Panic and generalized anxiety: Are they separate disorders?

J. psychrat. Rex. Vol. 24, Suppl. 2. pp. 157-162, 1990 Printed in Great Britain.

0

PANIC AND GENERALIZED

0022.3956/9il $3.00 + .oO 1990 Pergamon Press plc

ANXIETY: ARE THEY SEPARATE

DISORDERS? MYRNA *Professor of Epidemiology in Psychiatry, of Clinical-Genetic Epidemiology,

M. WEISSMAN*

College of Physicians and Surgeons, Columbia University; Chief, Division New York State Psychiatric Institute, New York, New York, U.S.A.

Summary-Evidence that panic and generalized anxiety disorder are separate disorders is presented from a review of epidemiological, family, and twin studies. Generalized anxiety disorder and panic disorder have been shown to have different rates and risk factors in the community and different family aggregation, which is consistent with the separation of the disorders. The one small twin study using Diqnostic and Sfarisrical Manual, Third Edition criteria also supports the separation between these disorders. The concordance for panic disorder is greater among monozygotic than among dizygotic twins. There undoubtedly are overlaps between these disorders, and some patients with generalized anxiety disorder may later develop panic disorder; however, the results thus far support the separation of these disorders.

INTRODUCTION

from epidemiological community surveys and from genetic epidemiological studies will be reviewed to determine the extent to which the data support the separation of panic disorder from generalized anxiety disorder. Epidemiological surveys are based on probability samples of persons living in the community regardless of whether or not these individuals have ever received treatment for the condition studied. Reliance only on samples of persons undergoing treatment can present a false view of the boundaries between disorders because of the tendency of persons with more serious, complicated, and comorbid conditions to seek treatment. Epidemiological data that include the range of disorders including mild untreated forms may be more informative. If disorders such as generalized anxiety disorder and panic disorder have different epidemiologies (i.e. different risks), this suggests but is insufficient to prove their separateness. Genetic epidemiological studies can provide another clue to the relationship between disorders. Family and twin studies are the most common type of evidence used. If the EVIDENCE

prevalence of a disorder suggests its distinctiveness.

is increased and breeds true in biological family members, this For example, if the prevalence of generalized anxiety disorder

Address correspondence to Myma M. Weissman, Ph.D., Professor of Epidemiology and Psychiatry, College of Physicians and Surgeons, Columbia University, Chief; Division of Clinical-Genetic Epidemiology, New York State Psychiatric Institute, 722 West 168th Street, P.O. Box 14, New York, New York, 10032, U.S.A. This work was supported in part by Grant MJ28274 and MH37592 from the Affective and Anxiety Disorders Research Branch, National Institute of Mental Health, Rockville, Maryland; and from the John D. and Catherine T. MacArthur Foundation Mental Health Research Network on Risk and Protective Factors in the Major Mental Disorders. 157

MYRNA M. WEISSMAN

158

is increased in the biological relative of a proband with generalized anxiety disorder and if the prevalence of panic disorder is not increased, this finding suggests that generalized anxiety disorder and panic disorder are separate disorders. An increase in panic disorder in the relatives of patients with generalized anxiety disorder suggests that one disorder is an alternate form of the other, and thus suggests similarities between disorders. Family studies cannot determine whether transmission is genetic. In twin studies, further information on the genetic transmission can be obtained. Monozygotic (MZ) twins have an identical genetic endowment, while dizygotic (DZ) twins are no more similar genetically than other siblings. Assuming that the environment is similar for MZ and DZ twins, a higher concordance for a disease in MZ than DZ twins suggests the importance of heredity in the development of the disease. EPIDEMIOLOGICALDATA At least seven recently completed community surveys use modern diagnostic criteria and provide some information on rates of the different anxiety disorders in the community (WEISSMAN et al., 1978; UHLENHUTH et al., 1983; REGIER et al, 1984; CANINO et al., 1987; MURPHY, 1986; ANGST et al., 1987; WITTCHEN, 1986). Table 1 shows the site, year of study, and the number of persons studied. The largest of these studies is the National Institute of Mental Health Epidemiologic Catchment Area (ECA) Survey, which was conducted between 1980 and 1984. This was a probability sample of more than 18,000 adults, using the Diagnostic Interview Schedule (DIS), which generated DSM-III diagnoses. The study was independently conducted at five sites in the United States: New Haven, Connecticut; Baltimore, Maryland; St. Louis, Missouri; Durham area, North Carolina; and Los Angeles, California (UCLA). Based on data from several studies, 2.5/100 to 8.1/100 meet the criteria for generalized anxiety disorder in any one year (Table 2). These rates are higher in women and may be higher in the lower social classes. Based on data from several different studies, only about 1% (range, 0.4/100 to 1.6/100) met the criteria for panic disorder in any one- to 12-month period (Table 3). The rates are

TABLE 1. COMMUNITYSURVEYS ANXlETl’

DISORDERS

USING

ASSESSING

DSM-IIIORRDC* Sample Size

New Haven 1975 National (U.S.) 1979 ECA (5 U.S. Sites) 1980-84 Puerto Rico 1984 1952 Stirling County I970 Zurich 1978 Munich 1981

511 3161 18,527 1551 1003 I074 3902 501

*RDC= Research Diagnostic Criteria

AREPANICANDGENERALIZED ANXIETY SEPARATE DISORDERS?

