Effect of combined cognitive-behavioural therapy and endurance training on cortisol and salivary alpha-amylase in panic disorder

Highlights

• We examine changes in cortisol and alpha-amylase in patients with panic disorder.

• Patients underwent endurance training or control condition (light exercise).

• We find significantly lower sC-levels in the training group at a 7-month follow-up.

• There are no group differences in sAA levels during the study period.

• We find evidence for a decelerated effect of endurance-training on the HPA-system.

Abstract

Current data point to an alteration of both the hypothalamo-pituitary-adrenal (HPA)-system and the peripheral transmission of catecholamines in anxiety disorders. There is also some evidence for the effect of several components of cognitive-behavioural interventions such as coping and control and for an effect of exercise training on the neuroendocrine stress response in healthy subjects as well as patients suffering from distinct (mental) disorders. This double-blind, controlled study investigated the effect of cognitive-behavioural therapy (CBT) in combination with either high-level endurance training or low-level exercise on salivary cortisol (sC) and on levels of salivary alpha-amylase (sAA) in patients suffering from panic disorder (PD) with and without agoraphobia. In comparison to the low-level exercise condition, there were significantly lower sC-levels in the experimental group performing high-level endurance training at a 7-month follow-up. In contrast, there were no group differences in sAA levels during the study period.

In this trial, we found evidence for a decelerated effect of endurance-training on HPA-system’s functioning in PD. Further studies addressing the alteration of sAA levels in this population might investigate physical exercise different in intensity and duration.

Introduction

Stress-related mental conditions such as depression and anxiety disorders have been linked to alterations of the hypothalamo-pituitary-adrenal(HPA)-system. While there is strong evidence for an increased activity of the HPA-system in depression, studies addressing the HPA-system’s functioning in DSM-IV-anxiety disorders revealed mixed results (Bosch et al., 2012, Plag et al., 2013). Compared to healthy controls, unchanged as well as increased basal levels of cortisol were observed in patients suffering from panic disorder (PD; e.g. Bandelow et al., 2000, Kathol et al., 1989, Petrowski et al., 2010) and there is some evidence for a hyper- as well as a hyposensitivity of the HPA-system in response to (non-)pharmacological challenges in PD (Coryell et al., 1989, Erhardt et al., 2006, Petrowski et al., 2010, Petrowski et al., 2013).

HPA-system’s functioning has shown to be sensitive for cognitive-behavioural intervention not only in healthy subjects (Gaab et al., 2003), but also in patients with somatic and mental illness. For example, in patients suffering from human immunodeficiency virus (HIV) or breast cancer, cognitive-behavioural stress management has been shown to reduce cortisol levels and led to a prevention of increases in the cortisol/dehydroepaindrosterone sulphate ratio (Antoni et al., 2000, Cruess et al., 1999, Cruess et al., 2000). In PD patients, a cognitive intervention targeting a reduction in novelty as well as an increase in cognitive coping and control was followed by a decrease in corticotrophin- (ACTH-) and cortisol plasma-levels in response to a pharmacological panicogenic challenge with pentagastrin (Abelson et al., 2005).

Besides cognitive(-behavioural) procedures, physical activity has also been shown to lead to changes in HPA-system activity. Several studies investigating the short-term effect of physical exercise found an increase in endocrine parameters linked to the stress-response (e.g. Deuster et al., 1989, Luger et al., 1987) but results concerning a long-term adaption of the HPA-system remained more inconclusive. While no changes or a rise in cortisol levels were found after long-term physical activity (Bobbert et al., 2005, Duclos et al., 2001, Mäestu et al., 2003), several studies also reported decreased levels of cortisol in association with endurance training or competition (Lucía et al., 2001, Uusitalo et al., 1998). Although former data point to an influence of cognitive(-behavioural) interventions on HPA-system activity in healthy subjects as well as in patients suffering from distinct somatic illness or PD, the effect of prolonged physical exercise on cortisol-levels in anxiety disorders and, in particular, in PD-patients are unknown.

Besides the HPA-system, the autonomic nervous system (ANS) is known to be a further important component of the stress response. Especially, the sympathetic nervous system (SNS) as one of the two branches of the ANS, has shown to be responsible for several components of the stress-related systemic activation via the secretion of the catecholamines epinephrine and norepinephrine in the adrenal cortex. Among regulation of heart rate and blood pressure adrenergic mechanisms are also directly involved in the secretion of salivary alpha amylase (sAA) by stimulation of the salivary glands (for details see Nater and Rohleder, 2009). sAA, a salivary enzyme mainly responsible for the digestion of macromolecules within food, also shows a characteristic diurnal pattern in healthy humans with the highest activity in the evening hour (e.g. Rohleder et al., 2004). Since dysregulation of SNS was shown in patients suffering from different anxiety disorders such as panic disorder or posttraumatic stress disorder (Coupland et al., 2003, Southwick et al., 1999), sAA is suggested as a surrogate marker for the SNS-activity (e.g. Granger et al., 2007, Nater and Rohleder, 2009) and clinical trials also investigated sAA-activity in these populations. In comparison to healthy controls, higher sAA-activity was found in several anxiety disorders at baseline as well as in response to several experimental stressors (for an overview see Schumacher et al., 2013). To date, there are no studies addressing the effect of physical activity or cognitive-behavioural interventions on sAA-activity in patients suffering from anxiety disorders.

The aim of this study was to assess the effect of a disorder-specific cognitive-behavioural therapy (CBT) as well as the combination of CBT and long-term physical activity on stress-related biological parameters in patients with PD. We hypothesized that long-term physical activity (high-level endurance training) would be associated with a more pronounced and sustained decrease in salivary-cortisol (sC) and sAA levels than a training programme containing low-level exercises with very little strain as a control condition.