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.

Keywords: Categorical and phenotypic approach; Depression; Diffusion-weighted imaging; Fractional anisotropy value; Voxel-based analysis.

Fig. 1

Axial, coronal and sagittal brain slices showing significant differences of the FA values between MDD and CTL groups. Voxels with negative t-values (MDD < Control) are shown in blue and positive values (MDD > Control) with red. The acronym gCC indicates the genu of corpus callosum (CC); sCC, splenium of CC; ACR, anterior of the corona radiata; PTR, posterior thalamic radiation; ILF, inferior longitudinal fasciculus; PLIC, posterior Limb of the internal capsule; CCG, cingulum. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)

Fig. 2

Axial, coronal and sagittal brain slices showing significant correlation between FA values and clinical variables: (A) WDRS, (B) STAI-YA and (C) SHAPS within the MDD group. Voxels with negative correlation are shown in blue and positive correlation with red. The acronym gCC indicates the genu of corpus callosum (CC); bCC, body of CC; ACR, anterior of the corona radiata; PTR, posterior thalamic radiation; ILF, inferior longitudinal fasciculus; SCR, superior, superior corona radiata; CCG, cingulum. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)