Migraine, major depression and panic disorder: a prospective epidemiologic study of young adults

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1 Migraine, major depression and panic disorder: a prospective epidemiologic study of young adults Naomi Breslau. Glenn C Davis Department of Psychiatry, Henry Ford Hospital Detroit, MI Ce1!.halal~ Breslau N, Davis Gc. Migraine. major depression and panic disorder: a prospective epidemiologic study of young adults. Cephalalgia 1992;12: Oslo. ISSN We examined prospectively the risk for major depression (MOD) and panic disorder in persons with prior history of migraine. A random sample of 995 young adults was interviewed in 1989 and reinterviewed in A history of migraine at baseline increased fourfold the risk for MOD during the follow-up interval. A history of any anxiety disorder exacerbated the risk for MOD in persons with migraine. Persons with a history of migraine were twelve times more likely to become cases of panic disorder than those with no history of migraine. The risk for MOD and/or panic disorder was unrelated to whether or not migraine was active during the year preceding the baseline interview or in remission for more than one year. The findings suggest that migraine, major depression and anxiety disorders might share common predispositions. 0 Anxiety, epidemiology, major depression, migraine, panic disorder, prospective study Naomi Breslau, Director of Research, Department of Psychiatry, Henry Ford Hospital, 2799 W. Grand Boulevard, Detroit, MI USA; Received 8 August 1991, accepted 22 January 1992 We have previously reported a lifetime association between migraine and major depression (MOD) in an epidemiologic study of young adults (1). We reported additionally that a high proportion (84%) of persons with a history of migraine plus MDD met criteria for ananxiety disorder. In persons with the triad of disorders (i.e. migraine, MOD, and any anxiety disorder) the onset of the anxiety disorder generally preceded that of migraine, which in turn preceded the onset of MDD. Not all anxiety disorders were equal with respect to their temporal relationship with migraine. Simple phobia and social phobia generally preceded the onset of migraine, whereas panic disorder seldom occurred before the age at which migraine attacks began (1). Compared to persons with migraine alone, persons with migraine plus any anxiety disorder were far more likely to have subsequently developed major depression (1). The identification of a pattern of illness course in a subset of persons with migraine, in whom anxiety disorders had preceded migraine onset and MOD followed the onset of migraine, are consistent with other epidemiologic data (2, 3), Nonetheless, these findings have remained suggestive, as the evidence to date has been based on retrospective reports, subject to recall bias. In this report, we present prospective data from a 14 months' follow-up study. in which panic attacks and episodes of major depression during the interval period were ascertained. As young adults-21 to 30 years of age at baseline-the respondents in this study are in a period of increased risk for major depression and panic disorder, thus constituting a strategic sample for testing prospectively hypotheses about the associations of these psychiatric disorders with migraine, We examine prospectively the following hypotheses: (1) A history of migraine at baseline increases the risk for first incidence MDD; (2) the risk for first incidence MOD in persons with a history of migraine plus an anxiety disorder is markedly higher than in persons with a history of migraine alone, and higher than the sum of the risks in persons with migraine alone and anxiety alone; (3) a history of migraine at baseline increases the risk for first incidence panic disorder. Methods A random sample of 1,200 was drawn from all 21 to 30-year-old members of a large HMO (400,000 members) in southeastern Michigan. Baseline data were gathered in 1989 in personal interviews, and telephone follow-up interviews were conducted in 1990, approximately 14 months later. Participation rate at baseline was 84% and follow-up completion rate was 99.1%. The analysis was performed on data from 995 respondents, on whom complete follow-up data were available. The sample was 62% female and 81% white. Other characteristics of the sample are depicted in Table 1. More detailed information on the sample and its representativeness appears elsewhere (1). The NIMH-Diagnostic Interview Schedule (DIS) (4), revised to cover DSM-II1-R disorders, was used at baseline to measure history of affective, anxiety, and substance use disorders. Baseline data (T 1) were gathered by personal interviews in respondent's homes and follow-up data (T 2 ) were gathered in telephone interviews, covering symptoms that occurred during the fourteen months' interval since T1

