Elsevier

Psychiatry Research

Volume 186, Issues 2–3, 30 April 2011, Pages 310-314
Psychiatry Research

Decreased hair cortisol concentrations in generalised anxiety disorder

https://doi.org/10.1016/j.psychres.2010.09.002Get rights and content

Abstract

Previous research examining hypothalamic–pituitary–adrenal (HPA) axis activity in generalised anxiety disorder (GAD) has suggested a general hypercortisolism. These studies have mostly relied on salivary, plasma or urinary assessments, reflecting cortisol secretion over short time periods. The current study utilised the novel method of cortisol assessment in hair to obtain a retrospective index of cortisol secretion over a prolonged period of time. Hair cortisol levels were determined in 15 GAD patients and in 15 age- and gender-matched controls. In addition, participants collected six saliva samples (on awakening, + 30 min, 12:00, 16:00, 20:00 h and at bedtime) on two consecutive weekdays for the assessment of the diurnal cortisol profile. Results revealed significantly lower (50–60%) cortisol levels in the first and second 3-cm hair segments of GAD patients compared to those of controls. No significant between-group differences were seen in diurnal cortisol profiles. The hair cortisol findings tentatively suggest that under naturalistic conditions GAD is associated with hypocortisolism. If corroborated by future research, this demonstrates the important qualities of cortisol measurement in hair as an ecologically valid, retrospective index of long-term cortisol secretion and as a marker for psychiatric disorders associated with hypo- or hypercortisolism.

Introduction

The hypothalamus-pituitary–adrenal (HPA) axis with its peripherally active hormone cortisol constitutes an important neuroendocrine response system. Altered activity of the HPA axis as a result of chronic stress has been considered to play a role in the aetiology of several psychiatric disorders (Miller et al., 2007). An important condition in this respect is generalised anxiety disorder (GAD), which is characterized by excessive anxiety and uncontrollable worry about various life problems and circumstances that occur on the majority of days for at least 6 months (American Psychiatric Association, 2000). Although these features of GAD suggest that suffering from this condition might involve repeated stressful experiences which over time could lead to an altered cortisol secretory pattern, little research to date has examined the neuroendocrine changes underlying GAD.

The currently available evidence on HPA axis functioning in GAD shows a heterogeneous picture. A number of studies have provided support for the notion that GAD is associated with an upregulation of adrenocortical activity; i.e. hypercortisolism. In two earlier studies, elevated dexamethasone nonsuppression rates were found in GAD patients (Schweizer et al., 1986, Tiller et al., 1988), indicating reduced negative feedback sensitivity of the HPA axis. More recently, Mantella et al. (2008) showed that GAD patients exhibited an elevated diurnal cortisol profile compared to a healthy control group. In addition, both cognitive therapy (Tafet et al., 2005) and pharmacological treatment (Pomara et al., 2005) of GAD has been reported to be associated with an attenuation of plasma cortisol levels. On the other hand, a number of studies have failed to show aberrant adrenocortical activity in GAD. Rosenbaum et al. (1983) found no differences between 24-h urinary cortisol levels of GAD patients and those of a healthy control group. Similarly, two other studies reported no differences in plasma cortisol levels between GAD patients and healthy controls (Hoehn-Saric et al., 1991) or between patients with major depressive disorder, GAD and control participants (Kelly and Cooper, 1998).

An important factor in the above findings is the assessment of cortisol levels. Whilst the use of salivary, plasma or urinary samples constitute well-established methods, it is important to note that these reflect acutely circulating cortisol levels (saliva or plasma) or mean cortisol secreted over a somewhat longer period (usually 24 h; urine). It can be argued that estimates obtained via these techniques are less well-suited for reflecting normal, long-term cortisol secretion under naturalistic circumstances since the HPA axis is a system which is highly reactive and which shows considerable intra-individual variability (e.g. Hellhammer et al., 2007).

Only recently, a novel technique of assessing endogenous concentrations of cortisol in human hair was introduced (Raul et al., 2004). Importantly, as it is assumed that cortisol is incorporated into the hair shaft during hair growth, the examination of cortisol levels in a specific hair segment should provide a retrospective measure of cortisol secretion over the time period during which the hair segment had grown (for a review see Gow et al., 2010, Kirschbaum et al., 2009). This notion has been broadly supported by animal as well as human research. In male rhesus macaques, strong positive correlations between hair cortisol and mean salivary cortisol levels have been reported (Davenport et al., 2006) and in domestic cats and dogs, hair cortisol levels correlated strongly with cortisol concentrations in faeces (Accorsi et al., 2008). In humans, elevated hair cortisol levels were reported in patients with Cushing's syndrome, a condition associated with hypercortisolism (Thomson et al., 2010), and recent work by our group was able to show that the well-established twofold increase in cortisol levels during the third trimester of pregnancy was also reflected in hair segments assumed to have grown over this time period (Kirschbaum et al., 2009). Furthermore, evidence has been reported confirming marker qualities of hair cortisol levels with respect to chronic stress (Davenport et al., 2006, Kalra et al., 2007, Yamada et al., 2007). Finally, whilst some indication was seen that hair cortisol levels in humans show a monotonic decline from scalp-near to more distal hair segments, i.e. are gradually washed out; we have recently provided evidence suggesting that hair analysis can provide a valid retrospective reflection of cortisol secretion for a period of up to six months (Kirschbaum et al., 2009).

The aim of the present study was to compare long-term HPA axis activity in GAD patients and matched healthy controls via the assessment of hair cortisol levels. Despite some heterogeneity in the previous literature, most evidence suggests that GAD is associated with hypercortisolism and hence it was predicted that higher hair cortisol levels would be found in GAD patients than in the control group. To allow a comparison of different methodologies of cortisol assessment, saliva samples for the measurement of a full diurnal cortisol profile were also obtained besides hair samples. Finally, it was investigated whether the previously reported wash out effect was also evident in the current hair samples.

Section snippets

Participants

Participant recruitment was conducted via local advertisements and flyers. Overall, 95 participants were screened for admission to the study on the basis of health-related questions and the DSM-IV criteria of GAD. 19 participants were then interviewed face-to-face using the Munich-Composite International Diagnostic Interview (M-CIDI; Wittchen and Pfister, 1997), a standardized diagnostic instrument for the assessment of DSM-IV mental disorders. M-CIDI diagnoses were confirmed by an experienced

Results

Table 1 illustrates demographic, hair-related and clinical characteristics of GAD and control participants as well as results of group comparisons. The table shows that the two groups were well-matched on the examined demographic and hair-related characteristics. As expected, GAD patients scored lower on measures of physical and psychological well-being at the time of the study. They also obtained higher scores on measures of depressive symptoms (BDI-II), pathological worry (PSWQ) as well as

Discussion

In this study we set out to investigate whether GAD is associated with aberrant HPA axis activity by examining cortisol concentrations in hair, a method assumed to provide a retrospective index of cortisol secretion over a protracted period of time. Our results show 50–60% lower hair cortisol levels in GAD patients than in healthy controls, which is at variance with previous evidence from research using measures of short-term cortisol secretion. On the other hand, no group differences in

Acknowledgment

This study was supported by a grant from the German Research Foundation (DFG; DE 1162/3-1).

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