Glucocorticoids enhance extinction-based psychotherapy

Behavioral exposure therapy of anxiety disorders is believed to rely on fear extinction. Because preclinical studies have shown that glucocorticoids can promote extinction processes, we aimed at investigating whether the administration of these hormones might be useful in enhancing exposure therapy. In a randomized, double-blind, placebo-controlled study, 40 patients with specific phobia for heights were treated with three sessions of exposure therapy using virtual reality exposure to heights. Cortisol (20 mg) or placebo was administered orally 1 h before each of the treatment sessions. Subjects returned for a posttreatment assessment 3–5 d after the last treatment session and for a follow-up assessment after 1 mo. Adding cortisol to exposure therapy resulted in a significantly greater reduction in fear of heights as measured with the acrophobia questionnaire (AQ) both at posttreatment and at follow-up, compared with placebo. Furthermore, subjects receiving cortisol showed a significantly greater reduction in acute anxiety during virtual exposure to a phobic situation at posttreatment and a significantly smaller exposure-induced increase in skin conductance level at follow-up. The present findings indicate that the administration of cortisol can enhance extinction-based psychotherapy.

[1]  J. Krystal,et al.  A Meta-analysis of D-cycloserine and the Facilitation of Fear Extinction and Exposure Therapy , 2022 .

[2]  D. D. de Quervain,et al.  Enhancing exposure therapy for anxiety disorders with glucocorticoids: from basic mechanisms of emotional learning to clinical applications. , 2010, Journal of anxiety disorders.

[3]  Michael Davis,et al.  Behavioral and Neural Analysis of Extinction , 2002, Neuron.

[4]  Brenda K. Wiederhold,et al.  A Review of Virtual Reality as a Psychotherapeutic Tool , 1998, Cyberpsychology Behav. Soc. Netw..

[5]  W. Dunlap,et al.  Meta-Analysis of Experiments With Matched Groups or Repeated Measures Designs , 1996 .

[6]  T. Borkovec,et al.  Credibility of analogue therapy rationales , 1972 .

[7]  M R Crager,et al.  Analysis of covariance in parallel-group clinical trials with pretreatment baselines. , 1987, Biometrics.

[8]  Barbara O Rothbaum,et al.  Cognitive enhancers as adjuncts to psychotherapy: use of D-cycloserine in phobic individuals to facilitate extinction of fear. , 2004, Archives of general psychiatry.

[9]  Oliver T. Wolf,et al.  Effects of oral cortisol treatment in healthy young women on memory retrieval of negative and neutral words , 2005, Neurobiology of Learning and Memory.

[10]  Jan Schweckendiek,et al.  Investigating the impact of sex and cortisol on implicit fear conditioning with fMRI , 2010, Psychoneuroendocrinology.

[11]  James L. McGaugh,et al.  Stress and glucocorticoids impair retrieval of long-term spatial memory , 1998, Nature.

[12]  Joseph E LeDoux,et al.  Preventing the return of fear in humans using reconsolidation update mechanisms , 2010, Nature.

[13]  S. Mineka,et al.  The relevance of recent developments in classical conditioning to understanding the etiology and maintenance of anxiety disorders. , 2008, Acta psychologica.

[14]  J. Abelson,et al.  Cardiac and neuroendocrine responses to exposure therapy in height phobics: desynchrony within the 'physiological response system'. , 1989, Behaviour research and therapy.

[15]  Douglas W. Barrett,et al.  Behavioral effects of metyrapone on Pavlovian extinction , 2004, Neuroscience Letters.

[16]  K. Abrari,et al.  Administration of corticosterone after memory reactivation disrupts subsequent retrieval of a contextual conditioned fear memory: Dependence upon training intensity , 2008, Neurobiology of Learning and Memory.

[17]  G. Kovacs,et al.  Dose-dependent action of corticosteroids on brain serotonin content and passive avoidance behavior , 1977, Hormones and Behavior.

[18]  D. D. de Quervain,et al.  Preventive effect of beta-adrenoceptor blockade on glucocorticoid-induced memory retrieval deficits. , 2007, The American journal of psychiatry.

[19]  M. Kindt,et al.  Beyond extinction: erasing human fear responses and preventing the return of fear , 2009, Nature Neuroscience.

[20]  B. Roozendaal,et al.  Glucocorticoids and the regulation of memory in health and disease , 2009, Frontiers in Neuroendocrinology.

[21]  Andreas Papassotiropoulos,et al.  Low-dose cortisol for symptoms of posttraumatic stress disorder. , 2004, The American journal of psychiatry.

[22]  M. Krijn,et al.  Treatment of acrophobia in virtual reality: the role of immersion and presence. , 2004, Behaviour research and therapy.

[23]  Tony W Buchanan,et al.  Enhanced memory for emotional material following stress-level cortisol treatment in humans , 2001, Psychoneuroendocrinology.

[24]  Benno Roozendaal,et al.  Glucocorticoids and the regulation of memory consolidation , 2000, Psychoneuroendocrinology.

[25]  P. Venables,et al.  Committee report. Publication recommendations for electrodermal measurements. , 1981, Psychophysiology.

[26]  Bram Vervliet,et al.  The repeated confrontation with videotapes of spiders in multiple contexts attenuates renewal of fear in spider-anxious students. , 2007, Behaviour research and therapy.

[27]  Joseph E LeDoux.  The Emotional Brain, Fear, and the Amygdala , 2003, Cellular and Molecular Neurobiology.

