- Email: [email protected]
Assortative mating for major affective disorder
Journal of Affecrrve Duorders, Elsevier Biomedical Press
5 (1983) 9- 1I
Assortative Mating for Major Affective Disorder Brent Waters L* Irene Marchenko I,**, Nola Abrams I-***, Donna &ley I,*** and David Kalin * * * * Royal Ottawa Hosprtal, 1145 Carlrng Avenue, Ottawa KIZ 7K4, Ont. (Canada) (Received (Accepted
1 March, 1982) 26 May, 1982)
Summary The families of 26 married bipolar manic depressives were examined in detail. The rate of affective disorder in their spouses, and the parents and siblings of their spouses, was ascertained. The prevalence of affective disorder among the parents and siblings and of the spouses of age- and social class-matched schizophrenics and well controls was also ascertained. Finally, the prevalence of affective and other psychiatric disorders in the adult offspring of the bipolar probands was ascertained and related to the presence or absence of affective disorder in the spouse. We did not find clear evidence of assortative mating for major affective disorder, although dual mating for affective disorder had the expected result of increasing the risk for affective disorder in the adult offspring.
Introduction Complex developmental traits such as intelligence are the product of both genetic and cultural inheritance (Rice et al. 1978). One may expect that these traits would be randomly distributed through the population, and that individuals would mate independent of these traits, that is randomly, as well. This does not appear to be so. There is a strong tendency for assortative mating; for like to marry like. Assortative
This study was supported by Health and Welfare, Canada, of the Royal Ottawa Hospital. * Psychiatrist-m-Carge, Royal Ottawa Hospital. ** Research Assistant, Royal Ottawa Hospital. *** Former Research AssIstants, Royal Ottawa Hospital. ****Family Practitioner, 476 Holland Avenue, Ottawa.
0165-0327/83/OOOt-0000/$03.00
0 1983 Elsevier Biomedical
Grant
Pres
6606-1662-44
and the Research
Fund
IO
mating has also been reported in psychiatric patients (Kreitman 1964; Hagnell and Kreitman 1974). In this paper, we will focus on the question of whether systematic assortative mating has contributed to the transmission of primary or major affective disorder. This is an important issue, as it is known that the risk of concordant illness in the offspring of the dual mating of two schizophrenic or two manic-depressive parents may exceed 50% (Slater and Cowie 1971). Two studies have reported evidence that affective disorder may come from both sides of the families of bipolar patients (Perris 1971; Slater et al. 1971). Subsequently, there have been two record studies suggesting that bipolar patients themselves mate assortatively for manic-depression (Stevens 1969; Fowler and Tsuang 1975). In addition, there are five reports of controlled interview studies of assortative mating for primary or major affective disorder (Gershon et al. 1973, 1975; Dunner et al. 1976; Negri et al. 1979; Baron et al. 1981). In each, the control group consisted of subjects who had no known previous history of psychiatric illness. Gershon et al.‘s (1973) American study, Dunner et al. (1976) and Baron et al. (198 1) found a significantly increased rate of affective disorder among the wives of bipolar men whereas Gershon et al’s (1975) Israeli study and Negri et al. (1979) did not. Only Baron found a higher than expected rate of affective disorder among the husbands of bipolar women (Baron et al. 1981). Only Gershon’s American study found that the wives of bipolar males had a strong family history of affective disorder. Four studies agreed that the husbands of the female BP’s did not have a family history of affective disorder (Gershon et al. 1973, 1975; Dunner 1976; Negri 1979). Finally, it was the most rigorous Israeli study of Gershon et al. (1975) which failed to find any evidence of dual mating for affective disorder. It is also important to note that when there was dual mating of patients with affective disorder, almost all the spouses had a history of unipolar disorder. That is, they met criteria for Major Depressive Disorder. Dual matings of bipolar proband and spouse were extremely rare. None of these five controlled studies have been without limitations. All used psychiatrically well controls approximately, though not always deliberately, matched for age and sex with the probands, but none of the studies attempted to control for socio-economic status. This may have been a significant omission as bipolar manicdepression is concentrated among the socio-economically privileged but schizophrenia, alcoholism and minor depression are most prevalent in more disadvantaged socio-economic groups (Petterson 1977; Weissman and Myers 1978). In addition, the reliability of case ascertainment was also a problem. With the exception of Gershon’s Israeli study, the spouses were not always interviewed so the proband had to be relied upon to provide information on the spouse and the spouses relatives. This necessarily weakens the Family History design, already a less reliable method than the Family Study design (Mendlewicz et al. 1975). Finally, diagnostic criteria were similar but not identical. Though Gershon, Negri and Baron distinguished major depressions from minor depressions, Dunner considered all depressions together. In our study, we have tested for assortative mating for major affective disorder in
I1
the spouses of bipolar patients in three ways. (1) We examine whether major affective disorder occurs at all in the spouses of bipolar patients. Such unions would be dual matrngs for affective disorder. (2) We examine whether the spouses of bipolar patients with any affective disorder (major or minor) have a stronger fumzb history of affective disorder than the spouses without affective disorder, or the spouses of age- and social class-matched schizophrenic and normal controls. We did not compare rates of disorder in the three groups of spouses as numbers were small, however we expected that their extended families would provide larger numbers and permit a valid comparison of family history. (3) We examine whether a personal or family history of affective disorder in the spouses of bipolar patients increased the rate of affectrve disorder m therr udult offspring. We would expect all three tests to be positive if assortative mating for major affective disorder in fact occurs.
