Altered white matter connectivity in young people exposed to childhood abuse: a tract-based spatial statistics (TBSS) and tractography study

Altered white matter connectivity in young people exposed to childhood abuse: a tract-based spatial statistics (TBSS) and tractography study

J Psychiatry Neurosci 2019;44(4):E11-E20 | PDF | Appendix

Lena Lim, PhD*; Heledd Hart, PhD*; Henrietta Howells, PhD; Mitul A. Mehta, PhD; Andrew Simmons, PhD; Kah Mirza, MBBS; Katya Rubia, PhD

Background: Childhood abuse is associated with structural brain abnormalities. Few studies have investigated white matter tract abnormalities in medication-naive, drug-free individuals who experienced childhood abuse. We examined the association between childhood abuse and abnormalities in white matter tracts in that population, controlling for psychiatric comorbidities.

Methods: We collected diffusion tensor imaging data for age- and sex-matched youth with childhood abuse, psychiatric controls (matched for psychiatric diagnoses) and healthy controls. Tract-specific analysis was conducted using tractography. Tract-based spatial statistics (TBSS) was used to assess group differences in fractional anisotropy (FA) at the whole-brain level.

Results: We included 20 youth who experienced childhood abuse, 18 psychiatric controls and 25 healthy controls in our analysis. Tractography analysis showed abuse-specific reduced tract volume in the inferior longitudinal fasciculus (ILF) and inferior frontal-occipital fasciculus (IFoF) in the abuse group relative to both healthy and psychiatric controls. Furthermore, abnormalities in the left IFoF were associated with greater abuse severity. The TBSS analysis showed significantly reduced FA in a left-hemispheric cluster comprising the ILF, IFoF and corpus callosum splenium in the abuse group relative to healthy and psychiatric controls.

Limitations: It is unclear to what extent pubertal development, malnutrition and prenatal drug exposure may have influenced the findings.

Conclusion: Childhood abuse is associated with altered structure of neural pathways connecting the frontal, temporal and occipital cortices that are known to mediate affect and cognitive control. The abuse-specific deficits in the ILF and IFoF suggest that fibre tracts presumably involved in conveying and processing the adverse abusive experience are specifically compromised in this population.


*These authors contributed equally to this work.

Submitted Dec. 12, 2017; Revised Sept. 3, 2018; Accepted Nov. 10, 2018; Published online on Apr. 9, 2019

Acknowledgments: L. Lim and H. Howells were supported by the Reta Lila Weston Trust for Medical Research and the Kids Company UK. L. Lim was also supported by the Lee Kong Chian School of Medicine, Nanyang Technological University Singapore Fellowship Grant (grant number L0491050). H. Howells was supported by the Wellcome Trust (grant number 103759/Z/14/Z). A. Simmons and K. Rubia received research support from the UK Department of Health via the National Institute for Health Research (NIHR) Biomedical Research Centre (BRC) for Mental Health at South London and the Maudsley NHS Foundation Trust and Institute of Psychiatry, Psychology and Neuroscience, King’s College London. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health. The authors thank all the individuals who participated in this study and their families, as well as the staff of Kids Company London for their help with recruitment.

Affiliations: From the Department of Child & Adolescent Psychiatry, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, London, UK (Lim, Hart, Mirza, Rubia); the Lee Kong Chian School of Medicine, Imperial College – Nanyang Technological University Singapore, Singapore (Lim); the NatBrainLab, Department of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, London, UK (Howells); and the Department of Neuroimaging, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, London, UK (Mehta, Simmons).

Competing interests: M. Mehta has acted as a consultant for Cambridge Cognition and Lundbeck and has received fees from Shire for contribution towards education. K. Mirza has received research and educational grants from GlaxoSmithKline and Shire pharmaceuticals; served on the advisory boards of Janssen, Eli Lilly and Shire pharmaceuticals; and received honoraria for speaking at conferences organized by Janssen, Eli Lilly and Shire pharmaceuticals. K. Rubia has received speaker’s honoraria from Lilly and Shire. No other competing interests declared.

Contributors: L. Lim, H. Hart, M. Mehta, K. Mirza and K. Rubia designed the study. L. Lim, H. Hart and A. Simmons acquired the data, which L. Lim, H. Hart, H. Howells and K. Rubia analyzed. L. Lim and K. Rubia wrote the article, which all authors reviewed. All authors approved the final version to be published and can certify that no other individuals not listed as authors have made substantial contributions to the paper.

DOI: 10.1503/cjs.170241

Correspondence to: L. Lim, Lee Kong Chian School of Medicine, Imperial College London – Nanyang Technological University Singapore, Experimental Medicine Building Level 7, 59 Nanyang Drive, Singapore 636921; Lena.lim@ntu.edu.sg / Lena.lim@kcl.ac.uk