AMERICAN JOURNAL OP EPIDEMIOLOGY
Vol
Copyright © 1990 by The Johns Hopkins University School of Hygiene and Public Health All rights reserved
131, No. 2
Printed m U S.A
RISK FACTORS FOR THE ONSET OF PANIC DISORDER AND OTHER PANIC ATTACKS IN A PROSPECTIVE, POPULATION-BASED STUDY PENELOPE M. KEYL1 AND WILLIAM W. EATON1
Keyt, P. M. (Dept of Epidemiology, Johns Hopkins U. School of Hygiene and Public Health, Baltimore, MD 21205), and W. W. Eaton. Risk factors for the onset of panic disorder and other panic attacks in a prospective, population-based study. Am J Epidemiol 1990;131:301-11. A total of 383 cases of incident panic attack were identified among 12,823 participants in the Epidemiologic Catchment Area Program over various 12-month periods in 1980-1983. These cases not phobia-stimulated were compared with 766 controls. Risk factors were examined for the onset of panic attacks, with attacks categorized as panic disorder, severe and unexplained panic attacks, or other panic attacks. Risk factors were also examined for the onset of attacks in which cardiovascular symptoms were experienced and those in which psychologic symptoms were experienced. Females were at greater risk than males for each category of attacks (relative odds ranged from 1.36 to 2.25). Persons aged 65 years or older were at lower risk than younger persons (relative odds, compared with 30- to 44-year-olds, ranged from 0.26 to 0.71). A history of cardiac symptoms, shortness of breath, depression or a major grief episode, drug abuse or dependence, alcohol abuse or dependence, and seizures were each strongly associated with panic attacks. A history of cardiac symptoms was more strongly associated with attacks in which cardiovascular symptoms were experienced than with attacks in which psychologic symptoms were experienced (relative odds, 8.36 vs. 2.23). A history of seizures was more strongly associated with attacks with psychologic symptoms than with attacks with cardiovascular symptoms (relative odds, 5.21 vs. 1.58). age factors; anxiety disorders; alcohol drinking; cardiovascular system; depression; panic; seizures; substance abuse
A variety of fear responses exist in humans (1). Panic attacks are distinguished from other fear responses by their intensity, their short duration, and the fact that they often occur without any identifiable
cause. The spontaneous nature of most panic attacks and the fact that they are often accompanied by symptoms associated with the autonomic nervous system have led many researchers to concentrate on bi-
Received for publication April 28,1988, and in final • ment of Epidemiology, The Johns Hopkins University form July 24, 1989. School of Hygiene and Public Health, 615 N. Wolfe • Abbreviations: DIS, Diagnostic Interview Schedule; St., Baltimore, MD 21205. DSM-III, Diagnostic and Statistical Manual of Mental The Epidemiologic Catchment Area Program is a Disorders, third edition. series of five epidemiologic research studies performed 1 Department of Epidemiology, The Johns Hopkins by independent research teams in collaboration with University School of Hygiene and Public Health, Bal- staff of the Division of Biometry and Epidemiology of timore, MD. the National Institute of Mental Health (NIMH). 1 Department of Mental Hygiene, The Johns Hop- During the period of data collection, the Epidemiologic kins University School of Hygiene and Public Health, Catchment Area Program was supported by cooperaBaltimore, MD. tive agreements. Reprint requests to Dr. Penelope M. KeyL, Depart301
Downloaded from https://academic.oup.com/aje/article-abstract/131/2/301/138045 by Georgetown University user on 02 June 2018
302
KEYL AND EATON
ologic aspects of this disorder. It has been determined that lactate, caffeine, and other substances may induce panic attacks in those with a history of attacks but not in those without such a history (2). Certain medications can block the occurrence of both lactate-induced and spontaneous attacks (2). Thus, it seems plausible that there is a biologic component in the etiology of panic attacks. However, it seems likely that environmental stimuli are also involved in the etiology of panic attacks. Panic attacks are sometimes associated with phobic situations, especially fear of incapacitation when outside a familiar environment (agoraphobia). If panic is considered an extreme form of fear response, it seems reasonable to expect that the occurrence of panic attacks may be related to the degree of stress in the environment, the threshold for a response when exposed to stress, or a combination of these. In searching for risk factors for panic attacks, whether those meeting the criteria for diagnosis as panic disorder or those occurring less frequently or which are less severe in nature, it is important to consider both individual and environmental differences. In this paper, we present data on the onset of panic attacks based on a two-wave The NIMH Principal Collaborators were Drs. Darrel A. Regier, Ben Z. Locke, and William W Eaton (through October 1, 1983) and Jack Burke (from October 1, 1983, through March 1, 1987); the NIMH Project Officers were Drs. Carl A. Taube and William Huber. The Principal Investigators and CoInvestigators from the five sites were: Yale University (Cooperative Agreement U01 MH 34224)—Drs. Jerome K. Myers, Myrna M. Weissman, and Gary L. Tischler; The Johns Hopkins University (Cooperative Agreement U01 MH 33870)—Drs. Morton Kramer, Ernest Gruenberg, and Sam Shapiro; Washington University, St, Louis (Cooperative Agreement U01 MH 35386)—Drs. Dan Blazer and Linda George; and University of California, Los Angeles (Cooperative Agreement U01 MH 35865)—Drs. Marvin Kamo, Richard L. Hough, Javier I. Escobar, M. Audrey Bumam, and Dianne Timbers. Dr. Rudolf Hoehn-Saric provided valuable comments on the experience of symptoms during a panic attack. Preparation of this paper was supported by NIMH Grant MH41908.
Downloaded from https://academic.oup.com/aje/article-abstract/131/2/301/138045 by Georgetown University user on 02 June 2018
population-based field survey, the Epidemiologic Catchment Area Program.. We have already presented data on the prevalence of panic attacks and panic disorder from the first wave of the survey (3). This paper is an analysis of panic attacks which have occurred for the first time in a person's life. We examine several sociodemographic and other possible risk factors, as well as the question of whether risk factors are similar for different classifications of panic attacks. MATERIALS AND METHODS
This study is based on data collected as part of the National Institute of Mental Health Epidemiologic Catchment Area Program during various 12-month periods in 1980-1983. This program consists of community surveys carried out in five locations in the United States: Baltimore, Maryland; Durham, North Carolina; Los Angeles, California; New Haven, Connecticut; and St. Louis, Missouri. The methods of these surveys have been described elsewhere (4). Briefly, the surveys included persons aged 18 years or older, selected at random from households in the probability samples. Each person was interviewed, in person, twice: an initial interview and a follow-up interview 12 months later. Response rates for the initial interview at the five locations ranged from 76 to 80 percent. Seventy-six to 86 percent of responders to the initial interview responded to the follow-up interview. Classifications of pathology according to Diagnostic and Statistical Manual of Mental Disorders, Third Edition (DSM-III) criteria (5), made via the interview questions of the Diagnostic Interview Schedule (DIS) (6), are referred to as DIS/ DSM-III diagnoses. As part of each interview, the interviewer asked, "Have you ever had a spell or attack when all of a sudden you felt frightened, anxious, or very uneasy in situations when most people would not be afraid?" Those who reported that they had experienced such a spell or attack were asked whether or not each of 12 autonomic symptoms was
RISK FACTORS FOR PANIC DISORDER AND PANIC ATTACKS
present in their worst attacks. Those experiencing an attack were also asked whether the attack was severe enough to lead them to: 1) seek help from a doctor or other health professional; 2) take medication more than once; or 3) judge that the attack "interfered with my life or activities a lot." If the attack was severe by any of these criteria, a series of questions followed which focused on potential nonpsychiatric explanations for the attack, including ingestion of drugs or medication, use of alcohol, or physical illness or injury. An attack meeting the severity criteria with none of these as an explanation for the attack was termed a "severe, unexplained attack." A series of attacks which were severe and unexplained, which occurred often enough to meet the criteria for DSMIII, which were accompanied by four or more autonomic symptoms, and which occurred at least once in the absence of a phobic stimulus was termed "panic disorder." The 12,823 people who reported that they had never experienced a panic attack at the time of their first interview and who completed a follow-up interview were selected for this analysis of onset of panic attacks. Responses to the follow-up interview by these persons were used to estimate the annual incidence of panic disorder and other types of panic attacks. A case-control approach was then used for a multivariate analysis of risk factors associated with the onset of panic attacks. A total of 383 cases were identified who reported the onset of panic attacks between the initial and follow-up interviews. We selected 766 controls from the people remaining, all of whom had never experienced a panic attack by the follow-up interview. Within each of the five survey locations, controls were selected randomly using a systematic sample and a 2:1 casexontrol ratio. Multivariate logistic regression was used for the analysis of cases and controls. Information on sociodemographic and other variables considered as
Downloaded from https://academic.oup.com/aje/article-abstract/131/2/301/138045 by Georgetown University user on 02 June 2018
303
possible risk factors was based on responses at the time of the initial interview. The symptoms which accompany panic attacks cover a broad range, including symptoms which relate to the cardiovascular system (for example, "chest pain"), those which are perceptual (for example, "things around you seem unreal"), and symptoms reflecting more general bodily states (for example, feeling "dizzy"). If panic attacks have diverse etiologies, it is possible that a clue to this etiologic heterogeneity might be found through an examination of the symptoms experienced during an attack. Analyses were carried out which were designed to reveal a dimensional structure to the symptoms, if such a structure existed. A matrix was created of the cross-product ratios for the presence or absence of each symptom during an attack by the presence or absence of each other symptom. These data were treated as a similarity matrix for input into the nonmetric multidimensional scaling procedure (7). This procedure places each symptom in an n-dimensional space in which distances between pairs of symptoms represent their similarity. A stress coefficient measures the degree to which the ranks of the symptom pairs' distances in this derived space replicate the observed pair ranks in the matrix of cross-products ratio. The placing of the symptoms in a space which successfully replicates the ranking of pair values is sometimes very informative about the structure of the data. RESULTS
