Psychological Mechanisms of Migraines
Peter D. Drummond
Jan Passchier
Although it is generally recognized that migraine is a somatic disorder, several psychological mechanisms appear to influence the frequency and severity of its expression. We discuss the relevance of psychological stressors, the personality and psychopathology associated with migraine, and the importance of the way the patient copes with stress and headaches. We also briefly consider the implications for treatment (reviewed in more detail in Chapter 48).
When patients are asked what triggers their episodes of migraine, the majority nominate “stress.” By itself this is not very informative, because the situational context can range from minor hassles or time pressures through to major life changes. Nevertheless, it is now widely accepted that negative moods and personality traits that increase emotional vulnerability to negative life events do heighten the risk of migraine headaches. Unfortunately, the attack itself can be an additional source of stress because of the associated pain and discomfort, and because of disruption to daily routines. This may heighten susceptibility to recurrent attacks.
From a conceptual point of view, one of the most convenient ways to define stress is that it develops when demands outweigh resources. Clearly, what is demanding varies enormously from one person to another, because each of us has different strengths and weaknesses and we are each faced with different challenges. However, when demands do outweigh resources, the outcome is likely to be a negative emotional state (e.g., fear, anger, anxiety, or depression) and activation of protective autonomic and neuroendocrine responses. Persistence or fatigue of these responses may trigger individual episodes of headache. Moreover, depletion of hormonal supplies or energy reserves during prolonged stress could provoke processes (e.g., perivascular inflammation or abnormal pain modulation) that, ultimately, increase susceptibility to recurrent attacks of headache.
PROSPECTIVE STUDIES OF STRESS AND MIGRAINE
The most direct test of association between stress and migraine is to prospectively investigate stressful events and mood changes preceding attacks of migraine. Information from a representative sample of such studies is presented in Table 41-1.
In general, prospective studies show that the frequency of stressful events is greater than normal on days preceding attacks of migraine than on other days (37,40). However, this effect varies somewhat between studies, possibly because of variation in headache frequency between different samples of subjects or because of variation in the length of data collection. In some but not all studies, mood changes were found to precede headache by a day or more (12,29), the most conspicuous changes being increases in fatigue, time pressures, alertness and, depressed mood.
To tease out the link between stressful life events, mood changes, and migraine, Sorbi et al. (56) collected mood ratings (alertness, tension, annoyance, irritability, depression, and fatigue), headache symptomatology, ratings of the incidence and stressfulness of daily hassles, sleep quality, and stage of menstrual cycle from 19 female migraine patients for 10 weeks. Data were analyzed in various ways in relation to the time period before attacks of migraine (56, 57, 58). In comparison to headache-free days, the incidence of daily hassles was greater during the afternoon preceding an evening or nighttime attack of migraine. The timing of evening and nighttime attacks is consistent with the notion of migraine developing during a period of relaxation after stress, as opposed to during the stressful experience itself. Attacks that started in the morning or afternoon were preceded by an increase in the incidence or burden of daily hassles during the previous few hours or day, and were preceded by increases in tenseness, irritability and fatigue for one or more days. Spierings et al. (58) postulated that several days of tension can produce fatigue and
irritability, culminating in extreme emotional tension and ultimately resulting in an afternoon attack of migraine. Morning attacks often began after a particularly stressful period, associated with feelings of tension and fatigue that developed over the preceding few days. The notion that migraine develops during the period of recovery from stress might also apply to morning attacks, because feelings of fatigue were not relieved by sleep. Taken together, the results of this prospective study suggest that relaxation after stress, persistent tension, and fatigue not relieved by sleep each increase the likelihood of migraine.
irritability, culminating in extreme emotional tension and ultimately resulting in an afternoon attack of migraine. Morning attacks often began after a particularly stressful period, associated with feelings of tension and fatigue that developed over the preceding few days. The notion that migraine develops during the period of recovery from stress might also apply to morning attacks, because feelings of fatigue were not relieved by sleep. Taken together, the results of this prospective study suggest that relaxation after stress, persistent tension, and fatigue not relieved by sleep each increase the likelihood of migraine.
TABLE 41-1 Prospective Studies of Stress and Migraine | ||||||||||||||||||||||||||||||||||||
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Holm et al. (35) investigated headache activity in relation to how well 20 female undergraduates coped with stressful life events over an 8-week period. Each subject reported symptoms consistent with the diagnosis of migraine in a preliminary questionnaire and telephone interview, but subjects did not record headache symptomatology prospectively. Thus, these findings apply to headaches in general but not to migraine in particular. Subjects recorded the occurrence and psychological impact of minor stressful events, their appraisal of the events, and how well they coped with them in a daily diary. They also recorded the intensity of headaches four times daily. In the majority of cases, the timing of migraine attacks was associated with the number and intensity of daily hassles, the appraisal of these hassles as threatening, and lack of resources to cope with the hassles. This relationship appeared to be reciprocal: stress preceded the headache in some cases but developed after the headache in others, perhaps contributing to the next attack of headache. A relationship between phase of the menstrual cycle and ratings of stress was identified in 20% of the subjects (42); thus, hormonal changes may sometimes interact with psychological disturbances to influence the onset of headache.
