Hypothalamus–Pituitary–Adrenal Axis Hyperresponsiveness Is Associated with Increased Social Avoidance Behavior in Social Phobia

BACKGROUND Social avoidance and inhibition in animals is associated with hyperresponsiveness of the glucocorticoid stress-system. In humans, the relation between glucocorticoid stress-reactivity and social avoidance behavior remains largely unexplored. We investigated whether increased cortisol stress-responsiveness is linked to increased social avoidance behavior in patients with social anxiety disorder (SAD). METHODS Patients with SAD (n = 18) as well as two control groups of healthy participants (n = 22) and patients with posttraumatic stress disorder (PTSD; n = 17), respectively, performed a social approach-avoidance task (AA-task) in a baseline condition and in a social stress condition (provided by the Trier Social Stress Test). The AA-task is a computerized reaction-time task measuring the speed of manual approach and avoidance responses to visually presented social threat cues (angry faces). Salivary cortisol, blood pressure, and subjective anxiety were assessed throughout the experiment. RESULTS Patients with SAD showed larger cortisol responses to the social stress test, as compared with healthy and PTSD control subjects. Most crucially, these increased cortisol responses were significantly correlated to the increase in social avoidance behavior measured by the AA-task in the social stress condition in SAD. An additional regression analysis showed that the cortisol responses predicted the stress-induced increase in social avoidance tendencies over and above the effects of blood pressure and subjective anxiety. CONCLUSIONS These findings provide the first evidence for a direct link between increased cortisol stress-responsiveness and social avoidance behavior in patients with SAD. The results support animal models of social avoidance and inhibition and might have important treatment implications.

[1]  A. Tobeña,et al.  Effects of Postnatal Handling of Rats on Emotional, HPA-Axis, and Prolactin Reactivity to Novelty and Conflict , 1996, Physiology & Behavior.

[2]  T. Heidenreich,et al.  Safety Behaviors and Social Performance in Patients With Generalized Social Phobia , 2006, Journal of Cognitive Psychotherapy.

[3]  Daniel A. Fitzgerald,et al.  Association between Amygdala Hyperactivity to Harsh Faces and Severity of Social Anxiety in Generalized Social Phobia , 2006, Biological Psychiatry.

[4]  S. Bögels,et al.  Validity of Two Questionnaires to Assess Social Fears: The Dutch Social Phobia and Anxiety Inventory and the Blushing, Trembling and Sweating Questionnaire , 1999 .

[5]  C. Kirschbaum,et al.  The 'Trier Social Stress Test'--a tool for investigating psychobiological stress responses in a laboratory setting. , 1993, Neuropsychobiology.

[6]  J. Romijn,et al.  Automated measurement of salivary cortisol. , 2003, Clinical chemistry.

[7]  R. Sapolsky.  Adrenocortical function, social rank, and personality among wild baboons , 1990, Biological Psychiatry.

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

[9]  K. Roelofs,et al.  The effects of stress-induced cortisol responses on approach–avoidance behavior , 2005, Psychoneuroendocrinology.

[10]  D F Klein,et al.  Generalized social phobia. Reliability and validity. , 1995, Archives of general psychiatry.

[11]  I. Toni,et al.  On the neural control of social emotional behavior. , 2009, Social cognitive and affective neuroscience.

[12]  D. M. Lyons,et al.  Salivary cortisol levels in socially phobic adolescent girls , 1999, Depression and anxiety.

[13]  A. Harvey,et al.  Cognitive Behavioural Processes Across Psychological Disorders: A Transdiagnostic Approach To Research And Treatment , 2004 .

[14]  D. A. Kenny,et al.  Estimating and testing mediation and moderation in within-subject designs. , 2001, Psychological methods.

[15]  O. Hart,et al.  The psychometric characteristics of the traumatic experiences checklist (TEC): first findings among psychiatric outpatients , 2002 .

[16]  A. Martínez,et al.  The AR face databasae , 1998 .

