سطح کورتیزول درون زا تحت تاثیر مواجهه درمانی در عنکبوت هراسی

Previous research in patients with phobia showed that the administration of glucocorticoids reduces fear in phobic situations and enhances exposure therapy. Glucocorticoids underlie a daily cycle with a peak in the morning and low levels during the evening and night. The aim of the present study was to investigate whether exposure is more effective when conducted in the morning when endogenous cortisol levels are high. Sixty patients meeting DSM IV criteria for specific phobia (animal type) were randomly assigned to one-session exposure treatment either at 08.00 a.m. (high cortisol group) or at 06.00 p.m. (low cortisol group). Participants returned for a posttreatment assessment one week after therapy and a follow-up assessment three months after therapy. Both groups showed good outcome, but patients treated in the morning exhibited significantly less fear of spiders in the behavioral approach test (BAT) and a trend for lower scores on the Fear of Spiders Questionnaire (FSQ) than patients treated in the evening. This effect was present at posttreatment and follow-up. Our findings indicate that exposure therapy is more effective in the morning than in the evening. We suggest that this may be due to higher endogenous cortisol levels in the morning group that enhance extinction memory.

Specific phobias are among the most common anxiety disorders with an estimated lifetime prevalence of 12.5% (Michael, Zetsche, & Margraf, 2007). They are characterized by marked and persistent fear that is excessive and unreasonable, cued by the presence or anticipation of a specific object or situation. A central mechanism in the pathogenesis of phobic disorders is associative learning or conditioning that leads to the formation of fear memory (Field, 2006, Michael and Ehlers, 2009, Michael et al., 2009 and Mineka and Oehlberg, 2008). Exposure to feared objects or situations is the treatment of choice for anxiety disorders (Choy et al., 2007, Hofmann and Smits, 2008 and Norton and Price, 2007). Exposure therapy is thought to rely on the extinction of the fear memory. Thus, exposure therapy is best conceptualized as a learning process in which new non-fear memory traces are established, which inhibit the old fear memories (Hermans, Craske, Mineka, & Lovibond, 2006). Even though exposure therapy is a highly successful treatment option, not all patients profit from it (Choy et al., 2007). Recently, several pharmacological agents have been proposed as boosters of exposure therapy (Bentz et al., 2010 and Vervliet, 2008). These new therapeutic approaches are based on the idea that the pharmacological agents facilitate the learning processes underlying the success of exposure therapy (Hofmann et al., 2006, Otto et al., 2007 and Rabinak et al., 2013). One agent that has been suggested to improve exposure therapy is cortisol. There is growing evidence from studies in humans and animals that cortisol has the potential to facilitate the processes leading to an enhanced extinction learning during exposure therapy. In detail, cortisol has been shown to enhance the consolidation of newly acquired material and inhibit the retrieval of previously learned material (for a review see de Quervain, Aerni, Schelling, & Roozendaal, 2009). This characteristic of cortisol makes it a promising tool to enhance exposure therapy for anxiety disorders, in which the retrieval of previously learned anxiety related material (e.g. spider is a dangerous animal that wants to harm me) should be inhibited and the consolidation of the newly learned corrective experiences (e.g. spider is not dangerous and does not do any harm) should be enhanced (Bentz et al., 2010). Two recent studies in patients found evidence that exogenous cortisol administration prior to exposure with feared stimuli or situations leads to a greater anxiety reduction than exposure without cortisol administration (Soravia et al., 2006). Cortisol was administered to 20 spider phobia patients and 40 social phobia patients in a double-blind placebo-controlled design. In the spider phobia study, repeated oral administration of cortisol (10 mg) 1 h before exposure to spider photographs induced a progressive reduction of stimulus-induced fear. In the social phobia study cortisol administered prior to a socially evaluative stressor reduced fear during the anticipation, exposure and recovery phase of the stressor. Based on these findings de Quervain and colleagues investigated the effects of cortisol administration on exposure therapy in height phobia. In a 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. Adding cortisol to exposure therapy resulted in a significantly greater reduction in fear of heights both at posttreatment and at follow-up (de Quervain et al., 2011). Thus, there is evidence that exposure therapy which is combined with exogenous cortisol administration is more effective than exposure therapy without cortisol administration. Cortisol is secreted as a response to stress and can be administered exogenously. However, cortisol secretion also underlies a daily cycle with a peak in the morning and low levels during the evening and night (Kirschbaum & Hellhammer, 1989). Several studies have shown that these endogenous variations in cortisol level also influence learning and memory processes (Preuss et al., 2009, Putman et al., 2004 and Van Honk et al., 2003). Thus, the aim of the present study was to investigate whether these diurnal variations in endogenous cortisol levels can be utilized for optimizing the effect of exposure therapy. In our study, sixty patients meeting DSM-IV criteria for specific phobia (animal type) were randomly assigned to receive three hours exposure treatment for spider phobia delivered in a single therapy session (as described by Ost, 1989) either at 08.00 a.m. (high cortisol group) or at 06.00 p.m. (low cortisol group). Patients returned for a posttreatment assessment one week after therapy and a follow-up assessment three months after therapy. The reduction in fear of spiders was measured with a behavioral approach test (BAT) and with the German version of the Fear of Spiders Questionnaire (FSQ, Szymanski & O'Donohue, 1995). Based on previous findings on exogenous cortisol administration (de Quervain et al., 2011, Soravia et al., 2006 and Suris et al., 2010), we predicted that patients who were treated in the morning (when endogenous cortisol levels are high) show greater reduction in fear of spiders as measured by the BAT and the FSQ as patients treated in the evening (when endogenous cortisol levels are low).