Elsevier

Psychoneuroendocrinology

Volume 119, September 2020, 104658
Psychoneuroendocrinology

Higher cortisol levels may proceed a manic episode and are related to disease severity in patients with bipolar disorder

https://doi.org/10.1016/j.psyneuen.2020.104658Get rights and content

Highlights

  • We used LC/MS analyzing hair cortisol in bipolar Ipatients Ito explore the role of the HPA-axis in the pathogenesis of bipolar disorder.

  • We found an indication for an altered functioning of the HPA-axis as shown by higher cortisol levels.

  • We found a peak in HCC prior to a manic episode, indicating a more severe dysregulation of the HPA-axis prior to a manic episode.

  • We found a potential relationship between long term cortisol and the severity of the disease, marked by the number of mood episodes.

Abstract

Background

Regulation of the hypothalamic-pituitary-adrenal (HPA) axis is implicated in the pathogenesis of bipolar disorder (BD). However, the relationship between HPA-activity and disease severity is not fully elucidated. In this pilot study we aimed to explore the temporal relationship between HPA-activity and the risk of a manic episode in BD patients type I, by assessing long-term hair cortisol concentrations (HCC). Second, we explored the relation between HCC and the number of previous episodes.

Methods

Hair samples were collected from 45 BD I patients in euthymic or manic state and compared to 17 controls. From each participant, two hair samples of 3 cm length were used to measure long-term cortisol, reflecting retrospect time frames of 1–3 months and 4–6 months respectively prior to sampling.

Results

HCC in the BD group was slightly higher than in the control group in both hair segments (p = 0.049 and 0.03; after adjustment for age, sex, BMI and hair washing frequency p = 0.222 and 0.139). A significant peak in hair cortisol was observed prior to a manic episode (p = 0.036). Furthermore, we found a positive correlation between the number of mood episodes HCC (p = 0.03).

Conclusions

Our results indicate that long-term cortisol levels are slightly higher in BD, and in particular elevated in the months prior to a manic relapse. In addition HCC are positively associated with the number of previous mood episodes in the course of BD type I.

Introduction

Bipolar Disorder (BD) is a severe mental illness, characterized by a chronic and unpredictable course. Understanding the pathophysiological processes is crucial to identify new potential therapeutic targets. Current pharmacological and psychotherapeutic treatment results in long term stability in only one third of BD patients, leaving two thirds in urgent need of novel treatment options (Renes et al., 2014).

Endocrine systems seem to play a role in the pathogenesis of BD. The hypothalamus – pituitary – adrenal (HPA) axis, as one of the key systems, shows an altered functioning, characterized by higher cortisol levels (Belvederi Murri et al., 2016; Cervantes et al., 2001; Daban et al., 2005; Deshauer et al., 2003; Jabben et al., 2011; Langan, McDonald 2009; Linkowski et al., 1994; Schmider et al., 1995) a decrease of number of glucocorticoid receptors (Bei et al., 2009; Fries et al., 2014) and a decreased sensitivity in the negative feedback response (Vieta et al., 1999; Watson et al., 2004) in BD patients as compared to healthy individuals. This has been found during episodes (state phenomenon) and in between episodes (trait phenomenon). Results also indicate a role in the staging of the disease, with a more severe dysregulation in those with a higher number of mood episodes (Watson et al., 2004), suggesting chronicity of both endocrine as mood dysregulation.

However, results concerning HPA-axis functioning in BD have been conflicting and are difficult to interpret and compare across studies, which may be due to 1) heterogeneity of patient groups, with differences in disease type, phase and stage, and, 2) methodological issues regarding the assessment of the functioning of the HPA-axis by using time point measures of cortisol in serum or saliva which are under the influence of the circadian rhythm, diurnal pulsatile secretion, and acute psychological or physiological stress. These constantly changing levels complicate the interpretation of serum and saliva cortisol measurements. By using analysis of cortisol in scalp hair, as a method to monitor chronic HPA axis functioning, we can solve these shortcomings of time point measures. This technique measuring hair cortisol concentrations (HCC) has been proven to be a useful marker of long-term systemic cortisol. (Sauvé et al., 2007; van Uum et al., 2008; Manenschijn et al., 2011)

Until now, only few studies have been published reporting HCC in BD. Our group previously observed higher HCC in BD patients with an older age of onset (Manenschijn et al., 2011). Streit et al. (2016) found higher HCC in BD patients compared to controls (CON) and also found a correlation between manic symptoms and HCC.

The aim of this study is to explore long-term cortisol in relationship to relapses to a manic episode. We included an extensively defined cohort of BD type I patients in a euthymic state, either with or without a manic episode prior to hair sampling in order to distinguish between state and trait. In addition, we explored the severity of the disease, by studying the number of mood episodes and long-term cortisol exposure.

Section snippets

Study design

This study is part of a large case-control study, the Dutch Bipolar Cohort (DBC), investigating genetic and phenotypic information of patients with bipolar disorder type I, first degree relatives and controls (CON). The study design is described in more detail by Vreeker et al. (2016), [PMID: 30303059]. In brief, patients were recruited via clinicians, the Dutch patients’ association for BD, pharmacies and advertisements. Healthy controls were recruited via advertisements and among individuals

Results

In total, 45 BD patients and 17 CON were enrolled in this study (Fig. 1). No differences between groups were found regarding demographics, BMI, corticosteroid use and hair characteristics (Table 1).

Discussion

In this pilot study we found a relationship between increased Hair Cortisol Concentrations (HCC), indicative of increased HPA activity, and a higher probability of a manic episode in BD patients type I. Second, we show a positive association between HCC and the number of previous episodes, representing the disease chronicity.

In the current study we aimed to unravel whether increased cortisol exposure is a condition preceding a mood episode or rather a consequence of a manic or depressive

Declaration of Competing Interest

None.

Financial disclosures

None.

Acknowledgments

EFCvR is supported by an Erasmus MC research fellowship, a fellowship of the Netherlands Brain Foundation (grant number F2011(1)-12), and a Vidi grant of the Netherlands Organization for Scientific Research (grant number 91716453). The Dutch Bipolar Cohort was supported by the National Institute of Mental Health (Grant number: R01MH 090 553).

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