Review article
Biomarkers in burnout: A systematic review

https://doi.org/10.1016/j.jpsychores.2010.10.012Get rights and content

Abstract

Background

Burnout is a stress state characterized by symptoms of mental exhaustion and physical fatigue, detachment from work, and feelings of diminished competence. Several biomarkers have been tested for association with burnout, but the results are conflicting.

Aim

The objective of this review was to identify potential biomarkers for burnout.

Methods

We carried out a systematic review of studies comparing biomarkers in individuals with burnout and healthy controls, or individuals with low scores and those with high scores on burnout questionnaires. Literature searches in MEDLINE and EMBASE were performed. We describe biomarkers on which at least three studies were available. Where appropriate, a meta-analysis was carried out.

Results

We identified 31 studies on 38 biomarkers involved in the hypothalamus–pituitary–adrenal axis, autonomic nervous system, immune system, metabolic processes, antioxidant defense, hormones, and sleep. At least 3 studies were available for cortisol in saliva and blood, blood pressure, heart rate, cholesterol, dehydroepiandrosterone sulfate, (numbers or activity of) natural killer cells, C-reactive protein, and prolactin. The comparability of studies was limited, due to differences in the methods used to characterize patients and controls, to assess biomarkers, and to control for confounders. Furthermore, burnout was operationalized in different ways. Meta-analyses showed no differences for cortisol awakening response and cortisol awakening response after administration of dexamethasone, cortisol in blood, and blood pressure.

Conclusions

No potential biomarkers for burnout were found, largely due to the incomparability of studies. We emphasize the need for a dimensional and longitudinal approach in future research to account for the heterogeneity of burnout.

Introduction

Burnout is a stress state characterized by such symptoms as mental exhaustion and physical fatigue, detachment from work, diminished competence, loss of energy, increased irritability and sleep, and concentration problems that can occur irrespective of the type of profession [1]. Yearly, approximately 10%–15% of the working population in The Netherlands suffers from burnout [2]. In 2008, 17% of all reported occupational diseases concerned work-related psychological problems [3]. In The Netherlands, the welfare of the employees who yearly report ill because of stress at work costs 1.7 billion Euros [4]. Therefore, it is important to prevent and treat burnout effectively.

Risk factors include a high workload, monotonous tasks, conflict with superiors or colleagues, and exposure to aggressive behavior of customers [5]. According to the widely used demand–control model, the risk of developing burnout is higher if there is a combination of high psychological demands and poor job resources [6]. However, it remains unclear why some people develop burnout, whereas others do not. Furthermore, psychological treatment, consisting of relaxation therapy, cognitive therapy, learning of coping skills, and reactivation, can reduce complaints effectively. However, individuals differ widely in the rate of recovery. It is largely unknown which factors influence treatment refractoriness. As burnout is a stress state, it has been hypothesized that the autonomous nervous system (ANS) and the hypothalamus–pituitary–adrenal axis (HPA axis) are involved. Most studies on the behavior of these systems focused on acute stress. During acute stress, the sympathetic part of the ANS is activated and the parasympathetic part is down-regulated. These are reflected in peripheral blood by the release of catecholamines via the ANS and by release of cortisol via the HPA axis. There is an increase in both heart rate and blood pressure. The immune system is temporarily suppressed, and metabolism becomes catabolic. Among patients with burnout, an increased incidence of common cold, flu-like illness, and gastroenteritis has been reported [7]. Therefore, several studies have investigated if biomarkers involved in the immune response were associated with burnout.

After stress, all processes return to normal. It is hypothesized that in burnout the ANS and HPA axis have become exhausted due to prolonged or recurrent stress. It has been postulated that, as a consequence, burnout will be accompanied by abnormal (low) blood levels of adrenaline and cortisol and their metabolites. In addition, vital functions, such as heart rate and blood pressure, are expected to remain overactivated and metabolism and the immune system to be compromised. These dysfunctions would be responsible for the symptom of physical fatigue. However, it is unlikely that these biological changes are responsible for the other symptoms of burnout [i.e., feelings of emotional exhaustion (EE), detachment from work, and diminished competence].

In order to investigate the evidence for a role of ANS, the HPA axis, and the vital functions mentioned above, we reviewed the literature until December 2008 on studies of biomarkers in burnout.

Section snippets

Search strategy

Articles published until December 2008 were identified through a search of PUBMED (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi) and EMBASE (http://www.ovid.com). An overview of the search strategy is given in Table 1.

The inclusion criteria were as follows: (1) published clinical trials and observational studies; (2) studies that compared biological markers between healthy individuals and participants who suffered from burnout, or biological markers between individuals with high scores and

Results

In total, 655 articles were identified and screened by titles and abstracts. Of these, 576 were excluded because they did not report on the association between burnout and biomarkers, leaving 79 articles that were retrieved for detailed assessment. A total of 31 articles, in which 38 biomarkers were tested, met all inclusion criteria (Fig. 1; Table 2).

The biomarkers concerned the HPA axis, hormones other than stress hormones, the ANS, the immune system, metabolic processes, antioxidant defense

Discussion

In our review of the literature, we found 31 articles that fulfilled our inclusion criteria. Together, these articles investigated 38 potential biomarkers covering many physiological processes. For some parameters, the number and quality of the studies permitted a meta-analysis. This was the case with the CAR assessed in saliva, systolic blood pressure, and diastolic blood pressure. No relationship with burnout was found. For the other biomarkers, the number of studies was too small for a

Acknowledgments

We thank Prof. Theo Stijnen and Dr. Massoud Boroujerdi for their statistical assistance.

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