2 86 N Breslall. GC Davis Table I. Sample characteristics (tl = 995). % (n) Sex Female 62.0 (617) Male 38.0 (378) Race Black 19.1 (l90) White 80.9 (805) Education < High School 3.6 (36) High School 21.0 (209) Part College 45.9 (457) ~College 29.4 (293) Marital status Married 45.1 (449) Sep/Divorced 5.3 (53) Never Married 49.6 (493) Descriptions of the NIMH-DIS and infonnation o~ its reliability and validity have been ref,0rted previously (5, 6). The NIMH-DIS is a ful y structured interview designed to be administered by trained lay interviewers. An extensive training program, developed by the authors of the DIS, was used to assure close adherence to the questionnaire and the sequence of follow-up probes. Interviewers in the 14 months' follow-up study were blind to the infonnation gathered in the baseline interviews. Major depression is defined in DSM-III-R (7) as the presence of at least five ~ro~ a list of nine depressiv~ symptoms occurring within the same two weeks period. with at least one of the symptoms pertaining to depressed mood or loss of interest or pleasure. The following symptom groups are listed in DSM-III-R definition of MOD: dysphoria. loss of interest or pleasure, weight loss or weight gain, insomnia or hypersomnia, psychomotor agitation or re~ardati~n, fatigue, feelings of worthl~s.snes.s or.excesslve guilt, concentration problems, suicidal ideations or attempt. Panic Disorder is defined in DSM-I1I-R as four panic attacks occurring within a four-week period, or one or more attacks followed by a period of at least a month of persistent fear of having another attack. The essential features of panic attacks are unpredictable episodes of sudden, intense appr~hensi?n or fear, accompanied by four of the followmg thirteen symptoms: dyspnea, dizziness, palpit~tion,.trembling, sweating, choking, nausea or abdominal dl~tress, depersonalization or derealization, paresthesia, hot. or cold flashes. chest pain or discomfort, fear of dying and fear of going crazy.. The T 1 interview included a sequence of questions on the defining features of migraine, adapted from the diagnostic criteria published in 1988 by the Headache Classification Committee of the International Headache Society (8). These criteria are as follows: A. At least five attacks. B. Headache attacks lasting more than 4 h. C. At least two of the following features: (1) Unila}, eral location; (2) pulsating; (3) inhibits or prohibits daily activities; (4) aggravation by routine physical activities. D. At least one of the following: (1) Nausea or vomiting; (2) photophobia and phonophobia. In this analysis, the diagnostic classification of the respondents at baseline refers to "lifetime" disorders. A respondent was classified at T 1 as having a lifetime disorder if diagnostic criteria for the specified disorder have ever been met, whether or not there have been recent symptoms. Thus, for example, the risk for MOD was calculated for all persons who have ever met criteria for migraine. relative to those who have never met criteria for migraine, as ascertained at the baseline interview. Statistical analysis To estimate the risk for MOD in persons with migraine plus any anxiety disorder and persons with migraine alone, we classified the subs~t at.risk (Le. those with no history of MOD at basehne) into four mutually exclusive categories: (1) no migraine. no anxiety disorder; (2) no migraine, any anxiety disorder; (3) migraine, no anxiety disorder; (4) migraine and any anxiety disorder. Any anxiety di~order is defined as one or more of the following. phobia, panic disorder, obsessive-compulsive disorder (OCD), generalized anxiety disorder (GAD!. and post-traumatic stress disorder (PT~D). Multivariable logistic regression was used, WIth the four mutually exclusive categories, of which the category with neither migraine nor anxiety served as the reference group. Odds ratios (OR) and 95% con.fidence intervals (Cl) were calculated from the legis tic regression. OR with 95% CI that exceed 1.0 indicate a statistically Significant increased risk for MOD. In subsequent analyses, respondents' sex and T history of other affective and substance use disorders were included as covariates in the equation The risk for first incidence MOD and first incidence panic disorder, associated with T t history of m~graine, were estimated in separate model~. Additionally, we estimated the risk for these dlsorder~. taking into account their co-occurrence. The analysis involves specifying the logistic regression model so that the key binary independent variable (that is. T, history of migraine: yes/no) is placed on the dependent variable side of the equation, with the mutually exclusive categories of the dependent variable (that is, first onset MOD alone, panic alone, and their joint occurrence, relative to neither) placed on the independent variables side, together wit~ ~ovariates of interest. The strength of the association between T I history of migraine and each category