Method (1) Selection
of subjects (u) Bipolarprobands: From a large sample of bipolar patients at the Royal Ottawa Hospital, 26 (14 male, 12 female) were selected who met the Research Diagnostic Criteria (RDC) for bipolar illness, had an intact marriage and whose spouse was available also for interview (Spitzer et al. 1978). Sixteen of these couples had 54 adult offspring, 51 of whom were interviewed. Two offspring had suicided and one was not available for interview. Intact marriages were selected as the spouse and offspring were more easily available than if separation and divorce had dispersed and alienated family members. (b) Schizophrenic controls: From the Depot Medication Clinic of the Royal Ottawa Hospital, 15 schizophrenics (7 male, 8 female), aged between 35 and 65 were selected who met the RDC criteria for schizophrenia, had an intact marriage and whose spouse was available also for interview. (c) Non-psychratric controls: From a local family practice serving a predominantly upper-middle class population, 17 (8 male, 9 female) non-psychiatrically ill patients between 35 and 65 years of age were selected who had an intact marriage and whose spouse was available also for interview. (2) Procedure All interviews were conducted by two of the authors (BW, IM). The interviewers were not blind to the control or proband status of the subjects. (a) Bipolar proband families: After obtaining the appropriate signed institutional consent forms, the proband and spouse were interviewed separately about their past and present psychiatric status. We employed the semi-structured Schizophrenia and Affective Disorder Schedule, Life-time version; the SADS-L (Spitzer et al. 1977). To determine the family-history data on their respective parents and siblings, we employed the Family History interview developed by the same group which gener-
12
ates diagnostic data consistent with the SADS-L (Spitzer and Endicott 1977). Personal socio-economic status, and that of family of origin (the job of the subjects’ father when the subject was 15 years old) was determined using the eight point Blishen and McRoberts socio-economic index for occupations (Blishen and McRoberts 1976). The 51 available offspring were also interviewed using the SADS-L, after the appropriate signed institutional consents were obtained. (b)Schizophrenic control families: The schizophrenic and his family were interviewed about their parents and siblings only, using the Family History interview. We did not questzon them about themselves. Socio-economic status of family of origin was determined in the same way as for the bipolar proband families. (c) Non-psychiattw control familres: The same methodology was employed as that for schizophrenic control families. Again, the subjects were only interviewed about parents and siblings but not about themselves.
Results (I) Psychlatrlc illness in spouses of bipolar probands We did not find significant differences in age, present social class, social class of family of origin and size of family of origin between the bipolar probands and their spouses. In terms of psychiatric illness, all 26 probands suffered from bipolar affective disorder. Eighteen of the 26 spouses (69%) met criteria for past or present psychiatric illness. Psychiatric illness was evenly distributed between the sexes and was not clustered amongst the wives of male probands. Of the ill spouses, 12 met the criteria for pure affective disorder (5 Major Depression, 7 Minor Depression), 1 for affective spectrum disorder (Alcoholism) and 5 for other disorders (all were Other Psychiatric Disorder). In 12 of the 18 cases, the spouses’ psychiatric illness appeared by history to have developed after that of the proband, and in 6 cases it developed before. In addition, in every case of Major or Minor Depression in the spouses, precipitating events were described, although such retrospective recall must be suspect. (2) Family hlstory of psychlatrlc illness m spouses, of bipolar probands and controls Forty-one of the parents and siblings of the probands met criteria for psychiatric disorder, as did 25 of the parents and siblings of the spouses. The difference in overall prevalence of psychiatric disorder, which approached significance, could be entirely accounted for by a considerable excess of major pure affective disorder in the parents and siblings of the bipolar probands. Ten were described as Bipolar and 9 as Major Depressive, compared with only 5 Major Depressive subjects among the parents and sibling of the spouses. Six parents and siblings of bipolar probands had Minor Depression compared with only 2 parents and siblings of spouses. Furthermore, when we separated spouses by depressive diagnosis (See Table l), we found that there was a non-significant trend towards a higher rate of pure affective and affective spectrum disorder among the parents and siblings of spouses who had a
13
TABLE FAMILY
1 HISTORY
OF SPOUSES
OF BP PROBANDS Spouse
Parents
and siblings
Pure affectwe
Affectwe
Other
spectrum
Well Ill Bipolar Major Depr. Mmor Depr. Suicide
MLIJO~ Depr.
