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

BackgroundPrior 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.FindingsThe 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.ConclusionsThese findings add to a growing literature highlighting the role of the insula in the pathophysiology of anxiety disorders.

[1]  A. Craig,et al.  How do you feel — now? The anterior insula and human awareness , 2009, Nature Reviews Neuroscience.

[2]  D. Grupe,et al.  Uncertainty and anticipation in anxiety: an integrated neurobiological and psychological perspective , 2013, Nature Reviews Neuroscience.

[3]  P. Lang,et al.  THE ANXIETY SPECTRUM AND THE REFLEX PHYSIOLOGY OF DEFENSE: FROM CIRCUMSCRIBED FEAR TO BROAD DISTRESS , 2012, Depression and anxiety.

[4]  Murray B. Stein,et al.  Anticipation of Aversive Visual Stimuli Is Associated With Increased Insula Activation in Anxiety-Prone Subjects , 2006, Biological Psychiatry.

[5]  S. Shankman,et al.  A psychophysiological investigation of threat and reward sensitivity in individuals with panic disorder and/or major depressive disorder. , 2013, Journal of abnormal psychology.

[6]  C. Grillon,et al.  Depressed mood enhances anxiety to unpredictable threat , 2011, Psychological Medicine.

[7]  Murray B. Stein,et al.  Intolerance of uncertainty correlates with insula activation during affective ambiguity , 2008, Neuroscience Letters.

[8]  A. Simmons,et al.  Anxiety positive subjects show altered processing in the anterior insula during anticipation of negative stimuli , 2011, Human brain mapping.

[9]  Christian Grillon,et al.  Major Depression Is Not Associated with Blunting of Aversive Responses; Evidence for Enhanced Anxious Anticipation , 2013, PloS one.

[10]  B. Morris,et al.  Emotion-modulated startle in anxiety disorders is blunted by co-morbid depressive episodes , 2010, Psychological Medicine.

[11]  Christopher K. Hsee,et al.  Risk as Feelings , 2001, Psychological bulletin.

[12]  J. Rabe-Jabłońska,et al.  [Affective disorders in the fourth edition of the classification of mental disorders prepared by the American Psychiatric Association -- diagnostic and statistical manual of mental disorders]. , 1993, Psychiatria polska.

[13]  P. Lang International affective picture system (IAPS) : affective ratings of pictures and instruction manual , 2005 .

[14]  J. M. Moran,et al.  Interactions between transient and sustained neural signals support the generation and regulation of anxious emotion. , 2013, Cerebral cortex.

[15]  H. Critchley,et al.  A common role of insula in feelings, empathy and uncertainty , 2009, Trends in Cognitive Sciences.

[16]  D. Fitzgerald,et al.  Anterior insula responds to temporally unpredictable aversiveness: an fMRI study , 2014, Neuroreport.

[17]  D. Watson Rethinking the mood and anxiety disorders: a quantitative hierarchical model for DSM-V. , 2005, Journal of abnormal psychology.

[18]  Janet B W Williams,et al.  Diagnostic and Statistical Manual of Mental Disorders , 2013 .

[19]  A. Simmons,et al.  Dorsolateral prefrontal cortex activation during emotional anticipation and neuropsychological performance in posttraumatic stress disorder. , 2012, Archives of general psychiatry.

[20]  A. Craig Significance of the insula for the evolution of human awareness of feelings from the body. , 2011, Annals of the New York Academy of Sciences.

[21]  R. McNally,et al.  Psychological approaches to panic disorder: a review. , 1990, Psychological bulletin.

[22]  S. Mineka,et al.  A modern learning theory perspective on the etiology of panic disorder. , 2001, Psychological review.

[23]  Thomas Straube,et al.  Waiting for spiders: Brain activation during anticipatory anxiety in spider phobics , 2007, NeuroImage.