Background
Migraine, a common disabling disease, accounts for a large proportion of non-fatal disease related burden worldwide [
1]. In a review study on global burden of disease in 2013, migraine and mild-to-moderate mental disorders such as depressive and anxiety disorders were main causes of burden in this category for the Korean public [
2]. Migraine has several comorbidities and modifiable risk factors. In published literature, vascular accidents, depression, anxiety, epilepsy, and sleep problems are commonly associated with migraine. Attack frequency, caffeine, medication overuse, obesity, snoring or sleep apnea, psychiatric comorbidity, and stressful life events have been suggested as modifiable risk factors for migraine complications such as vascular events and chronic migraine (CM) [
3]. All these factors will reduce the quality of life (QOL) of migraine patients [
3,
4]. In addition, psychiatric comorbidity and psychological distress may negatively affect the outcome of migraine patients [
5].
It has been found that migraine patients have higher levels of perceived stress than healthy controls [
6,
7]. In addition, identified stress levels are higher in migrainous women than those in migrainous men [
6]. Moreover, stress can trigger migraine attacks. About 80% of migraine patients with identifiable triggers have reported that stress is a common trigger [
8]. In a Korean hospital-based study, stress is the most common trigger for episodic migraine, followed by sleep deprivation and fatigue [
9]. In addition, 57.7% of patients have indicated fatigue as a headache trigger [
9]. It has been suggested that stress might be a predisposing factor in new-onset migraine [
10]. Stress might also play a role in migraine chronification [
11].
Although a stressful condition is likely to be associated with migraine, the level of perceived stress between episodic migraine (EM) and CM has not been delineated yet. Therefore, the first aim of this study was to determine the level of perceived stress in EM and CM patients. Factors associated with perceived stress in migraine patients have not been reported yet. If predictors for perceived stress of migraine patients can be identified, a guideline can be developed for clinicians to manage stress adequately. Therefore, the second aim of this study was to identify predictors for perceived stress in migraine patients. In addition, although it is known that migraine and comorbid disorders will reduce QOL of patients, the impact of stress on QOL has not been reported. Therefore, the third aim of this study was to delineate the impact of stress on QOL to provide information for clinicians.
Discussion
Our study revealed that the level of perceived stress was significantly higher in CM patients than that in controls. Although several factors including clinical and psychosomatic factors were associated with perceived stress, our data demonstrated that CM appeared to be a critical factor for perceived stress. Perceived stress was correlated well with migraine-specific QOL.
While a higher level of perceived stress has been previously reported in migraine patients compared to that in healthy controls in two studies [
6,
7], there was no difference in mean PSS score between migraine patients and controls after controlling for depression and anxiety in this study. This reveals that depression and anxiety are major determinants of perceived stress in migraine patients and controls. It is known that stressful events can cause depression and anxiety. In response to stress, corticotropin releasing factor (CRF) regulates the activity of hypothalamic-pituitary-adrenal (HPA) axis and triggers changes in serotonin receptors [
27]. CRF is also known to influence anxiety responses with CRF receptor 1 being particularly important [
28]. In a cohort study, it has been found that stressful events contribute to comorbidity of migraine and major depression [
29]. Depression and anxiety can also aggravate stressful conditions. In epilepsy patients, depression and anxiety have direct effect on perceived stress [
30]. Under these circumstances, depression and anxiety are not likely to be unique for perceived stress in patients with migraine.
After investigating the relationship between migraine chronicity and perceived stress, it was found that CM patients had higher levels of perceived stress than controls. CM was selected as a critical factor for perceived stress after adjusting for depression, anxiety, and insomnia by multivariate analyses. It has been reported that CM patients are more likely to have depression, anxiety, sleep problems, and poor QOL compared to EM patients [
31,
32]. These conditions might induce stressful conditions in CM patients to some extent. Our data demonstrated that CM appeared to be a migraine-specific factor for perceived stress. Stressful life events are likely to trigger migraine events [
8,
9]. They might be risk factors for CM [
11]. Repeated stress may lead to functional and structural alteration in the brain network. These changes in brain states may occur as a result of repeated migraine attacks through maladaptive coping mechanisms [
33]. The cascade of these effects can lead to further deterioration of adaptation, causing transformation or chronification of the disease [
33]. Therefore, clinicians should identify perceived stress by counseling migraine patients. They need to modify perceived stress through pharmacological or non-pharmacological interventions such as cognitive behavioral therapy and biofeedback to avoid transformation or chronification of migraine [
34].
Our results revealed that the level of perceived stress was significantly associated with the role function and emotional function of migraine patients. Chronic stress may trigger migraine attacks [
8,
9] or induce CM [
11,
33], subsequently restricting or preventing participation in social or work related activities [
35]. Therefore, chronic stress might affect emotions of migraine patients. That is the reason why clinicians should identify and modify stress.
Our study has some limitations. First, subjects were from a single tertiary hospital. Therefore, our results cannot be generalized. Second, this was a cross-sectional study. Causal relationships between variables could not be confirmed. A longitudinal study is recommended to verify the causal relationship between perceived stress and CM. Third, the level of perceived stress was measured for the preceding month. Therefore, state of stress over a month was unknown. A long-term observational study is needed to evaluate the impact of CM on perceived stress.
Conclusions
In conclusion, it was found that the level of perceived stress was significantly higher in CM patients than that in controls. Among several factors associated with perceived stress, CM appeared to be a critical factor for perceived stress. Significant negative correlations between perceived stress and migraine-specific QOL was found in this study.
Acknowledgements
The authors thank Ju-Hui Lee, a neuropsychologist, for helping in the completion of self-report questionnaires.