Spouse Minor Depr.
Spouse Not Depressed
(5)
(7)
(14)
17 5
32 9
54 10
(1)
1 1 _
3 _ _
_ 1 1
Alcohol Drug Ab. Antlsoc.
3
4
4
_
_
_
Schlz. Other dis.
_ _
1 2
_ 3
history of Major Depression (23%) than among the parents and siblings of spouses who had a history of Minor Depression (IS!%), or who were free of a history of depression (11%). To determine whether the lower family history of affective discrders in the spouses nevertheless exceeded that found in the general community, we compared these results with the prevalence of psychiatric disturbance in the parents and siblings of our schizophrenic and normal controls and their respective spouses. For the purpose of our comparisons, we selected from our pool of subjects the 15 BP probands, 15 schizophrenic controls and 15 normal controls who were most closely matched for both age and social class of origin (See Table 2). Looking at the family histories of the six groups, only two comparisons reached statistical significance. First, the rate of pure affective disorder (Bipolar, Major and Minor Depression) among the parents and siblings of the bipolar patients was significantly greater than among the parents and siblings of their spouses (Fisher’s exact test for probability; PC 0.002). Second, the rate of other disorder (Schizophrenia and Other Psychiatric Disorder) was significantly higher among the parents and siblings of the schizophrenic controls compared with any of the other groups (Analysis of variance; F = 4.3, df = 42 and 2, P < 0.05). These are expected, given the evidence for the heritability of PAD and schizophrenia. The prevalence of affective spectrum disorder (either of Alcoholism, Drug Abuse or Antisocial Personality together with depression) was similar for all three groups of spouses. (3) Offspring psychiatric disorder Looking at the sixteen bipolar families where we had interviewed or had information on 53 of the 54 adult offspring, 3 of the spouses had a history of Major
2 **
4
Schu. Other dis.
Other
* PiO.05. ** P <0.002.
1 3
_
I
_
I 6’ 9
5
I
3
12 10
4.8
48.3
Schiz’s spouse
_ _
(1)
(1) I _ _
1 _
_
92 17
4.0
45.5
Schlz. control
2 0
70 13
44
46.3
6 _ _
7 5 _
AND SPOUSES
Bipolar’s spouse
CONTROLS
Alcohol Drug Ab. Antlsoc.
Major Depr. Mmor Depr. Suicide
68 24
4.0
45.5
Bipolar proband
OF BP PROBANDS.
Affective spectrum
affective
Pure
Total well rels. Total 111rels.
Mean family SEC
Bipolar
AND SIBLINGS
Mean age subj.
PARENTS
TABLE 2
2 2
_
4
_
4
(1)
2 1 (1)
_
1
57 I1
53
48.0
Non-psych. spouse
1
71 6
47
46.1
Non-psych control
15 TABLE
3
AFFECTIVE
DISORDER
IN SPOUSES
Total well rels. Total 111rels. Pure affective
Bipolar Major Depr. Mmor Depr. Smclde
Affective spectrum
Alcohol Drug Ab. Antisoc.
Other
Schiz. Other dls.
AND OFFSPRING
OF BIPOLAR
PROBANDS
Spouse Major Depr.
Spouse Minor Depr.
Spouse not depressed
(3)
(3)
(10)
Rels.
Offs.
Rels.
Offs.
Rels.
Offs.
