Cortisol levels in hair are altered in irritable bowel syndrome - A case control study in primary care
Introduction
Irritable bowel syndrome (IBS) is a symptom-based diagnosis and affects 10–25% of the general population. It has a female predominance and the majority is diagnosed in primary care [1], [2]. Quality of life among IBS patients is impaired with the illness seriously affecting everyday working and social life in addition to an increased use of health care resources [3].
Stress plays a major role in the complex pathophysiology of IBS [4], [5], [6]. Early adverse life events are associated with a vulnerability to develop IBS [7]. Later on in life stress plays crucial parts in the first onset of IBS and also in the severity of gastrointestinal (GI) symptoms [8].
The individual's response to physical and psychological stress includes activation of the hypothalamic pituitary adrenal (HPA)-axis and the autonomic nervous system [9]. Corticotrophin releasing factor involved in the HPA-axis, and also expressed in the gut, modulates inflammation, visceral hypersensitivity, gut permeability and motility [10], [11]. The reverse is also true and the gut influences processes in the brain [12]. This reciprocal relationship has also been suggested regarding everyday perceived stress and gastrointestinal (GI) symptoms [13].
Hypocortisolism is thought to be an important but not yet completely understood maladaptive consequence of chronic stress exposure and HPA-axis dysfunction resulting in a vulnerability to develop stress-related bodily disorders [14], [15]. Exposure to chronic stress initially activates the HPA axis producing elevated secretion of cortisol but over time the activity subsides and cortisol secretion falls below normal levels [15].
A dysregulated HPA-axis in IBS-patients has previously been suggested [16]. A recent study showed lower morning cortisol levels as well as a reduced total release of cortisol in the morning in females with IBS compared to controls [17]. In a meta-analysis from 2011 there was no statistically significant difference in baseline levels of cortisol in IBS patients compared to controls [18]. However baseline levels of cortisol in studies are often measured just before sigmoidoscopy or rectal extensions, which may elicit acute anticipatory responses with a hyperactive HPA axis [19]. In previous studies of IBS, cortisol was measured in blood, saliva or urine. These are acute, point-in-time measures that therefore can only relate to a short preceding time interval of stress exposure [20]. However those point-in-time measures have been used to study changes in the normal diurnal rhythm and response to psychological and physiological stress [16], [17]. Recently a method of measuring cumulative concentration of cortisol for longer periods has been developed through the measurement of hair cortisol concentrations (HCC) [20], [21]. Cortisol is retained in the hair strands [20] that grows at an approximate rate of 1 cm per month [22]. Through extracting cortisol an index of cumulative exposure over an extended period is provided. The method has been demonstrated to be valid and reliable [23].
To date, cortisol in hair levels as a measure of HPA axis activity averaged over a period of time has not been studied in IBS. Since stress and other psychological factors, which have been shown to be relevant to IBS, are dispositional or trait characteristics, it is expected that HCC will be a relevant marker of physiologic stress response and add further information on the previously suggested dysregulated HPA-axis in IBS. We hypothesized that hair cortisol levels in IBS patients would be lower than those found in non-IBS controls and that IBS patients would demonstrate higher levels of self-reported stress.
Section snippets
Material and methods
The study adopted a case-control design in a defined region in south-east Sweden (The County Council of Östergötland). Ten Primary Health Care centers (PHCs), in the three major cities of the region, joined the study. These PHCs are responsible for primary care of a population of around 150, 000 inhabitants (about 1/3 of the region). Of the three cities, one could be labeled as a white-collar city (academic) and two as blue-collar cities (industrial) [24]. The selected ten PHCs were chosen to
Sociodemographic and clinical characteristics
IBS patients were older than non-IBS patients. Regarding gender and psychosocial environment the two groups were more comparable. IBS patients tended to live more alone and work less than non-IBS patients and more IBS-patients were born abroad. IBS patients were more likely to report extra intestinal pain disorders, sleeping disturbances and psychiatric comorbidities than non-IBS patients, but the major internal medical diseases were similarly reported in both groups. IBS patients reported more
Discussion
The most important finding of this study is a possible overrepresentation of low HCC individuals among IBS patients. At the same time IBS patients reported higher perceived stress than non-IBS patients, confirming a well-established relationship between psychosocial stress and IBS.
This is, to our knowledge, the first study with HPA axis activity averaged over a period of time (3 months) in IBS. Our findings suggest that a portion of IBS patients could suffer from hypocortisolism, due to a
Conclusion
For the first time HCC has been measured in IBS and revealed a possible suppression of the HPA-axis activity in a considerable portion of IBS patients. Hence IBS-related symptoms in these patients could be associated with hypocortisolism. This study also supports previous findings that IBS is associated with psychosocial stress. However all significant associations in this study were very weak or weak. Further prospective studies regarding IBS, HCC, early life events and gastrointestinal
Acknowledgments, funding and disclosure
The authors wish to thanks all the Primary Health Care Centers and patients which participated in the study. This study was partly funded by a grant from FORSS (Research fund in South of Sweden).
ÅF, EG and SW participated in the study design and coordination, AKN and VT completed the data collection. ÅF, EG, VT, AKN, SW, ET and MPJ analyzed the data and drafted the manuscript. All authors contributed to analysis and interpretation of data, and read and approved the final manuscript.
No competing
Funding
This study was supported by the research council of Southeast Sweden (FORSS).
Competing interest
The authors declare that they have no competing interest.
Financial disclosure
The authors have no conflicts of interest relevant to this article to disclose.
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