The epidemiology of anxiety disorders: Rates, risks and familial patterns

J. psychiaf. Rex, Vol. 22, Suppl. 1, pp. 99-114, Printed in Great Britain.

1988

THE EPIDEMIOLOGY

0

OF ANXIETY

RISKS AND FAMILIAL hh-RliA

M.

DISORDERS:

OOZZ-3956/88 $3&O+ .OO 1988 Pergamon Press plc

RATES,

PATTERNS*

WEISSMAN

College of Physicians & Surgeons of Columbia University, 722 West 168th Street, Box 14, New York, NY 10032, U.S.A. (Revised 23 February 1987) Summary-This paper reviews what we know about the epidemiology and familial patterns of anxiety disorders. Focus is on the current studies based on specified diagnostic criteria. Data are presented, when available, on the subclassifications of the anxiety disorders. Data from epidemiologic and family studies support the notion that anxiety disorders have a relatively high prevalence and are familal, that they are heterogeneous, and that some are related to depression. It suggests that there is an increased probability that a person with one anxiety disorder will have another or will have a major depression during his or her lifetime. Data also suggest that panic disorder has the most severe consequence in terms of morbid risk to first-degree relatives, particularly risk to children, and that there may be a relationship between adult and childhood anxiety disorders. Potential research areas are given. INTRODUCTION

anxiety has been called by KLEIN (1981) a key word in psychiatry, it is also quite an ambiguous one. The semantic ambiguity of anxiety disorders, the difficulty in separating trait from state conditions, and the heterogeneity of expression create an epidemiologic nightmare. Moreover, until the recent acceptance of Klein’s notions about anxiety disorders, now incorporated in Diagnostic and Statistical Manual of Mental Disorders, Third Edition (DSM-III) (AMERICAN PSYCHIATRIC ASSOCIATION, 1980), the anxiety disorders usually had not been subdivided into different disorders such as phobia, panic, generalized anxiety disorders. This paper reviews what we know about the epidemiology and familial patterns of anxiety disorders. Focus is on the current studies based on specified diagnostic criteria. Data are presented, when available, on the subclassifications of the anxiety disorders. WHILE

EPIDEMIOLOGY:

RATES AND RISKS IN ADULTS

Studies prior to specified diagnostic criteria The epidemiology of anxiety states prior to the development of specified diagnostic criteria has been reviewed by MARKSand LADER (1973). Their review is described because it is usually referenced as the source of epidemiologic data on anxiety disorders. Although different diagnostic criteria and time periods between studies were used and the anxiety disorders were not separated out, Marks and Lader found surprising agreement among the five population studies conducted in the United States, the United Kingdom, and Sweden between 1943 and 1966. Anxiety states were fairly common (around 2.0-4.7 out of 100 *This paper adapted from a chapter in Anxiety and the Anxiety Disorders (Edited by TUMA,A. H. and J. D.), pp. 275-296. Lawrence Erlbaum Associates, Hillsdale, N.J. 99

IMASER,

100

MYRNAM. WEISSMAN TABLE 1. Co-ITY

Study place (yr) Bmm~*,

SURVEYSOP ANXIETYSTATES~ms/lOO

Sample size

Period prevalence

Male

Female

Total

5 yr

0.5

1.2

-

Lifetime

0.3

0.1

-

Current

-

-

2.9

Lifetime

1.3

3.4

-

Lifetime 1 yr Unspecified LYr Current LYr

1.5 2.6 4.0

3.8 1.5 3.7 6.8

3.9 0.5 3.2 5.4

Norway (1951)

Ah members of community F~GMMING*,Denmark (1951) 3467 MURPHY, Canada (1952) (for reference see Moannv, 1010 1980) ESSEN-MOLLERet al. *, 2550 Sweden (1956) HAGNELL*,SWEDEN(1966) 2568 BRUN~TTI*,France (1976) 101 V_Xrs&n~*, Finland (1976) 1000 BROU~Net al*., U.K. (1977) 612 ANGSTand DOELER-MIKOLA, Zurich (1982) 591 *From CAREYet al. (1980).

current prevalence) and were more prevalent in women, particularly younger women between 16 and 40 yr of age. We conducted a separate review of epidemiologic studies, as presented in Tables 1 and 2. Nine additional community studies of anxiety states were found. The time periods and diagnostic methods varied so that little can be said definitively. However, the additional studies show that the rates are higher in women than in men and are usually in the range reported by MARKS and LADER (1973) regardless of the time period assessed. This latter finding is curious, since one would expect that lifetime prevalence rates would be higher than one-year rates. Not shown here, three of the nine studies (BRRMER, 1951; FRRMMING, 1951; HAGNELL, 1966) separated out from the anxiety states, neurasthenia, which was quite similar in description to panic attacks. It was described as an episodic event the chief symptoms of which were fear, apprehension, inattention, palpitations, respiratory distress, dizziness, faintness, sweating, tremor, chest pains, and feeling of impending disaster. These TABLE 2. COMMUNITYSURVEYSOF PHOBIAS

