Effects of early-life adversity on white matter diffusivity changes in patients at risk for major depression

Effects of early-life adversity on white matter diffusivity changes in patients at risk for major depression


J Psychiatry Neurosci 2012;37(1):37-45

Thomas Frodl, MD, MA; Angela Carballedo; Andrew J. Fagan, PhD; Danuta Lisiecka, MSc, MA; Yolande Ferguson, MSc, MB; James F. Meaney, MB

Frodl, Carballedo, Lisiecka, Ferguson — Department of Psychiatry, School of Medicine, Trinity College Institute of Neuroscience & Trinity Centre for Health Sciences, The Adelaide and Meath Hospital incorporating the National Children’s Hospital and St. James’s Hospital, Trinity College, Dublin, Ireland; Fagan, Meaney — Centre of Advanced Medical Imaging, St. James’s Hospital, Trinity College Dublin, Ireland


Background: Relatives of patients with major depressive disorder (MDD) and people who experienced early-life adversity are at risk for MDD. The aim of our study was to investigate whether unaffected first-degree healthy relatives (UHRs) of patients with MDD show changes in white matter fibre connections compared with healthy controls and whether there are interactions between early-life adversity and these microstructural changes.
Methods: Unaffected, healthy first-degree relatives of patients with MDD and healthy controls without any family history for a psychiatric disease underwent high angular resolution diffusion imaging with 61 diffusion directions. Data were analyzed with tract-based spatial statistics, and findings were confirmed with tractography.
Results: Twenty-one UHRs and 24 controls participated in our study. The UHRs showed greater fractional anisotropy than controls in the body and splenium of the corpus callosum, inferior fronto-occipital fasciculus (IFO), left superior longitudinal fasciculus (SLF) and right fornix. The UHRs who experienced more early-life adversity had greater fractional anisotropy than those with less early-life adversity in the splenium of the corpus callosum, fornix, IFO and SLF; in controls, early-life adversity was found to be associated with decreased fractional anisotropy in these fibre tracts.
Limitations: Studying participants’ strategies for coping with early-life adversity would have been helpful. Crossing fibres in tracts are a general limitation of the method used.
Conclusion: Altogether, our findings provide evidence for greater fractional anisotropy in UHRs and for interaction between early-life adversity and family risk on white matter tracts involved in cognitive–emotional processes. Whether stronger neural fibre connections are associated with more resilience against depression needs to be addressed in future studies.

Submitted Mar. 23, 2011; Revised May 26, June 22, 2011; Accepted June 24, 2011.

Acknowledgments: We thank Science Foundation Ireland for a fund to conduct the present research, awarded to T. Frodl (grant no. SFI/07/SK/B1214C Science Foundation Strokes Professorship Grant) as well as Health Research Board Ireland for funding the research Centre of Advanced Medical Imaging.

Competing interests: None declared; as above for T. Frodl.

Contributors: T. Frodl, A. Carballedo and J.F. Meaney designed the study. All authors acquired the data, which T. Frodl and J.F. Meaney analyzed. T. Frodl, D. Lisiecka and Y. Ferguson wrote the article, which T. Frodl, A. Carballedo, A.J. Fagan and J.F. Meaney reviewed. All authors approved publication.

DOI: 10.1503/jpn.110028

Correspondence to: Prof. T. Frodl, Department of Psychiatry, Institute of Neuroscience, Trinity College Dublin, Dublin 2, Ireland; thomas.frodl@tcd.ie