A review of white matter microstructure alterations of pathways of the reward circuit in depression

BACKGROUND: Depressed mood, anhedonia, psychomotor retardation and alterations of circadian rhythm are core features of the depressive syndrome. Its neural correlates can be located within a frontal-striatal-tegmental neural network, commonly referred to as the reward circuit. It is the aim of this article to review literature on white matter microstructure alterations of the reward system in depression. METHOD: We searched for diffusion tensor imaging (DTI)-studies that have explored neural deficits within the cingulum bundle, the uncinate fasciculus and the supero-lateral medial forebrain bundle/anterior thalamic radiation - in adolescent and adult depression (acute and remitted), melancholic depression, treatment-resistant depression and those at familial risk of depression. The relevant diffusion MRI literature was identified using PUBMED. RESULTS: Thirty-five studies were included. In people at familial risk for depression the main finding was reduced fractional anisotropy (FA) in the cingulum bundle. Both increases and decreases of FA have been reported in the uncinate fasciculus in adolescents. Reductions of FA in the uncinate fasciculus and the anterior thalamic radiation/supero-lateral medial forebrain bundle during acute depressive episodes in adults were most consistently reported. LIMITATIONS: Non-quantitative approach. CONCLUSIONS: Altered cingulum bundle microstructure in unaffected relatives may either indicate resilience or vulnerability to depression. Uncinate fasciculus and supero-lateral medial forebrain bundle microstructure may be altered during depressive episodes in adult MDD. Future studies call for a careful clinical stratification of clinically meaningful subgroups