White Matter Microstructure Variations Increase Risk for Depression in Adolescents

In adolescents with subthreshold depression, early fractional anisotropy (FA) variations in tracts projecting from the corpus callosum to the anterior cingulated cortex may confer a greater risk for transition to depression, according to the results of a study published in the American Journal of Psychiatry.

Helene Vulser, MD, PhD, of INSERM, Research Unit UMR 1000, Research Unit “Neuroimaging and Psychiatry,” Paris; University Paris-Saclay, Gif-sur-Yvette, France; University Paris Descartes, Paris, and colleagues recruited 96 adolescents with subthreshold depression and 336 healthy controls drawn from a community-based cohort. Using diffusion tensor imaging and whole brain tract-based spatial statistics (TBSS), the researchers assessed white matter microstructure when the participants were age 14. They reassessed these individuals for depression at age 16.

The odds ratio (OR) for depression in patients with subthreshold depression at age 14 was 3.96. Higher scores on neuroticism and hopelessness at age 14 also increased the risk for a diagnosis of depression at age 16 (P <.001).

In adolescents with subthreshold depression, the researchers found lower FA and higher radial diffusivity in the anterior corpus callosum. Tractography analysis also demonstrated lower FA in the right cingulum streamlines, as well as lower FA and higher mean diffusivity in tracts connecting the corpus callosum to the anterior cingulate cortex. FA values in these tracts mediated the risk for transitioning from subthreshold depression at baseline to depression at follow-up, with lower FA values increasing the risk for subsequent depression and accounting for 21% of the total variance (P =.01) in the relationship between subthreshold depression at baseline and depression at age 16.

Of note, while the lower FA values in tracts connecting the corpus callosum to the anterior cingulated cortex conferred a greater risk for depression, it did not do so for other psychiatric illnesses. In contrast, higher scores on neuroticism and hopelessness at age 14 increased the risk not only for depression but also for other diagnoses.

The investigators suggest that these adolescents may have delayed white matter maturation or early alterations in tracts connecting the anterior corpus callosum to the anterior cingulate cortex, and this may carry a high risk for transition to depression.

Reference

Vulser H, Paillere Martinot M-L, Artiges E, et al. Early variations in white matter microstructure and depression outcome in adolescents with subthreshold depression [published online August 16, 2018]. Am J Psychiatry. doi:10.1176/appi.ajp.2018.17070825