Elsevier

Psychoneuroendocrinology

Volume 101, March 2019, Pages 246-252
Psychoneuroendocrinology

Long-term glucocorticoid levels measured in hair in patients with depressive and anxiety disorders

https://doi.org/10.1016/j.psyneuen.2018.11.019Get rights and content

Highlights

  • The highest level of hair cortisol was found in patients with current comorbid anxiety and depression.

  • Remitted depression and anxiety were not related to cortisol or cortisone levels assessed in hair.

  • Cortisone measured in hair and the ratio between cortisol and cortisone were not related to anxiety or depression diagnoses.

Abstract

Background

Depressive and anxiety disorders have been linked to a dysregulated hypothalamus-pituitary-adrenal (HPA)-axis. Hair cortisol levels (HairF) reflect integrated long-term cortisol regulation and are therefore promising endocrine markers of chronic (psychological and physical) stress.

Our aim was to assess hair cortisol levels in persons with a depressive and/or anxiety disorder and to compare their levels with that of persons in remission and healthy controls.

Methods

Data from 1166 participants of the Netherlands Study of Depression and Anxiety (NESDA) were used, including 266 participants with a recent (1-month) diagnosis of a depressive and/or anxiety disorder, 655 participants with a diagnosis in remission, and 245 healthy controls. HairF was measured in the proximal three cm of scalp hair, using LC–MS/MS.

Results

Compared to the healthy controls no differences on HairF or HairE levels were found for depressive and anxiety disorders alone. However the presence of a comorbid depressive and anxiety disorder was significantly associated with increased HairF levels (β = 0.07; p = .031), as was the severity of depressive symptoms (β = 0.06; p = .029), but no differences were found on HairE nor the HairF:HairE ratio.

Conclusions

Persons with current diagnosis of comorbid depression and anxiety show moderately higher levels of cortisol than patients with only depression or anxiety, or patients in remission and healthy controls, which may be indicative of a chronic state of hyperactivation of the HPA axis.

Introduction

Dysregulation of the hypothalamus-pituitary-adrenal (HPA) axis may result in increased or decreased levels of its end-product, cortisol. A disproportionate change in cortisol levels is one of the main hypothesized pathophysiological mechanisms underlying depressive and anxiety disorders (Casper et al., 1988; Elnazer and Baldwin, 2014; Hilbert et al., 2014; Vreeburg et al., 2009, 2010). However, findings have been inconsistent regarding relative hyper- or hypocortisolism in different (subtypes of) disorders. So far, most studies examining cortisol in depressive disorders observed higher levels of cortisol (see meta-analyses: (Belvederi Murri et al., 2014; Knorr et al., 2010)), whereas both higher and lower levels have been found in relation to anxiety disorders. For instance, higher levels of cortisol have been found for panic disorder and agoraphobia (Vreeburg et al., 2010) but lower levels have also been found for social phobia and PTSD (Zorn et al., 2017). Moreover, due to the high comorbidity between depression and anxiety, many studies include samples of comorbid patients and it may well be that this comorbid group has a distinct cortisol pattern from depression and anxiety alone (Morris et al., 2012).

Most of the preceding studies measured cortisol in urine, blood or saliva. One shortcoming of these methods is that they only reflect cortisol levels over a relatively short time period, i.e. minutes to several days, thereby not reflecting chronic exposure to cortisol excretion, which likely is more relevant in terms of health effects. Another question that remains to be answered is whether altered cortisol levels represent a trait or state effect in depressive (Lok et al., 2012) and anxiety disorders. One possibility to shed more light on these issues is the use of long-term cortisol concentrations as measured in hair segments.

Hair cortisol concentrations (HairF) are assumed to reflect integrated long-term (e.g. 1 cm of hair is assumed to represent 1 month) cortisol levels, and have been proposed as a promising endocrine marker of chronic stress. Indeed, higher HairF in patients with depression compared to healthy controls have been reported (Caparros-Gonzalez et al., 2017; Dettenborn et al., 2012a,b; Pochigaeva et al., 2017; Wei et al., 2015), while, other studies showed no difference (Herane-Vives et al., 2018; Hinkelmann et al., 2013; Kuehl et al., 2015). Research on HairF and anxiety disorders has also reported differences between cases and controls; e.g. posttraumatic stress disorder (PTSD) has been associated with increased HairF in the months after the trauma, followed by decreased HairF in the longer run (for review see (Steudte-Schmiedgen et al., 2016)). And a small recent study on hair cortisol levels among patients with MDD and/or GAD found that MDD patients show lower cortisol levels than controls, GAD and comorbid patients (Steudte-Schmiedgen et al., 2016). To summarize, first studies on hair cortisol levels have been published, but there still is a considerable lack of consistent information on the relationship with depressive and anxiety disorder characteristics such as age of onset, duration of disorder, severity, and use of antidepressants. Furthermore, most studies involved small samples (many less than n = 50), which may partially explain discrepant results across studies.

