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Background  Prior studies suggest that hyperactive insula responding to unpredictable aversiveness is a core feature of anxiety disorders. However, no study to date has investigated the neural correlates of unpredictable aversiveness in those with panic disorder (PD) with comorbid major depressive disorder (MDD). The aim of the current study was to examine group differences in neural responses to unpredictable and predictable aversiveness in 41 adults with either 1) current PD with comorbid MDD (PD-MDD), 2) current MDD with no lifetime diagnosis of an anxiety disorder (MDD-only), or 3) no lifetime diagnosis of psychopathology. All participants completed a functional magnetic resonance imaging (fMRI) scan while viewing temporally predictable or unpredictable negative or neutral images.    Findings  The results indicated that individuals with PD-MDD exhibited greater bilateral insula activation to unpredictable aversiveness compared with controls and individuals with MDD-only (who did not differ). There were no group differences in insula activation to predictable aversiveness.    Conclusions  These findings add to a growing literature highlighting the role of the insula in the pathophysiology of anxiety disorders.

Insula response to unpredictable and predictable aversiveness in individuals with panic disorder and comorbid depression