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Psychiatry Research 66 (1997) 69-71

Brief report

Panic attacks: a twin study

Giampaolo Perna, Daniela Caldirola, Cinzia Arancio, Laura Bellodi”

Artier)? Disorderrv Chical and Research Unit, Depcmnent of h%urop.sychiatric Sciences, Ixtitulo ScienfiJico H. Snn Raffaele. Uniuer.Gly of Milm, ~7~7 Prirletll 2% Mihn 201-77, It&

Received 27 November 1995; rev&d 22 July 1996; accepted I Octohcr 1996

Abstract

The role of genetic factors in panic disorder (PD) and sporadic panic attacks (SPAS) was investigated. A total of 120 twins recruited from the general population were interviewed for the presence of anxiety disorders and SPAS. A significantly higher concordance among MZ than DZ twins was found for PD (73 5% vs. 0%) but not for SPAS (57%

vs. 43%). These results confirm a significant role of genetic factors in PD but suggest that genetic factors might not be crucial for the development of SPAS. 0 1997 Elscvier Science Ireland Ltd. All rights reserved

Keywords: Panic disorder; Panic attacks; Genetic; Twins

1. Introduction

The existence of a strong familial loading for PD has been repeatedly reported (Weissman, 1993) and some studies suggest that subjects with SPAS who do not meet DSM criteria for PD share many demographic, clinical and epidemiological characteristics with panic patients (Norton et al., 1985) and react like panic patients to provoking

*Corresponding author. Tel: ~39 2 26433315; fax: +39 2

26433265.

procedures (Perna et al., 1995). Noyes et al. (1986) reported a higher prevalence of subjects with SPAS in families of panic patients than in families of patients with generalized anxiety disorder and we reported a prevalence of PD in the families of subjects with SPAS similar to the one found in PD patients and higher than that in families of healthy controls (Perna et al., 1995). These data suggest that subjects with panic attacks, whether or not they subsequently develop the full-fledged dis- order, might share at least some aspects of the same familial vulnerability with patients with PD.

Although family studies support the familiality of PD and suggest a common familial vulnerabil-

0165.1781/97/$17.00 0 1997 Elsevier Science Ireland Ltd. All rights reserved

PI/ SO1 65- 1751(96)02950-02

70 G. Perna et al. /Psychiatry Research 66 (1997) 69-71

ity to PD and SPAS, twin studies may clarify the relative contributions of genetic and environmen-

tal factors. A higher concordance for PD and/or SPAS in MZ than in DZ twins might be con- sidered to be evidence of the importance of ge-

netic factors. Some twin studies examined panic attacks in the context of the genetics of neurosis (McKinnon et al., 1990; Andrews et al., 1990), but only a few studies discussed panic attacks in the context of DSM criteria. These studies showed a

higher concordance rate in MZ than DZ twins for

PD and/or agoraphobia with panic attacks (Torgersen, 1983; Skre et al., 1993; Kendler et al.,

1993). We investigated the genetic background of PD

and SPAS comparing the twin concordance rate for PD and SPAS in a sample of same-sexed twins

obtained from the Italian general population.

2. Methods

A total of 155 same-sex pairs of twins, ran- domly taken from the Register-Office List of Twins covering all twin births in Milan from 1957 to 1974, were personally contacted by telephone and they were asked ‘to participate in a study of the role of genetic factors in anxiety disorders’. Sixty (39%),pairs accepted. Our sample included 34 pairs of DZ and 26 pairs of MZ twins. De- termination of the twins’ zygosity was made by a questionnaire that has been reported to predict zygosity correctly in 95% of cases, when com- pared with results obtained by blood analysis of genetic markers (Torgersen, 1979, 1983).

Two experienced psychiatrists, blind to the di- agnostic assessment of the co-twin, examined the presence of a lifetime history of PD or SPAS according to DSM IV diagnostic criteria, using a non-structured clinical interview. The overall agreement of the two raters for the presence or

absence of PD and SPAS previously assessed on a sample of 72 subjects from the general population showed a Cohen’s K coefficient of, respectively, 1.00 and 0.95.

