Courtney P Gilchrist1, Deanne K Thompson2, Claire E Kelly3, Richard Beare4, Christopher Adamson5, Thijs Dhollander6, Katherine Lee7, Karli Treyvaud8, Lillian G Matthews9, Mary Tolcos10, Jeanie L Y Cheong11, Terrie E Inder12, Lex W Doyle13, Angela Cumberland10, Peter J Anderson14. 1. School of Health and Biomedical Sciences, RMIT University, Melbourne, Victoria, Australia; Victorian Infant Brain Studies, Murdoch Children's Research Institute, Melbourne, Victoria, Australia; Developmental Imaging, Murdoch Children's Research Institute, Melbourne, Victoria, Australia. Electronic address: courtney.gilchrist@mcri.edu.au. 2. Victorian Infant Brain Studies, Murdoch Children's Research Institute, Melbourne, Victoria, Australia; Developmental Imaging, Murdoch Children's Research Institute, Melbourne, Victoria, Australia; Department of Paediatrics, University of Melbourne, Melbourne, Victoria, Australia. 3. Victorian Infant Brain Studies, Murdoch Children's Research Institute, Melbourne, Victoria, Australia; Developmental Imaging, Murdoch Children's Research Institute, Melbourne, Victoria, Australia; Turner Institute for Brain and Mental Health, School of Psychological Science, Monash University, Melbourne, Victoria, Australia. 4. Developmental Imaging, Murdoch Children's Research Institute, Melbourne, Victoria, Australia; Department of Medicine, Monash University, Melbourne, Victoria, Australia. 5. Developmental Imaging, Murdoch Children's Research Institute, Melbourne, Victoria, Australia; Department of Electrical Engineering, University of Melbourne, Melbourne, Victoria, Australia. 6. Developmental Imaging, Murdoch Children's Research Institute, Melbourne, Victoria, Australia. 7. Victorian Infant Brain Studies, Murdoch Children's Research Institute, Melbourne, Victoria, Australia; Clinical Epidemiology and Biostatistics Unit, Murdoch Children's Research Institute, Melbourne, Victoria, Australia; Department of Paediatrics, University of Melbourne, Melbourne, Victoria, Australia. 8. Victorian Infant Brain Studies, Murdoch Children's Research Institute, Melbourne, Victoria, Australia; Department of Psychology and Counselling, La Trobe University, Melbourne, Victoria, Australia; Newborn Research, Royal Women's Hospital, Melbourne, Victoria, Australia. 9. Victorian Infant Brain Studies, Murdoch Children's Research Institute, Melbourne, Victoria, Australia; Monash Biomedical Imaging, Monash University, Melbourne, Victoria, Australia; Turner Institute for Brain and Mental Health, School of Psychological Science, Monash University, Melbourne, Victoria, Australia; Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts. 10. School of Health and Biomedical Sciences, RMIT University, Melbourne, Victoria, Australia. 11. Victorian Infant Brain Studies, Murdoch Children's Research Institute, Melbourne, Victoria, Australia; Department of Obstetrics and Gynaecology, University of Melbourne, Melbourne, Victoria, Australia; Newborn Research, Royal Women's Hospital, Melbourne, Victoria, Australia. 12. Victorian Infant Brain Studies, Murdoch Children's Research Institute, Melbourne, Victoria, Australia; Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts. 13. Victorian Infant Brain Studies, Murdoch Children's Research Institute, Melbourne, Victoria, Australia; Department of Paediatrics, University of Melbourne, Melbourne, Victoria, Australia; Department of Obstetrics and Gynaecology, University of Melbourne, Melbourne, Victoria, Australia; Newborn Research, Royal Women's Hospital, Melbourne, Victoria, Australia. 14. Victorian Infant Brain Studies, Murdoch Children's Research Institute, Melbourne, Victoria, Australia; Turner Institute for Brain and Mental Health, School of Psychological Science, Monash University, Melbourne, Victoria, Australia. Electronic address: peter.j.anderson@monash.edu.
Abstract
BACKGROUND: Children born very preterm (VP) are at higher risk of emotional and behavioral problems compared with full-term (FT) children. We investigated the neurobiological basis of internalizing and externalizing symptoms in individuals born VP and FT by applying a graph theory approach. METHODS: Structural and diffusion magnetic resonance imaging data were combined to generate structural connectomes and calculate measures of network integration and segregation at 7 (VP: 72; FT: 17) and 13 (VP: 125; FT: 44) years. Internalizing and externalizing symptoms were assessed at 7 and 13 years using the Strengths and Difficulties Questionnaire. Linear regression models were used to relate network measures and internalizing and externalizing symptoms concurrently at 7 and 13 years. RESULTS: Lower network integration (characteristic path length and global efficiency) was associated with higher internalizing symptoms in VP and FT children at 7 years, but not at 13 years. The association between network integration (characteristic path length) and externalizing symptoms at 7 years was weaker, but there was some evidence for differential associations between groups, with lower integration in the VP group and higher integration in the FT group associated with higher externalizing symptoms. At 13 years, there was some evidence that associations between network segregation (average clustering coefficient, transitivity, local efficiency) and externalizing symptoms differed between the VP and FT groups, with stronger positive associations in the VP group. CONCLUSIONS: This study provides insights into the neurobiological basis of emotional and behavioral problems after preterm birth, highlighting the role of the structural connectome in internalizing and externalizing symptoms in childhood and adolescence.
BACKGROUND: Children born very preterm (VP) are at higher risk of emotional and behavioral problems compared with full-term (FT) children. We investigated the neurobiological basis of internalizing and externalizing symptoms in individuals born VP and FT by applying a graph theory approach. METHODS: Structural and diffusion magnetic resonance imaging data were combined to generate structural connectomes and calculate measures of network integration and segregation at 7 (VP: 72; FT: 17) and 13 (VP: 125; FT: 44) years. Internalizing and externalizing symptoms were assessed at 7 and 13 years using the Strengths and Difficulties Questionnaire. Linear regression models were used to relate network measures and internalizing and externalizing symptoms concurrently at 7 and 13 years. RESULTS: Lower network integration (characteristic path length and global efficiency) was associated with higher internalizing symptoms in VP and FT children at 7 years, but not at 13 years. The association between network integration (characteristic path length) and externalizing symptoms at 7 years was weaker, but there was some evidence for differential associations between groups, with lower integration in the VP group and higher integration in the FT group associated with higher externalizing symptoms. At 13 years, there was some evidence that associations between network segregation (average clustering coefficient, transitivity, local efficiency) and externalizing symptoms differed between the VP and FT groups, with stronger positive associations in the VP group. CONCLUSIONS: This study provides insights into the neurobiological basis of emotional and behavioral problems after preterm birth, highlighting the role of the structural connectome in internalizing and externalizing symptoms in childhood and adolescence.
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