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

Mitzy Kennis,Arthur R Rademaker,Elbert Geuze,Sanne J.H Van Rooij,René S Kahn

doi:10.12688/f1000research.2-289.v2

Mitzy Kennis, Arthur R Rademaker + Show 3 more

Open Access

https://doi.org/10.12688/f1000research.2-289.v2

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Abstract

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, which may reflect the presence of depressive specific symptoms such as rumination. Functional connectivity of the subgenual ACC with the thalamus was reduced, potentially related to more severe deficits in executive functioning in the PTSD+MDD group versus the PTSD-MDD group. 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 PTSD patients that were using medication were excluded from analyses. Thus, resting state functional connectivity of the subgenual ACC can distinguish PTSD+MDD from PTSD-MDD, and this may therefore be used as a neurobiological marker for comorbid MDD in the presence of PTSD. As PTSD+MDD are more treatment resistant, these findings can also guide treatment development, for example by targeting the subgenual ACC network with treatment.

Highlights

Posttraumatic stress disorder (PTSD) is an anxiety disorder that can develop after a traumatic event
The PTSD+major depressive disorder (MDD) group differed from the PTSD-MDD group in total PTSD severity (CAPS score; p=0.008), which appeared to be largely driven by differences in avoidance and emotional numbing symptom scores
Increased subgenual anterior cingulate cortex (ACC) connectivity with the perigenual ACC was found in PTSD+MDD versus PTSD-MDD, which is in line with neuroimaging studies that have found increased resting state functional connectivity between the subgenual ACC and perigenual ACC in MDD versus controls[20,21,22]

Summary

Introduction

Posttraumatic stress disorder (PTSD) is an anxiety disorder that can develop after a traumatic event. It is characterized by reexperiencing the traumatic event, avoidance of trauma reminders and emotional numbing symptoms, and increased arousal[1]. PTSD frequently co-occurs with other Axis I psychiatric disorders, such as major depressive disorder (MDD2). Studies have demonstrated that comorbidity between mood and anxiety disorders increases risk for cardiovascular disease, autoimmune diseases and mortality[6,7]. Studies investigating the neurobiology of PTSD often comprise patients with and without comorbid MDD. Studies have demonstrated that comorbidity between the mood and anxiety disorders increases risk for CVD and mortality (Philips et al, 2009). I would have thought that the amygdala region would have been a more appropriate second choice, especially given the many past studies that have focused on the amygdala as a region of interest in patients with PTSD

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