Widespread white matter but focal gray matter alterations in depressed individuals with thoughts of death

Background: Past work demonstrates that depressed individuals with suicidal thoughts or behaviors exhibit specific neuroanatomical alterations. This may represent a distinct phenotype characterized by specific findings on neuroimaging, but it is unclear if these findings extend to individuals with milder thoughts of death. We examined this question in outpatients with recurrent Major Depressive Disorder not receiving antidepressant treatment. Methods: We examined 165 subjects: 53 depressed without thoughts of death, 21 depressed with thoughts of death, and 91 healthy comparison subjects. Participants completed 3 T cranial MRI, including anatomical and diffusion tensor imaging acquisitions. Automated methods measured regional gray matter volumes in addition to cortical thickness. White matter analyses examined diffusion measures within specific fiber tracts and included voxelwise comparisons. Results: After adjustment for multiple comparisons, the depressed group with thoughts of death did not exhibit differences in regional gray matter volume, but did exhibit reduced cortical thickness in frontoparietal regions and the insula. This depressed group with thoughts of death also exhibited widespread white matter differences in fractional anisotropy and radial diffusivity. These differences were observed primarily in posterior parietal white matter regions and central white matter tracts adjacent to the basal ganglia and thalamus. Conclusions: Mild thoughts of death are associated with structural alterations in regions of the salience network, default mode network, and thalamocortical circuits. Further work is needed to understand the pathological basis of these findings. Published by Elsevier Inc.