Functional activity of the caudate mediates the relation between early childhood microstructural variations and elevated metabolic syndrome scores
Pei Huang,
Mya Thway Tint,
Marissa Lee,
Zhen Ming Ngoh,
Peter Gluckman,
Yap Seng Chong,
Weiping Han,
Yu Fu,
Caroline Lei Wee,
Marielle V. Fortier,
Kai Keng Ang,
Yung Seng Lee,
Fabian Yap,
Johan G. Eriksson,
Michael J. Meaney,
Ai Peng Tan
Affiliations
Pei Huang
Singapore Institute for Clinical Sciences (SICS), Agency for Science, Technology and Research (A*STAR), Singapore
Mya Thway Tint
Singapore Institute for Clinical Sciences (SICS), Agency for Science, Technology and Research (A*STAR), Singapore
Marissa Lee
Singapore Institute for Clinical Sciences (SICS), Agency for Science, Technology and Research (A*STAR), Singapore
Zhen Ming Ngoh
Singapore Institute for Clinical Sciences (SICS), Agency for Science, Technology and Research (A*STAR), Singapore; Yong Loo Lin School of Medicine, National University of Singapore, Singapore
Peter Gluckman
Singapore Institute for Clinical Sciences (SICS), Agency for Science, Technology and Research (A*STAR), Singapore; Centre for Human Evolution, Adaptation and Disease, Liggins Institute, University of Auckland, Auckland, New Zealand
Yap Seng Chong
Singapore Institute for Clinical Sciences (SICS), Agency for Science, Technology and Research (A*STAR), Singapore; Department of Obstetrics & Gynaecology, National University Hospital Singapore, Singapore
Weiping Han
Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (A*STAR), Singapore; Center for Neuro-Metabolism and Regeneration Research, Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Guangzhou, China; School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China
Yu Fu
Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (A*STAR), Singapore
Caroline Lei Wee
Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (A*STAR), Singapore
Marielle V. Fortier
Singapore Institute for Clinical Sciences (SICS), Agency for Science, Technology and Research (A*STAR), Singapore; Department of Diagnostic and Interventional Radiology, KK Women's and Children's Hospital, Singapore
Kai Keng Ang
Institute for Infocomm Research, Agency for Science, Technology and Research (A*STAR), Singapore; School of Computer Science and Engineering, Nanyang Technological University, Singapore
Yung Seng Lee
Department of Paedatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
Fabian Yap
Department of Paediatrics, Endocrinology Service, KK Women's and Children's Hospital, Singapore, Singapore
Johan G. Eriksson
Singapore Institute for Clinical Sciences (SICS), Agency for Science, Technology and Research (A*STAR), Singapore; Department of Obstetrics and Gynaecology and Human Potential Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Department of General Practice and Primary Health Care, University of Helsinki, Helsinki, Finland; Folkhälsan Research Center, Helsinki, Finland
Michael J. Meaney
Singapore Institute for Clinical Sciences (SICS), Agency for Science, Technology and Research (A*STAR), Singapore; Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Department of Psychiatry, Douglas Mental Health University Institute, McGill University, Montreal, Quebec, Canada; Brain – Body Initiative, Agency for Science and Technology (A*STAR), Singapore
Ai Peng Tan
Singapore Institute for Clinical Sciences (SICS), Agency for Science, Technology and Research (A*STAR), Singapore; Department of Diagnostic Imaging, National University Hospital Singapore, Singapore; Corresponding author at: Department of Diagnostic Imaging, National University Health System, 1E Kent Ridge Rd 119228, Singapore
Background: Metabolic syndrome score in children assesses the risk of developing cardiovascular disease in future. We aim to probe the role of the caudate in relation to the metabolic syndrome score. Furthermore, using both functional and structural neuroimaging, we aim to examine the interplay between functional and structural measures. Methods: A longitudinal birth cohort study with functional and structural neuroimaging data obtained at 4.5, 6.0 and 7.5 years and metabolic syndrome scores at 8.0 years was used. Pearson correlation and linear regression was used to test for correlation fractional anisotropy (FA) and fractional amplitude of low frequency fluctuations (fALFF) of the caudate with metabolic syndrome scores. Mediation analysis was used to test if later brain measures mediated the relation between earlier brain measures and metabolic syndrome scores. Inhibitory control was also tested as a mediator of the relation between caudate brain measures and metabolic syndrome scores. Results: FA at 4.5 years and fALFF at 7.5 years of the left caudate was significantly correlated with metabolic syndrome scores. Post-hoc mediation analysis showed that fALFF at 7.5 years fully mediated the relation between FA at 4.5 years and metabolic syndrome scores. Inhibitory control was significantly correlated with fALFF at 7.5 years, but did not mediate the relation between fALFF at 7.5 years and metabolic syndrome scores. Conclusions: We found that variations in caudate microstructure at 4.5 years predict later variation in functional activity at 7.5 years. This later variation in functional activity fully mediates the relation between microstructural changes in early childhood and metabolic syndrome scores at 8.0 years.