Incidence was calculated for five classifications of panic attacks: 1) those meeting the criteria of the DSMHI (by definition, these excluded phobia-stimulated cases); 2) phobia-stimulated, severe, and unexplained; 3) spontaneous, severe, and unexplained; 4) other phobia-stimulated; and 5) other spontaneous. Table 1 shows the annual incidence of panic attacks by type of attack. The overall
304
KEYL AND EATON
annual incidence for panic disorder was 2.4 per 1,000 persons. The incidence of attacks with the least restrictive criteria, other panic attacks, was seven times higher than this, 17.6 per 1,000 persons. Within both of the categories in which phobia-stimulated attacks could be compared with spontaneous attacks, the incidence of spontaneous attacks was 10 times that of phobiastimulated attacks. For the multivariate analysis of risk fac-
tors, only spontaneous panic attacks were considered since there were so few cases of the phobia-stimulated attacks. The results of the analysis of the sociodemographic variables age, sex, race, marital status, and occupational prestige are shown in table 2 for panic disorder, severe and unexplained attacks, and other attacks. The relative odds for each variable was adjusted for any confounding due to the effects of the other variables listed. Occupational prestige was
TABLE l
Estimated annual incidence of panic disorder and panic attacks, by seuenty and spontaneity, among respondents in the EpidemuMogic Catchment Area Program, 1960-1983 Annual incidence per 1,000 persons Panic disorder
All sites No. of cases
2.4 31
Severe, unexplained panic attadu
Other panic attacks
Phobic
Spontaneous
Phobic
Spontaneous
0.9 11
9.0 115
1.6 21
16.0 205
TABLE 2
Relative odds of incident panic attacks according to sociodemographic characteristics, by seuenty of the attacks: Epidemiologic Catchment Area Program, 1980-1983 Relative odds (95% confidence interval) Variable
Age* (years) 18-29 45-64 65+
Panic disorder
Severe, unexplained panic attack!
1.52(0 50-4.64) 1.86 (0.64-5.43) 0.39 (0 10-1.48)
0.87 (0.49-1.56) 0.94 (0.53-1.67) 0.48 (0.27-0 87)
Other panic attacks
Age—males (years) 18-29 45-64 65+
2.04 (1.03-4.04) 0.88 (0.39-1.95) 0.65 (0.30-1.39)
Age—females (years) 18-29 45-64 65+
0.45 (0.19-1.10) 0.75 (0.27-2.09) 0.71 (0.27-1.84)
Female
2.14 (0.83-5.49)
1.46 (0.93-2.29)
2.25 (1.11-4.56)
Black Other nonwhite
0.75(0 26-2.14) 0.69 (0.22-2.18)
0.68 (0.38-1.21) 0.32 (0.14-0.73)
0.77 (0.48-1.22) 0.59 (0.35-0.98)
Not married Males Females
0.93 (0.4O-2.14)
1.17 (0.76-1.80)
Occupational prestiget
0.80 (0 67-0.96)
1.82 (1.05-3.17) 0.55 (0.27-1.11) 0.95 (0.87-1.04)
0.99 (0.93-1.06)
* Compared with 30- to 44-year-olds. t For an increase of 10 percentiles within the distnbution for the occupational prestige scale (see text).
Downloaded from https://academic.oup.com/aje/article-abstract/131/2/301/138045 by Georgetown University user on 02 June 2018
RISK FACTORS FOR PANIC DISORDER AND PANIC ATTACKS
based on the scale developed by Nam et al. (8). The score on this scale represents the percentile position for the individual's occupational group in the distribution for all occupational groups in the United States of a composite measure based on education and income. The contributions of two additional variables were examined; years of formal education and employment status. These two variables explained almost none of the variation in onset of panic attack, for any criteria of panic attack, and were not included in any further analysis. Interactions between sex and age, sex and marital status, and sex and race were examined, since other investigators have noted sexspecific associations between age, marital status, and race and other disorders in which stress is believed to play a role (9, 10). Interactions were found between sex and age and between marital status and age, but only for the category "other panic attacks." Some of the results in table 2 were not statistically significant, but there was a general consistency of results across the three different categories of panic attack. Females had an increased risk for the onset of attacks. Relative odds for females ranged from 1.46 to 2.25 (for two of the three models, the relative odds were significant at p < 0.05). Nonwhites had a lower risk for attacks than whites. The relative odds for blacks compared with whites ranged from 0.68 to 0.77, and those for other nonwhites compared with whites ranged from 0.32 to 0.69. Occupational prestige had a protective effect against panic disorder (relative odds = 0.80, p < 0.05), but this effect diminished for severe, unexplained attacks and disappeared for other attacks. Persons aged 65 years or older showed a lower risk compared with 30- to 44-year-olds, but there was no consistent age effect for people aged 18-29 or 45-64 years. The risk for other panic attacks for the youngest age group studied, 18-29 years, was sexspecific. For males, this age group had an increased risk compared with 30- to 44year-olds (relative odds = 2.04), while for
Downloaded from https://academic.oup.com/aje/article-abstract/131/2/301/138045 by Georgetown University user on 02 June 2018
305
females this age group had a protective effect (relative odds = 0.45). There was little effect associated with marital status for panic disorder and severe unexplained attacks, but for other attacks there was a sex-specific effect of not being married. For males, not being married increased the risk for this category of attacks (relative odds = 1.82, p = 0.04), while for females it reduced the risk (relative odds = 0.55, p = 0.09). The lifetime histories of six factors noted at the initial interview were examined for their association with a subsequent onset of panic attacks. A history of cardiac symptoms was examined because of the possible relation between such cardiovascular conditions as mitral valve prolapse and panic disorder (11, 12) and because of the cardiovascular nature of some of the symptoms which accompany a panic attack. A history of cardiac symptoms was considered to be present at the first interview if a history of chest pain, palpitations, or shortness of breath was reported during questions concerned with somatization disorder. A history of shortness of breath was also examined alone, because there is a growing interest in the role of carbon dioxide in provoking panic attacks (13). The DIS/ DSM-III diagnosis of Major Depressive Disorder was examined as a risk factor because of the controversy concerning the distinction between anxiety and depression (14). People who met the criteria for diagnosis of depression but for whom the episode was triggered by grief were included since the depressive reaction itself, regardless of cause, might trigger the onset of panic attacks. The DIS/DSM-III diagnosis of Drug Abuse or Dependence was included because of findings suggesting that drugs, especially marijuana and cocaine, have strong stimulant effects on the heart (15). The DIS/DSM-m diagnosis of Alcohol Abuse or Dependence was included because alcohol has such a pervasive effect on health in general. The occurrence of a seizure or convulsion since 12 years of age was included because of the possible relation of panic attacks to epilepsy (1,16). The word-
306
KEYL AND EATON
ing of the question about seizures included ity. The horizontal dimension includes five the definition "where you were unconscious symptoms equally far to the right: breathbut your body jerked." The rarity of a ing difficulty; heart pounding; tightness or history of seizures made it impossible to pain in the chest; smothering sensation; include this factor in analyses of panic dis- and fear of dying. The first four are the order. most obviously associated with the cardioThese six factors all had strong associ- vascular system. The question for eliciting ations with the onset of panic disorder, responses regarding the fifth symptom was severe, unexplained panic attacks, and worded as follows: "Were you afraid either other panic attacks, both with and without that you might die or that you might act in adjustment for the sociodemographic vari- a crazy way?" This symptom is somewhat ables (table 3). A lifetime history of depres- high on this dimension but not as high as sion or a major grief episode was the strong- the other four, presumably because the perest of the risk factors, with adjusted relative son fears that he or she is experiencing a odds ranging from 3.35 to 8.14. The effects heart attack. The vertical dimension is for each factor tended to be stronger for more difficult to label. The four symptoms panic disorder than for the other two cate- which stand out are: a sense of unreality, gories, but the confidence intervals were fingers and feet tingling; trembling and shaking; and fear of dying or of acting wider because there were fewer cases. Figure 1 shows the result of the ordinal crazy. While people may not actually tremmultidimensional scaling of the 12 symp- ble and shake during a panic attack, it is toms. The stress coefficient for this two- possible that they sense themselves ready dimensional solution was 0.24, and the im- to do so. Based on the symptoms experiprovement after adding a third dimension enced, we have tentatively labeled this didid not appear to justify the extra complex- mension "psychologic" or "psychosensory." TABLE 3
Crude and adjusted* relative odds of incident panic attacks according to the presence of selected disorders and conditions, by severity of the attacks: Epidenuologic Catchment Area Program, 1980-1983 Relative odds (96% confidence interval) Disorder/ condition
Cardiac symptoms Crude Adjusted Shortness of breath Crude Adjusted Depression or major grief episode Crude Adjusted Drug abuse or dependence Crude Adjusted Alcohol abuse or dependence Crude Adjusted Seizures Crude Adjusted
Severe, unexplained pome attacks
Other panic attacks
3.45 (1.42-8.38) 2.53 (0.92-6.93)
2.59 (1.58-4.24) 2.16 (1.27-3.68)
1.94 (1.33-2.84) 1.87 (1.24-2.82)
2.08 (0.74-5.84) 2.93 (0.95-9.07)
3.61 (2.09-6.25) 3.79 (2.10-6.82)
1.98 (1.23-3.21) 1.89 (1.12-3.19)
8.53 (3.53-20.64) 8.14 (2.94-22.58)
4.86 (2.63-8.96) 4.24 (2.24-8.02)
4.21 (2.47-7.16) 3.35 (1.92-5.85)
3.29 (0.94-11.59) 2.74 (0.56-13.49)
3.28 (1.56-6.90) 3.45 (1.56-7.62)
4.10 (2.28-7.39) 2.70 (1.40-5.18)
3.24 (1.40-7.51) 5.15 (1.75-15.17)
1.96 (1.15-3.36) 2.34 (1.28-4.28)
2.27 (1.49-3.46) 2.40 (1.48-3.87)
-t -t
1.74 (0.48-6.32) 2.15 (0.56-8.27)
1.58 (0.55--t.56) 1.79 (0.60-5.36)
Panic disorder
* Adjusted for the sociodemographic variables shown in table 2. t The rarity of a history of seizures made it impossible to include this factor in analyses of panic disorder.