Data were analyzed by Student f-tests, chi- square analyses and Fisher’s exact tests. To ana- lyze concordance rate between MZ and DZ pairs of twins, the ‘proband-wise’ method was applied

Table 1

Panic disorder and lifetime history of sporadic panic attacks in

pairs of MZ (n = 26) and DZ (n = 34)

Monozygotic Dizygotlc

pairs of twins pail-s of twins

Without panic attacks 15 18

Concordant for PD 4 0

Discordant for PD 2 5

Concordant for SPAS 2 3

Discordant for SPAS 2 7

Partly concordant (PD - SPAS) I 1

and rates compared calculating z-scores for dif-

ferences between concordance rates.

3. Results

There were no statistical differences for age (mean ages; MZ: 27.9 &- 4.9 years, DZ: 29.5 i 4.9 years), educational level (MZ: 14.4 _+ 3.2 years; DZ: 13.6 f 2.9 years) or sex distribution (MZ: 6 male pairs and 20 female pairs; DZ: 11 male pairs and 23 female pairs) between MZ and DZ twins.

Of the 120 twins examined, 17 (14.1%) were

assigned a diagnosis of PD, 12 (71%) also with agoraphobia and 21 (18%) had lifetime histories positive for SPAS, never satisfying DSM IV crite- ria for PD. There were no statistically significant differences for mean ages between twins with PD and twins with SPAS. In 7 pairs of MZ twins and in 6 pairs of DZ twins, at least one of the twins was assigned a diagnosis of PD. In 5 pairs of MZ twins and 11 pairs of DZ twins, at least one of the twins experienced SPAS.

Table 1 reports PD and SPAS in MZ and DZ twins.

Looking at PD, among MZ pairs, 4 were con- cordant and 3 discordant, while among DZ pairs, none were concordant and 6 discordant.

Proband-wise concordance rates for PD were sig- nificantly higher (Fisher’s exact test, one-tailed: P = 0.007; test of the difference between two pro- portions: z = 2.4, P < 0.018; 95% confidence in- terval for the difference: 0.233-1.227) in MZ pairs (8/11, 73%) th an in DZ pairs (O/6, 0%). For SPAS, 2 MZ pairs were concordant and 3 discor- dant, while among DZ pairs, 3 were concordant

G. Perna el al. /Psychiatry Research 66 (1997) 69-71 71

and 7 discordant. The concordance rate in MZ pairs was 57% while in DZ pairs, it was 43%. In 1

MZ and 1 DZ pair, a twin was diagnosed as having PD while the co-twin had a positive lifetime

history of SPAS.

4. Discussion

The results of this study might be considered preliminary, since the sample of twins examined was not very large. The higher than expected prevalence of PD (14.1%) reported for general

populations (Weissman, 1993) might be the result of the way subjects were recruited which probably

made subjects who had anxiety diseases more interested in participation in the study. However,

the prevalence of sporadic panic attacks was simi- lar to the prevalence reported for general popula- tions (Norton et al., 1985; Weissman, 1993).

Our results support a significant role of genetic factors in PD since the differences between MZ (73%) and DZ (0%) concordances are in line with the results obtained by previous studies (Torger- sen, 1983; Skre et al., 1993). In these studies, MZ concordance ranged between 31% and 42% while DZ concordance ranged between 0% and 17%. Concordance for SPAS was only slightly higher in MZ (57%) than in DZ twins (43%), thus suggest- ing that genetic factors might not play a crucial

role for the development of SPAS. It could be speculated that the recurrence of panic attacks, able to induce the development of PD, might be the expression of abnormal pathogenetic mecha- nisms mainly related to an underlying genetic vulnerability while sporadic panic attacks might be more heterogeneous entities which might in- clude both panic attacks related to a genetic predisposition and panic attacks induced by envi- ronmental/cognitive factors, not able to prime a complete disorder.

Some limitations must be recognized. The rela- tively small size of our sample makes a type 1 error possible and, since the collection of retro-

spective information relies on the probands’ me-

mories, we cannot exclude that some of the sub- jects with SPAS may have been, in fact, ‘hidden’ PD patients in the past, or may develop a full-

fledged PD in the future. In addition, diagnoses were made by unstructured interviews and were limited to a single anxiety disorder which may

give an incomplete picture. Finally, twins who were concordant for anxiety disorders may have selectively volunteered for the study.

In conclusion, our findings confirm a relevant role of genetic factors in PD but suggest that

genetic factors might not be decisive for the de- velopment of SPAS.

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