159

TABLE2. GENERALIZED ANXIETY DISORDERS

New Haven

National (US) Zurich Stirling County

1952 1970

Durham, NC-ECA

Prevalence Period

Rates/ 100

1 month 1 year 1year Current Current Current

2.5 6.4 2.3 5.0 4.6 8.1

ECA = Epidemiologic Catchment Area

TABLE3. RATESOFPANIC DISORDER Period (Months)

Rates/100

Mean of 5 ECA Sites

6

0.8

New Haven Zurich National (U.S.) Munich Puerto Rico

1 12 12 6 6

0.4 1.6 1.2 1.1 1.1

ECA = Epidemiologic Catchment Area

higher in persons aged 25 to 44 years, and in urban areas. The age of onset is in the mid 30s. There is no strong correlation to race or education. The rates are slightly higher in women, but this is not considered across studies. Genetic family studies Three family studies (HARRIS et al., 1983; CROWE et al., 1983; NOYES et al., 1986) provide data on the relationship between panic disorder and generalized anxiety disorder (Table 4). All three studies examined the rate of panic disorder and generalized anxiety disorder in the first degree relatives of probands with panic disorder and controls. The study by NOYESet al. (1986) also included a proband group with generalized anxiety disorder. All three studies included direct interviews with first degree relatives. The findings in all three were quite similar: 1. The frequency of panic disorder was higher among first degree relatives of panic probands as compared with relatives of control probands. (Expressed as lifetime rates per 100, the findings were 20.5 versus 4.2; 17.3 versus 1.8; and 149 versus 3.5 respectively.) 2. The rates of panic disorder did not differ among first degree relatives of probands with generalized anxiety disorder as compared with relatives of control probands (4.1 versus 3.5).

Ih(l

MYRNA M. WHSSMAN

Morbid Risk/100 in First Degree Relatives Proband

Panic

GAD’

Panic Controls

20.5 4.2

h.S 5.3

HARKIS it ul. 1YX3

PXllC Control\

17.3 1.x

4.x 3.h

CKOWI: Ct U/. I’)83

GAD Panic Controls

4.1 I-1.9 1.5

19.5 5.4 35

NOYES et (I/. 1086

* GAD = Generalized Anxiety Disorder

3 . The rates of generalized anxiety disorder were _ panic probands as compared with relatives of versus 3.5). 4. The frequency of generalized anxiety disorder probands with generalized anxiety disorder controls (19.5 versus 3.5) or of panic probands

These results support the separation

of generalized

not increased among first degree relatives of controls (6.5 versus 5.3: 4.8 versus 3.8; 5.4 was higher among first degree relatives of as compared with first degree relatives of (19.5 versus 5.4). anxiety disorder and panic disorder,

There is only one twin study (Torgerson. 19X3) available with relevant data, and the samples are quite small (Table 5). This study supported the separation of generalized anxiety disorder from panic and showed little evidence that generalized anxiety disorder is influenced by genetic factors. In this study, the frequency of anxiety disorder with panic

Proband Diagnosi\ Panic Disorder or Agoraphobia with Panic

Co-Twin Diagnosis Anxiety Digorder With Panic Without Panic (5%) (%)

N

MZ DZ

31 0

IS 25

I.3 16

Generalized Anxiety MZ DZ

0 IO

17 I0

12 20

* Data derived from Torgersen. IY83.

ARE PANICANDGENERALIZED ANXIETYSEPARATE DISORDERS?

attacks was higher (3 1%) in the MZ co-twin with panic disorder, and no the DZ co-twin. Only 10% of the DZ co-twins and no MZ co-twins with disorder had an anxiety disorder with panic attacks. Although not psychiatric disorders were frequent in the co-twins of probands with disorder, suggesting the heterogeneity of generalized anxiety disorder.