3 of the dependent variable can be estimated by the odds-ratio, holding constant the other variables in the model (9). Results Baseline rates of migraine, major depression and anxiety disorders At baseline, 128 persons, or 12.9% of the sample, met criteria for migraine at any time in their lives. Data on the associations of migraine with sex, race and education in this sample were published previously (I). The lifetime rates of major depression (MOD), specific anxiety disorders, and any anxiety disorder in persons with a history of migraine vs those with no history of migraine are presented in Table 2. Odds ratios adjusted for respondents' sex are included as well. The odds for MOD in persons with migraine were fourfold higher than in persons with no history of migraine. The relative odds of specific anxiety disorders, with the exception of phobia. were even higher; the odds for phobia were increased approximately twofold. Sex-specific analyses revealed that, although MOD and anxiety disorders were more common in females than males, the odds for these disorders in persons with migraine relative to persons with no migraine were similar in males and females. Odds ratios for MOD in females and males were 4.1 (95% CI, ) and 4.9 (95% CI, ), respectively. ORs for panic disorder were 6.2 (95% CI, ) and 5.5 ( ), respectively, and for any anxiety disorder, 2.9 (95% CI, ) and 2.5 ( ), respectively. First incidence MDD at follow-up Of the total subset at risk for first incidence MOD at the beginning of the follow-up period, i.e. those with no history of MOD at baseline (n = 861), 34 Table 2. Baseline lifetime rates (per 100) of MDD and anxiety disorders in persons with and without migraine. and sex adjusted odds ratios (n = 995). Migraine No migraine (n = 128) (n = 867) AOR (95% en- MDD ( ) Panic disorder ( ) OCD ( ) GAD ( ) Phobia ( ) Any anxiety ( ) OCD = Obsessive-compulsive disorder. GAD = Generalized anxiety disorder. Sex adjusted odds ratios and 95% confidence intervals. Migraine. major depression and panic disorder 87 Table J. First incidence major depression by T 1 history of migraine and any anxiety disorder and odds ratios (n = 861). T 1 history Rate/100 OR (95% en- No migraine. no anxiety 2.5 Reference (n = 603) No migraine. anxiety ( ) (n = 174) Migraine, no anxiety ( ) (n =52) Migraine plus anxiety ( ) (n =32) Persons with T 1 history of major depression (n = 134) were deleted. Any anxiety disorder includes phobia. panic disorder, obsessive-compulsive disorder. generalized anxiety disorder and posttraumatic stress disorder. "Odds ratios (OR) and 95% confidence intervals (Cl) were calculated in a multivariable logistic regression. experienced an episode of MDD during the followup interval. The rate of first incidence MOD was significantly higher in persons with T 1 history of migraine (n = 84) than in persons with no T 1 history of migraine (n = 777), 11.9% vs 3.1%, respectively. The risk for MDO in persons with a history of migraine, relative to persons with no history of migraine, was 4.24 (95% CI, ). The modifying effect of a history of any anxiety disorder on the risk for first incidence MDO associated with migraine can be seen by examining Table 3. Compared to the reference group of persons with neither migraine nor anxiety, persons with T 1 history of migraine alone had more than twice the rate of MOD, 2.5% vs 5.8%, respectively, although the difference was not statistically significant (p = 0.17). The rate of first incidence MDD in persons with T 1 history of migraine plus any anxiety disorder was 21.9%, representing an elevenfold increased risk, relative to the reference group. The relative odds for MOO in persons with migraine plus any anxiety disorder was substantially higher than what might be expected from the sum of the relative odds in persons with migraine alone and any anxiety disorder alone. In an additional analysis, respondents' sex and T1 history of other affective and substance use disorders were included in the model as covariates. The adjusted odds ratio for new incidence MOD in persons with T I history of migraine plus any anxiety disorder was only slightly lower than the unadjusted odds ratio (OR = 9.69; 95% CI, ). First incidence panic disorder at foj/ow-up The analysis of first incidence panic disorder was conducted on 965 persons who reported that they had never experienced panic disorder at the time of their baseline interview. A total of 13 persons

4 88 N Breslau, GC Davis reported the first occurrence of panic disorder between the baseline and the follow-up interview. The rate of first incidence panic disorder was significantly higher in persons with T1 history of migraine (n = 114) than in persons with no T J history of migraine (n = 851), 7.0% vs 0.6%, respectively (odds ratio = 12.77; 95% CI, ). First incidence panic disorder and MDD, independently and jointly Because MOD and panic disorder are strongly associated (10-12), we examined their risks in persons with migraine, taking into account the extent to which their first incidence might have been experienced jointly. The analysis of the onset of panic disorder and MOD, alone and jointly, was performed on 849 persons who reported that they had never experienced either disorder at the time of the first interview. A total of 37 cases were identified who experienced MOD, panic disorder or both between T) and T z, in the absence of a prior history of either disorder. The rate of these first occurrences in persons with T1 history of migraine was 13.8%, compared to 3.4% in persons with no T 1 history of migraine. In Table 4 appear the rates of first incidence MOD alone, panic disorder alone, and MOD plus panic disorder in persons with and without TJ history of migraine. Odds ratios and 95% CI are presented for each diagnostic