Decreased Resting-State Connectivity between Neurocognitive Networks in Treatment Resistant Depression

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.

Decoupling of the amygdala to other salience network regions in adolescent-onset recurrent major depressive disorder

“…In contrast, this was not evident in the comparison between SE MDDs and HCs, offering further evidence that the recurrence of illness may lead to disruption of SN function through decoupling. To date, a few studies have implicated decreased network coupling in treatment-resistant depression (de Kwaasteniet et al 2015; Dichter et al 2015); however, our results suggest that this decoupling may occur much earlier in the course of recurrent MDD. Moreover, weakened connectivity between the left amygdala and right caudate among multiple MDEs compared with HCs indicates an effect of burden.…”

Behavioral activation can normalize neural hypoactivation in subthreshold depression during a monetary incentive delay task

“…(Lisiecka et al, 2011). Moreover, the connectivity between DLPFC and angular gyrus is known to decrease in treatment resistant depression (de Kwaasteniet et al, 2015). Therefore, the pattern of changes in VLPFC and angular gyrus observed in the present study might be associated with improvements of negative emotional regulation through cognitively mediated strategies.…”

Cortical abnormalities and association with symptom dimensions across the depressive spectrum

“…This may suggest that excessive worry in association with volumetric reductions in the VLPFC may indicate risk for depressive illness and recurrence. Furthermore, reductions in the right VLPFC CV may be related to disruption in prefrontal cortical cognitive control as has been shown in functional studies of worry (Owens, Derakshan, and Richards 2015) and anxiety (de Kwaasteniet et al 2015). Moreover, rumination, a cognitive symptom related to worry, crosses diagnostic boundaries with other psychiatric conditions, has been related to abnormalities in negative valence systems (Woody and Gibb 2015), and has been shown to mediate the association between depressive and anxiety disorders (McLaughlin and Nolen-Hoeksema 2011).…”