Test (TT) for foresighted planning. Two statistical approaches were used to analyze the data. First, correlations between ADHD trait intra-pair differences and WCST and TT scores were calculated. Second, the significance of those intra-pair differences on WCST and TT, using ADHD as categorical variable in clinically discordant pairs, was tested. Results: Both analysing strategies revealed a link between ADHD on one hand, and foresighted planning and inhibitory control on the other hand mediated by non-shared environmental factors. The first statistical approach yielded positive correlations between intra-pairs differences on the AP scale and intra-pair differences on two subscales of the TT: total rule violation (r s 50 . 41) and rule-violation-per-item-ratio (r s 50 . 38). Findings in categorically discordant pairs were consistent, showing within-pair differences on the same subtests (z-1 . 63, P50 . 05, one-tailed and z521 . 60, P50 . 05, one-tailed). Conclusions: Findings confirm previous research suggesting ADHD to be a quantitative extreme on a continuum with executive functions being a cognitive marker of ADHD traits. Non-shared environmental factors appear to influence planning skills and inhibitory control. Introduction Attention-deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by motor overactivity, inattention and impulsivity. The defining criteria for ADHD outlined by the recently published 5th edition of the Diagnostic and Statistical Manual (DSM-5; American Psychiatric Association, 2013) include international journal of developmental
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    • "Roots of Autism and ADHD Twin Study in Sweden (RATSS) uses the co-twin control or twin-differences design (Martin et al., 1997). Only a moderate number of studies have specifically addressed discordant MZ twin pairs for ASD (e.g., Hu et al., 2006; Kates et al., 1998, 2004, 2009; Mitchell et al., 2009; Wong et al., in press), ADHD (e.g., Castellanos et al., 2003; Lehn et al., 2007; Pearsall-Jones et al., 2008, 2009; Sharp et al., 2003; van't Ent et al., 2009) or traits of both disorders (e.g., Groen-Blokhuis et al., 2011; Ronald et al., 2010). The findings have been promising, indicating medical history (e.g., ADHD: low birth weight and delayed physical growth/motor development in cases), neuromorphological differences (e.g., ASD: reduced caudate, amygdala , hippocampus, and cerebellar volumes, differences in cortical folding within the partial lobe; ADHD: reduced caudate nucleus and prefrontal lobe volumes in cases), and differential gene expression patterns on DNA microarrays (e.g., ASD: ASS, NAGLU, FLAP, and ROBO I) in the affected twin. "
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    ABSTRACT: Neurodevelopmental disorders affect a substantial minority of the general population. Their origins are still largely unknown, but a complex interplay of genetic and environmental factors causing disturbances of the central nervous system's maturation and a variety of higher cognitive skills is presumed. Only limited research of rather small sample size and narrow scope has been conducted in neurodevelopmental disorders using a twin-differences design. The Roots of Autism and ADHD Twin Study in Sweden (RATSS) is an ongoing project targeting monozygotic twins discordant for categorical or dimensional autistic and inattentive/hyperactive-impulsive phenotypes as well as other neurodevelopmental disorders, and typically developing twin controls. Included pairs are 9 years of age or older, and comprehensively assessed for psychopathology, medical history, neuropsychology, and dysmorphology, as well as structural, functional, and molecular brain imaging. Specimens are collected for induced pluripotent (iPS) and neuroepithelial stem cells, genetic, gut bacteria, protein-/monoamine, and electron microscopy analyses. RATSS's objective is to generate a launch pad for novel surveys to understand the complexity of genotype-environment-phenotype interactions in autism spectrum disorder and attention-deficit hyperactivity disorder (ADHD). By October 2013, RATSS had collected data from 55 twin pairs, among them 10 monozygotic pairs discordant for autism spectrum disorder, seven for ADHD, and four for other neurodevelopmental disorders. This article describes the design, recruitment, data collection, measures, collected pairs' characteristics, as well as ongoing and planned analyses in RATSS. Potential gains of the study comprise the identification of environmentally mediated biomarkers, the emergence of candidates for drug development, translational modeling, and new leads for prevention of incapacitating outcomes.
    Twin Research and Human Genetics 04/2014; 17(3):1-13. DOI:10.1017/thg.2014.12 · 1.92 Impact Factor
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    • "Roots of Autism and ADHD Twin Study in Sweden (RATSS) uses the co-twin control or twin-differences design (Martin et al., 1997). Only a moderate number of studies have specifically addressed discordant MZ twin pairs for ASD (e.g., Hu et al., 2006; Kates et al., 1998, 2004, 2009; Mitchell et al., 2009; Wong et al., in press), ADHD (e.g., Castellanos et al., 2003; Lehn et al., 2007; Pearsall-Jones et al., 2008, 2009; Sharp et al., 2003; van't Ent et al., 2009) or traits of both disorders (e.g., Groen-Blokhuis et al., 2011; Ronald et al., 2010). The findings have been promising, indicating medical history (e.g., ADHD: low birth weight and delayed physical growth/motor development in cases), neuromorphological differences (e.g., ASD: reduced caudate, amygdala , hippocampus, and cerebellar volumes, differences in cortical folding within the partial lobe; ADHD: reduced caudate nucleus and prefrontal lobe volumes in cases), and differential gene expression patterns on DNA microarrays (e.g., ASD: ASS, NAGLU, FLAP, and ROBO I) in the affected twin. "
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