[28]  P. Venables,et al.  Publication recommendations for electrodermal measurements. , 1981 .

[29]  O. Wolf,et al.  Arousal and cortisol interact in modulating memory consolidation in healthy young men. , 2006, Behavioral neuroscience.

[30]  Joseph E LeDoux,et al.  Contributions of the Amygdala to Emotion Processing: From Animal Models to Human Behavior , 2005, Neuron.

[31]  Chris R Brewin,et al.  Psychological theories of posttraumatic stress disorder. , 2003, Clinical psychology review.

[32]  Naomi M Simon,et al.  Augmentation of exposure therapy with D-cycloserine for social anxiety disorder. , 2006, Archives of general psychiatry.

[33]  G. Fink,et al.  Increased cortisol levels in cognitively challenging situations are beneficial in young but not older subjects , 2008, Psychopharmacology.

[34]  B. Rothbaum,et al.  A controlled study of virtual reality exposure therapy for the fear of flying. , 2000, Journal of consulting and clinical psychology.

[35]  J. Margraf,et al.  Dips: Diagnostisches Interview Bei Psychischen Storungen , 1994 .

[36]  Hilla Peretz,et al.  Ju n 20 03 Schrödinger ’ s Cat : The rules of engagement , 2003 .

[37]  Frank H Wilhelm,et al.  Salivary Cortisol Response During Exposure Treatment in Driving Phobics , 2003, Psychosomatic medicine.

[38]  D. C. Cohen,et al.  Comparison of self-report and overt-behavioral procedures for assessing acrophobia. , 1977 .

[39]  G. Quirk,et al.  Neural Mechanisms of Extinction Learning and Retrieval , 2008, Neuropsychopharmacology.

[40]  Andrew J Vickers,et al.  The use of percentage change from baseline as an outcome in a controlled trial is statistically inefficient: a simulation study , 2001, BMC medical research methodology.

[41]  Bruce S. McEwen,et al.  Stress, memory and the amygdala , 2009, Nature Reviews Neuroscience.

[42]  A. Hamm,et al.  Specific phobias. , 2018, The lancet. Psychiatry.

[43]  J. Margraf,et al.  «Angst vor der Angst»: Ein neues Konzept in der Diagnostik der Angststörungen , 1993 .

[44]  O. Wolf,et al.  A meta-analytic review of the effects of acute cortisol administration on human memory , 2005, Psychoneuroendocrinology.

[45]  N. Cozzarelli.  PNAS Early Edition. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[46]  Christopher J Patrick,et al.  The psychophysiology of anxiety disorder: fear memory imagery. , 2003, Psychophysiology.

[47]  B. Roozendaal,et al.  Acute cortisone administration impairs retrieval of long-term declarative memory in humans , 2000, Nature Neuroscience.

[48]  D. D. de Quervain,et al.  Glucocorticoids reduce phobic fear in humans. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[49]  P. Lang.  The Cognitive Psychophysiology of Emotion , 2019, Anxiety and the Anxiety Disorders.

[50]  O. Wolf,et al.  Impaired Memory Retrieval after Psychosocial Stress in Healthy Young Men , 2005, The Journal of Neuroscience.

[51]  Michael J. Singer,et al.  Measuring Presence in Virtual Environments: A Presence Questionnaire , 1998, Presence.

[52]  M J de Leon,et al.  Cortisol differentially affects memory in young and elderly men. , 2001, Behavioral neuroscience.

[53]  J. Gómez-Amor,et al.  The impact of cortisol reactivity to acute stress on memory: Sex differences in middle-aged people , 2011, Stress.

[54]  B Bohus,et al.  Adrenocortical hormones and avoidance behaviour of rats. , 1968, International journal of neuropharmacology.

[55]  M. Krijn,et al.  Virtual reality treatment versus exposure in vivo: a comparative evaluation in acrophobia. , 2002, Behaviour research and therapy.

[56]  Jacob Cohen.  Statistical Power Analysis for the Behavioral Sciences , 1969, The SAGE Encyclopedia of Research Design.

[57]  B. Roozendaal.  1999 Curt P. Richter award. Glucocorticoids and the regulation of memory consolidation. , 2000, Psychoneuroendocrinology.

[58]  R. McNally.  Mechanisms of exposure therapy: how neuroscience can improve psychological treatments for anxiety disorders. , 2007, Clinical psychology review.

[59]  Edward L. Bennett,et al.  Memory facilitating and anti-amnesic effects of corticosteroids , 1978, Pharmacology Biochemistry and Behavior.

[60]  E. Walker,et al.  Diagnostic and Statistical Manual of Mental Disorders , 2013 .

[61]  Dirk Hermans,et al.  Extinction in Human Fear Conditioning , 2006, Biological Psychiatry.

[62]  Oliver T. Wolf,et al.  Cortisol and memory retrieval in women: influence of menstrual cycle and oral contraceptives , 2005, Psychopharmacology.

[63]  K. Lu,et al.  Systemic and Intra-Amygdala Administration of Glucocorticoid Agonist and Antagonist Modulate Extinction of Conditioned Fear , 2006, Neuropsychopharmacology.

[64]  M. Kozak,et al.  Emotional processing of fear: exposure to corrective information. , 1986, Psychological bulletin.

[65]  R. Greene,et al.  Postreactivation Glucocorticoids Impair Recall of Established Fear Memory , 2006, The Journal of Neuroscience.

[66]  M. Bouton.  Context, ambiguity, and unlearning: sources of relapse after behavioral extinction , 2002, Biological Psychiatry.