(12)
(12)
(12)
(7)
(50)
(34)
9 3
4 8
10
2
5 2
45 5
16 18
_
4* 3
_ _
_ _
_ _
1 _
5 4 4
_
(1)
_
(I)
_
1
_
3
_ 1
_ _
_ _
1 _
_
_
2 _
1 1 (1) 1
_
_
2
_
_ 4
* P eo.05
Depression and 3 had a history of Minor Depression (See Table 3). It should be noted that although these 16 families were drawn from the same full cohort of 26 bipolar families, only 11 of the families had been among the 15 selected for the controlled study (see section 2 above). When the spouse had suffered .a Major Depression, offspring were significantly more likely to have suffered major pure affective disorder (Bipolar or Major Depression) than if the spouse had suffered a Minor Depression (Fisher’s exact test for probability, PC 0.05) or no depression (x2 = 3.96, P ~0.05).There was no significant difference in the prevalence of Minor Depression or affective spectrum disorders across the three groups of offspring, however if the spouse had not been depressed there was a non-significant trend for disorder in the offspring to have been Other Psychiatric Disorder. Furthermore, there was also a non-significant trend for Major Depressive spouses to have a family history of pure affective disorder, and for non-depressed spouses to have a family history of affective spectrum and other psychiatric disorder.
Discussion We cannot report confirmatory evidence of assortative mating for major affective disorder in this small sample of bipolar manic-depressive patients. First, affective disorder in the spouses of bipolar patients, though major in intensity in some cases,
16
generally developed after the onset of the proband’s illness, and was inevitably recalled as being secondary to life events. Second, among the spouses of bipolar patients, there was a trend for a history of both Major and Minor Depression to be associated with a history of pure affective disorder or affective spectrum disorder in parents and siblings. However, when we controlled for age and social class of family of origin, we were unable to demonstrate a stronger family history of pure affective or affective spectrum disorder in the spouses of bipolar probands than in the spouses of schizophrenic and normal controls, That is, there did not appear to be assortative mating for a family history of affective disorder. Third, having a spouse ill with Major Depression significantly enhanced the risk to major pure affective disorder in the offspring of bipolar patients. These spouses may also have a stronger family history of affective disorder, whereas non-depressed spouses have a stronger family history of affective spectrum and other psychiatric disorder, and their offspring may be more prone to other psychiatric disorder than the offspring of Major or Minor Depressive spouses. Our results confirm that the spouses of bipolar manic depressives are liable to depressions, but they suggest that the depressions are usually precipitated rather than primary. Furthermore, the presence of either a primary or a precipitated Major Depression in the spouses of bipolar manic-depressives may be associated with a stronger family history of affective disorder in only those spouses, and is significantly associated with an increased risk to major affective disorder (Bipolar, Major Depression) in their offspring. However this latter finding is simply a reaffirmation of the phenomenon of dual mating for major affective disorder and its consequences for the offspring are the same as has been reported by others (Slater and Cowie 1971; Fischer 1980; Fischer and Gottesman 1980). The results may have been biased by the selection of intact marriages, however we are not aware of data which suggests that broken marriages of manic depressives show a preponderance of spousal affective disorder. The scanty available data suggest that the marriages of manic-depressives are the same qualitatively as those of the rest of the population (Frank et al. 1981). The sample size in this study is small and we did not do a psychiatric assessment on the controls because of this. However, we believe that the design is sound and that it points the way for larger, methodologically, more sound studies which will provide definitive answers on the as yet unresolved question of assortative mating for major affective disorders.
References Baron, M., Mendlewicz, J., Gruen, R., et al., Assortatlve matmg in affectwe disorders, J. Aff DIS.. 3 (1981) 167-171. Bhshen, B.R. and McRoberts, H.A., A revised socloecononuc mdex for occupations m Canada, Can Rev. Sot. Anthrop., 13 (1976) 71-80. Dunner, D.L., Flelss, J.L., Addonizlo, G., et al., Assortatlve matmg m primary affectwe disorder, Blol. Psychat., 11(1976) 43-51 Fischer, M., Twm studies and dual mating studies m defmmg mama. In: R. Belmaker and H. Van Praag (Eds.), Mama - An Evolving Concept, Spectrum Pubhcatlons, Holhswood, NY, 1980, pp. 43-60.
