Amygdala activation and its functional connectivity during perception of emotional faces in social phobia and panic disorder.

Social phobia (SP) and panic disorder (PD) have been associated with aberrant amygdala responses to threat-related stimuli. The aim of the present study was to examine amygdala function and its connectivity with medial prefrontal cortex (mPFC) during emotional face perception in PD and SP, and the role of illness severity. Blood oxygen level dependent responses while perceiving emotional facial expressions were compared in 14 patients with PD, 17 patients with SP, 8 patients with comorbid PD and SP, and 16 healthy controls. We found that PD, but not SP, was associated with amygdala and lingual gyrus hypoactivation during perception of angry, fearful, happy and neutral faces, compared to healthy participants. No significant effect of PD and SP diagnoses was found on amygdala-mPFC connectivity. A positive correlation of anxiety symptom severity was found on amygdala-dorsal anterior cingulate and dorsal mPFC connectivity during perception of fearful faces. Amygdala hypoactivation suggests reduced responsiveness to positive and negative emotional faces in PD. Symptom severity, but not the presence of PD and SP diagnosis per se, explains most of the abnormalities in amygdala-mPFC connectivity during perception of fearful faces.

[1]  A. Mathews,et al.  Brief standard self-rating for phobic patients. , 1979, Behaviour research and therapy.

[2]  Joseph E LeDoux.  Emotion Circuits in the Brain , 2000 .

[3]  Jason A. Elias,et al.  Increased activation of the anterior cingulate cortex during processing of disgust faces in individuals with social phobia , 2005, Biological Psychiatry.

[4]  Daniel A. Fitzgerald,et al.  Amygdala reactivity to emotional faces at high and low intensity in generalized social phobia: A 4-Tesla functional MRI study , 2007, Psychiatry Research: Neuroimaging.

[5]  M. Guazzelli,et al.  Is Social Phobia a “Mis-Communication” Disorder? Brain Functional Connectivity during Face Perception Differs between Patients with Social Phobia and Healthy Control Subjects , 2010, Front. Syst. Neurosci..

[6]  M. Weissman,et al.  Social Phobia: Comorbidity and Morbidity in an Epidemiologic Sample , 1992 .

[7]  Katharina Domschke,et al.  Imaging genetics of anxiety disorders , 2010, NeuroImage.

[8]  S. Rombouts,et al.  Frontiers in Systems Neuroscience Systems Neuroscience , 2022 .

[9]  A. Etkin,et al.  Functional neuroimaging of anxiety: a meta-analysis of emotional processing in PTSD, social anxiety disorder, and specific phobia. , 2007, The American journal of psychiatry.

[10]  T. Furmark,et al.  Genotype over-diagnosis in amygdala responsiveness: affective processing in social anxiety disorder. , 2009, Journal of psychiatry & neuroscience : JPN.

[11]  D. Klein,et al.  Delineating the boundaries of social phobia: Its relationship to panic disorder and agoraphobia , 1990 .

[12]  Luca Passamonti,et al.  Anxiety predicts a differential neural response to attended and unattended facial signals of anger and fear , 2009, NeuroImage.

[13]  M. Keller,et al.  Characteristics and predictors of social phobia course in a longitudinal study of primary‐care patients , 2010, Depression and anxiety.

[14]  Thomas Straube,et al.  Effect of task conditions on brain responses to threatening faces in social phobics: An event-related functional magnetic resonance imaging study , 2004, Biological Psychiatry.

[15]  M. Åsberg,et al.  A New Depression Scale Designed to be Sensitive to Change , 1979, British Journal of Psychiatry.

[16]  Justine M. Kent,et al.  Neuroanatomical Hypothesis of Panic Disorder, Revised , 2004 .

[17]  Nicola Vanello,et al.  Differential modulation of neural activity throughout the distributed neural system for face perception in patients with Social Phobia and healthy subjects , 2008, Brain Research Bulletin.

[18]  T. Allison,et al.  Differential Sensitivity of Human Visual Cortex to Faces, Letterstrings, and Textures: A Functional Magnetic Resonance Imaging Study , 1996, The Journal of Neuroscience.

[19]  V. Arolt,et al.  fMRI amygdala activation during a spontaneous panic attack in a patient with panic disorder , 2007, The world journal of biological psychiatry : the official journal of the World Federation of Societies of Biological Psychiatry.

[20]  P. Cuijpers,et al.  The Netherlands Study of Depression and Anxiety (NESDA): rationale, objectives and methods , 2008, International journal of methods in psychiatric research.

[21]  T. Egner,et al.  Emotional processing in anterior cingulate and medial prefrontal cortex , 2011, Trends in Cognitive Sciences.

[22]  A. Beck,et al.  An inventory for measuring clinical anxiety: psychometric properties. , 1988, Journal of consulting and clinical psychology.

[23]  S. Rauch,et al.  What is an anxiety disorder? , 2009, Depression and anxiety.

