Associations Between Depression/Anxiety and Headache Frequency in Migraineurs

A Cross-Sectional Study

Hsuan-Te Chu, MD; Chih-Sung Liang, MD; Jiunn-Tay Lee, MD; Ta-Chuan Yeh, MD; Meei-Shyuan Lee, PhD; Yueh-Feng Sung, MD, PhD; Fu-Chi Yang, MD, PhD


Headache. 2018;58(3):407-415. 

In This Article


In this study, we found that the severity of depression (BDI and HADS depression scores) and anxiety (HADS anxiety score) were related to migraine frequency, after adjusting for gender, age, BMI, employment, education, smoking, alcohol consumption, coffee consumption, MIDAS score, and PSQI total score. These correlations were maintained in subgroups of patients who had migraines with or without auras. For all three measures, group mean scores were highest for the chronic frequency group. We did not see any significant gender-related differences.[11]

Our finding of a positive relationship between increased migraine frequency, with or without auras, and depression and anxiety is consistent with prior findings.[11] Moreover, the mean BDI score for our nonmigraine control group was similar to that reported by studies conducted in Germany[22] and Taiwan.[4] Although we ruled out the presence of emotion-induced headache[23] in this study, it remains to be determined whether recurrent headaches may be a manifestation of emotional disturbance.

Previous studies have suggested a positive relationship between headache frequency in migraineurs and the presence of depression and anxiety,[9] but without grouping the number of days with migraine attacks, the presence of aura, and comparison to nonmigraine control subjects. Thus, we employed narrower bins of attack frequency differentiation (1-4, 5–8, 9–14, and ≥15 hd/months). This work also differs from prior studies in that we included a nonmigraine control group and accounted for potential confounding factors, such as alcohol consumption, employment, and sleep quality. We found that migraineurs who smoked and, to a lesser extent, who attained higher levels of education, tended to have higher migraine frequencies. The suggested influence of smoking on migraines is consistent with a prior cross-sectional population study that reported higher prevalence of headaches among smokers than nonsmokers.[24]

Our present finding that poor sleep was associated with greater migraine frequency is also consistent with prior work showing that migraine frequency correlates with poor sleep quality and a higher prevalence of sleep difficulties.[4] Additionally, after adjusting for baseline characteristics, our multivariate factor analysis indicated that sleep quality may be an independent predictor of emotional distress. Thus, the effects of poor sleep quality on migraine-related variables appeared independent to the presence of affective comorbidities.[25]

Factors such as emotional distress and incidence of headache may influence each other via some common pathophysiological mechanism. First, pain severity has been shown to correlate with emotion intensity.[26] More specifically, emotional responses have the potential to alter pain perception by modulating nociceptive signaling in the descending pain pathway.[27] The periaqueductal gray, which controls descending pain modulation, projects to serotonergic neurons in the medulla as well as to noradrenergic neurons in the pons and tegmentum.[28] Central serotonin activity may become diminished when a person experiences successive migraine attacks, which may predispose one to recurrent headaches; moreover, the resultant low serotonin concentrations may lead to a decline in pain perception threshold.[29] Second, a recent meta-analysis confirmed that patients with chronic pain have an elevated risk of developing depression.[30] Third, the pathophysiology of migraine encompasses activation of the trigeminovascular pathway via pain signals initiated in peripheral intracranial nociceptors, and a dysfunction of central regulation of neural excitability and pain.[31] Central monoaminergic disturbances appear to be common to migraine and depression/anxiety.[32] Reduced systemic serotonin levels have been detected in migraineurs during and between attacks.[33] Further, it has been suggested that migraines may be caused by a dopamine-noradrenalin imbalance in pain matrix neurons due to aberrant tyrosine metabolism.[34] The central monoaminergic dysfunction model of migraines has led to antidepressant prophylactic treatment.[35] Central sensitization and hypothalamic-pituitary-adrenal axis dysregulation have also been implicated in both migraine and affective disorders.[36] Interestingly, migraines with auras, comorbid with anxiety disorders and major depression, have been associated with the NcoI polymorphism in the DRD2 gene.[37] Regardless of whether a common pathogenesis underlies migraines and depression/anxiety, the current literature suggests that mood and anxiety disorders may worsen migraines, while poorly controlled migraines may exacerbate emotional problems.

An interrelationship between migraines and emotional distress has also been described in adolescents and children.[38] Notably, recurrent headaches have been linked with anxiety and depression in early adolescence,[39] and children who have headaches have an increased risk of developing serious depressive symptoms.[40] Sleep and mood disorders are also common in adolescents with migraines, and teenagers with chronic migraine are particularly prone to dysthymia and sleep issues.[29]

This study had several strengths, which included its controlled study design, large number of subjects, demographically similar groups, differentiated subgroups, use of validated questionnaires, consideration of sleep quality and RLS, analysis of migraine subgroups (with or without auras), and robust statistical analysis. However, this study had several limitations worth mentioning. First, the use of a cross-sectional design limited our ability to make causal inferences. Second, the use of study population from a department within a single hospital limits the broad generalizability of our findings. Third, emotional symptoms were evaluated with self-rated scales rather than with an objective assessment. Furthermore, all subjects completed the screening questionnaire and were interviewed by a board-certified neurologist and headache specialist regarding the migraine attacks. Despite this evaluation process, there might be a few nonmigraine headaches not distinguished from migraine attacks. Additionally, there were fewer subjects in the chronic migraine group than in other migraine groups. Thus, future studies should focus on increasing the recruitment of patients with chronic migraines. In addition, in the present study, the control group included individuals with infrequent episodic tension-type headaches (<6 days/year) defined according to the International Classification of Headache Disorders, 3rd edition (beta version).[17] A previous study suggests that tension-type headache is associated with psychiatric disorders, including anxiety and depression, especially in individuals with a high frequency of headache episodes.[41] However, infrequent episodic tension-type headaches may have less impact on psychiatric disorders. In this study, out of 179 nonmigraine subjects, 20 had infrequent episodic tension-type headaches. We will try to exclude this population in the future to maintain homogeneity in the control group. Another limitation of our study is that most participants with high frequencies and chronic headaches had been prescribed migraine preventing agents, such as calcium channel blockers, β-blockers, antiepileptic drugs, or even antidepressants. All these preventive medications may have effects on depression or anxiety. But for the maximal benefit of participants, we used the preventive intervention to improve their quality of life. In the future, we will take that into consideration and exclude this confounding problem.

In conclusion, the present findings support the hypothesis that greater migraine frequency, with or without auras, is associated with increased symptom scores of anxiety and depression. Poor sleep quality, as indicated by the PSQI score, was also found to be an independent predictor of more severe depression and anxiety symptoms. Taken together, these findings suggest that preventive pharmacological treatments may reduce the risk of depression and anxiety problems in migraineurs.