17 Fischer, M. and Gottesman, I.I., A study of offspring of parents both hospitahzed for psychiatric disorders. In: L.N. Robms, P.J. Clayton and J.W Wmg (Eds.), The Social Consequences of Psychiatric Illness, Brunner-Mazel, New York, 1980, pp. 75-90. Fowler, R.C. and Tsuang, M.T, Spouses of schrzophremcs - A bhnd comparative study, Compr. Psychiat., 16 (1975) 339-342. Frank, E., Targum, S., Gershon, ES., et al., Annual Meetmg, American Psychiatric Association, May 1981. Gershon, E.S., Dunner, D.L., Sturt, L. et al., Assortative mating m the affective disorders, Biol. Psychiat., 7 (1973) 63-74. Gershon, E.S., Mark, A., Cohen, N., et al., Transmitted factors in the morbid risk of affective disorders - A controlled study, J Psychrat. Res., 12 (1975) 283-299. Hagnell, 0. and Krettman, N., Mental illness m married pans m a total population, Brit. J. Psychiat., 125 (1974) 293-302. Kreitman, N., The patients spouse, Brit. J. Psychiat., 110 (1964) 159-173. Mendlewicz, J., Fleiss, J.L., Catlado, M., et al., The accuracy of the family history method m studies of affective illness, Arch Gen. Psychiat., 32 (1975) 309-314. Negro, F., Melica, A.M., Zuliam, R , et al., Assortative mating and affective disorders, J. Affect, Dis., I (1979) 247-253. Perris, C., Abnormahty on paternal and maternal sides - Observation in bipolar (mamc-depressive) and umpolar depressive psychoses, Brit. J. Psychiat., 118 ( 197 1) 207-2 10. Petterson, U., Manic-depressive illness - Investigation of social factors, Acta Psychiat. Stand., Suppl. 269 (1977) 43-54. Rice, J., Clonmger, CR. and Reich, T., Multifactorial inheritance with cultural transmission and assortative mating, Part 1 (Descriptive and basic properties of the unitary models), Amer. J. Hum. Genet., 30 (1978) 618-643. Slater, E. and Cowie, V., The Genetics of Mental Drsorders, Oxford University Press, London, 1971. Slater, E., Maxwell, J. and Price, I.S., Distribution of ancestral secondary cases in bipolar affective disorders, Brit. J. Psychiat , 118 (1971) 215-218. Spitzer, R.L. and Endicott, J , Family History - Research Diagnostic Criteria, Biometrics Research, New York, 1977. Spitzer, R.L., Endicott. J. and Robins, E., Schizophrenia and affective disorders schedule, life-time version, Biometrics Research, New York, 1977. Spitzer, R.L., Endicott, J. and Robins, E., Research diagnostic criteria - Rationale and reliabrhty, Arch. Gen. Psychiat., 35 (1978) 773-782. Stevens, B.C., Marriage and Fertility of Women Suffering from Schizophrenia or Affective Disorders (Institute of Psychiatry, Maudsley Monograph No. 19). Oxford Umversity Press, London, 1969. Weissman, M.M. and Myers, J.K., Affective disorders m a U.S. urban commumty, Arch. Gen. Psychiat., 35 (1978) 1304-1311.
5 (1983) 9- 1I
Assortative Mating for Major Affective Disorder Brent Waters L* Irene Marchenko I,**, Nola Abrams I-***, Donna &ley I,*** and David Kalin * * * * Royal Ottawa Hosprtal, 1145 Carlrng Avenue, Ottawa KIZ 7K4, Ont. (Canada) (Received (Accepted
1 March, 1982) 26 May, 1982)
Summary The families of 26 married bipolar manic depressives were examined in detail. The rate of affective disorder in their spouses, and the parents and siblings of their spouses, was ascertained. The prevalence of affective disorder among the parents and siblings and of the spouses of age- and social class-matched schizophrenics and well controls was also ascertained. Finally, the prevalence of affective and other psychiatric disorders in the adult offspring of the bipolar probands was ascertained and related to the presence or absence of affective disorder in the spouse. We did not find clear evidence of assortative mating for major affective disorder, although dual mating for affective disorder had the expected result of increasing the risk for affective disorder in the adult offspring.
Introduction Complex developmental traits such as intelligence are the product of both genetic and cultural inheritance (Rice et al. 1978). One may expect that these traits would be randomly distributed through the population, and that individuals would mate independent of these traits, that is randomly, as well. This does not appear to be so. There is a strong tendency for assortative mating; for like to marry like. Assortative
This study was supported by Health and Welfare, Canada, of the Royal Ottawa Hospital. * Psychiatrist-m-Carge, Royal Ottawa Hospital. ** Research Assistant, Royal Ottawa Hospital. *** Former Research AssIstants, Royal Ottawa Hospital. ****Family Practitioner, 476 Holland Avenue, Ottawa.