Study place (yr) Type of phobia AGRAS ei al.,

Sample size

Vermont (1969) 325 Agoraphobia Total phobias Severely disabling phobias COSTELLO, Canada (1982) 449 All phobias including Agoraphobia Severely disabling phobias ANGSTand DOBLER-MIKOLA 591 Zurich (1982) All phobias including Agoraphobia

Rates1100 period prevalence 1 yr

1 yr

Current 1 yr

Male

Female

Total

-

-

0.63 7.7 0.22

-

-

19.4 -

0.70

0.6 1.2

4.9 4.9

2.6 3.0

ANXIETY DISORDERS: RATES,

RISKS

ANDFAMILIAL PATTERNS

101

occurred in the absence of other illness and existed independently of specific external situations. In between attacks, the patient felt relieved but not completely well. The rates of these attacks were slightly lower than those of anxiety states and, again, were more common among women. Two studies (AGRASet al., 1969; ANGSTet al., 1982) reported community annual rates of mild phobias in the range of about 6-7 out of 100 (Table 2). One study (COSTELLO, 1982) reported very high annual rates of all types of phobias in women (19.4/100). However, when the criteria of severe impairment were added, these rates were markedly reduced, 0.22/100 (AGRASet al., 1969) and 0.70/100 per year (COSTELLO,1982). The annual rates of agoraphobia were also considerably lower, 0.631100. Studies using specified diagnostic criteria With the recent improvements in the reliability of psychiatric diagnoses, including use of structured diagnostic interviews and specified criteria, it was possible to obtain reliable information on the epidemiology of psychiatric disorders. Currently, data are available from three epidemiologic surveys conducted in the United States. 1975 survey--New Haven. The first application of the new structured diagnostic interview techniques was incorporated in a pilot survey of persons living in the New Haven, Connecticut area from 1975-1976. Five hundred and eleven persons (a follow-up of a probability sample) were interviewed by clinically trained persons using the Schedule for Affective Disorders and Schizophrenia-Lifetime Version (SADS-L) which generated RDC (WEISSMANet al., 1978). The current rate of any anxiety disorder (RDC) was 4.3/100. This was similar to the rate of major or minor depression (not shown here), also 4.31100, and to the rates of anxiety states reviewed by MARKSand LADER(1973). The current prevalence rates of the specific anxiety disorders were as follows: generalized anxiety (GAD) 2.5/100; phobic disorder 1.4/100; and panic disorder 0.4/100. No current cases of obsessive-compulsive disorder were found in this sample of 500. Since RDC were used, post-traumatic stress disorder (PTSD) was not assessed. Phobias were not categorized as to type in this study. This study found an overlap within the anxiety disorders and between the anxiety disorders and major or minor depression. Over 80% of persons with GAD, 17% with panic disorder, and 19% with phobia had at least one of the other anxiety disorders in their lifetime. Thirty per cent of persons with phobias had panic disorder at some time in their life. There was an overlap of the anxiety disorders with major depression: over 7% of persons with GAD, 2% with panic disorder, and 4% with phobia had major depression at some time in their life. Sample sizes were too small to interpret rates by many sociodemographic or other risk factors. However, GAD was slightly more common on middle and younger aged women, non-whites, persons not currently married, and those in the lower socioeconomic classes. This study also pointed out the importance of population studies to determine the magnitude of the anxiey disorders. Only about a quarter of persons with any current anxiety disorder received treatment for an emotional disorder in the past year. Although they were not being treated for their anxiety disorder, they tended to be high utilizers of health facilities for nonpsychiatric reasons. Their use was higher than persons with any other psychiatric