Downloaded from https://academic.oup.com/aje/article-abstract/131/2/301/138045 by Georgetown University user on 02 June 2018
RISK FACTORS FOR PANIC DISORDER AND PANIC ATTACKS
307
L 1 0-
1 K
0
F A
a - 1 0-
C
dzzmest
j
sense of unreaflty L
H
-ZS
breaming difficulty
0 fingen and fe«t tingflng E lightness or pam In chast F smothering sensation G fasting (amt H sweating 1 trembing and shaking J ho Of cold flashes
E -00
A
-1.5
-0.5
05
15
(ear of dying
2.S
FIGURE 1. Placement of 12 symptoms accompanying incident panic attacks in two-dimensional space created by ordinal multidimensional scaling: Epidemiologic Catchment Area Program, 1980-1983.
Other approaches show that the cardiovascular dimension is quite robust but that the psychologic dimension is not. The technique of dichotomous factor analysis (17) yielded adequate two- and three-factor solutions which always included a strong first cardiovascular factor but not a clear psychologic factor. Since these two dimensions may relate to distinct risk factors (1, 16), we carried out analyses of risk factors for attacks defined by the symptoms experienced in the worst attack. To examine whether persons experiencing cardiovascular symptoms during their worst attack had similar risk factors as those experiencing psychologic symptoms, we formed two symptom-defined subgroups of cases from among all cases of panic attacks: 1) cases in which at least three of the following symptoms were reported: heart pounding; breathing difficulty, tightness or pain in the chest; and smothering sensation (panic attacks with cardiovascular symptoms; there were 65 such cases); and 2) cases in which at least three of the following symptoms were present: a sense of unreality; fingers and feet tingling; trembling and shaking; and fear of dying (panic attacks with psychologic symptoms; there were 48 such cases). These symptom - defined case groups
Downloaded from https://academic.oup.com/aje/article-abstract/131/2/301/138045 by Georgetown University user on 02 June 2018
were each compared with the controls for the same factors examined for the severitydefined case groups. These two subgroups were not defined as being mutually exclusive. There were 19 people who met the criteria for both subgroups. Table 4 presents data analogous to those in table 2. The relative odds for the risk factors in table 4 were quite similar for both case groups and also quite similar to those in table 2. Table 5 presents data analogous to those in table 3. The relative odds for a history of cardiac symptoms was much higher for attacks with "cardiovascular symptoms" than for attacks with "psychologic symptoms" (8.36 vs. 2.23) and for either panic disorder or severe, unexplained panic attacks (8.36 vs. 2.53 or 2.16). A similar pattern, but with somewhat smaller differences, was seen for the relative odds for a history of shortness of breath. For a history of depression or a major grief episode, a history of drug abuse or dependence, .and a history of alcohol abuse or dependence, the relative odds were very similar for attacks with either "cardiovascular" or "psychologic" symptoms, and these were slightly higher than those in table 3, except in the case of a history of alcohol abuse or dependence, for which the relative odds for attacks with either "cardiovascular" or "psychologic" symptoms were about the same as that for panic disorder. A history
308
KEYL AND EATON TABLE 4
Relative odds of panic attacks with cardiovascular symptoms and panic attacks with psychologic symptoms, according to sociodemographic characteristics: Epidemiologic Catchment Area Program, 1980-1983 Relative odds (95% confidence interval) Variable
Cardiovascular symptoms
Psychologic symptoms
Age* (years) 18-29 46-64 65+
0.80 (0.37-1.69) 1.41 (0.71-2.78) 0.26 (0.11-0.64)
1.74 (0.78-3.89) 1.16 (0.48-233) 0.28 (0.09-0.84)
Female
1.36 (0.76-2.42)
1.46 (0.74-2.86)
Black Other nonwhite
0.79 (0.38-1.64) 0.91 (0.43-1.93)
0.93 (0.42-2.07) 0.68 (0.27-1.74)
Not married
1.66 (0.94-2.95)
1.62 (0.83-3.16)
Occupational prestiget
0.89 (0.79-0.99)
0.92 (0.80-1.04)
* Compared with 30- to 44-year-olds. t For an increase of 10 percentiles within the distribution for the occupational prestige scale. TABLE 5
Adjusted' relative odds of panic attacks with cardiovascular symptoms and panic attacks with psychologic symptoms, according to the presence of selected disorders and conditions: Epidemiologic Catchment Area Program, 1980-1983 Relative odds (95% confidence interval) condition
Cardiac symptoms Shortness of breath Depression or major grief episode Drug abuse or dependence Alcohol abuse or dependence Seizures
Cardiovascular symptoms 8.36 5.88 9.88 5.28 4.82 1.58
(3.70-18.89) (2.95-11.69) (4.88-20.03) (2.16-12.91) (2.39-9.72) (0.32-7.71)
Psychologic symptoms 2.23 (1.02-4.89) 3.06 (1.23-7.56) 10.84 (5.02-23.40) 4.91 (1.92-12.55) 4.59 (2.11-9 97) 5.21 (1.25-21.75)
" Adjusted for the sociodemographic variables shown in table 2.