161

cases were found in generalized anxiety shown here, other generalized anxiety

Linkage studies

Recent advances in molecular genetics have led to a growing number of genetic markers that can be used to examine linkage of a disorder to a marker on a chromosome. The ultimate goal is the eventual identification and study of the gene itself. Panic disorder is a likely candidate for study with linkage markers. There is (1) vertical transmission from one generation to the next; (2) reasonably higher lifetime morbidity risk among first degree relatives (15% to 20%); (3) concordance in MZ twins. While it must be emphasized that all these findings are based on very small samples, nonetheless the evidence is sufficiently suggestive to warrant application of genetic linkage approaches. In November 1987, preliminary findings from a linkage study of panic disorders using red cell antigens and protein polymorphisms as genetic markers were reported by CROWE et al. (1987). Twenty-nine markers in 26 families with panic disorder provided suggestive linkage at one locus mapped to chromosome 16 or 22. Interestingly. when the families with only generalized anxiety disorder among relatives were excluded from the analysis, the results were not weakened, suggesting that generalized anxiety disorder did contribute to the findings. These findings must be considered preliminary but illustrative of the new genetic approaches and their potential for understanding heterogeneity and etiology. SUMMARY Evidence for the distinction between panic disorder and generalized anxiety disorder has been presented from epidemiological, family, and twin studies. The findings show that these two disorders have (1) different rates, (2) different family aggregations. and (3) different concordance patterns in MZ and DZ twins. More specifically:

The rates of generalized anxiety disorder are considerably higher (2.5% to 8% current prevalence) than that of panic disorder. The rates of generalized anxiety disorder are consistently higher in women. The current prevalence of panic disorder is about I %. and the sex ratios vary. Generalized anxiety disorder and panic disorder have different family aggregations, consistent with the separation of the disorders. The one twin study available using DSM-III criteria also supports the distinctions rather than the similarities between the disorders. Panic disorder is higher in MZ than in DZ twins and generalized anxiety disorder is not. While the disorders undoubtedly overlap and some generalized anxiety disorders may develop into panic disorders, the results thus far support the separation of these disorders for further research.

MYKNAM. WEISSMAN

162

REFERENCES ANGST, J.. VOLLKATH. M., MERIKANGX. K. R., & ERNST, C. (1987) Comorbidity of anxiety and depression in the Zurich cohort study of young adults. In Maser. J. D. & Cloninger, R. C. (Eds.) Comorhidity ofMood and An,tiut~ Disorders. (pp. 123-137) Washington D.C.: American Psychiatric Press, Inc. CANINO. G. J.. BIRD. H. R., SHROIIK P. E.. R~BIO-S~PF~, M., BRAVO. M.. & MARTINEZ.R. (1987) The prevalence of specific psychiatric disorders in Puerto Rico. AKIT Gen. Pswhrutry. 44. 727-735. CROWE, R. R.. NOYES. R. JR.. P,%uI.s. D. S.. & SLYM~Y. D. J. (1983) A family study of pamc disorder. AK/I. C;CY. Pswhicrtry. 40. 1OhS1069. CRONE. R. R.. N~YES, R. JR.. WII.SON. A. F., Et.xoN, R. C.. & W,%RD.L. J. ( 1987) A Ii&age study of panic disorder. Arch. Gen. Psychiatry. 44, 933-937. HARRIS. E. L.. NOYES, R. JR.. CROWE. R. R.. & CHAUDIIRY,D. R. (19X3) A family study of agoraphobia. Arch. GCT. Psychiatty

40, 1061-1064.

MURPHY,J. ( 1986) Trends in depression and anxiety: men and women. Aua. Psyc~hrcrtn Stand. 73. 113.127. Novts, R. JR., CRowr-. R. R., HARRIS. E. L.. HAMRA. B. J.. MCCHESNEY. C. M.. & CHAUDHRY. D. R. (1986) Relationship between panic disorder and agoraphobia. Arch. Gcn. Psychiatry. 43, 227.232. Rt(iit~. D. A.. MYERS. J. K.. KRAMER. M., RIX~NS, L. N.. BI.AZER. D. B.. & Hotlcx. R. I. (1984) The NIMH Epidemiologic Catchment Area Program: historical context. major ob.jectives, and study population characteristics. At-ch. Gen. Pswhiatr!.

41.934-941.

TORIXRSEIV.S. (1983) Genetic factor in anxiety disorders. Alr,h. Gen. Psyc,hiutp 40. 1085-1089. UHLEWIJTFI, E. D., BAI.TER, M. D., MEI.I.INGER,G. D.. CISIN, 1. H., & CuwrHoRNF, J. (19X3) Symptom checklist syndromec in the general population: correlation with psychotherapeutic drug use. Awh. Gen. Pswhicrtty 40, 1167-l 173. W~ISSM~N, M. M.. MYERS, J. K.. & HARmG, P. S. (1978) Psychiatric disorders in a Unlted States urban community: 1975-76. Am. .I P.syhratry. 135.459-462. WF.ISS’~/~.~N, M. M. (1988) The epidemiology of panic disorder and agoraphobia. In R. E. Hales & A. J. France (Us.) Amvkun Psyhicrtrk Association Annuul Re~~ir~~ ofP.ywhiatry Vol. 7. Washington. DC: American Psychiatric Press Inc. WITTCH~N,H. U. (1986) Contribution of epidemiological data to the classification of anxiety disorders. In I. Han & H. U. Wlttchen (Eds.), Panic, Phohros, (pp. I X-27). New York: Springer-Verlag.