Huey-Ling Chiang1,2, Yung-Chin Hsu3,4, Chi-Yuan Shang1, Wen-Yih Isaac Tseng3,5, Susan Shur-Fen Gau1,6. 1. Department of Psychiatry, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan. 2. Department of Psychiatry, Far Eastern Memorial Hospital, New Taipei City, Taiwan. 3. Institute of Medical Device and Imaging, National Taiwan University College of Medicine, Taipei, Taiwan. 4. AcroViz Technology Inc., Taipei, Taiwan. 5. Molecular Imaging Center, National Taiwan University, Taipei, Taiwan. 6. Graduate Institute of Clinical Medicine, and Graduate Institute of Brain and Mind Sciences, National Taiwan University College of Medicine, Taipei, Taiwan.
Abstract
BACKGROUND: Brain structural alterations are frequently observed in probands with attention-deficit/hyperactivity disorder (ADHD). Here we examined the microstructural integrity of 76 white matter tracts among unaffected siblings of patients with ADHD to evaluate the potential familial risk and its association with clinical and neuropsychological manifestations. METHODS: The comparison groups included medication-naïve ADHD probands (n = 50), their unaffected siblings (n = 50) and typically developing controls (n = 50, age-and-sex matched with ADHD probands). Whole brain tractography was reconstructed automatically by tract-based analysis of diffusion spectrum imaging (DSI). Microstructural properties of white matter tracts were represented by the values of generalized fractional anisotropy (GFA), fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD) and axial diffusivity (AD). RESULTS: Compared to the control group, ADHD probands showed higher AD values in the perpendicular fasciculus, superior longitudinal fasciculus I, corticospinal tract, and corpus callosum. The AD values of unaffected siblings were in the intermediate position between those of the ADHD and control groups. These AD values were significantly associated with ADHD symptoms, sustained attention and working memory, for all white matter tracks evaluated except for the perpendicular fasciculus. Higher FA and lower RD values in the right frontostriatal tract connecting ventrolateral prefrontal cortex (FS-VLPFC) were associated with better performance in spatial span only in the unaffected sibling group. CONCLUSIONS: Abnormal AD values of specific white matter tracts among unaffected siblings of ADHD probands suggest the presence of familial risk in this population. The right FS-VLPFC may have a role in preventing the expression of the ADHD-related behavioral phenotype. CLINICALTRIALS.GOV NUMBER: NCT01682915.
BACKGROUND: Brain structural alterations are frequently observed in probands with attention-deficit/hyperactivity disorder (ADHD). Here we examined the microstructural integrity of 76 white matter tracts among unaffected siblings of patients with ADHD to evaluate the potential familial risk and its association with clinical and neuropsychological manifestations. METHODS: The comparison groups included medication-naïve ADHD probands (n = 50), their unaffected siblings (n = 50) and typically developing controls (n = 50, age-and-sex matched with ADHD probands). Whole brain tractography was reconstructed automatically by tract-based analysis of diffusion spectrum imaging (DSI). Microstructural properties of white matter tracts were represented by the values of generalized fractional anisotropy (GFA), fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD) and axial diffusivity (AD). RESULTS: Compared to the control group, ADHD probands showed higher AD values in the perpendicular fasciculus, superior longitudinal fasciculus I, corticospinal tract, and corpus callosum. The AD values of unaffected siblings were in the intermediate position between those of the ADHD and control groups. These AD values were significantly associated with ADHD symptoms, sustained attention and working memory, for all white matter tracks evaluated except for the perpendicular fasciculus. Higher FA and lower RD values in the right frontostriatal tract connecting ventrolateral prefrontal cortex (FS-VLPFC) were associated with better performance in spatial span only in the unaffected sibling group. CONCLUSIONS: Abnormal AD values of specific white matter tracts among unaffected siblings of ADHD probands suggest the presence of familial risk in this population. The right FS-VLPFC may have a role in preventing the expression of the ADHD-related behavioral phenotype. CLINICALTRIALS.GOV NUMBER: NCT01682915.