102

MYRNA M. WEISSMAN

disorder or with no psychiatric disorder. Persons with panic disorder were the highest users of psychotropic drugs, especially the minor tranquilizers. The 1979 national survey of psychotherapeutic drug use. Prom a symptom checklist administered by survey interviewers in a large-scale (N= 3161) survey of psychotherapeutic drug use, some DMS-III diagnostic counterparts were identified (UHLENHUTH et al., 1983). GAD was the most common disorder (6.4/100 one-year prevalence), followed by phobias other than agoraphobia (2.3/100) and agoraphobia/panic (1.2/100). The rates of all the anxiety disorders were higher in women than in men, showing a two to threefold difference, As reported in the 1975 New Haven survey, use of antianxiety agents was highest in the agoraphobia/panic group. Because of the different diagnostic groupings between the 1975 and this 1979 survey, only direct comparisons with the GAD diagnosis are possible. The rates of GAD were higher in this 1979 survey (6.4%) as compared to the 1975 New Haven survey (2.5%). However, it should be noted that the former is a one-year rate, and the latter a current rate. The period difference and the somewhat different diagnostic classifications and sample sizes could account for the differences in rates. Both studies report higher rates in women in all the anxiety disorders studied. 1982 epidemiologic catchment area study survey (ECA). Preliminary data on rates of some anxiety disorders (panic, obsessive-compulsive, and agoraphobia) based on the DSMIII are available from a large-scale United States community survey currently underway. This study may ultimately provide the most comprehensive epidemiologic data. Because of the need for accurate epidemiologic information and because of the demonstration that the new methods were feasible in community studies and could be adapted for lay interviewers (Robins et al., 1981), the National Institute of Mental Health (NIMH), Division of Biometry and Epidemiology, initiated in 1980 an epidemiologic catchment area community study in the U.S.A. (REGIER et al., 1984). Among the objectives of this multi-site longitudinal study was to provide information on (1) the prevalence and incidence of specific psychiatric disorders in the community; and (2) for newly developed mental disorders (i.e. incidence cases), the concomitant factors associated with or causative of the disorder. Each catchment area had at least 200,000 inhabitants and boundaries that coincide with one or more continuous comprehensive Community Mental Health Center (CMHC) cat&n-rent areas. Yale University in New Haven, Connecticut, received the first such grant, followed by Johns Hopkins in Baltimore, Maryland, and Washington University in St Louis, Missouri, and subsequently by Duke University in Durham, North Carolina, and the University of California in Los Angeles. The information presented is preliminary and will be limited to DSM-III diagnoses of agoraphobia, obsessive-compulsive, and panic disorder for the first wave from the three sites. Data on GAD or PTSD are not yet available. Only community subjects are included. The details of the study including diagnostic methods, sampling, and design are described elsewhere (MYERS et al., 1984; ROBINS et al., 1981). Table 3 shows the six-month prevalence rates of panic, obsessive-compulsive disorder, and agoraphobia in five sites. As can be seen, the rates of panic are similar in all five sites (0.6-1.0 out of 100). The rates were higher in women and there was no strong

ANXIETY DISORDERS:RATES, RISKSAND FA~~ILIAI. PATTERNS

103

TABLE3. SIX-MONTH PBBULBNCEOFDIS/DSM-III PANIC,OBSESSIVECOMPUIXvEDISORDERS AND AGORAPHOBIA LNFIVEU.S. SITBS Sites New Haven Baltimore St Louis Piedmont Los Angeles

Panic

Obsessive-compulsive disorder

Agoraphobia

Rates/100 0.6 1.0 0.9 0.7 0.9

Rates/100 1.4 2.0 1.3 2.1 0.1

Rates/100 2.8 5.8 2.7 5.4 3.2

relationship with race or education, nor with age (data not shown here). Ages 25-44 yr were the highest period of risk, and the rates were generally lower in persons 65 yr and older. The rates of obsessive-compulsive disorder were also similar in the five sites (1.3-2.1 out of 100). The rates were higher in women, and there was no strong relationship with age. The rates of agoraphobia have wider variations between sites (2.7-5.8 out of 100) and are considerably higher than the other anxiety diagnoses and than the reports from earlier studies. The rates are two to fourfold higher in women than man, and twofold higher in less educated persons and non-whites. There was no consistent age finding for agoraphobia overall. The lowest rates were in ages 65 yr and older. The source of this variability is under investigation. It may be due to differences in interviewer instructions and wording between sites. These methodologic differences between sites have been corrected for the subsequent interviewing waves. Rates of phobia are also sensitive to the criteria of impairment. Although many persons have phobias, a considerably smaller number have severe disabling impairments from their phobias.

EPIDEMIOLOGY:

RATES AND RISKS IN CHILDREN

In general, there is a paucity of available data on the epidemiology of child psychiatric disorders based on studies of community samples. The situation is no less true for the anxiety disorders. After a review of the literature, ORVASCHFJL and WEISSMAN (1986) concluded that only data on the prevalence of anxiety symptoms were available. On the basis of seven community surveys (see Table 4), they concluded that anxiety symptoms of all types were quite prevalent for children of all ages and of both sexes. A determination of risk factors from the available data was premature, but there was some suggestive information reported. On the whole, anxiety symptoms were more prevalent in girls than in boys, although there was considerable variation as a function of the type of anxiety and the age of the child. Anxiety symptoms showed a general decline with age, although some types of phobias have onset in early adult or later adult life. There was also some indication that anxiety symptoms were more prevalent in black than in white children and more prevalent in children from lower rather than higher socioeconomic background. Finally, the significance of these childhood anxieties and the evidence regarding the relationship between anxiety symptoms and other indicators of child psychopathology was unclear. Even less was known about the long-term significance of anxiety symptoms of childhood.