category. The rate of first incidence MOD alone was higher than the rate of first incidence panic disorder alone or panic disorder plus MOD, 7.5%, vs 2.5% and 3.8%, respectively. Odds ratios for panic disorder, alone and with MOD, were higher than for MOD alone, although these estimates have a wide confidence interval due to the small number of first incidence cases of panic disorder in the sample. Because migraine was found to be associated also with increased rates of other anxiety disorders (1 3), and because persons with other anxiety disorders are at increased risk for MOO and panic disorder, we include in Table 4 the odds ratios adjusted for T, history of other anxiety disorders. These were, phobia, obsessive-compulsive disorder, generalized anxiety disorder, and post-traumatic stress disorder. CEPHALALGIA 12 (19921 The adjusted relative odds for panic disorder alone and for MOD plus panic disorder were 9.5 and 25.2, respectively. The adjusted relative odds for MOD alone in this group were 2.5. We examined also whether the rate of first incidence MOD and/or panic disorder in persons with a history of migraine varied by the recency of their migraine attacks. It has been previously suggested that the increased rate of depression in persons with migraine might be interpreted as a psychologic reaction to recurrent migraine attacks (1, 2). A reaction of that sort can be assumed to have its onset in proximal relationship to the time of iljness rather than after a long period of remission. Thus, an increased.rate of new psychiatric disorders in persons with active migraine (i.e. migraine attacks during the year preceding the baseline interview), compared to persons with past migraine (i.e. last migraine attack having occurred more than one year before the baseline interview), would support the interpretation that the increased risk for these disorders reflects a psychologic reaction to migraine attacks. The rate of first incidence MOD and/or panic disorder in persons with past migraine (n = 26) was slightly higher than in persons with active migraine (n = 54), 15.4% and 13.0%, respectively. This finding does not support the interpretation that MOD (or panic disorder). even when they occur for the first time after the onset of migraine, are reactions to recent migraine attacks. Discussion The analysis of the prospective data from this epidemiologic study yielded the following results: (I) a history of migraine increased the risk for major depression: (2) a history of any anxiety disorder modified the relationship between migraine and the emergence of MOD: the risk for MOO was significantly increased in persons with migraine plus an anxiety disorder, but not in persons with migraine alone; (3) a history of migraine increased the risk for panic disorder: (4) a simultaneous analysis of these psychiatric risks revealed that persons with a history of migraine were at increased risk for panic disorder. MOD, and their joint occurrence: (5) the risk for the Table 4. First incidence panic disorder and MOD, alone and jointly, by T 1 history of migraine (n = 849) (Rate/IOO and odds ratios). Migraine No migraine (n = 80) (n = 769) OR (95% 0) AOR (95% CI)" Panic/no MOD ( ) 9.5 ( ) MOD/No panic ( ) 2.5 ( ) MOD plus panic ( ) 25.2 ( ) Persons with T I history of MOD or panic disorder were deleted. Odds ratios adjusted for T I history of other anxiety disorders (i.e. phobia, GAD. OCD, PTSO).

5 development of these psychiatric disorders in persons with a history of migraine was unrelated to the recency of their migraine attacks. and was equally increased in persons with recent attacks and in persons who have not experienced migraine attacks for one year or more. The prospective data from this study provide strong support for previous reports on the lifetime prevalence of MOD and anxiety disorders in persons with migraine ( ). They confirm previous retrospective findings on the role of early anxiety disorder in exacerbating the risk for MOD in persons with migraine (1. 2). It is especially with respect to the chronologie order of migraine and the psychiatric disorders associated with it that the prospective data are most useful, as they address the concerns that findings based on retrospective data are subject to recall bias and inaccuracies concerning the timing of events. These data also provide the first evidence that persons with a history of migraine are far more likely than others to become new cases of panic disorder. and especially, panic disorder plus MOD. The observed sequence does not necessarily imply that migraine "caused" MOD or panic disorder. The increased incidence of MOD and panic disorder in persons with migraine might be due to common predisposition, with the sequence among them determined by disease specific age of onset. Our findings on the relationship between new psychiatric disorders and recency of migraine is consistent with this interpretation. According to these prospective data, the increased risk for panic disorder and/or MOD was unrelated to whether or not those with history of migraine have had recent migraine attacks. Specifically. the rate of new disorders in persons whose last migraine attack had occurred more than