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

[25]  Olga V. Demler,et al.  Lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the National Comorbidity Survey Replication. , 2005, Archives of general psychiatry.

[26]  A. Ehlis,et al.  Neural correlates of spontaneous panic attacks , 2011, Journal of Neural Transmission.

[27]  Fanny Eugène,et al.  Amygdala activation in the processing of neutral faces in social anxiety disorder: Is neutral really neutral? , 2006, Psychiatry Research: Neuroimaging.

[28]  Bruce Fischl,et al.  A Role for the Human Dorsal Anterior Cingulate Cortex in Fear Expression , 2007, Biological Psychiatry.

[29]  J. A. Boer,et al.  rCBF differences between panic disorder patients and control subjects during anticipatory anxiety and rest , 2002, Biological Psychiatry.

[30]  J. Francis,et al.  Characteristics and course of panic disorder and panic disorder with agoraphobia in primary care patients. , 2007, Primary care companion to the Journal of clinical psychiatry.

[31]  Thomas Weiss,et al.  Dynamic activation of the anterior cingulate cortex during anticipatory anxiety , 2009, NeuroImage.

[32]  P. Whalen,et al.  The structural and functional connectivity of the amygdala: From normal emotion to pathological anxiety , 2011, Behavioural Brain Research.

[33]  J. A. Boer,et al.  Functional Magnetic Resonance Imaging Correlates of Emotional Word Encoding and Recognition in Depression and Anxiety Disorders , 2012, Biological Psychiatry.

[34]  Karl J. Friston,et al.  Statistical parametric maps in functional imaging: A general linear approach , 1994 .

[35]  Paul J. Laurienti,et al.  An automated method for neuroanatomic and cytoarchitectonic atlas-based interrogation of fMRI data sets , 2003, NeuroImage.

[36]  Thomas Straube,et al.  Common and Distinct Brain Activation to Threat and Safety Signals in Social Phobia , 2005, Neuropsychobiology.

[37]  M. Posner,et al.  Cognitive and emotional influences in anterior cingulate cortex , 2000, Trends in Cognitive Sciences.

[38]  S. Sara,et al.  Hippocampal Sharp Wave/Ripples during Sleep for Consolidation of Associative Memory , 2009, PLoS ONE.

[39]  P. Whalen.  Fear, Vigilance, and Ambiguity , 1998 .

[40]  Dick J. Veltman,et al.  Amygdala responses to emotional faces in twins discordant or concordant for the risk for anxiety and depression , 2008, NeuroImage.

[41]  A. Aleman,et al.  Functional MRI correlates of visuospatial planning in out‐patient depression and anxiety , 2011, Acta psychiatrica Scandinavica.

[42]  Bruce W. Smith,et al.  Response to emotional expressions in generalized social phobia and generalized anxiety disorder: evidence for separate disorders. , 2008, The American journal of psychiatry.

[43]  M. Paulus,et al.  Time-Varying Amygdala Response to Emotional Faces in Generalized Social Phobia , 2007, Biological Psychiatry.

[44]  M. Czisch,et al.  Unstable Prefrontal Response to Emotional Conflict and Activation of Lower Limbic Structures and Brainstem in Remitted Panic Disorder , 2009, PloS one.

[45]  D. Yurgelun-Todd,et al.  fMRI of fearful facial affect recognition in panic disorder: the cingulate gyrus-amygdala connection. , 2006, Journal of affective disorders.

[46]  Karl J. Friston,et al.  Psychophysiological and Modulatory Interactions in Neuroimaging , 1997, NeuroImage.

[47]  Henk J Groenewegen,et al.  Disorder-specific neuroanatomical correlates of attentional bias in obsessive-compulsive disorder, panic disorder, and hypochondriasis. , 2005, Archives of general psychiatry.

[48]  U Klose,et al.  fMRI reveals amygdala activation to human faces in social phobics , 1998, Neuroreport.

[49]  Gregory G. Brown,et al.  Increased amygdala activation to angry and contemptuous faces in generalized social phobia. , 2002, Archives of general psychiatry.

[50]  D. Pine,et al.  Neural response to self- and other referential praise and criticism in generalized social phobia. , 2008, Archives of general psychiatry.

[51]  S. Rauch,et al.  Neurocircuitry of anxiety disorders , 2003, Current psychiatry reports.

[52]  G. Andrews,et al.  The psychometric properties of the Composite International Diagnostic Interview , 1998, Social Psychiatry and Psychiatric Epidemiology.

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

[54]  A. Aleman,et al.  Neural correlates of perception of emotional facial expressions in out-patients with mild-to-moderate depression and anxiety. A multicenter fMRI study , 2011, Psychological Medicine.

[55]  Mats Fredrikson,et al.  Disentangling the web of fear: Amygdala reactivity and functional connectivity in spider and snake phobia , 2009, Psychiatry Research: Neuroimaging.