In-patient treatment and structural dysconnectivity in major depression – A longitudinal connectome study

Altered brain structural connectivity has been implicated in the pathophysiology of Major Depressive Disorder (MDD), yet its stability over time and responsiveness to treatment remain unclear. This study utilized network science to analyze the white matter connectome based on longitudinal magnetic resonance imaging data in MDD. In MDD patients (n = 109) undergoing various in-patient treatments (including n = 50 receiving electroconvulsive therapy (ECT)), we compared pre-treatment and six-week follow-up data to that of healthy controls (HC; n = 43). There was a significant group (MDD vs. HC)-by-time (pre vs. post) interaction (pFWE < 0.05; network based statistic t-threshold = 1.5, component size: 404 edges; Cohen's d = 0.104, 95% CI [0.102, 0.106]), which was driven by MDD patients showing significantly increased connectivity strength post-treatment in a widespread brain network. The observed changes in connectivity were not found in HC and were not confined to any specific treatment, indicating a general effect unrelated to particular therapies like ECT. Furthermore, the level of connectivity increase was linked to a reduction of depression symptoms (pFWE < 0.05; network based statistic t-threshold = 1.5, component size: 304 edges, partial η2 = 0.041, 95% CI [0.038, 0.044]), suggesting a link between neuroplastic effects and effective treatment. Brain connectome alterations show a dynamic pattern during treatment in MDD, indicative of a potential new biomarker for treatment response in MDD. Results underline the importance of considering brain connectome changes and neuroplastic mechanisms as potential treatment targets in MDD.