Altered functional connectivity in posttraumatic stress disorder with versus without comorbid major depressive disorder: a resting state fMRI study

Posttraumatic stress disorder (PTSD) is an anxiety disorder that is often diagnosed with comorbid depressive disorder. Therefore, neuroimaging studies investigating PTSD typically include both patients with and without comorbid depression. Differences in activity of the anterior cingulate cortex (ACC) and insula have been shown to differentiate PTSD patients with and without major depressive disorder (MDD). Whether or not comorbid MDD affects resting state functional connectivity of PTSD patients has not been investigated to our knowledge. Here, resting state functional connectivity of PTSD patients with (PTSD+MDD; n=27) and without (PTSD-MDD; n=23) comorbid MDD was investigated. The subgenual ACC and insula were investigated as seed regions. Connectivity between the subgenual ACC and perigenual parts of the ACC was increased in PTSD+MDD versus PTSD-MDD. Reduced functional connectivity of the subgenual ACC with the thalamus was found in the PTSD+MDD group versus the PTSD-MDD group. These results remained significant after controlling for PTSD severity. In addition, the PTSD+MDD group showed reduced functional connectivity of the insula with the hippocampus compared to the PTSD-MDD group. However, this cluster was no longer significantly different when controlling for PTSD severity. Thus, resting state functional connectivity of the subgenual ACC may distinguish PTSD+MDD from PTSD-MDD. As PTSD patients with comorbid MDD are more treatment resistant, this result may be important for treatment development.