Glucocorticoids enhance extinction-based psychotherapy

Abstract

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, doubleblind, 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.memory | retrieval | consolidation P hobic disorders can be characterized as disorders involving disturbed emotional learning and memory resulting in an enhanced fear response. A central mechanism in the pathogenesis of anxiety disorders is associative learning or conditioning that leads to formation of a fear memory (1-5). In phobic individuals, exposure to a phobic stimulus almost invariably provokes retrieval of stimulus-associated fear memory, which leads to the fear response (6-9). Exposure-based behavioral therapy of phobia is thought to rely on extinction of these fear responses (10-13). Extinction occurs when conditioned responding to a stimulus decreases when the reinforcer is omitted (12,14). Accordingly, fear reduction induced by exposure therapy is the result of decrements in the conditioned response over successive extinction trials. Extinction leads to the formation of an alternative set of nonfearful memory associations (extinction memory) that competes with, but does not erase original fear memory associations (14, 15). Considering the importance of extinction learning for exposure therapy, pharmacological interventions aimed at enhancing extinction processes are promising approaches to enhance exposure therapy, as it has been demonstrated with D-cycloserine (16-18).Glucocorticoids (cortisol in humans, corticosterone in rodents) are stress hormones released from the adrenal cortex and it has long been recognized that they readily enter the brain and affect learning and memory (19-24). Importantly, basic research studies in animals and humans have shown that the mnemonic effects of glucocorticoids can facilitate extinction processes (22,(25)(26)(27)(28)(29). Therefore, we aimed at investigating whether the administrati...

Sleep enhances exposure therapy

“…A maximum of 13 stations was available and participants spent a total of 45 min in the virtual environment. This highly standardized exposure protocol was similar to the one used in a study of VR exposure in height phobia (De Quervain et al 2011).…”

“…However, some patients do not respond to this form of treatment, achieve only partial symptom remission, or fear often returns following initially successful therapy (Mystkowski et al 2002. Consequently, the development of novel and innovative approaches to increase therapeutic effectiveness is a primary challenge in current research on treatment of anxiety disorders (Ressler et al 2004;McNally, 2007;De Quervain, 2011).…”

Single dose of l -dopa makes extinction memories context-independent and prevents the return of fear

“…In any case, our human data further support the conclusion from our rodent experiments that L-dopa administration directly after extinction makes extinction memories context-independent and protects from return of fear when a CS is encountered in a context that differs from the extinction context. Context-independency is not produced by, or has not been investigated in, other drugs tested in clinical studies for their ability to boost extinction-based therapy (49)(50)(51).…”

Glucocorticoid Administration Improves Aberrant Fear-Processing Networks in Spider Phobia

“…Their release is enhanced in response to a stressor to enable responses to any environmental hazards and glucocorticoid receptors are ubiquitously expressed in the brain (Myers et al, 2014). In animals and healthy humans, glucocorticoids reduce memory retrieval (de Quervain et al, 1998(de Quervain et al, , 2000 and recent clinical studies have found that in patients with chronic post-traumatic stress disorder, social phobia, spider phobia, and acrophobia, the administration of glucocorticoids reduces the ability to recall traumatic or fearful memories, and enhances the extinction of such memories (Aerni et al, 2004;van Peer et al, 2010;Soravia et al, 2006;de Quervain et al, 2011). A recent neuroimaging study showed that glucocorticoid administration altered amygdala reactivity related to the retrieval of aversive memories, the presentation of emotionally salient face pictures and predicted reward (BuadesRotger et al, 2016;van Marle et al, 2013;Montoya et al, 2014).…”