5 Limitations

Several limitations must be considered when interpreting the results of the current study.
First, this study only compared the comorbid patient group (MDD+AD) with patients with MDD alone. Future research comparing comorbid patients with patients with only anxiety disorders and no MDD would be essential to gain further insight into the specific pathophysiology of this group of disorders.
In addition, the close connection of the VAN to the amygdala plays a key role in the interpretation of RSFC changes in patients with anxiety disorders. Several studies have shown altered RSFC between the VAN and the amygdala (Pisoni et al., 2021; Williams, 2016). The amygdala is known to play a central role in the development and maintenance of anxiety disorders (Rauch et al., 2003). One possibility from a network perspective is that the amygdala functions by signalling saliency to the insula, a key node of the VAN (Menon, 2011; Paulus & Stein, 2006). Thus, disruptions in amygdala function and its connectivity to the VAN are thought to alter the ability of the VAN to adequately switch between the DMN and the ECN (Paulus & Stein, 2006). Because we utilized the networks as defined by Yeo et al. (2011), the amygdala was not included in our analysis. However, several authors, including Menon (2011), consider the amygdala as part of the salience network, commonly equalized with or seen as a part of the VAN (Yeo et al., 2011). Therefore, we suggest this as an important issue for further research.
Medication was not found to have a significant effect on the results. However, there are findings that antidepressant medication influences RSFCs (Rolls et al., 2019) and in our study the effect of medication may not have been detected since only 25 % of patients were unmedicated at the time of the study. Thus, future studies should focus on antidepressant-free patients