PERSONALITY, PSYCHOPATHOLOGY, AND MIGRAINE
It has been recognized for some time that patients referred to tertiary treatment centers such as specialized pain or headache clinics often have personality traits that influence the referral decision. For example, Ziegler and Paolo (68) compared the headache symptoms and psychological profiles of clinic patients with others who had not sought medical treatment for headaches in the past 2 years. Clinic patients had higher scores on the Hypochondriasis, Depression, Hysteria, Psychaesthenia, and Social Introversion scales of the MMPI-2 than the nonclinical group, even when findings were adjusted for differences in the severity of the patients’ most intense headaches. These findings suggest that the clinical stereotype of the perfectionistic, rigid, hostile, and resentful migraine sufferer probably derives as much from referral bias as from a specific involvement of these traits in migraine. Nevertheless, a link between migraine and neuroticism has been detected in several well-controlled community-based studies (see below); furthermore, the prevalence of anxiety disorders and major depression is higher than normal in community-based migraine samples, as reviewed below.
PSYCHIATRIC DISORDERS
Cross-sectional studies have demonstrated that depression and anxiety disorders are associated both with migraine and nonmigrainous headache. For instance, Zwart et al. (70) identified odds ratios (ORs) between migraine and depression of 2.7 and between migraine and anxiety of 3.2 in the Nord-Trondelag Health Study of a community sample of more than 50,000 subjects aged 20 years and above. Although ORs were somewhat lower for nonmigrainous headache, headache frequency appeared to be more relevant for these associations than diagnostic category.
The association between migraine and the appearance of affective disorders in young adults has also been investigated prospectively in several large community-based samples. The advantage of a prospective design over a conventional cross-sectional design is that it provides some insight into the time sequence of any association that may exist. Breslau et al. (8) used structured interviews, based on current diagnostic criteria for migraine and psychiatric disorders, to measure the lifetime history of these disorders; 3.5 years later the interviews were repeated to identify the new development of the psychiatric symptoms and migraine over this time period. A strong association between migraine and major depression was detected in the lifetime history data. Importantly, depression preceded migraine as often as migraine preceded depression both in the lifetime history data and prospectively, indicating no clear direction of causality. A similar association between migraine and specific anxiety disorders was also detected in the same community-based sample (7). A large, cross-sectional community survey of major depression, migraine and severe nonmigrainous headache by Breslau et al. (10) confirmed the bidirectional relationship between migraine and lifetime prevalence of depression. In contrast, major depression did not increase the risk for severe nonmigrainous headache.
Pine et al. (50) followed an initial cohort of 776 children and adolescents for 9 years. Psychiatric diagnoses were established during detailed standard interviews, whereas headache status was investigated by asking subjects if “they had a history of migraine or chronic headache at any time in their life that prevented them from doing things they would usually do” (p. 156). Adolescents with a diagnosis of major depression reported a history of headache approximately twice as often as those without this diagnosis; furthermore, major depression in adolescence predicted the development of chronic headaches in early adulthood. An association between simple phobias, overanxiousness, and headaches was also identified; however, this association seemed to be caused by a link with symptoms of depression. The generality of these findings is limited by the sketchy assessment of headache, and by the likelihood of unreported episodes of major depression between assessments. Nevertheless, the findings document an association between major depression and the later development of chronic headache.
Swartz et al. (61) identified a strong cross-sectional association between lifetime psychiatric diagnoses of major depression and panic disorder and the development of migraine headaches in a cohort of 1343 subjects followed for 13 to 15 years. The odds of developing migraine increased slightly for those with a history of phobia at the initial interview; however, this relationship did not hold for other psychiatric disorders. The lack of a predictive relationship between affective disorders and migraine could be because of the age of the cohort (all members were aged at least 18 years in the initial interview) or due to selection bias (all members with a history of any form of headache at the initial interview were excluded from follow up).
Breslau et al. (9) recently followed a cohort of 496 migraine sufferers, 151 individuals with severe nonmigrainous headache, and 539 control subjects with no history of severe headaches for 2 years. In contrast to the findings of Swartz et al. (61), major depression at baseline increased the likelihood of developing migraine threefold during the 2-year follow up (but did not influence the frequency of attacks or headache-related disability in those with migraine at baseline). Conversely, migraine at baseline increased the risk of developing major depression five-fold during the 2-year follow up. Because there was no predictive association between major depression and severe nonmigrainous headaches, a predisposition to report somatic and psychological symptoms of distress does not explain the findings.
Recent research has also hinted at a relationship between migraine and a range of anxiety disorders meeting the diagnostic criteria of psychiatric classification systems. For example, in a telephone survey of more than half of the residents of Washington County aged between 12 and 29 years, the risk of having a headache in the previous week was increased for those with a history of panic attacks, particularly when the headache was associated with migrainous features (59). The temporal sequence between migraine and panic disorder was not addressed in this survey. However, in a prospective study by Breslau and Davis (7), panic disorder developed more frequently in subjects with migraine than in controls over a 14-month study period.
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