Location Sample source Sample size Age of sample

41%

43%

7.7%

us Community 325 Children and adults Subject or mother

(1969)

et al.

AGRAS

*Based on ORVASC~ELand WEISSMAN(1986).

Separation concerns Other anxieties

Results Fears and/or worries

Mother

us Community 482 6-12 yr

Design

Informants

LAPOUSE and MONK (1958)

18.0% (Tension) 18.O% (Nerves)

16.5%

Teacher

us School 1753 5-8 yr

and QUAY (1971)

WERRY

12.8070(Fears) 2.6% (Worries)

Mother

UK Community 705 3 yr

(1975)

et al.

RICHMAN KASTRUP (1975)

IN CHILDREN*

13.7% 8.0% (Nightmares)

4.0%

Parent

Denmark Community 175 5-6 yr

TABLE4. STUD~S RBPORTINO P~IXVALENCE OF ANXIETY

14.0070(Fears) 8.0% (Worries)

Mother

us Community 100 3 yr

EARLS (1980)

2-43% (Fears) 4-33% (Worries)

Subject

Japan Community 2500 11-12 yr

Ann and MASUI (1981)

ANXIBTYDISORDERS: RATES,RISKSAND F~IAL

PATTERNS

105

FAMILIAL PATTERNS

The familial nature of anxiety disorders was noted over a century ago (COHENet al., 1951), and subsequent writers have frequently cited the occurrence of additional cases within a patient’s family (WOOD, 1941). Hence, the notion that anxiety disorders are familial is not new. COHENet al. (1951) identified 19 separate reports published between 1869 and 1948 in which a familial predisposition to anxiety disorders was described. In addition, they reported on the results of a study in which the careful systematic collection of family history data revealed that two-thirds of the patients had at least one other affected relative. Despite these early findings, until recently anxiety disorders received little attention from investigators interested in the inheritance of psychiatric disorders. Recent family studies of first-degree relatives of probands with anxiety neurosis have been reviewed by CAREY and GOTTESMAN(1981). Table 5 shows a similarity in rates (15AOO) of anxiety neurosis among relatives. All of these rates were obtained from family history data (i.e. information collected only from the proband regarding his/her relatives). CROWE et al. (1983) presented the first and only comprehensive family study of probands with panic disorder alone, using specified (DSM-III, RDC) diagnostic criteria. In this study, a majority of the relatives were interviewed. The rates of illness obtained were higher than reported in the family history studies, but the patterns were the same. More women were affected, and the risk to siblings increased with the number of affected parents. There have been attempts to explain the familial patterns observed with genetic models (MINER, 1973; PAULS et al., 1979; PAULS et al., 1980; SLATER and SHIELDS, 1969). However, no genetic

hypotheses

have been conclusively

rejected.

Family study of depression and anxiety disorders: adults Recent results from the Yale family-genetic study of probands with both affective and anxiety disorders provide additional information on familial patterns. Data are available on both the probands’ adult first-degree relatives and their offspring ages 6-17 yr. The details of this study including the methodology are described fully (LECKMYANet al., 1983a, b; WEISSMAN et al., 1982, 1984a, b).

TABLET .FREQ~ENCY~PAN~IET~NEIJR~~I~ AMONG FIRST DEGREE RELATIVES OF ANXIEXY NEUROTICS

Family history studies* BROWN MCINNES NOYESet al.?

Cona~ et al.

Rate/100 all first degree relatives 15.5 14.9

18.4 15.6

*Based on CAREY and GOTTESMAN (1982). tRates for Noms et al., are age-corrected risks; all others are not.

