Jung-Chi Chang1,2,3, Hsiang-Yuan Lin4,5, Jinglei Lv6, Wen-Yih Issac Tseng7,8, Susan Shur-Fen Gau9,10,11,12. 1. Department of Psychiatry, National Taiwan University Hospital, Taipei, Taiwan. 2. Department of Psychiatry, National Taiwan University Hospital, Hsin-Chu Branch, Hsin-Chu, Taiwan. 3. Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan. 4. Azrieli Adult Neurodevelopmental Centre and Adult Neurodevelopment and Geriatric Psychiatry Division, Centre for Addiction and Mental Health, Toronto, Ontario, Canada. 5. Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada. 6. Sydney Imaging and School of Biomedical Engineering, University of Sydney, Camperdown, NSW, Australia. 7. Graduate Institute of Brain and Mind Sciences, National Taiwan University College of Medicine, Taipei, Taiwan. 8. Institute of Medical Device and Imaging, National Taiwan University College of Medicine, Taipei, Taiwan. 9. Department of Psychiatry, National Taiwan University Hospital, Taipei, Taiwan. gaushufe@ntu.edu.tw. 10. Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan. gaushufe@ntu.edu.tw. 11. Graduate Institute of Brain and Mind Sciences, National Taiwan University College of Medicine, Taipei, Taiwan. gaushufe@ntu.edu.tw. 12. Department of Psychiatry, College of Medicine, National Taiwan University, Taipei, Taiwan. gaushufe@ntu.edu.tw.
Abstract
BACKGROUND: Despite the effectiveness of methylphenidate for treating ADHD, up to 30% of individuals with ADHD show poor responses to methylphenidate. Neuroimaging biomarkers to predict medication responses remain elusive. This study characterized neuroanatomical features that differentiated between clinically good and poor methylphenidate responders with ADHD. METHODS: Using a naturalistic observation design selected from a larger cohort, we included 79 drug-naive individuals (aged 6-42 years) with ADHD without major psychiatric comorbidity, who had acceptable baseline structural MRI data quality. Based on a retrospective chart review, we defined responders by individuals' responses to at least one-month treatment with methylphenidate. A nonparametric mass-univariate voxel-based morphometric analysis was used to compare regional gray matter volume differences between good and poor responders. A multivariate pattern recognition based on the support vector machine was further implemented to identify neuroanatomical indicators to predict an individual's response. RESULTS: 63 and 16 individuals were classified in the good and poor responder group, respectively. Using the small-volume correction procedure based on the hypothesis-driven striatal and default-mode network masks, poor responders had smaller regional volumes of the left putamen as well as larger precuneus volumes compared to good responders at baseline. The machine learning approach identified that volumetric information among these two regions alongside the left frontoparietal regions, occipital lobes, and posterior/inferior cerebellum could predict clinical responses to methylphenidate in individuals with ADHD. CONCLUSION: Our results suggest regional striatal and precuneus gray matter volumes play a critical role in mediating treatment responses in individuals with ADHD.
BACKGROUND: Despite the effectiveness of methylphenidate for treating ADHD, up to 30% of individuals with ADHD show poor responses to methylphenidate. Neuroimaging biomarkers to predict medication responses remain elusive. This study characterized neuroanatomical features that differentiated between clinically good and poor methylphenidate responders with ADHD. METHODS: Using a naturalistic observation design selected from a larger cohort, we included 79 drug-naive individuals (aged 6-42 years) with ADHD without major psychiatric comorbidity, who had acceptable baseline structural MRI data quality. Based on a retrospective chart review, we defined responders by individuals' responses to at least one-month treatment with methylphenidate. A nonparametric mass-univariate voxel-based morphometric analysis was used to compare regional gray matter volume differences between good and poor responders. A multivariate pattern recognition based on the support vector machine was further implemented to identify neuroanatomical indicators to predict an individual's response. RESULTS: 63 and 16 individuals were classified in the good and poor responder group, respectively. Using the small-volume correction procedure based on the hypothesis-driven striatal and default-mode network masks, poor responders had smaller regional volumes of the left putamen as well as larger precuneus volumes compared to good responders at baseline. The machine learning approach identified that volumetric information among these two regions alongside the left frontoparietal regions, occipital lobes, and posterior/inferior cerebellum could predict clinical responses to methylphenidate in individuals with ADHD. CONCLUSION: Our results suggest regional striatal and precuneus gray matter volumes play a critical role in mediating treatment responses in individuals with ADHD.
Entities:
Keywords:
ADHD; Methylphenidate; Striatum; Support vector machine; Treatment response; VBM