of seizures was an exception to the general pattern for the risk factors examined. The relative odds for attacks with "psychologic" symptoms were higher than those for "cardiovascular" symptoms and those in table 3, although the confidence intervals were much wider for this risk factor because it was reported so infrequently. DISCUSSION The results of these analyses on incident cases of panic attack support many of the findings suggested by the analysis of the prevalent panic attacks ascertained at the initial interview of the Epidemiologic Catchment Area Program (3). Von Korff et
Downloaded from https://academic.oup.com/aje/article-abstract/131/2/301/138045 by Georgetown University user on 02 June 2018
al. (3) concluded, on the basis of these prevalent cases, that there is no clear distinction between panic disorder and panic attacks in terms of sociodemogTaphic factors and age of onset. This study similarly finds no clear distinction between panic disorder and severe, unexplained panic attacks on the basis of incident attacks. This suggests that future epidemiologic studies o f t^e etiology or natural history of panic attacks should not be limited to cases of DSM-III panic disorder. Some differences were noted in this study between panic disorder and severe, unexplained panic attacks and other attacks. These differences were the Finding of sex-specific associations
RISK FACTORS FOR PANIC DISORDER AND PANIC ATTACKS
for the age group 18-29 years and for not being married at the time of the initial interview. One possible explanation for this is that the category "other attacks" includes persons whose attacks had nonpsychiatric explanations, including the ingestion of drugs or medication, use of alcohol, or physical illness or injury. Ingestion of drugs and alcohol, in particular, might tend to be more prevalent among unmarried males and males in the age range 18-29 years than among unmarried females and females aged 18-29. These results strongly support the use of the DIS symptom probe structure, which separates symptoms according to these factors. The strong association found for depression or a major grief episode is consistent with findings by other investigators (1820). The distinction between the diagnoses of depression and anxiety disorder was emphasized in the DSM-EII when anxiety disorders were elevated to a distinct nosologic entity, but the issue is still debated (2, 14, 21). These data show that drug abuse is associated with an increased risk for the onset of panic disorder and for all levels of severity of panic attacks. These results are consistent with other work from this data set (22). The elevated risk for those with a history of alcohol abuse or dependence is consistent with the idea that withdrawal from alcohol produces panic attacks. It is puzzling that the risk for other panic attacks among this group is as high as the risk for severe, unexplained panic attacks. It may be that the probe questions which attempt to establish whether alcohol was a cause of the panic attack are not interpreted by the respondent as including withdrawal from alcohol (23), reducing the difference between unexplained and other attacks. The two-wave structure of this research design suggests that recall bias is not an explanation for these results. Information on risk factors was collected at the first wave, before the onset of the attacks. The reliability of the diagnosis is also important
Downloaded from https://academic.oup.com/aje/article-abstract/131/2/301/138045 by Georgetown University user on 02 June 2018
309
to consider. The reliability of the diagnosis of panic disorder has been assessed using a survey interviewer trained in a manner very similar to that of interviewers in the Epidemiologic Catchment Area Program and a psychiatrist who had gone through a similar training (24,25). The psychiatrist was blind to the results of the lay interviewer; however, he or she was permitted to ask additional questions or to ask for clarification of answers after conducting each section of the interview in verbatim form. The reliability estimates based on a comparison of the results after the psychiatrist's initial round of questions with those of the lay interviewer are probably biased somewhat low as a consequence of differences with regard to training in psychopathology and the psychiatrist's knowledge that he or she will be able to ask more questions at the end of the section. Published data from this study show a reliability just barely on the margin of acceptability (kappa = 0.41). However, this low reliability is due, in part, to the lack of reliability for the question, "Have you ever had three spells like this in a 3-week period?" A positive response to this question is required for a diagnosis of panic disorder. Classification by lifetime occurrence of any panic attack (versus no occurrence over a lifetime) which does not utilize the question on recurrence is much more reliable. Unpublished data from the same study show a kappa value of 0.68. The reliability of the occurrence of an "intense" panic attack (i.e., an attack in which four or more psychophysiologic symptoms occurred) is also acceptable (kappa = 0.62). The lack of reliability for the question on recurrence may explain the generally similar findings in the study for panic disorder and severe, unexplained panic attacks. The stability of results across levels of severity of panic attacks contrasts with the differences which appear when attacks are characterized by the types of symptoms occurring concomitantly. Attacks occurring with cardiovascular symptoms are strongly related to prior cardiovascular symptoms, shortness of breath, depression, drug use,
310
KEYL AND EATON
and alcohol use, but not to seizures. The pattern is similar to that for severe and unexplained attacks in general, which is not surprising, since the cardiovascular symptoms are quite common in attacks in general. However, the relations are stronger for attacks with cardiovascular symptoms than for severe, unexplained attacks or panic disorder. For the attacks occurring with psychologic symptoms, the pattern is different. The relative odds are generally stronger than for severe, unexplained attacks or panic disorder, as was true for attacks with cardiovascular symptoms; but here the seizure variable is markedly stronger, and the history of cardiac symptoms is not stronger. A history of cardiac symptoms is a strong risk factor for attacks with cardiovascular symptoms but not for attacks with psychologic symptoms, whereas a history of seizures is a strong risk factor for attacks with psychologic symptoms but not for attacks with cardiovascular symptoms. While the factors examined have been described as potential risk factors, in the case of cardiac symptoms, shortness of breath, and seizures it is possible that these actually represent subclinical panic-like attacks. If this is the case, then the associations found between the history of these symptom reports and the symptoms reported during a subsequent panic attack would actually represent further evidence for there being two types of panic attacks, with people tending to experience either one or the other. Future research would benefit from a more detailed examination of the symptoms occurring during a panic attack. Only four psychosensory or psychologic symptoms were available in these data. Two of these (fingers and feet tingling and trembling and shaking) were not clearly psychologic in nature, and one (fear of dying or of acting crazy) blended features of the cardiovascular dimension into the psychologic dimension. In the revision of the DSM-III, somewhat more detail in this area has been added, by splitting apart the symptom of fear of dying from the symptom on fear of
Downloaded from https://academic.oup.com/aje/article-abstract/131/2/301/138045 by Georgetown University user on 02 June 2018
going crazy or of doing something uncontrolled. More detailed symptom reports may help elucidate a potential separate etiology for these two types of panic attacks. REFERENCES
1. Marks IM. Fears, phobias, and rituals: panic, anxiety, and their disorders. New York: Oxford University Press, 1987. 2. Aronson TA. Is panic disorder a distinct diagnostic entity 9 A critical review of the borders of a syndrome. J Nerv Mental Dis 1987,175:584-94. 3. Von Korff M, Eaton WW, Keyl PM. The epidemiology of panic attacks and panic disorder results of three community surveys. Am J Epidemiol 1985;122:970-81. 4. Eaton WW, Kessler LG, eds. Epidemiologic field methods in psychiatry: The NIMH Epidemiologic Catchment Area Program. Orlando, FL: Academic Press, Inc, 1985. 5. American Psychiatric Association. Diagnostic and statistical maniml of mental disorders. 3rd ed. (DSM-III). Washington, DC: American Psychiatric Association, 1980. 6. Robins LN, Helzer JE, Croughan J, et al. The NIMH Diagnostic Interview Schedule: its history, characteristics, and validity. Arch Gen Psychiatry 1981:38:381-9. 7. Schiffman S3, Reynolds ML, Young FW. Introduction to multidimensional scaling: theory, methods, and applications. New York: Academic Press, Inc, 1981. 8. Nam CB, LaRocque J, Powers MG, et aL Occupational status scores: stability and change. Proceedings of the Social Statistics Section of the American Statistical Association. Washington, DC: American Statistical Association, 1975. 9. Radloff L. Sex differences in depression: the effects of occupation and marital status. Sex Roles 1975:1:249-65. 10. Warheit GJ, Holzer CE, Bell RA, et a l Sex, marital status, and mental health: a reappraisal. Soci Forces 1976;55:459-70. 11. Liberthson RR, Sheehan DV, King ME, et al. The prevalence of mitral valve prolapse in patients with panic disorders. Am J Psychiatry 1986:143: 511-15. 12. Crowe RR, Pauls DL, Kerber RE, et al. Panic disorder and mitral valve prolapse. In: Klein DF, Rabkin JG, eds. Anxiety: new research and changing concepts. New York: Raven Press, • 1981:103-14. 13. Gnei EJL, Lousberg H, van den Hout MA, et al. COt vulnerability in panic disorder. Psychol Res 1987:20:87-95. 14. Eaton WW, Ritter C. Distinguishing anxiety and depression with field survey data. Psychol Med 1988:18:155-66. 15. Wu TC, Tashkin DP, Djahed B, et aL Pulmonary hazards of smoking marijuana as compared with tobacco. N Engl J Med 1988:318:347-51. 16. Boulenger JP, Bierer LM, Uhde TW, et aL Psychosensory phenomena in panic and affective disorders. In: Shagass C, Josiassen RC, Bridger WH,
RISK FACTORS FOR PANIC DISORDER AND PANIC ATTACKS
17. 18.
19.
20.
et al, eds. Biological psychiatry 1985. New York. Elsevier Scientific Publishing Co, Inc. 1986:4635. Muthen B. Contributions to factor analysis of dichotomous variables. Psychometrika 1978;43: 551-60. Beitman BD, Basha I, Flaker G, et aL Major depression in cardiology chest pain patients without coronary artery disease and with panic disorder. J Affective Disord 1987;13:51-9. Breier A, Charney DS, Heniger GB. Major depression in patients with agoraphobia and panic disorder. Arch Gen Psychiatry l984;41:1129-35. Leckman JF, Weissman MM, Merikangas, 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: 1056-60.
Downloaded from https://academic.oup.com/aje/article-abstract/131/2/301/138045 by Georgetown University user on 02 June 2018
311
21. Kendler KS, Heath AC, Martin NG, et al. Symptoms of anxiety and depression: same genes, different environments? Arch Gen Psychiatry 1987, 44:451-7. 22. Anthony JC, Tien AY, Petronis KR. Epidemiologic evidence on cocaine use and panic attacks. Am J Epidemiol 1989; 129:543-9. 23. George DT, Zerby A, Noble S, et al. Panic attacks and alcohol withdrawal: Can subjects differentiate the symptoms 7 Biol Psychiatry 1988;24:240-3. 24. Helzer JE, Robins LN, McEvoy LT, et aL A comparison of clinical and Diagnostic Interview Schedule diagnosis: physicians' re-examination of lay-interviewed cases in the general population. Arch Gen Psychiatry 1985;42--657-66. 25. Robins LN, Helzer JE, Croughan J, et al. National Institute of Mental Health Diagnostic Interview Schedule: its history, characteristics, and validity. Arch Gen Psychiatry 1981,38:381-9.