106

MYRNA M. WEISSMAN

The study included 215 probands (82 normal controls drawn from a community sample and 133 probands with major depression), 1331 of their adult first-degree relatives, and 194 of their children ages 6-17 yr. Diagnoses were based on the RDC for all probands and adult first-degree relatives, and on the DSM-III for children ages 6-17 yr. The first-degree relatives of individuals with major depression plus an anxiety disorder were at greater risk for major depression, as well as anxiety disorders, than were the relatives of individuals with major depression without an anxiety disorder (LECKMAN et al., 1983a). This increased risk appears to be present whether or not the anxiety disorder occurred solely in association with episodes of major depression or was temporally separate. The findings did not support the prevailing DSM-III and RDC nosologic convention in which episodes of anxiety disorder that are concomitant with episodes of major depression are not diagnosed. In subsequent analyses, we diagnosed anxiety disorders regardless of their temporal sequence with depression. For the next analysis, we looked more closely at the specific anxiety disorders using a diagnostic hierarchy for probands with depression and anxiety disorders: agoraphobia > panic disorder > generalized anxiety disorder. Operationally, this meant that depressed probands with both agoraphobia and panic disorder would be classified as depressed with agoraphobia and so forth (LECKMAN et al., 1983b) Table 6 presents the observed rate/100 among the first-degree relatives of persons with major depression with and without anxiety disorders, anxiety disorder, alcoholism, and other psychiatric disorder. The probands with depression plus disorder or generalized anxiety disorder show a high rate of major depression among their first-degree relatives, with approximately 20000 of the relatives being affected. This compares with 11S/100 of the relatives of depressed probands with agoraphobia, 10.7/100 of relatives of depressed probands without any anxiety disorders, and only 5.6/100 of the relatives of the normal controls. In general, the first-degree relatives of probands with major depression and panic disorder had the highest rates of illness. They showed increased rates of major depression, anxiety disorders, and alcoholism when compared to the relatives of either the normal controls or the depressed probands without an anxiety disorder. These findings are independent of when the anxiety disorder occurred as well as independent of the presence of secondary alcohol abuse. Relatives of probands with major depression and generalized anxiety disorder show an increase of major depression compared to the relatives of either the normal controls or the depressed probands without an anxiety disorder. Table 7 compares the rates of major depression (primary and secondary), anxiety, and alcohol abuse among first-degree relatives of probands with depression and panic disorders found in the Yale and Iowa studies, since similar diagnostic criteria were used in both studies. Although the rates are not age corrected, there is considerable similarity in the rates of depression among the relatives of the normal probands (about 61100) and among the relatives of the probands with depression only and the probands with panic disorder only (lO/lOO). There is considerably more anxiety among the relatives of probands with panic disorder only, and considerably more anxiety, major depression, and alcohol abuse in the probands with both panic disorder and depression. In presenting the Iowa data, we included relatives with primary and secondary depression. In the original Iowa data, secondary

75.2 60.1 41.4 56.2 46.5

521 338 133 96 243

19.8

11.5

19.6

10.7

5.6

0.4

2.1

3.8

2.1

0

Panic

4.5

1.0

3.8

9.1

5.2

10.5

6.2

4.0

1.2 2.1

GAD

14.0

8.3

15.8

10.7

10.4

21.1

8.9

7.9

5.2 9.2

Alcohol Abuse

Total Anxiety

GROUPINGS BY ANXIETY*

Phobia

RELATIVES BYPROBAND

Major Depression

RATES OF DIAGNOSES AMONG

Nat risk Normal

6.

*Based on LECKMAN et al. (1983). tWith hierarchy applied to anxiety disorders as outcome measures.

Normal Major Depression, no anxiety Major Depression plus Panic Disorder Major Depression plus Agoraphobia Major Depression plus GAD

Proband group?

TABLE

18.5

16.7

18.8

16.6

9.7

Other

108

MYRNAM. WEISSMAN TABLE 7. RATES/NO OF

Proband group

DIAGNOSES AMONG RELATIVES BY PROBAND (YALE/IOWA)*

Nat risk

Normal (Iowa) Normal (Yale) Panic alone (Iowa) Depression alone (Yale) Depression plus Panic

262 521 278 338 133

GROWS

Diagnosis of relatives (Rates/lo) Major Total Alcohol Anxiety Depression’/’ Abuse 6.5 5.6 10.1 10.7 19.6

6.5 5.2 25.2 9.2 15.8

4.9 7.9 9.0 8.9 21.1

*Presented by LECKMAN et al., American Psychiatric Association Annual Meeting, Toronto, Canada, 1982. TIncludes both primary and secondary depression.

depression was not included, and they did not find familial aggregation of major depression in relatives of probands with panic disorder (CROWE et al., 1983; SHADER et al., 1982). When the data were re-examined with both primary and secondary depression assessed, the elevated rates of major depression were found. Family study of depression and anxiety disorders: children Finally, we looked at the rates for DSM-III diagnosis in 194 of the probands’ children ages 6-17 yr. The subgroups of probands were the same as those in Table 6, with the one exception (WEISSMAN et al., 1984). Included in the depression and phobia group were those probands who had social and simple phobia as well as agoraphobia, since we were examining the outcome of the different phobias in children. The highest rates of illness were in the children of probands with both depression and panic disorder. The rates of major depression (26.31100) and separation anxiety (36.8/100) were highest in their children. These findings give support to the association between childhood separation anxiety and panic disorder suggested by KLEIN and GITTELMAN-KLEIN (1978). WHAT’S ON THE HORIZON

