The treatment of depressive episodes is well established, with clearly demonstrated effectiveness of antidepressants and psychotherapies. However, more than one-third of depressed patients do not respond to treatment. Identifying the brain structural basis of treatment-resistant depression could prevent useless pharmacological prescriptions, adverse events, and lost therapeutic opportunities.
Methods:
Using diffusion magnetic resonance imaging, we performed structural connectivity analyses on a cohort of 154 patients with mood disorder (MD) and 77 sex- and age-matched healthy control (HC) participants. To assess illness improvement, the patients with MD went through two clinical interviews at baseline and at 6-month follow-up and were classified based on the Clinical Global Impression-Improvement score into improved or not-improved (NI). First, the threshold-free network-based statistics (NBS) was conducted to measure the differences in regional network architecture. Second, nonparametric permutations tests were performed on topological metrics based on graph theory to examine differences in connectome organization.
Results:
The threshold-free NBS revealed impaired connections involving regions of the basal ganglia in patients with MD compared with HC. Significant increase of local efficiency and clustering coefficient was found in the lingual gyrus, insula, and amygdala in the MD group. Compared with the NI, the improved displayed significantly reduced network integration and segregation, predominately in the default-mode regions, including the precuneus, middle temporal lobe, and rostral anterior cingulate.
Conclusions:
This study highlights the involvement of regions belonging to the basal ganglia, the fronto-limbic network, and the default mode network, leading to a better understanding of MD disease and its unfavorable outcome.
Impact Statement
Different treatments have been developed for patients suffering from mood disorder (MD). Yet, more than one-third of depressed patients do not respond to them. The present study provides statistical analysis of brain structural networks using the threshold-free network-based statistics and graph theoretical approaches based on a large cohort of patients with MD. This enabled the identification of salient regions involved in MD and the process of treatment-resistant depression. Some of the findings are coherent with the results based on functional connectivity, which strengthens the motivation to jointly study both structural and functional connectivity.
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