Specific alterations of resting-state functional connectivity in the triple network related to comorbid anxiety in major depressive disorder

The brain's default mode network (DMN) and the executive control network (ECN) switch engagement are influenced by the ventral attention network (VAN). Alterations in resting-state functional connectivity (RSFC) within this so-called triple network have been demonstrated in patients with major depressive disorder (MDD) or anxiety disorders (ADs). This study investigated alterations in the RSFC in patients with comorbid MDD and ADs to better understand the pathophysiology of this prevalent group of patients. Sixty-eight participants (52.9% male, mean age 35.3 years), consisting of 25 patients with comorbid MDD and ADs (MDD + AD), 20 patients with MDD only (MDD) and 23 healthy controls (HCs) were investigated clinically and with 3T resting-state fMRI. RSFC utilizing a seed-based approach within the three networks belonging to the triple network was compared between the groups. Compared with HC, MDD + AD showed significantly reduced RSFC between the ECN and the VAN, the DMN and the VAN and within the ECN. No differences could be found for the MDD group compared with both other groups. Furthermore, symptom severity and medication status did not affect RSFC values. The results of this study show a distinct set of alterations of RSFC for patients with comorbid MDD and AD compared with HCs. This set of dysfunctions might be related to less adequate switching between the DMN and the ECN as well as poorer functioning of the ECN. This might contribute to additional difficulties in engaging and utilizing consciously controlled emotional regulation strategies. This study highlights alterations of resting-state functional connectivity within the well-established triple network model in patients with comorbid depression and anxiety disorders. The clusters found within the cingulate and paracingulate and frontal areas may play an important role in the specific symptomatology of comorbid MDD and AD.image