Adults In the next several years, data from the ECA will provide information on the prevalence, incidence, and risk factors that is lacking for some of the anxiety disorders (phobias, panic, obsessive-compulsive disorder) based on the DSM-III in five U.S. sites. Information on the relationship between the anxiety disorders and other adult psychiatric disorders will also be available. The ECA will have data on GAD from the second wave on several centres and on PTSD from the second wave of the St Louis center. Efforts to understand the variability and possible unreliability of rates of phobias between Baltimore and the other sites are underway, but as yet unresolved. While the ECA has included a number of demographic and social risk factors, it must be acknowledged that no biological risk factors (e.g. frequency of mitral valve prolapse, response to pharmacologic challenge) have been included. These might best be investigated

ANXIETY DISORDERS: RATES, RLSKS AND FAMILIAL PATTERNS

109

in high-risk individuals using case-control designs comparable to, as well as included in, the family studies described. Children and adolescents Study of the epidemiology of all psychiatric disorders and of the anxiety disorders in children is virgin territory. As the epidemiologic methodology for studies of children currently under development at the NIMH becomes available, the ECA approach should be applied to surveys of children and adolescents. While the epidemiologic studies will provide information on rates and risks for the anxiety disorders, there are many key questions not answered. The following list, of course, is by no means exhaustive. Do adult anxiety disorders transmit to children? While the Yale study suggested that some adult anxiety disorders transmitted anxiety and depression to children, to our knowledge there has been no systematic, blind, case-controlled study of the young children of adult probands with anxiety disorder or of the adult parents of children with anxiety disorder. Relevant data available from a few small studies suggest an association between adult and childhood anxiety disorders in families (BERGet al., 1974a, b; GITTELMAN-KLEIN, 1975; GITTELMAN-KLEIN and KLEIN, 1980). There have been several studies of the children of psychiatrically ill patients (RUTTER, 1966) and the children of depressives (BEARIXLEEet al., 1983; ORVASCHEL, 1983: WEISSMAN et al., 1984c). In general, these studies found that children of parents with a major affective disorder were at high risk for depression. Since most of the studies focused on depression in both the parents and children, with few exceptions, data on anxiety disorders in the children were not reported. Moreover, none of the studies included an assessment of any accompanying anxiety disorders in the depressed probands. If the convention of not diagnosing anxiety disorder when it occurs with depression were followed, then the anxiety disorders would have been missed in the depressed parent probands, further obscuring findings of anxiety in the children. Future studies should diagnose depression and anxiety disorders separately even if they co-occur. Are adult and childhood anxiety disorders similar? The data suggest that the children of patients with agoraphobia or panic disorder are beginning to manifest similar disorders themselves, in particular, separation anxiety. A number of investigators have made similar retrospective observations about the onset of adult anxiety disorder in childhood or early adulthood (AGRASet al., 1969; BERG, 1976; BERG et al., 1947b; BUGLASSet al., 1977; KLEIN, 1964; ROTH, 1960; TYRER and TYRER, 1974). However, longitudinal studies of children or adolescents with anxiety disorders are needed to determine the degree to which childhood disorders are precursors of adult anxiety or of depressive states. These studies should include matched control groups of normal children and children with depressive disorders in order to determine the specificity of the childhood anxiety disorders, as well as to allow for calculations of relative risks. Are the anxiety disorders related? While the Yale study of children found support for a distinction between GAD and panic or agoraphobia, this distinction was not found when adult relatives of probands were studied. Careful studies of families are needed that select probands with GAD only, with panic disorder, with and without agoraphobia, as well as

110

MYRNA M. WEISSMAN

select the range of phobias, and study adult relatives and minor children of these probands using the best current methodology. These studies should include control groups, blind diagnostic assessments, and best estimate of diagnosis from direct interviews with relatives and from multiple informants. Studies such as these will help determine if familial aggregation is similar between the anxiety disorders. Longitudinal studies of adults with varying forms of anxiety disorders would also be useful to determine the relationship between the onset of the anxiety disorder, e.g. is one anxiety disorder the precursor of another? Does the presence of one anxiety disorder increase the risk of another? Are anxiety and depression related? The current studies of families of children and of adult relatives of probands with depression and anxiety disorders and with anxiety disorders alone (CROWE et al., 1983; LECKMAN et al., 1983; WEISSMAN et al., 1984b) suggest a relationship between depression and anxiety disorders. This relationship is also suggested by the fact that patients with anxiety disorders respond to tricyclic and other antidepressant medications. Controlled family studies of children and of adult relatives of probands with panic disorder, with and without agoraphobia, with agoraphobia alone, or with secondary depression and primary anxiety disorders, in which careful attention is paid to the diagnosis of depression as well as the other disorders in relatives, would be useful. SUMMARY OF FINDINGS AND POSSIBLE FUTURE RESEARCH