0165-0327/83/OOOt-0000/$03.00
0 1983 Elsevier Biomedical
Grant
Pres
6606-1662-44
and the Research
Fund
IO
mating has also been reported in psychiatric patients (Kreitman 1964; Hagnell and Kreitman 1974). In this paper, we will focus on the question of whether systematic assortative mating has contributed to the transmission of primary or major affective disorder. This is an important issue, as it is known that the risk of concordant illness in the offspring of the dual mating of two schizophrenic or two manic-depressive parents may exceed 50% (Slater and Cowie 1971). Two studies have reported evidence that affective disorder may come from both sides of the families of bipolar patients (Perris 1971; Slater et al. 1971). Subsequently, there have been two record studies suggesting that bipolar patients themselves mate assortatively for manic-depression (Stevens 1969; Fowler and Tsuang 1975). In addition, there are five reports of controlled interview studies of assortative mating for primary or major affective disorder (Gershon et al. 1973, 1975; Dunner et al. 1976; Negri et al. 1979; Baron et al. 1981). In each, the control group consisted of subjects who had no known previous history of psychiatric illness. Gershon et al.‘s (1973) American study, Dunner et al. (1976) and Baron et al. (198 1) found a significantly increased rate of affective disorder among the wives of bipolar men whereas Gershon et al’s (1975) Israeli study and Negri et al. (1979) did not. Only Baron found a higher than expected rate of affective disorder among the husbands of bipolar women (Baron et al. 1981). Only Gershon’s American study found that the wives of bipolar males had a strong family history of affective disorder. Four studies agreed that the husbands of the female BP’s did not have a family history of affective disorder (Gershon et al. 1973, 1975; Dunner 1976; Negri 1979). Finally, it was the most rigorous Israeli study of Gershon et al. (1975) which failed to find any evidence of dual mating for affective disorder. It is also important to note that when there was dual mating of patients with affective disorder, almost all the spouses had a history of unipolar disorder. That is, they met criteria for Major Depressive Disorder. Dual matings of bipolar proband and spouse were extremely rare. None of these five controlled studies have been without limitations. All used psychiatrically well controls approximately, though not always deliberately, matched for age and sex with the probands, but none of the studies attempted to control for socio-economic status. This may have been a significant omission as bipolar manicdepression is concentrated among the socio-economically privileged but schizophrenia, alcoholism and minor depression are most prevalent in more disadvantaged socio-economic groups (Petterson 1977; Weissman and Myers 1978). In addition, the reliability of case ascertainment was also a problem. With the exception of Gershon’s Israeli study, the spouses were not always interviewed so the proband had to be relied upon to provide information on the spouse and the spouses relatives. This necessarily weakens the Family History design, already a less reliable method than the Family Study design (Mendlewicz et al. 1975). Finally, diagnostic criteria were similar but not identical. Though Gershon, Negri and Baron distinguished major depressions from minor depressions, Dunner considered all depressions together. In our study, we have tested for assortative mating for major affective disorder in
I1
the spouses of bipolar patients in three ways. (1) We examine whether major affective disorder occurs at all in the spouses of bipolar patients. Such unions would be dual matrngs for affective disorder. (2) We examine whether the spouses of bipolar patients with any affective disorder (major or minor) have a stronger fumzb history of affective disorder than the spouses without affective disorder, or the spouses of age- and social class-matched schizophrenic and normal controls. We did not compare rates of disorder in the three groups of spouses as numbers were small, however we expected that their extended families would provide larger numbers and permit a valid comparison of family history. (3) We examine whether a personal or family history of affective disorder in the spouses of bipolar patients increased the rate of affectrve disorder m therr udult offspring. We would expect all three tests to be positive if assortative mating for major affective disorder in fact occurs.
