Abstract
Approximately one-third of patients with major depressive disorder (MDD) do not achieve remission after various treatment options and develop treatment resistant depression (TRD). So far, little is known about the pathophysiology of TRD. Studies in MDD patients showed aberrant functional connectivity (FC) of three “core” neurocognitive networks: the salience network (SN), cognitive control network (CCN), and default mode network (DMN). We used a cross-sectional design and performed resting-state FC MRI to assess connectivity of the SN, CCN, and both anterior and posterior DMN in 17 severe TRD, 18 non-TRD, and 18 healthy control (HC) subjects. Relative to both non-TRD and HC subjects, TRD patients showed decreased FC between the dorsolateral prefrontal cortex and angular gyrus, which suggests reduced FC between the CCN and DMN, and reduced FC between the medial prefrontal cortex and precuneus/cuneus, which suggests reduced FC between the anterior and posterior DMN. No significant differences in SN FC were observed. Our results suggest that TRD is characterized by a disturbance in neurocognitive networks relative to non-TRD and HC.
Highlights
About one-third of patients with major depressive disorder (MDD) do not respond to two or more adequate prescribed antidepressants
The duration of the current depressive episode and the number of past treatments were significantly higher in the treatment resistant depression (TRD) group: 83.3 (±44.6) months and 6.5 (±2.7) treatments in TRD versus 11.9 (±8.9) months and 1.8 (±2.6) treatments in MDD
RESTING-STATE NETWORKS To probe the networks of interest, we assessed whole-brain voxelwise positive correlations with the three seed ROIs (p < 0.05 family wise error (FWE) corrected, Figure 1). These analyses showed that the cognitive control network (CCN) consisted of the dorsolateral prefrontal cortex (DLPFC), dorsal anterior cingulate cortex (ACC), caudate, and inferior parietal gyrus
Summary
About one-third of patients with major depressive disorder (MDD) do not respond to two or more adequate prescribed antidepressants. They are considered to be suffering from treatment resistant depression (TRD) [1, 2], which is associated with an overall worse prognosis and higher medical costs [3]. Few neuroimaging studies have investigated the neural mechanisms underlying TRD, mostly focusing on regional brain activity and yielding equivocal results [4, 5]. FC analysis quantifies the temporal correlation of neuronal activity patterns of anatomically separated brain regions [10, 11] and can be used to investigate the interaction within and between brain networks. Several studies showed aberrant FC within and between the salience network (SN) [12, 13], cognitive control network (CCN) [12], and default mode network (DMN) [7, 8, 12] in depressive patients
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