Summary of findings This review of the epidemiology and familial factors of anxiety disorders indicates the following. (1) Anxiety disorders in adults are common, heterogeneous, and familial. (2) The rates and risks for the different anxiety disorders in adults vary; a rough estimate for all anxiety disorders is about 4-8 out of 100 annual prevalence. The ECA data over the next few years will provide a more accurate estimate of prevalence and incidence of all the anxiety disorders. Based on the two studies available using precise diagnostic techniques, there is some agreement that GAD is the most common and panic disorder the least common of the anxiety disorders; that the anxiety disorders are most common in women, younger populations (although this varies), and in the less educated (again, this varies). There are no epidemiologic data on PTSD (a recent article suggests that this diagnosis should be viewed with caution, SPARRand PANKRATZ,1983), and only one of the two studies assessed obsessive-compulsive disorder. (3) There is an overlap within the anxiety disorders and between the anxiety disorders and depression. There is an increased probability that a person with one anxiety disorder will have another, or will have a major depression during his or her lifetime. (4) Only about a quarter of persons with anxiety disorders receive treatment for these problems. However, these persons are high users of health care facilities for reasons other than emotional problems. persons with panic disorders have the highest use of psychotropic drugs. (5) There are no epidemiologic population studies of anxiety disorders in children. The studies available survey fears and anxiety symptoms and suggest that these are common in children, especially girls, and some decline with age in children.

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(6) Studies of families support the familial nature of anxiety although the precise rates vary with the methods used. The earlier studies did not divide the anxiety disorders into subtype. The current studies show that first-degree relatives of probands with anxiety disorders have increased rates of anxiety disorder and of depression. (7) When anxiety disorders are examined in the context of depression in family studies, the results show that anxiety disorders are common in both the depressed probands and their first-degree relatives. (8) The first-degree relatives of depressed probands with secondary anxiety disorders have higher rates of depression and of anxiety disorder regardless of whether the proband’s anxiety is associated with or occurs separately from the depression. The higher rates of depression, anxiety disorder, and alcoholism are highest in the relatives of probands with depression and panic disorder. (9) The children (ages 6-17 yr) of probands with depression and panic disorder have very high rates of depression, separation anxiety, and other anxiety disorders. (10) The relationship between depression and anxiety is not clear. The family studies suggest that depression and anxiety may be part of a shared diathesis; that anxiety disorders are heterogeneous and separate disorders. Panic disorder may be the most severe form of the anxiety disorders, using familial transmission as the criteria for severity. The family data suggest that the risk of major depression and separation anxiety is markedly increased among the offspring (ages 6-17 yr) of probands with depression and panic disorder. Possible future research Potentially useful areas of future research include the following. (a) The assessment of biological risk factors (e.g. assessment of mitral valve prolapse, response to pharmacologic challenge) in future epidemiologic studies. These studies are more feasible if conducted in individuals at high risk for anxiety disorders using family case-control design studies, perhaps drawing the sample from community studies. (b) Large-scale ECA type of study in children and adolescents to determine rates (prevalence and incidence) and risk factors. (c) Well-designed, case-control, family studies of the adult and fist-degree relatives and the young children of adults with varying types of anxiety disorders (e.g. agoraphobia with and without panic, obsessive-compulsive disorder, primary anxiety disorder, and secondary depression) to learn more about the relationship among anxiety disorders and between anxiety disorders and depression; and to learn more about the relationship between the adult and childhood anxiety disorders. (d) Longitudinal studies of children with anxiety disorders to learn about the course, pattern, and implications of these disorders in children and their relationship to the adult forms. Although this is in contradiction to the current DSM-III convention, future research studies involving the anxiety disorders should diagnose anxiety disorders even if they occur solely in association with episodes of major depression. Taken together, there are many promising areas of epidemiologic and family study research for the anxiety disorders which can provide increasing information on nosology, magnitude, risks, course, and consequences of the anxiety disorders.