Method (1) Selection
of subjects (u) Bipolarprobands: From a large sample of bipolar patients at the Royal Ottawa Hospital, 26 (14 male, 12 female) were selected who met the Research Diagnostic Criteria (RDC) for bipolar illness, had an intact marriage and whose spouse was available also for interview (Spitzer et al. 1978). Sixteen of these couples had 54 adult offspring, 51 of whom were interviewed. Two offspring had suicided and one was not available for interview. Intact marriages were selected as the spouse and offspring were more easily available than if separation and divorce had dispersed and alienated family members. (b) Schizophrenic controls: From the Depot Medication Clinic of the Royal Ottawa Hospital, 15 schizophrenics (7 male, 8 female), aged between 35 and 65 were selected who met the RDC criteria for schizophrenia, had an intact marriage and whose spouse was available also for interview. (c) Non-psychratric controls: From a local family practice serving a predominantly upper-middle class population, 17 (8 male, 9 female) non-psychiatrically ill patients between 35 and 65 years of age were selected who had an intact marriage and whose spouse was available also for interview. (2) Procedure All interviews were conducted by two of the authors (BW, IM). The interviewers were not blind to the control or proband status of the subjects. (a) Bipolar proband families: After obtaining the appropriate signed institutional consent forms, the proband and spouse were interviewed separately about their past and present psychiatric status. We employed the semi-structured Schizophrenia and Affective Disorder Schedule, Life-time version; the SADS-L (Spitzer et al. 1977). To determine the family-history data on their respective parents and siblings, we employed the Family History interview developed by the same group which gener-
12
ates diagnostic data consistent with the SADS-L (Spitzer and Endicott 1977). Personal socio-economic status, and that of family of origin (the job of the subjects’ father when the subject was 15 years old) was determined using the eight point Blishen and McRoberts socio-economic index for occupations (Blishen and McRoberts 1976). The 51 available offspring were also interviewed using the SADS-L, after the appropriate signed institutional consents were obtained. (b)Schizophrenic control families: The schizophrenic and his family were interviewed about their parents and siblings only, using the Family History interview. We did not questzon them about themselves. Socio-economic status of family of origin was determined in the same way as for the bipolar proband families. (c) Non-psychiattw control familres: The same methodology was employed as that for schizophrenic control families. Again, the subjects were only interviewed about parents and siblings but not about themselves.
Results (I) Psychlatrlc illness in spouses of bipolar probands We did not find significant differences in age, present social class, social class of family of origin and size of family of origin between the bipolar probands and their spouses. In terms of psychiatric illness, all 26 probands suffered from bipolar affective disorder. Eighteen of the 26 spouses (69%) met criteria for past or present psychiatric illness. Psychiatric illness was evenly distributed between the sexes and was not clustered amongst the wives of male probands. Of the ill spouses, 12 met the criteria for pure affective disorder (5 Major Depression, 7 Minor Depression), 1 for affective spectrum disorder (Alcoholism) and 5 for other disorders (all were Other Psychiatric Disorder). In 12 of the 18 cases, the spouses’ psychiatric illness appeared by history to have developed after that of the proband, and in 6 cases it developed before. In addition, in every case of Major or Minor Depression in the spouses, precipitating events were described, although such retrospective recall must be suspect. (2) Family hlstory of psychlatrlc illness m spouses, of bipolar probands and controls Forty-one of the parents and siblings of the probands met criteria for psychiatric disorder, as did 25 of the parents and siblings of the spouses. The difference in overall prevalence of psychiatric disorder, which approached significance, could be entirely accounted for by a considerable excess of major pure affective disorder in the parents and siblings of the bipolar probands. Ten were described as Bipolar and 9 as Major Depressive, compared with only 5 Major Depressive subjects among the parents and sibling of the spouses. Six parents and siblings of bipolar probands had Minor Depression compared with only 2 parents and siblings of spouses. Furthermore, when we separated spouses by depressive diagnosis (See Table l), we found that there was a non-significant trend towards a higher rate of pure affective and affective spectrum disorder among the parents and siblings of spouses who had a
13
TABLE FAMILY
1 HISTORY
OF SPOUSES
OF BP PROBANDS Spouse
Parents
and siblings
Pure affectwe
Affectwe
Other
spectrum
Well Ill Bipolar Major Depr. Mmor Depr. Suicide
MLIJO~ Depr.
Spouse Minor Depr.
Spouse Not Depressed
(5)
(7)
(14)
17 5
32 9
54 10
(1)
1 1 _
3 _ _
_ 1 1
Alcohol Drug Ab. Antlsoc.
3
4
4
_
_
_
Schlz. Other dis.
_ _
1 2
_ 3
history of Major Depression (23%) than among the parents and siblings of spouses who had a history of Minor Depression (IS!%), or who were free of a history of depression (11%). To determine whether the lower family history of affective discrders in the spouses nevertheless exceeded that found in the general community, we compared these results with the prevalence of psychiatric disturbance in the parents and siblings of our schizophrenic and normal controls and their respective spouses. For the purpose of our comparisons, we selected from our pool of subjects the 15 BP probands, 15 schizophrenic controls and 15 normal controls who were most closely matched for both age and social class of origin (See Table 2). Looking at the family histories of the six groups, only two comparisons reached statistical significance. First, the rate of pure affective disorder (Bipolar, Major and Minor Depression) among the parents and siblings of the bipolar patients was significantly greater than among the parents and siblings of their spouses (Fisher’s exact test for probability; PC 0.002). Second, the rate of other disorder (Schizophrenia and Other Psychiatric Disorder) was significantly higher among the parents and siblings of the schizophrenic controls compared with any of the other groups (Analysis of variance; F = 4.3, df = 42 and 2, P < 0.05). These are expected, given the evidence for the heritability of PAD and schizophrenia. The prevalence of affective spectrum disorder (either of Alcoholism, Drug Abuse or Antisocial Personality together with depression) was similar for all three groups of spouses. (3) Offspring psychiatric disorder Looking at the sixteen bipolar families where we had interviewed or had information on 53 of the 54 adult offspring, 3 of the spouses had a history of Major
2 **
4
Schu. Other dis.