[17]  P. Ekman.  Pictures of Facial Affect , 1976 .

[18]  D. M. Lyons,et al.  Stress-Level Cortisol Treatment Impairs Inhibitory Control of Behavior in Monkeys , 2000, The Journal of Neuroscience.

[19]  S. Shelton,et al.  Individual differences in freezing and cortisol in infant and mother rhesus monkeys. , 1998, Behavioral neuroscience.

[20]  A. Beck,et al.  An inventory for measuring depression. , 1961, Archives of general psychiatry.

[21]  Aleix M. Martinez,et al.  The AR face database , 1998 .

[22]  E. Hermans,et al.  Toward a framework for defective emotion processing in social phobia , 2006, Cognitive neuropsychiatry.

[23]  J. Thakore,et al.  HPA axis response to a psychological stressor in generalised social phobia , 2002, Psychoneuroendocrinology.

[24]  R. Rapee.  Recent Advances in the Treatment of Social Phobia , 1993 .

[25]  M. Rinck,et al.  Avoidance of emotional facial expressions in social anxiety: The Approach-Avoidance Task. , 2007, Behaviour research and therapy.

[26]  R. H. Phaf,et al.  Automatic affective evaluation does not automatically predispose for arm flexion and extension. , 2004, Emotion.

[27]  I. Lucki,et al.  Abnormal salivary cortisol levels in social phobic patients in response to acute psychological but not physical stress , 2001, Biological Psychiatry.

[28]  D. Clark,et al.  Social anxiety and attention away from emotional faces , 1999 .

[29]  Deborah C. Beidel,et al.  An empirically derived inventory to measure social fears and anxiety: The Social Phobia and Anxiety Inventory. , 1989 .

[30]  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.

[31]  A. Wells.  A cognitive model of social phobia , 1995 .

[32]  Tk Bouman,et al.  Enige ervaringen met de Beck Depression Inventory (BDI) , 1985 .

[33]  J. Honk,et al.  BASELINE SALIVARY CORTISOL LEVELS AND PRECONSCIOUS SELECTIVE ATTENTION FOR THREAT A Pilot Study , 1998, Psychoneuroendocrinology.

[34]  S. Bögels,et al.  New developments in the treatment of social phobia. , 2006 .

[35]  M. Franklin.  Social phobia : diagnosis, assessment, and treatment , 1996 .

[36]  Sohee Park,et al.  Modulation of attentional inhibition by norepinephrine and cortisol after psychological stress. , 2000, International journal of psychophysiology : official journal of the International Organization of Psychophysiology.

[37]  C. Kirschbaum,et al.  Two formulas for computation of the area under the curve represent measures of total hormone concentration versus time-dependent change , 2003, Psychoneuroendocrinology.

[38]  K. Roelofs,et al.  The effects of cortisol administration on approach–avoidance behavior: An event-related potential study , 2007, Biological Psychology.

[39]  Marian Joëls,et al.  Stress and cognition: are corticosteroids good or bad guys? , 1999, Trends in Neurosciences.

[40]  J. Wolpe,et al.  Psychotherapy by reciprocal inhibition , 1958, Conditional reflex.

[41]  J. Honk,et al.  Conscious and preconscious selective attention to social threat: different neuroendocrine response patterns , 2000, Psychoneuroendocrinology.

[42]  C. Kirschbaum,et al.  Salivary cortisol in psychoneuroendocrine research: Recent developments and applications , 1994, Psychoneuroendocrinology.

[43]  C. E. Barrett,et al.  Behavioral inhibition and glucocorticoid dynamics in a rodent model , 2007, Physiology and Behavior.

[44]  K. Roelofs,et al.  The effects of social stress and cortisol responses on the preconscious selective attention to social threat , 2007, Biological Psychology.

[45]  J. Gorman,et al.  Responses of “generalized” and “discrete” social phobics during public speaking , 1993 .