Vol
Copyright © 1990 by The Johns Hopkins University School of Hygiene and Public Health All rights reserved
131, No. 2
Printed m U S.A
RISK FACTORS FOR THE ONSET OF PANIC DISORDER AND OTHER PANIC ATTACKS IN A PROSPECTIVE, POPULATION-BASED STUDY PENELOPE M. KEYL1 AND WILLIAM W. EATON1
Keyt, P. M. (Dept of Epidemiology, Johns Hopkins U. School of Hygiene and Public Health, Baltimore, MD 21205), and W. W. Eaton. Risk factors for the onset of panic disorder and other panic attacks in a prospective, population-based study. Am J Epidemiol 1990;131:301-11. A total of 383 cases of incident panic attack were identified among 12,823 participants in the Epidemiologic Catchment Area Program over various 12-month periods in 1980-1983. These cases not phobia-stimulated were compared with 766 controls. Risk factors were examined for the onset of panic attacks, with attacks categorized as panic disorder, severe and unexplained panic attacks, or other panic attacks. Risk factors were also examined for the onset of attacks in which cardiovascular symptoms were experienced and those in which psychologic symptoms were experienced. Females were at greater risk than males for each category of attacks (relative odds ranged from 1.36 to 2.25). Persons aged 65 years or older were at lower risk than younger persons (relative odds, compared with 30- to 44-year-olds, ranged from 0.26 to 0.71). A history of cardiac symptoms, shortness of breath, depression or a major grief episode, drug abuse or dependence, alcohol abuse or dependence, and seizures were each strongly associated with panic attacks. A history of cardiac symptoms was more strongly associated with attacks in which cardiovascular symptoms were experienced than with attacks in which psychologic symptoms were experienced (relative odds, 8.36 vs. 2.23). A history of seizures was more strongly associated with attacks with psychologic symptoms than with attacks with cardiovascular symptoms (relative odds, 5.21 vs. 1.58). age factors; anxiety disorders; alcohol drinking; cardiovascular system; depression; panic; seizures; substance abuse
A variety of fear responses exist in humans (1). Panic attacks are distinguished from other fear responses by their intensity, their short duration, and the fact that they often occur without any identifiable
cause. The spontaneous nature of most panic attacks and the fact that they are often accompanied by symptoms associated with the autonomic nervous system have led many researchers to concentrate on bi-
Received for publication April 28,1988, and in final • ment of Epidemiology, The Johns Hopkins University form July 24, 1989. School of Hygiene and Public Health, 615 N. Wolfe • Abbreviations: DIS, Diagnostic Interview Schedule; St., Baltimore, MD 21205. DSM-III, Diagnostic and Statistical Manual of Mental The Epidemiologic Catchment Area Program is a Disorders, third edition. series of five epidemiologic research studies performed 1 Department of Epidemiology, The Johns Hopkins by independent research teams in collaboration with University School of Hygiene and Public Health, Bal- staff of the Division of Biometry and Epidemiology of timore, MD. the National Institute of Mental Health (NIMH). 1 Department of Mental Hygiene, The Johns Hop- During the period of data collection, the Epidemiologic kins University School of Hygiene and Public Health, Catchment Area Program was supported by cooperaBaltimore, MD. tive agreements. Reprint requests to Dr. Penelope M. KeyL, Depart301
Downloaded from https://academic.oup.com/aje/article-abstract/131/2/301/138045 by Georgetown University user on 02 June 2018
302
KEYL AND EATON
ologic aspects of this disorder. It has been determined that lactate, caffeine, and other substances may induce panic attacks in those with a history of attacks but not in those without such a history (2). Certain medications can block the occurrence of both lactate-induced and spontaneous attacks (2). Thus, it seems plausible that there is a biologic component in the etiology of panic attacks. However, it seems likely that environmental stimuli are also involved in the etiology of panic attacks. Panic attacks are sometimes associated with phobic situations, especially fear of incapacitation when outside a familiar environment (agoraphobia). If panic is considered an extreme form of fear response, it seems reasonable to expect that the occurrence of panic attacks may be related to the degree of stress in the environment, the threshold for a response when exposed to stress, or a combination of these. In searching for risk factors for panic attacks, whether those meeting the criteria for diagnosis as panic disorder or those occurring less frequently or which are less severe in nature, it is important to consider both individual and environmental differences. In this paper, we present data on the onset of panic attacks based on a two-wave The NIMH Principal Collaborators were Drs. Darrel A. Regier, Ben Z. Locke, and William W Eaton (through October 1, 1983) and Jack Burke (from October 1, 1983, through March 1, 1987); the NIMH Project Officers were Drs. Carl A. Taube and William Huber. The Principal Investigators and CoInvestigators from the five sites were: Yale University (Cooperative Agreement U01 MH 34224)—Drs. Jerome K. Myers, Myrna M. Weissman, and Gary L. Tischler; The Johns Hopkins University (Cooperative Agreement U01 MH 33870)—Drs. Morton Kramer, Ernest Gruenberg, and Sam Shapiro; Washington University, St, Louis (Cooperative Agreement U01 MH 35386)—Drs. Dan Blazer and Linda George; and University of California, Los Angeles (Cooperative Agreement U01 MH 35865)—Drs. Marvin Kamo, Richard L. Hough, Javier I. Escobar, M. Audrey Bumam, and Dianne Timbers. Dr. Rudolf Hoehn-Saric provided valuable comments on the experience of symptoms during a panic attack. Preparation of this paper was supported by NIMH Grant MH41908.
Downloaded from https://academic.oup.com/aje/article-abstract/131/2/301/138045 by Georgetown University user on 02 June 2018
population-based field survey, the Epidemiologic Catchment Area Program.. We have already presented data on the prevalence of panic attacks and panic disorder from the first wave of the survey (3). This paper is an analysis of panic attacks which have occurred for the first time in a person's life. We examine several sociodemographic and other possible risk factors, as well as the question of whether risk factors are similar for different classifications of panic attacks. MATERIALS AND METHODS
This study is based on data collected as part of the National Institute of Mental Health Epidemiologic Catchment Area Program during various 12-month periods in 1980-1983. This program consists of community surveys carried out in five locations in the United States: Baltimore, Maryland; Durham, North Carolina; Los Angeles, California; New Haven, Connecticut; and St. Louis, Missouri. The methods of these surveys have been described elsewhere (4). Briefly, the surveys included persons aged 18 years or older, selected at random from households in the probability samples. Each person was interviewed, in person, twice: an initial interview and a follow-up interview 12 months later. Response rates for the initial interview at the five locations ranged from 76 to 80 percent. Seventy-six to 86 percent of responders to the initial interview responded to the follow-up interview. Classifications of pathology according to Diagnostic and Statistical Manual of Mental Disorders, Third Edition (DSM-III) criteria (5), made via the interview questions of the Diagnostic Interview Schedule (DIS) (6), are referred to as DIS/ DSM-III diagnoses. As part of each interview, the interviewer asked, "Have you ever had a spell or attack when all of a sudden you felt frightened, anxious, or very uneasy in situations when most people would not be afraid?" Those who reported that they had experienced such a spell or attack were asked whether or not each of 12 autonomic symptoms was
RISK FACTORS FOR PANIC DISORDER AND PANIC ATTACKS
present in their worst attacks. Those experiencing an attack were also asked whether the attack was severe enough to lead them to: 1) seek help from a doctor or other health professional; 2) take medication more than once; or 3) judge that the attack "interfered with my life or activities a lot." If the attack was severe by any of these criteria, a series of questions followed which focused on potential nonpsychiatric explanations for the attack, including ingestion of drugs or medication, use of alcohol, or physical illness or injury. An attack meeting the severity criteria with none of these as an explanation for the attack was termed a "severe, unexplained attack." A series of attacks which were severe and unexplained, which occurred often enough to meet the criteria for DSMIII, which were accompanied by four or more autonomic symptoms, and which occurred at least once in the absence of a phobic stimulus was termed "panic disorder." The 12,823 people who reported that they had never experienced a panic attack at the time of their first interview and who completed a follow-up interview were selected for this analysis of onset of panic attacks. Responses to the follow-up interview by these persons were used to estimate the annual incidence of panic disorder and other types of panic attacks. A case-control approach was then used for a multivariate analysis of risk factors associated with the onset of panic attacks. A total of 383 cases were identified who reported the onset of panic attacks between the initial and follow-up interviews. We selected 766 controls from the people remaining, all of whom had never experienced a panic attack by the follow-up interview. Within each of the five survey locations, controls were selected randomly using a systematic sample and a 2:1 casexontrol ratio. Multivariate logistic regression was used for the analysis of cases and controls. Information on sociodemographic and other variables considered as
Downloaded from https://academic.oup.com/aje/article-abstract/131/2/301/138045 by Georgetown University user on 02 June 2018
303
possible risk factors was based on responses at the time of the initial interview. The symptoms which accompany panic attacks cover a broad range, including symptoms which relate to the cardiovascular system (for example, "chest pain"), those which are perceptual (for example, "things around you seem unreal"), and symptoms reflecting more general bodily states (for example, feeling "dizzy"). If panic attacks have diverse etiologies, it is possible that a clue to this etiologic heterogeneity might be found through an examination of the symptoms experienced during an attack. Analyses were carried out which were designed to reveal a dimensional structure to the symptoms, if such a structure existed. A matrix was created of the cross-product ratios for the presence or absence of each symptom during an attack by the presence or absence of each other symptom. These data were treated as a similarity matrix for input into the nonmetric multidimensional scaling procedure (7). This procedure places each symptom in an n-dimensional space in which distances between pairs of symptoms represent their similarity. A stress coefficient measures the degree to which the ranks of the symptom pairs' distances in this derived space replicate the observed pair ranks in the matrix of cross-products ratio. The placing of the symptoms in a space which successfully replicates the ranking of pair values is sometimes very informative about the structure of the data. RESULTS