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Acknowledgment-This review was supported in part by Alcohol, Drug Abuse, and Mental Health Administration grants MH 28274 and MH 36197 from the Affective and Anxiety Disorders Research Branch, National Institute of Mental Health, Rockville, Maryland; and by the Yale ECA NIMH grant MH 40603-Ol Al. The Epidemiologic Catchment Area Program was established as a series of five epidemiologic research studies performed by independent research teams in collaboration with staff of the Division of Biometry and Epidemiology of the National Institute of Mental Health. The five sites are Yale University, UOl MH34224; Johns Hopkins University, UOl MH33870; Washington University, UOl MH33883; Duke University, UOl MH35386; University of California, Los Angeles, UOl MH35865. REFERENCES K. and MASUI,T. (1981) Age-sex trends of phobic and anxiety symptoms. Br. J. Psychiat. 138, 197-302. AGRAS,S., SYLVESTER, D. and OLIVEAU,D. (1969) The epidemiology of common fears and phobias. Comp. Psychiut. 10,151-156. AFRICAN PSYCHIATRIC ASSOCIATION (1980) Diagnostic and Statistical Manual of Mental Disorders, 3rd Edn. American Psychiatric Association, Washington, D.C. ANGST,J., DOBLER-M~KOLA, A. and SCHEIDEGGER, P. (1982) A panel study of anxiety states, panic attacks, and phobia among young adults. Paper read at the Research Conference on Anxiety Disorders, Panic Attacks and Phobias, Key Biscayne, Florida, 9 December 1982. BEARDSLEE, W. R., BEMPORAD,J., KELLER,M. B. and KLERMAN, G. L. (1983) Children of parents with major affective disorder: a review. Am. J. Psychiat. 140, 825-832. BERG, I. (1976) School phobia in the children of agoraphobic women. Br. J. Psychiat. 128, 86-89. BERG,I., BUTLER,A. and PRITCHARD,J. (1974a) Psychiatric illness in the mothers of school phobic adolescents. Br. J. Psychiat. 125, 466-467. BERG,I., MARKS,I., McGomn, R. and LEPSEDGE,M. (1974b) School phobia and agoraphobia. Psychol. Med. 4, 428-434. BLEATER, J. (1951) A social psychiatric investigation of a small community in nothern Norway. Actu psychiat. neural. stand. Suppl. 62, 121-124. BROWN,G. W., DAVIDSON, S., m, T., IMACLEAN, U., POLLACK,S. and PRUDO,R. 61977) Psychiatric disorder in London and North Uist. Sot. Sci. Med. 11,367-377. BRUNETTI,P. M. (1976) Rural Vaucluse: two surveys on the prevalence of mental disorders. In Social, Somatic and Psychiatric Studies of Geographically Defined Populations (Edited by ANDERSON,T., ASTRUP, C. and Forsdahl, A.) Acta psychiat. stand. Suppl. 263, 343-350. BUGLA~S, D., CLARKE,J., HENDERSON, A. S., KR~TMAN,N. and PRESLEY,A. S. (1977) A study of agoraphobic housewives. Psychol. Med. I, 73-86. CAREY, G. and GOTTESMAN, I. I. (1981) Twin and family studies of anxiety, phobic, and obsessive disorders. In Anxiety: New Research and Changing Concepts (Edited by KLEIN,D. F. and RA~KIN, J.), pp. 117-136. Raven Press, New York. CAREY,G., GOTTESMAN, I. I. and ROBINS,E. (1980) Prevalence rates for the neuroses: pitfalls in the evaluation of familiality. Psychol. Med. 10,437-443. COHEN,M. E., BADAZ., D. W., KILPATRICK, A., REED,E. W. and Wrnru, P. D. (1951) The high familial prevalence of neurocirculatory asthenia (anxiety neurosis, effort syndrome) Am. J. hum. Genet. 3, 126-158. COSTELLO, C. G. (1982) Fears and phobias in women: a community study. J. abnorm. Psychol. 91, 280-286. CRO\KE,R. R., NOYES,R., PAULS,D. L. and Slymen, D. (1983) A family study of panic disorder. Archs gen. Psychiat. 40, 1065-1069. CROWE,R. R., PALJLS,D. L., SLYMEN,D. J. and NOYES,R. (1980) A family study of anxiety neurosis. Archs gen. Psychiat. 31, 77-79. EARLS,F. (1980) The prevalence of behavior problems in three-year-old children. Archs gen. Psychiat. 37, 1153-1157. ESSEN-MOLLER, E., LARSSON,H., UDDENBERG,C. E. and WHITE, G. (1965) Individual traits and morbidity in a Swedish rural population. Actu psychiat. neural. stand. Suppl. 100. F~EMMING,K. H. (1951) The Expectation of Mental Infirmity in a Sample of the Danish Population. Occasional papers on Eugenics, No. 7. Cassell, London. GITTEL~~AN-KLEW, R. (1975) Psychiatric characteristics of the relatives of school phobic children. In Mental Health in Children (Edited by SIVA-SANKER,D. V.), pp. 325-334. PJD Publications, New York. GITTELMAN-KLEIN, R. and KLEIN,D. F. (1980) Separation anxiety in school refusal and its treatment with drugs. In Out of School (Edited by HERSOV,L. and BERG, I.), pp. 321-341. John Wiley, New York. HAGNELL,0. (1966) A Prospective Study of the Incidence of Mental Disorder. Svenka Bolfolaget, Norstedts. ABE,

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