one year before the baseline interview was similar to the rate in those with migraine attacks during the year preceding the baseline interview. Thus, these data do not support the notion that MOD (or panic disorder) in persons with migraine constitute psychologic sequelae of recurrent and disabling migraine attacks. A similar inference was made by Jarman et al. based on results from the tyramine test. a trait marker for depression that is independent of present state (14). Our data suggest that the link between migraine, MOD and anxiety disorders is more likely due to shared predispositions. although the nature of these predispositions remains to be determined. Inquiries into the shared predispositions to migraine and psychiatric disorders must take into account the cluster of psychopathology which includes, in addition to MDD, also anxiety disorders and suicidal ideation and attempts. A review of recent research reveals that similar neurochemical mechanisms have been implicated in these disorders. primarily serotonin abnormalities (IS -19). Migraine. major depression and panic disorder 89 Previously, we reported an increased lifetime prevalence of suicide attempts and suicidal ideations in persons with migraine with aura (1, 20). The very small number of new suicide attempts during the follow-up interval precluded the examination of this association prospectively. Furthermore. despite the relatively large sample size and the strategic age range of the sample. the total number of first incidence cases was small, limiting the statistical power of the study. particularly in multivariable analysis. Future follow-up studies of this cohort of young adults over longer intervals is expected to yield a larger number of new cases and will permit more precise estimates of risk and an analysis of risk according to migraine subtype. Acknotaledgements.r-r-This research was supported in part by grants from Kingswood Hospital. Ferndale. MI and a Research Scientist Development Award K02 MH (Dr Breslau) from the National Institute of Mental Health. Bethesda. MD. The generous cooperation of Health Alliance Plan is gratefully acknowledged. Dr KMA Welch provided invaluable advice and an incisive critique of an earlier version of the paper. References 1. Breslau N. Davis GC Andreski P. Migraine. psychiatric disorders. and suicide attempts: an epidemiologic study of young adults. Psychiatry Res 1991;37:]] Merikangas KR. Angst I. Isler H. Migraine and psychopathology. Arch Gen Psychiatry 1990;47: Merikangas KR. Risch NJ. Merikangas JR. et al. Migraine and depression: association and familial transmission. J Psychiatr Res 1988;22: Robins LN. Helzer IE. Cottier L, et al. NIMH diagnostic interview schedule, Version III. revised. ] Anthony JC Folstein MF, Romanski AJ. et al. Comparison of the lay Diagnostic Interview Schedule with a standardized psychiatric examination: experience in eastern Baltimore. Arch Gen Psychiatry 1985;42: Helzer JE. Robins LN. McEvoy OT. et al. A comparison of clinician and Diagnostic Interview Schedule diagnoses. Arch Gen Psychiatry 1985;42: American Psychiatric Association. Diagnostic and statistical manual of mental disorders: DSM-III-R. 3rd ed., Review. Washing~on. DC: American Psychiatric Press. ] Headache Classification Committee of the International Headache Society. Proposed classification and diagnostic criteria for headache disorders. cranial neuralgias and facial pain. Cephalalgia 1988;8(suppl 7): Schlesselman I. Case-control studies: design. conduct. analysis. New York: Oxford University Press. ] Breier A. Charney OS. Heninger GR. Maior depression in patients with agoraphobia and panic disorder. Arch Gen Psychiatry 1984;41: Leckman IF. Weissman MM. Merikangas KR. et al. Panic disorder and major depression: increased risk of depression. alcoholism. panic, and phobia disorders in families of depressed probands with panic disorder. Arch Gen Psychiatry 1983:40: Kendler KS, Heath AC Martin NG. et at. Symptoms of anxiety and depression: same genes. different environments: Arch Gen Psychiatry 1987;44: Stewart WF. Linet MS. Celentano DD. Migraine headaches and panic attacks. Psychosom Med 1989;51:559-69

6 90 N Breslau, GC Davis 14. Jarman 1. Fernandez M, Davies PTG, et al. High incidence of endogenous depression in migraine: confirmation by tyramine test. J Neurol Neurosurg Psychiatry 1990;53: Meltzer HY. Lowy MT. The serotonin hypothesis of depression. In: Meltzer HY ed Psychopharmacology: the third generation of progress. New York: Raven Press, 1987: Asberg M, Schalling D, Traskman-Bendz, et al. Psychobiology of suicide, impulsivity, and related phenomena. In: Meltzer HY ed Psychopharmacology: the third generation of progress. New York: Raven Press, 1987: D'Andrea G, Welch KMA, Riddle JM, et al. Platelet serotonin metabolism and ultrastructure in migraine. Arch Neurol 1989;46: Innis RB, Charney DS, Heninger GR. Differential JH_ imipramine platelet binding in patients with panic disorder and depression. Psychiatry Res 1981;21: Insel TR, Murphy DL. The psychopharmacological treatment of obsessive-compulsive disorder: a review. J Clln Pharmacol 1981;1: Breslau N. Migraine, suicidal ideation and suicide attempts. Neurology 1992;42:392-5