Incidence was calculated for five classifications of panic attacks: 1) those meeting the criteria of the DSMHI (by definition, these excluded phobia-stimulated cases); 2) phobia-stimulated, severe, and unexplained; 3) spontaneous, severe, and unexplained; 4) other phobia-stimulated; and 5) other spontaneous. Table 1 shows the annual incidence of panic attacks by type of attack. The overall
304
KEYL AND EATON
annual incidence for panic disorder was 2.4 per 1,000 persons. The incidence of attacks with the least restrictive criteria, other panic attacks, was seven times higher than this, 17.6 per 1,000 persons. Within both of the categories in which phobia-stimulated attacks could be compared with spontaneous attacks, the incidence of spontaneous attacks was 10 times that of phobiastimulated attacks. For the multivariate analysis of risk fac-
tors, only spontaneous panic attacks were considered since there were so few cases of the phobia-stimulated attacks. The results of the analysis of the sociodemographic variables age, sex, race, marital status, and occupational prestige are shown in table 2 for panic disorder, severe and unexplained attacks, and other attacks. The relative odds for each variable was adjusted for any confounding due to the effects of the other variables listed. Occupational prestige was
TABLE l
Estimated annual incidence of panic disorder and panic attacks, by seuenty and spontaneity, among respondents in the EpidemuMogic Catchment Area Program, 1960-1983 Annual incidence per 1,000 persons Panic disorder
All sites No. of cases
2.4 31
Severe, unexplained panic attadu
Other panic attacks
Phobic
Spontaneous
Phobic
Spontaneous
0.9 11
9.0 115
1.6 21
16.0 205
TABLE 2
Relative odds of incident panic attacks according to sociodemographic characteristics, by seuenty of the attacks: Epidemiologic Catchment Area Program, 1980-1983 Relative odds (95% confidence interval) Variable
Age* (years) 18-29 45-64 65+
Panic disorder
Severe, unexplained panic attack!
1.52(0 50-4.64) 1.86 (0.64-5.43) 0.39 (0 10-1.48)
0.87 (0.49-1.56) 0.94 (0.53-1.67) 0.48 (0.27-0 87)
Other panic attacks
Age—males (years) 18-29 45-64 65+
2.04 (1.03-4.04) 0.88 (0.39-1.95) 0.65 (0.30-1.39)
Age—females (years) 18-29 45-64 65+
0.45 (0.19-1.10) 0.75 (0.27-2.09) 0.71 (0.27-1.84)
Female
2.14 (0.83-5.49)
1.46 (0.93-2.29)
2.25 (1.11-4.56)
Black Other nonwhite
0.75(0 26-2.14) 0.69 (0.22-2.18)
0.68 (0.38-1.21) 0.32 (0.14-0.73)
0.77 (0.48-1.22) 0.59 (0.35-0.98)
Not married Males Females
0.93 (0.4O-2.14)
1.17 (0.76-1.80)
Occupational prestiget
0.80 (0 67-0.96)
1.82 (1.05-3.17) 0.55 (0.27-1.11) 0.95 (0.87-1.04)
0.99 (0.93-1.06)
* Compared with 30- to 44-year-olds. t For an increase of 10 percentiles within the distnbution for the occupational prestige scale (see text).
Downloaded from https://academic.oup.com/aje/article-abstract/131/2/301/138045 by Georgetown University user on 02 June 2018
RISK FACTORS FOR PANIC DISORDER AND PANIC ATTACKS
based on the scale developed by Nam et al. (8). The score on this scale represents the percentile position for the individual's occupational group in the distribution for all occupational groups in the United States of a composite measure based on education and income. The contributions of two additional variables were examined; years of formal education and employment status. These two variables explained almost none of the variation in onset of panic attack, for any criteria of panic attack, and were not included in any further analysis. Interactions between sex and age, sex and marital status, and sex and race were examined, since other investigators have noted sexspecific associations between age, marital status, and race and other disorders in which stress is believed to play a role (9, 10). Interactions were found between sex and age and between marital status and age, but only for the category "other panic attacks." Some of the results in table 2 were not statistically significant, but there was a general consistency of results across the three different categories of panic attack. Females had an increased risk for the onset of attacks. Relative odds for females ranged from 1.46 to 2.25 (for two of the three models, the relative odds were significant at p < 0.05). Nonwhites had a lower risk for attacks than whites. The relative odds for blacks compared with whites ranged from 0.68 to 0.77, and those for other nonwhites compared with whites ranged from 0.32 to 0.69. Occupational prestige had a protective effect against panic disorder (relative odds = 0.80, p < 0.05), but this effect diminished for severe, unexplained attacks and disappeared for other attacks. Persons aged 65 years or older showed a lower risk compared with 30- to 44-year-olds, but there was no consistent age effect for people aged 18-29 or 45-64 years. The risk for other panic attacks for the youngest age group studied, 18-29 years, was sexspecific. For males, this age group had an increased risk compared with 30- to 44year-olds (relative odds = 2.04), while for
Downloaded from https://academic.oup.com/aje/article-abstract/131/2/301/138045 by Georgetown University user on 02 June 2018
305
females this age group had a protective effect (relative odds = 0.45). There was little effect associated with marital status for panic disorder and severe unexplained attacks, but for other attacks there was a sex-specific effect of not being married. For males, not being married increased the risk for this category of attacks (relative odds = 1.82, p = 0.04), while for females it reduced the risk (relative odds = 0.55, p = 0.09). The lifetime histories of six factors noted at the initial interview were examined for their association with a subsequent onset of panic attacks. A history of cardiac symptoms was examined because of the possible relation between such cardiovascular conditions as mitral valve prolapse and panic disorder (11, 12) and because of the cardiovascular nature of some of the symptoms which accompany a panic attack. A history of cardiac symptoms was considered to be present at the first interview if a history of chest pain, palpitations, or shortness of breath was reported during questions concerned with somatization disorder. A history of shortness of breath was also examined alone, because there is a growing interest in the role of carbon dioxide in provoking panic attacks (13). The DIS/ DSM-III diagnosis of Major Depressive Disorder was examined as a risk factor because of the controversy concerning the distinction between anxiety and depression (14). People who met the criteria for diagnosis of depression but for whom the episode was triggered by grief were included since the depressive reaction itself, regardless of cause, might trigger the onset of panic attacks. The DIS/DSM-III diagnosis of Drug Abuse or Dependence was included because of findings suggesting that drugs, especially marijuana and cocaine, have strong stimulant effects on the heart (15). The DIS/DSM-m diagnosis of Alcohol Abuse or Dependence was included because alcohol has such a pervasive effect on health in general. The occurrence of a seizure or convulsion since 12 years of age was included because of the possible relation of panic attacks to epilepsy (1,16). The word-
306
KEYL AND EATON
ing of the question about seizures included ity. The horizontal dimension includes five the definition "where you were unconscious symptoms equally far to the right: breathbut your body jerked." The rarity of a ing difficulty; heart pounding; tightness or history of seizures made it impossible to pain in the chest; smothering sensation; include this factor in analyses of panic dis- and fear of dying. The first four are the order. most obviously associated with the cardioThese six factors all had strong associ- vascular system. The question for eliciting ations with the onset of panic disorder, responses regarding the fifth symptom was severe, unexplained panic attacks, and worded as follows: "Were you afraid either other panic attacks, both with and without that you might die or that you might act in adjustment for the sociodemographic vari- a crazy way?" This symptom is somewhat ables (table 3). A lifetime history of depres- high on this dimension but not as high as sion or a major grief episode was the strong- the other four, presumably because the perest of the risk factors, with adjusted relative son fears that he or she is experiencing a odds ranging from 3.35 to 8.14. The effects heart attack. The vertical dimension is for each factor tended to be stronger for more difficult to label. The four symptoms panic disorder than for the other two cate- which stand out are: a sense of unreality, gories, but the confidence intervals were fingers and feet tingling; trembling and shaking; and fear of dying or of acting wider because there were fewer cases. Figure 1 shows the result of the ordinal crazy. While people may not actually tremmultidimensional scaling of the 12 symp- ble and shake during a panic attack, it is toms. The stress coefficient for this two- possible that they sense themselves ready dimensional solution was 0.24, and the im- to do so. Based on the symptoms experiprovement after adding a third dimension enced, we have tentatively labeled this didid not appear to justify the extra complex- mension "psychologic" or "psychosensory." TABLE 3
Crude and adjusted* relative odds of incident panic attacks according to the presence of selected disorders and conditions, by severity of the attacks: Epidenuologic Catchment Area Program, 1980-1983 Relative odds (96% confidence interval) Disorder/ condition
Cardiac symptoms Crude Adjusted Shortness of breath Crude Adjusted Depression or major grief episode Crude Adjusted Drug abuse or dependence Crude Adjusted Alcohol abuse or dependence Crude Adjusted Seizures Crude Adjusted
Severe, unexplained pome attacks
Other panic attacks
3.45 (1.42-8.38) 2.53 (0.92-6.93)
2.59 (1.58-4.24) 2.16 (1.27-3.68)
1.94 (1.33-2.84) 1.87 (1.24-2.82)
2.08 (0.74-5.84) 2.93 (0.95-9.07)
3.61 (2.09-6.25) 3.79 (2.10-6.82)
1.98 (1.23-3.21) 1.89 (1.12-3.19)
8.53 (3.53-20.64) 8.14 (2.94-22.58)
4.86 (2.63-8.96) 4.24 (2.24-8.02)
4.21 (2.47-7.16) 3.35 (1.92-5.85)
3.29 (0.94-11.59) 2.74 (0.56-13.49)
3.28 (1.56-6.90) 3.45 (1.56-7.62)
4.10 (2.28-7.39) 2.70 (1.40-5.18)
3.24 (1.40-7.51) 5.15 (1.75-15.17)
1.96 (1.15-3.36) 2.34 (1.28-4.28)
2.27 (1.49-3.46) 2.40 (1.48-3.87)
-t -t
1.74 (0.48-6.32) 2.15 (0.56-8.27)
1.58 (0.55--t.56) 1.79 (0.60-5.36)
Panic disorder
* Adjusted for the sociodemographic variables shown in table 2. t The rarity of a history of seizures made it impossible to include this factor in analyses of panic disorder.
