White matter abnormalities in depression: A categorical and phenotypic diffusion MRI study

Abstract

Mood depressive disorder is one of the most disabling chronic diseases with a high rate of everyday life disability that affects 350 million people around the world. Recent advances in neuroimaging have reported widespread structural abnormalities, suggesting a dysfunctional frontal-limbic circuit involved in the pathophysiological mechanisms of depression. However, a variety of different white matter regions has been implicated and is sought to suffer from lack of reproducibility of such categorical-based biomarkers. These inconsistent results might be attributed to various factors: actual categorical definition of depression as well as clinical phenotype variability. In this study, we 1/ examined WM changes in a large cohort (114 patients) compared to a healthy control group and 2/ sought to identify specific WM alterations in relation to specific depressive phenotypes such as anhedonia (i.e. lack of pleasure), anxiety and psychomotor retardation –three core symptoms involved in depression. Consistent with previous studies, reduced white matter was observed in the genu of the corpus callosum extending to the inferior fasciculus and posterior thalamic radiation, confirming a frontal-limbic circuit abnormality. Our analysis also reported other patterns of increased fractional anisotropy and axial diffusivity as well as decreased apparent diffusion coefficient and radial diffusivity in the splenium of the corpus callosum and posterior limb of the internal capsule. Moreover, a positive correlation between FA and anhedonia was found in the superior longitudinal fasciculus as well as a negative correlation in the cingulum. Then, the analysis of the anxiety and diffusion metric revealed that increased anxiety was associated with greater FA values in genu and splenium of corpus callosum, anterior corona radiata and posterior thalamic radiation. Finally, the motor retardation analysis showed a correlation between increased Widlöcher depressive retardation scale scores and reduced FA in the body and genu of the corpus callosum, fornix, and superior striatum. Through this twofold approach (categorical and phenotypic), this study has underlined the need to move forward to a symptom-based research area of biomarkers, which help to understand the pathophysiology of mood depressive disorders and to stratify precise phenotypes of depression with targeted therapeutic strategies.

Sex differences: Transcriptional signatures of stress exposure in male and female brains

“…The implication of ERα levels in stress susceptibility has also been suggested by a recent study in mice . Finally, sexually dimorphic transcriptional changes can also be found in other less‐explored regions such as the internal capsule, a bundle of white matter that participates in the corticostriatum‐thalamic circuitry and is structurally altered in psychiatric patients . Interestingly, Barley, Dracheva, and Byne found evidence in this region for a sex‐specific transcriptomic signature of oligodendrocytes in MDD and bipolar disorder.…”

“…80 Finally, sexually dimorphic transcriptional changes can also be found in other lessexplored regions such as the internal capsule, a bundle of white matter that participates in the corticostriatum-thalamic circuitry and is structurally altered in psychiatric patients. 81,82 Interestingly, Barley, Dracheva, and Byne 83 found evidence in this region for a sex-specific transcriptomic signature of oligodendrocytes in MDD and bipolar disorder. Overall, targeted studies have proven useful to explore specific candidate genes that were suspected to contribute to the sex dimorphism in psychiatry.…”

Microstructural changes in the reward system are associated with post-stroke depression

“…Our finding of increased FA in the anterior middle cingulum might be biased by crossing projections in this area from the internal capsule. FA has previously been observed to be increased in the internal capsule 40 of patients with MDD. Future studies, using multi-shell diffusion MRI sequences may wish to investigate the crossing fiber populations in this region.…”

Microstructural changes in the reward system are associated with post-stroke depression

“…Our finding of increased FA in the anterior middle cingulum might be biased by crossing projections in this area from the internal capsule. FA has previously been observed to be increased in the internal capsule ( Coloigner et al, 2019 ) of patients with MDD. Future studies, using multi-shell diffusion MRI sequences may wish to investigate the crossing fiber populations in this region.…”