Transdiagnostic alterations in neural emotion regulation circuits – neural substrates of cognitive reappraisal in patients with depression and post-traumatic stress disorder

Abstract

Background: Impaired cognitive reappraisal, associated with the social functioning and well-being of patients affected by mood or anxiety disorders, is characterized by distinct neural activation patterns across clinical populations. To date, studies dedicated to identifying common and distinct neural activation profiles need to be clarified. The aim of the present study was to investigate transdiagnostic differences and commonalities in brain activation patterns during reappraisal-mediated downregulation of emotions. Methods: Cognitive reappraisal of negative images was contrasted with maintaining emotions during a control viewing condition. Brain activation in 35 patients with major depressive disorder (MDD), 20 patients with post-traumatic stress disorder (PTSD), and 34 healthy controls (HC) during cognitive reappraisal was compared. Moreover, the neural circuitry of emotion regulation in these clinical populations was examined using seed-to-voxel and voxel-to-voxel functional connectivity analyses. Results: Whole-brain fMRI analyses showed less right-lateralized activation of the inferior, middle, and superior frontal gyrus during cognitive reappraisal compared to viewing of negative images in MDD and PTSD patients compared to HCs. Right IFG activation was negatively correlated with the severity of anxiety and depressive symptomatology. In addition, increased seed-to-voxel connectivity of the right IFG as well as increased voxel-to-voxel connectivity was observed in PTSD patients compared to HCs and MDD patients. Conclusions: FMRI results therefore suggested a common deficit of depression and anxiety symptomatology reflected by reduced activation in right IFG during cognitive reappraisal as well as diagnosis specific effects in patients with PTSD based on seed-to-voxel and voxel-to-voxel connectivity showing an overactive and hyperconnected salience network. Findings highlight the role of transdiagnostic research to identify disorder specific brain patterns as well as patterns common across disorders.