Downloaded from https://academic.oup.com/aje/article-abstract/131/2/301/138045 by Georgetown University user on 02 June 2018
RISK FACTORS FOR PANIC DISORDER AND PANIC ATTACKS
307
L 1 0-
1 K
0
F A
a - 1 0-
C
dzzmest
j
sense of unreaflty L
H
-ZS
breaming difficulty
0 fingen and fe«t tingflng E lightness or pam In chast F smothering sensation G fasting (amt H sweating 1 trembing and shaking J ho Of cold flashes
E -00
A
-1.5
-0.5
05
15
(ear of dying
2.S
FIGURE 1. Placement of 12 symptoms accompanying incident panic attacks in two-dimensional space created by ordinal multidimensional scaling: Epidemiologic Catchment Area Program, 1980-1983.
Other approaches show that the cardiovascular dimension is quite robust but that the psychologic dimension is not. The technique of dichotomous factor analysis (17) yielded adequate two- and three-factor solutions which always included a strong first cardiovascular factor but not a clear psychologic factor. Since these two dimensions may relate to distinct risk factors (1, 16), we carried out analyses of risk factors for attacks defined by the symptoms experienced in the worst attack. To examine whether persons experiencing cardiovascular symptoms during their worst attack had similar risk factors as those experiencing psychologic symptoms, we formed two symptom-defined subgroups of cases from among all cases of panic attacks: 1) cases in which at least three of the following symptoms were reported: heart pounding; breathing difficulty, tightness or pain in the chest; and smothering sensation (panic attacks with cardiovascular symptoms; there were 65 such cases); and 2) cases in which at least three of the following symptoms were present: a sense of unreality; fingers and feet tingling; trembling and shaking; and fear of dying (panic attacks with psychologic symptoms; there were 48 such cases). These symptom - defined case groups
Downloaded from https://academic.oup.com/aje/article-abstract/131/2/301/138045 by Georgetown University user on 02 June 2018
were each compared with the controls for the same factors examined for the severitydefined case groups. These two subgroups were not defined as being mutually exclusive. There were 19 people who met the criteria for both subgroups. Table 4 presents data analogous to those in table 2. The relative odds for the risk factors in table 4 were quite similar for both case groups and also quite similar to those in table 2. Table 5 presents data analogous to those in table 3. The relative odds for a history of cardiac symptoms was much higher for attacks with "cardiovascular symptoms" than for attacks with "psychologic symptoms" (8.36 vs. 2.23) and for either panic disorder or severe, unexplained panic attacks (8.36 vs. 2.53 or 2.16). A similar pattern, but with somewhat smaller differences, was seen for the relative odds for a history of shortness of breath. For a history of depression or a major grief episode, a history of drug abuse or dependence, .and a history of alcohol abuse or dependence, the relative odds were very similar for attacks with either "cardiovascular" or "psychologic" symptoms, and these were slightly higher than those in table 3, except in the case of a history of alcohol abuse or dependence, for which the relative odds for attacks with either "cardiovascular" or "psychologic" symptoms were about the same as that for panic disorder. A history
308
KEYL AND EATON TABLE 4
Relative odds of panic attacks with cardiovascular symptoms and panic attacks with psychologic symptoms, according to sociodemographic characteristics: Epidemiologic Catchment Area Program, 1980-1983 Relative odds (95% confidence interval) Variable
Cardiovascular symptoms
Psychologic symptoms
Age* (years) 18-29 46-64 65+
0.80 (0.37-1.69) 1.41 (0.71-2.78) 0.26 (0.11-0.64)
1.74 (0.78-3.89) 1.16 (0.48-233) 0.28 (0.09-0.84)
Female
1.36 (0.76-2.42)
1.46 (0.74-2.86)
Black Other nonwhite
0.79 (0.38-1.64) 0.91 (0.43-1.93)
0.93 (0.42-2.07) 0.68 (0.27-1.74)
Not married
1.66 (0.94-2.95)
1.62 (0.83-3.16)
Occupational prestiget
0.89 (0.79-0.99)
0.92 (0.80-1.04)
* Compared with 30- to 44-year-olds. t For an increase of 10 percentiles within the distribution for the occupational prestige scale. TABLE 5
Adjusted' relative odds of panic attacks with cardiovascular symptoms and panic attacks with psychologic symptoms, according to the presence of selected disorders and conditions: Epidemiologic Catchment Area Program, 1980-1983 Relative odds (95% confidence interval) condition
Cardiac symptoms Shortness of breath Depression or major grief episode Drug abuse or dependence Alcohol abuse or dependence Seizures
Cardiovascular symptoms 8.36 5.88 9.88 5.28 4.82 1.58
(3.70-18.89) (2.95-11.69) (4.88-20.03) (2.16-12.91) (2.39-9.72) (0.32-7.71)
Psychologic symptoms 2.23 (1.02-4.89) 3.06 (1.23-7.56) 10.84 (5.02-23.40) 4.91 (1.92-12.55) 4.59 (2.11-9 97) 5.21 (1.25-21.75)
" Adjusted for the sociodemographic variables shown in table 2.
