The relationship between early life stress and microstructural integrity of the corpus callosum in a non-clinical population

Robert Paul¹, Lorrie Henry², Stuart M Grieve³, Thomas J Guilmette^2,4, Raymond Niaura⁴, Richard Bryant⁵, Steven Bruce¹, Leanne M Williams^3,6, Clark C Richard⁷, Ronald A Cohen⁴, Evian Gordon^3,7

¹University of Missouri, St. Louis, St. Louis, MO, USA; ²Providence College, Providence, RI, USA; ³The Brain Resource International Database, The Brain Resource Company, Ultimo, NSW, Australia; ⁴Brown Medical School, Department of Psychiatry, Providence, RI, USA; ⁵School of Psychology, University of New South Wales, Sydney, NSW, Australia; ⁶Brain Dynamics Centre, Westmead Millennium Institute, Westmead Hospital, Westmead, NSW, Australia; ⁷Cognitive Neuroscience Laboratory and School of Psychology, Flinders University, Adelaide, SA, Australia

Background: Previous studies have examined the impact of early life stress (ELS) on the gross morphometry of brain regions, including the corpus callosum. However, studies have not examined the relationship between ELS and the microstructural integrity of the brain.

Methods: In the present study we evaluated this relationship in healthy non-clinical participants using diffusion tensor imaging (DTI) and self-reported history of ELS.

Results: Regression analyses revealed significant reductions in fractional anisotropy (FA) within the genu of the corpus callosum among those exposed to the greatest number of early life stressors, suggesting reduced microstructural integrity associated with increased ELS. These effects were most pronounced in the genu of the corpus callosum compared to the body and splenium, and were evident for females rather than males despite no differences in total ELS exposure between the sexes. In addition, a further comparison of those participants who were exposed to no ELS vs. three or more ELS events revealed lower FA in the genu of the corpus callosum among the ELS-exposed group, with trends of FA reduction in the body and the whole corpus callosum. By contrast, there were no relationships between ELS and volumetric analysis of the CC regions. The two groups did not differ significantly on measures of current depression, stress or anxiety.

Conclusion: Our results reveal that greater exposure to ELS is associated with microstructural alterations in the white matter in the absence of significant volumetric changes. Importantly, our results indicate that exposure to ELS is associated with abnormalities on DTI despite the absence of clinically significant psychiatric symptoms. Future studies are needed to determine whether specific types of ELS are more likely to impact brain structure and function.