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What Is the Link Between Attention-Deficit/Hyperactivity Disorder and Sleep Disturbance? A Multimodal Examination of Longitudinal Relationships and Brain Structure Using Large-Scale Population-Based Cohorts

  • Shen, Chun1, 2
  • Luo, Qiang1, 3, 4, 2
  • Chamberlain, Samuel R.5
  • Morgan, Sarah5, 6
  • Romero-Garcia, Rafael5
  • Du, Jingnan1
  • Zhao, Xingzhong1
  • Touchette, Évelyne7
  • Montplaisir, Jacques8, 9
  • Vitaro, Frank10
  • Boivin, Michel11
  • Tremblay, Richard E.12, 13
  • Zhao, Xing-Ming1
  • Robaey, Philippe8, 14, 15
  • Feng, Jianfeng1, 16, 17, 18, 2
  • Sahakian, Barbara J.1, 4, 5
  • 1 Institute of Science and Technology for Brain-Inspired Intelligence, MOE Key Laboratory of Computational Neuroscience and Brain-Inspired Intelligence, Fudan University, Shanghai, China
  • 2 Shanghai Research Center for Brain Science and Brain-Inspired Intelligence, Institute of Brain-Intelligence Technology, Zhangjiang Laboratory, Shanghai, China
  • 3 State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science and Human Phenome Institute, Fudan University, Shanghai, China
  • 4 Behavioural and Clinical Neuroscience Institute, Department of Psychology, University of Cambridge, Cambridge, United Kingdom
  • 5 Department of Psychiatry, University of Cambridge, Cambridge, United Kingdom
  • 6 Alan Turing Institute, London, United Kingdom
  • 7 Department of Psychoeducation, Université du Québec à Trois-Rivières, Trois-Rivières, Québec, Canada
  • 8 Department of Psychiatry, Université de Montréal, Montréal, Québec, Canada
  • 9 Center for Advanced Research in Sleep Medicine, CIUSSS-NIM, Montréal, Québec, Canada
  • 10 School of Psychoeducation, Université de Montréal, Montréal, Québec, Canada
  • 11 School of Psychology, Université Laval, Québec City, Québec, Canada
  • 12 Department of Pediatrics and Psychology, Université de Montréal, Montréal, Québec, Canada
  • 13 School of Public Health, Physiotherapy and Sports Science, University College Dublin, Dublin, Ireland
  • 14 Department of Psychiatry, University of Ottawa, Ottawa, Ontario, Canada
  • 15 Children’s Hospital of Eastern Ontario, Ottawa, Ontario, Canada
  • 16 Collaborative Innovation Center for Brain Science, Fudan University, Shanghai, China
  • 17 School of Mathematical Sciences, Fudan University, Shanghai, China
  • 18 Department of Computer Science, University of Warwick, Coventry, United Kingdom
Published Article
Publication Date
Sep 15, 2020
DOI: 10.1016/j.biopsych.2020.03.010
PMID: 32414481
PMCID: PMC7445427
PubMed Central


Background Attention-deficit/hyperactivity disorder (ADHD) comorbid with sleep disturbances can produce profound disruption in daily life and negatively impact quality of life of both the child and the family. However, the temporal relationship between ADHD and sleep impairment is unclear, as are underlying common brain mechanisms. Methods This study used data from the Quebec Longitudinal Study of Child Development ( n  = 1601, 52% female) and the Adolescent Brain Cognitive Development Study ( n  = 3515, 48% female). Longitudinal relationships between symptoms were examined using cross-lagged panel models. Gray matter volume neural correlates were identified using linear regression. The transcriptomic signature of the identified brain-ADHD-sleep relationship was characterized by gene enrichment analysis. Confounding factors, such as stimulant drugs for ADHD and socioeconomic status, were controlled for. Results ADHD symptoms contributed to sleep disturbances at one or more subsequent time points in both cohorts. Lower gray matter volumes in the middle frontal gyrus and inferior frontal gyrus, amygdala, striatum, and insula were associated with both ADHD symptoms and sleep disturbances. ADHD symptoms significantly mediated the link between these structural brain abnormalities and sleep dysregulation, and genes were differentially expressed in the implicated brain regions, including those involved in neurotransmission and circadian entrainment. Conclusions This study indicates that ADHD symptoms and sleep disturbances have common neural correlates, including structural changes of the ventral attention system and frontostriatal circuitry. Leveraging data from large datasets, these results offer new mechanistic insights into this clinically important relationship between ADHD and sleep impairment, with potential implications for neurobiological models and future therapeutic directions.

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