The Link Between Structural and Functional Brain Abnormalities in Depression: A Systematic Review of Multimodal Neuroimaging Studies

BACKGROUND: Adequate and timely identification of depression is essential to improve patient care. A potential method to achieve this is by using neuroimaging. Many neuroimaging studies have revealed widespread abnormalities in brain structure and function in patients with depression, but in most studies only single neuroimaging modalities were used. Links between abnormalities in brain structure and function need to be therefore further explored in order to define diagnostic and therapeutic applications. METHODS: A systematic literature review according to preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines was conducted. RESULTS: Out of 2,516 articles, only 14 studies were eligible to be included. These studies combined structural and functional neuroimaging methods in depressed patients compared to controls. Four studies reported a negative relationship between brain structure and function within the default mode network: reduced gray or white matter integrity in depressed patients compared to healthy controls was associated with enhanced neural activity or connectivity. The other studies reported positive relationships (two studies), mixed relationships (two studies), or no link (six studies) between structural and functional brain abnormalities. CONCLUSION: This systematic literature review revealed no robust relationship between abnormalities in brain structure and function in patients with depression. Remarkably, only 14 studies could be included and four of these suggested enhanced default mode network connectivity associated with reduced structural brain integrity. In the ongoing development of the diagnostic and treatment applications of neuroimaging, large-scale studies that combine structural with functional neuroimaging are required to determine the relationship between structural and functional abnormalities in depression.