The development of new techniques to measure HairF has led to the possibility to measure other steroid hormones in scalp hair as well. One of these other hormones is cortisone, the inactive form of cortisol. The enzyme 11β-hydroxysteroid dehydrogenase type 1 (11βHSD-1) converts cortisone into active cortisol, whereas its counterpart 11β-hydroxysteroid dehydrogenase type 2 (11βHSD-2) converts active cortisol to inactive cortisone. The assessment of hair cortisone (HairE) in parallel to HairF has been postulated to provide even more insight into the cumulative amount of active and inactive glucocorticoids in the body, because for instance higher levels of free cortisol, could be due to a decreased conversion to cortisone rather than an increase in cortisol output. As such HairE levels may provide a useful and robust marker of long-term HPA axis activity (Stalder et al., 2013). Apart from the absolute levels of HairF and HairE, the cortisol-to-cortisone ratio is also of interest, as it may reflect the 11βHSD-activity (Zhang et al., 2013). The importance of this ratio in stress-related research has been emphasized by studies using urinary measures showing an altered ratio under stress (Plenis et al 2011) and demonstrating an enhanced ratio in depressed patients (Dekker et al 2012; Romer et al 2009), suggestive of an increased conversion to active cortisol by 11βHSD-1.

Measurement of hair cortisone concentrations (HairE) have been shown by our group and by others to be easily measurable and to correlate with HairF (Raul et al., 2004; Stalder et al., 2013; Staufenbiel et al., 2015; Zhang et al., 2013). Until now, no study has investigated HairF, HairE, the ratio HairF/HairE in relation to (characteristics of) depressive and anxiety disorders (and their comorbidity) while accounting for diverse covariates and using a large sample. Insight into the amounts of long-term cortisol and cortisone, as well as their ratio, may give new insights into the underlying pathophysiology of the HPA axis and its role in depressive and anxiety disorders.

In the present study, we used data from the Netherlands Study of Depression and Anxiety (NESDA) to examine whether there are differences in HairF, HairE and their ratio (HairF/HairE) between healthy control subjects and subjects with a depressive disorder or an anxiety disorder. By comparing healthy subjects, patients in remission and patients with current disorders we will be able to provide insight into state versus trait associations and we will also examine the impact of specific characteristics, such as symptom severity, age of onset and medication use, on the association between psychopathology and hair glucocorticoid levels.

Section snippets

Study sample

Data were used from the Netherlands Study of Depression and Anxiety (NESDA), an ongoing longitudinal cohort study on the predictors, course and consequences of depressive and anxiety disorders. The NESDA sample consisted of 2981 participants aged 18–65 years at inclusion, comprising persons with no depressive or anxiety disorder, persons who have had a disorder in the past, and persons with a current depressive and/or anxiety disorder. A detailed description of the NESDA study rationale,

Sample characteristics

Characteristics across groups are presented in Table 1. A total of 245 subjects had no current nor lifetime diagnoses (healthy controls), 655 participants were in remission (including 165 participants with remitted depressive disorder; 100 participants with remitted anxiety disorder and 390 participants with remitted comorbid depressive and anxiety disorders), and 266 participants presented with a current (past one month) diagnosis of depressive disorder (n = 78), anxiety disorder (n = 122), or

Discussion

The current study examined HairF and HairE levels as well as the ratio of HairF/HairE in a large sample with and without depression and anxiety. One aim of our study was to gain insight into the amounts of long-term cortisol and cortisone, as well as their ratio, in depressive and anxiety disorders. We found that the comorbid MDD/Anx group had significantly higher long-term HairF levels than healthy controls and patients with a specific current or remitted diagnosis. But we did not observe any

Conclusion

To conclude, this study demonstrates that persons with comorbid anxiety and MDD diagnoses and current severe symptoms of depression or anxiety show higher long-term levels of cortisol than patients in remission and healthy controls. Given that we only found significant differences in the group with current and severe symptoms our results suggests that hair cortisol can be considered a biomarker for state rather than trait of depressive and anxiety disorders.

Conflict of interest statement

None of the authors have any conflict of interest to report. None of the funding sources had any involvement in the design, analysis, writing of this study.

Financial disclosures

Dr. Penninx has received research funding from Jansen Research. The other authors have nothing to disclose.

Acknowledgements

The infrastructure for the NESDA study (www.nesda.nl) is funded through the Geestkracht Program of the Netherlands Organisation for Health Research and Development (Zon-MW, grant number 10-000-1002) and is supported by participating universities and mental health care organizations (VU University Medical Center, GGZ inGeest, Arkin, Leiden University Medical Center, GGZ Rivierduinen, University Medical Center Groningen, Lentis, GGZ Friesland, GGZ Drenthe, IQ Healthcare, Netherlands Institute for

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