TY - JOUR
T1 - Multimodal structural neuroimaging markers of brain development and ADHD symptoms
AU - Ball, Gareth
AU - Malpas, Charles B.
AU - Genc, Sila
AU - Efron, Daryl
AU - Sciberras, Emma
AU - Anderson, Vicki
AU - Nicholson, Jan M.
AU - Silk, Timothy J.
N1 - Funding Information:
Dr. Sciberras is supported by an NHMRC Career Development Fellowship (1110688). Dr. Anderson was supported by an NHMRC Senior Practitioner Fellowship (1079478). Dr. Nicholson was funded by the Australian Communities Foundation through the Roberta Holmes Chair for the Transition to Contemporary Parenthood Program (Coronella subfund). Dr. Efron is supported by a Clinical Scientist Fellowship from the Murdoch Children’s Research Institute.
Funding Information:
This study was funded by project grant 1065895 from the National Health and Medical Research Council of Australia (NHMRC). The Children’s Attention Project was funded by NHMRC project grant 1008522 and a grant from the Collier Foundation. The research was conducted within the Developmental Imaging research group, Murdoch Children’s Research Institute and the Children’s MRI Centre, Royal Children’s Hospital, Melbourne. It was supported by the Murdoch Children’s Research Institute, the Royal Children’s Hospital, the Royal Children’s Hospital Foundation, the Department of Paediatrics at the University of Melbourne, and the Victorian Government’s Operational Infrastructure Support Program. The authors also thank Dr. Michael P. Milham and the ADHD-200 consortium for making the ADHD-200 data set available to researchers. Funding for the NYU cohort was provided by NIMH (R01MH083246), Autism Speaks, the Stavros Niarchos Foundation, the Leon Levy Foundation, and an endowment provided by Phyllis Green and Randolph Coµwen.
Publisher Copyright:
© 2019 American Journal of Psychiatry.
PY - 2019/1
Y1 - 2019/1
N2 - Objective: Attention deficit hyperactivity disorder (ADHD) is a multifactorial disorder with diverse associated risk factors and comorbidities. In this study, the authors sought to understand ADHD from a dimensional perspective and to identify neuroanatomical correlates of traits and behaviors that span diagnostic criteria. Methods: Multimodal neuroimaging data and multiinformant cognitive and clinical data were collected in a densely phenotyped pediatric cohort (N=160; 70 with ADHD; age range, 9-12 years). Multivariate analysis identified associations between clinical and cognitive factors and multimodal neuroimaging markers (across tissue volume, cortical thickness, cortical area, and white matter microstructure). The resulting imaging markers were validated in an independent cohort (N=231; 132 with ADHD; age range, 7-18 years). Results: Four novel patterns of neuroanatomical variation that related to phenotypic variation were identified. The first imaging pattern captured association of head size with sex, socioeconomic status, and mathematics and reading performance. The second pattern captured variation associated with development and showed that individuals with delayed development were more likely to be receiving ADHD medication. The third pattern was associated with hyperactivity, greater comorbidities, poorer cognition, lower parental education, and lower quality of life. The fourth pattern was associated with a particular profile of poorer cognition and irritability independent of ADHD. The authors further demonstrated that these imaging patterns could predict variation in age and ADHD symptoms in an independent cohort. Conclusions: The findings suggest that ADHD presentation may arise from a summation of several clinical, developmental, or cognitive factors, each with a distinct neuroanatomical foundation. This informs the neurobiological foundations of ADHD and highlights the value of detailed phenotypic data in understanding the neurobiology underlying neurodevelopmental disorders.
AB - Objective: Attention deficit hyperactivity disorder (ADHD) is a multifactorial disorder with diverse associated risk factors and comorbidities. In this study, the authors sought to understand ADHD from a dimensional perspective and to identify neuroanatomical correlates of traits and behaviors that span diagnostic criteria. Methods: Multimodal neuroimaging data and multiinformant cognitive and clinical data were collected in a densely phenotyped pediatric cohort (N=160; 70 with ADHD; age range, 9-12 years). Multivariate analysis identified associations between clinical and cognitive factors and multimodal neuroimaging markers (across tissue volume, cortical thickness, cortical area, and white matter microstructure). The resulting imaging markers were validated in an independent cohort (N=231; 132 with ADHD; age range, 7-18 years). Results: Four novel patterns of neuroanatomical variation that related to phenotypic variation were identified. The first imaging pattern captured association of head size with sex, socioeconomic status, and mathematics and reading performance. The second pattern captured variation associated with development and showed that individuals with delayed development were more likely to be receiving ADHD medication. The third pattern was associated with hyperactivity, greater comorbidities, poorer cognition, lower parental education, and lower quality of life. The fourth pattern was associated with a particular profile of poorer cognition and irritability independent of ADHD. The authors further demonstrated that these imaging patterns could predict variation in age and ADHD symptoms in an independent cohort. Conclusions: The findings suggest that ADHD presentation may arise from a summation of several clinical, developmental, or cognitive factors, each with a distinct neuroanatomical foundation. This informs the neurobiological foundations of ADHD and highlights the value of detailed phenotypic data in understanding the neurobiology underlying neurodevelopmental disorders.
UR - http://www.scopus.com/inward/record.url?scp=85060019395&partnerID=8YFLogxK
U2 - 10.1176/appi.ajp.2018.18010034
DO - 10.1176/appi.ajp.2018.18010034
M3 - Article
C2 - 30220220
AN - SCOPUS:85060019395
SN - 0002-953X
VL - 176
SP - 57
EP - 66
JO - American Journal of Psychiatry
JF - American Journal of Psychiatry
IS - 1
ER -
