  Background: 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 MD patients 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. First, the threshold-free network-based statistics 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 network-based statistics revealed impaired connections
involvingregions of the basal ganglia in MD patients compared to 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
not-improved, 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.