of seizures was an exception to the general pattern for the risk factors examined. The relative odds for attacks with "psychologic" symptoms were higher than those for "cardiovascular" symptoms and those in table 3, although the confidence intervals were much wider for this risk factor because it was reported so infrequently. DISCUSSION The results of these analyses on incident cases of panic attack support many of the findings suggested by the analysis of the prevalent panic attacks ascertained at the initial interview of the Epidemiologic Catchment Area Program (3). Von Korff et
Downloaded from https://academic.oup.com/aje/article-abstract/131/2/301/138045 by Georgetown University user on 02 June 2018
al. (3) concluded, on the basis of these prevalent cases, that there is no clear distinction between panic disorder and panic attacks in terms of sociodemogTaphic factors and age of onset. This study similarly finds no clear distinction between panic disorder and severe, unexplained panic attacks on the basis of incident attacks. This suggests that future epidemiologic studies o f t^e etiology or natural history of panic attacks should not be limited to cases of DSM-III panic disorder. Some differences were noted in this study between panic disorder and severe, unexplained panic attacks and other attacks. These differences were the Finding of sex-specific associations
RISK FACTORS FOR PANIC DISORDER AND PANIC ATTACKS
for the age group 18-29 years and for not being married at the time of the initial interview. One possible explanation for this is that the category "other attacks" includes persons whose attacks had nonpsychiatric explanations, including the ingestion of drugs or medication, use of alcohol, or physical illness or injury. Ingestion of drugs and alcohol, in particular, might tend to be more prevalent among unmarried males and males in the age range 18-29 years than among unmarried females and females aged 18-29. These results strongly support the use of the DIS symptom probe structure, which separates symptoms according to these factors. The strong association found for depression or a major grief episode is consistent with findings by other investigators (1820). The distinction between the diagnoses of depression and anxiety disorder was emphasized in the DSM-EII when anxiety disorders were elevated to a distinct nosologic entity, but the issue is still debated (2, 14, 21). These data show that drug abuse is associated with an increased risk for the onset of panic disorder and for all levels of severity of panic attacks. These results are consistent with other work from this data set (22). The elevated risk for those with a history of alcohol abuse or dependence is consistent with the idea that withdrawal from alcohol produces panic attacks. It is puzzling that the risk for other panic attacks among this group is as high as the risk for severe, unexplained panic attacks. It may be that the probe questions which attempt to establish whether alcohol was a cause of the panic attack are not interpreted by the respondent as including withdrawal from alcohol (23), reducing the difference between unexplained and other attacks. The two-wave structure of this research design suggests that recall bias is not an explanation for these results. Information on risk factors was collected at the first wave, before the onset of the attacks. The reliability of the diagnosis is also important
Downloaded from https://academic.oup.com/aje/article-abstract/131/2/301/138045 by Georgetown University user on 02 June 2018
309
to consider. The reliability of the diagnosis of panic disorder has been assessed using a survey interviewer trained in a manner very similar to that of interviewers in the Epidemiologic Catchment Area Program and a psychiatrist who had gone through a similar training (24,25). The psychiatrist was blind to the results of the lay interviewer; however, he or she was permitted to ask additional questions or to ask for clarification of answers after conducting each section of the interview in verbatim form. The reliability estimates based on a comparison of the results after the psychiatrist's initial round of questions with those of the lay interviewer are probably biased somewhat low as a consequence of differences with regard to training in psychopathology and the psychiatrist's knowledge that he or she will be able to ask more questions at the end of the section. Published data from this study show a reliability just barely on the margin of acceptability (kappa = 0.41). However, this low reliability is due, in part, to the lack of reliability for the question, "Have you ever had three spells like this in a 3-week period?" A positive response to this question is required for a diagnosis of panic disorder. Classification by lifetime occurrence of any panic attack (versus no occurrence over a lifetime) which does not utilize the question on recurrence is much more reliable. Unpublished data from the same study show a kappa value of 0.68. The reliability of the occurrence of an "intense" panic attack (i.e., an attack in which four or more psychophysiologic symptoms occurred) is also acceptable (kappa = 0.62). The lack of reliability for the question on recurrence may explain the generally similar findings in the study for panic disorder and severe, unexplained panic attacks. The stability of results across levels of severity of panic attacks contrasts with the differences which appear when attacks are characterized by the types of symptoms occurring concomitantly. Attacks occurring with cardiovascular symptoms are strongly related to prior cardiovascular symptoms, shortness of breath, depression, drug use,
310
KEYL AND EATON
and alcohol use, but not to seizures. The pattern is similar to that for severe and unexplained attacks in general, which is not surprising, since the cardiovascular symptoms are quite common in attacks in general. However, the relations are stronger for attacks with cardiovascular symptoms than for severe, unexplained attacks or panic disorder. For the attacks occurring with psychologic symptoms, the pattern is different. The relative odds are generally stronger than for severe, unexplained attacks or panic disorder, as was true for attacks with cardiovascular symptoms; but here the seizure variable is markedly stronger, and the history of cardiac symptoms is not stronger. A history of cardiac symptoms is a strong risk factor for attacks with cardiovascular symptoms but not for attacks with psychologic symptoms, whereas a history of seizures is a strong risk factor for attacks with psychologic symptoms but not for attacks with cardiovascular symptoms. While the factors examined have been described as potential risk factors, in the case of cardiac symptoms, shortness of breath, and seizures it is possible that these actually represent subclinical panic-like attacks. If this is the case, then the associations found between the history of these symptom reports and the symptoms reported during a subsequent panic attack would actually represent further evidence for there being two types of panic attacks, with people tending to experience either one or the other. Future research would benefit from a more detailed examination of the symptoms occurring during a panic attack. Only four psychosensory or psychologic symptoms were available in these data. Two of these (fingers and feet tingling and trembling and shaking) were not clearly psychologic in nature, and one (fear of dying or of acting crazy) blended features of the cardiovascular dimension into the psychologic dimension. In the revision of the DSM-III, somewhat more detail in this area has been added, by splitting apart the symptom of fear of dying from the symptom on fear of
Downloaded from https://academic.oup.com/aje/article-abstract/131/2/301/138045 by Georgetown University user on 02 June 2018
going crazy or of doing something uncontrolled. More detailed symptom reports may help elucidate a potential separate etiology for these two types of panic attacks. REFERENCES
1. Marks IM. Fears, phobias, and rituals: panic, anxiety, and their disorders. New York: Oxford University Press, 1987. 2. Aronson TA. Is panic disorder a distinct diagnostic entity 9 A critical review of the borders of a syndrome. J Nerv Mental Dis 1987,175:584-94. 3. Von Korff M, Eaton WW, Keyl PM. The epidemiology of panic attacks and panic disorder results of three community surveys. Am J Epidemiol 1985;122:970-81. 4. Eaton WW, Kessler LG, eds. Epidemiologic field methods in psychiatry: The NIMH Epidemiologic Catchment Area Program. Orlando, FL: Academic Press, Inc, 1985. 5. American Psychiatric Association. Diagnostic and statistical maniml of mental disorders. 3rd ed. (DSM-III). Washington, DC: American Psychiatric Association, 1980. 6. Robins LN, Helzer JE, Croughan J, et al. The NIMH Diagnostic Interview Schedule: its history, characteristics, and validity. Arch Gen Psychiatry 1981:38:381-9. 7. Schiffman S3, Reynolds ML, Young FW. Introduction to multidimensional scaling: theory, methods, and applications. New York: Academic Press, Inc, 1981. 8. Nam CB, LaRocque J, Powers MG, et aL Occupational status scores: stability and change. Proceedings of the Social Statistics Section of the American Statistical Association. Washington, DC: American Statistical Association, 1975. 9. Radloff L. Sex differences in depression: the effects of occupation and marital status. Sex Roles 1975:1:249-65. 10. Warheit GJ, Holzer CE, Bell RA, et a l Sex, marital status, and mental health: a reappraisal. Soci Forces 1976;55:459-70. 11. Liberthson RR, Sheehan DV, King ME, et al. The prevalence of mitral valve prolapse in patients with panic disorders. Am J Psychiatry 1986:143: 511-15. 12. Crowe RR, Pauls DL, Kerber RE, et al. Panic disorder and mitral valve prolapse. In: Klein DF, Rabkin JG, eds. Anxiety: new research and changing concepts. New York: Raven Press, • 1981:103-14. 13. Gnei EJL, Lousberg H, van den Hout MA, et al. COt vulnerability in panic disorder. Psychol Res 1987:20:87-95. 14. Eaton WW, Ritter C. Distinguishing anxiety and depression with field survey data. Psychol Med 1988:18:155-66. 15. Wu TC, Tashkin DP, Djahed B, et aL Pulmonary hazards of smoking marijuana as compared with tobacco. N Engl J Med 1988:318:347-51. 16. Boulenger JP, Bierer LM, Uhde TW, et aL Psychosensory phenomena in panic and affective disorders. In: Shagass C, Josiassen RC, Bridger WH,
RISK FACTORS FOR PANIC DISORDER AND PANIC ATTACKS
17. 18.
19.
20.
et al, eds. Biological psychiatry 1985. New York. Elsevier Scientific Publishing Co, Inc. 1986:4635. Muthen B. Contributions to factor analysis of dichotomous variables. Psychometrika 1978;43: 551-60. Beitman BD, Basha I, Flaker G, et aL Major depression in cardiology chest pain patients without coronary artery disease and with panic disorder. J Affective Disord 1987;13:51-9. Breier A, Charney DS, Heniger GB. Major depression in patients with agoraphobia and panic disorder. Arch Gen Psychiatry l984;41:1129-35. Leckman JF, Weissman MM, Merikangas, 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: 1056-60.
Downloaded from https://academic.oup.com/aje/article-abstract/131/2/301/138045 by Georgetown University user on 02 June 2018
311
21. Kendler KS, Heath AC, Martin NG, et al. Symptoms of anxiety and depression: same genes, different environments? Arch Gen Psychiatry 1987, 44:451-7. 22. Anthony JC, Tien AY, Petronis KR. Epidemiologic evidence on cocaine use and panic attacks. Am J Epidemiol 1989; 129:543-9. 23. George DT, Zerby A, Noble S, et al. Panic attacks and alcohol withdrawal: Can subjects differentiate the symptoms 7 Biol Psychiatry 1988;24:240-3. 24. Helzer JE, Robins LN, McEvoy LT, et aL A comparison of clinical and Diagnostic Interview Schedule diagnosis: physicians' re-examination of lay-interviewed cases in the general population. Arch Gen Psychiatry 1985;42--657-66. 25. Robins LN, Helzer JE, Croughan J, et al. National Institute of Mental Health Diagnostic Interview Schedule: its history, characteristics, and validity. Arch Gen Psychiatry 1981,38:381-9.