Other
* PiO.05. ** P <0.002.
1 3
_
I
_
I 6’ 9
5
I
3
12 10
4.8
48.3
Schiz’s spouse
_ _
(1)
(1) I _ _
1 _
_
92 17
4.0
45.5
Schlz. control
2 0
70 13
44
46.3
6 _ _
7 5 _
AND SPOUSES
Bipolar’s spouse
CONTROLS
Alcohol Drug Ab. Antlsoc.
Major Depr. Mmor Depr. Suicide
68 24
4.0
45.5
Bipolar proband
OF BP PROBANDS.
Affective spectrum
affective
Pure
Total well rels. Total 111rels.
Mean family SEC
Bipolar
AND SIBLINGS
Mean age subj.
PARENTS
TABLE 2
2 2
_
4
_
4
(1)
2 1 (1)
_
1
57 I1
53
48.0
Non-psych. spouse
1
71 6
47
46.1
Non-psych control
15 TABLE
3
AFFECTIVE
DISORDER
IN SPOUSES
Total well rels. Total 111rels. Pure affective
Bipolar Major Depr. Mmor Depr. Smclde
Affective spectrum
Alcohol Drug Ab. Antisoc.
Other
Schiz. Other dls.
AND OFFSPRING
OF BIPOLAR
PROBANDS
Spouse Major Depr.
Spouse Minor Depr.
Spouse not depressed
(3)
(3)
(10)
Rels.
Offs.
Rels.
Offs.
Rels.
Offs.
(12)
(12)
(12)
(7)
(50)
(34)
9 3
4 8
10
2
5 2
45 5
16 18
_
4* 3
_ _
_ _
_ _
1 _
5 4 4
_
(1)
_
(I)
_
1
_
3
_ 1
_ _
_ _
1 _
_
_
2 _
1 1 (1) 1
_
_
2
_
_ 4
* P eo.05
Depression and 3 had a history of Minor Depression (See Table 3). It should be noted that although these 16 families were drawn from the same full cohort of 26 bipolar families, only 11 of the families had been among the 15 selected for the controlled study (see section 2 above). When the spouse had suffered .a Major Depression, offspring were significantly more likely to have suffered major pure affective disorder (Bipolar or Major Depression) than if the spouse had suffered a Minor Depression (Fisher’s exact test for probability, PC 0.05) or no depression (x2 = 3.96, P ~0.05).There was no significant difference in the prevalence of Minor Depression or affective spectrum disorders across the three groups of offspring, however if the spouse had not been depressed there was a non-significant trend for disorder in the offspring to have been Other Psychiatric Disorder. Furthermore, there was also a non-significant trend for Major Depressive spouses to have a family history of pure affective disorder, and for non-depressed spouses to have a family history of affective spectrum and other psychiatric disorder.
Discussion We cannot report confirmatory evidence of assortative mating for major affective disorder in this small sample of bipolar manic-depressive patients. First, affective disorder in the spouses of bipolar patients, though major in intensity in some cases,
16
generally developed after the onset of the proband’s illness, and was inevitably recalled as being secondary to life events. Second, among the spouses of bipolar patients, there was a trend for a history of both Major and Minor Depression to be associated with a history of pure affective disorder or affective spectrum disorder in parents and siblings. However, when we controlled for age and social class of family of origin, we were unable to demonstrate a stronger family history of pure affective or affective spectrum disorder in the spouses of bipolar probands than in the spouses of schizophrenic and normal controls, That is, there did not appear to be assortative mating for a family history of affective disorder. Third, having a spouse ill with Major Depression significantly enhanced the risk to major pure affective disorder in the offspring of bipolar patients. These spouses may also have a stronger family history of affective disorder, whereas non-depressed spouses have a stronger family history of affective spectrum and other psychiatric disorder, and their offspring may be more prone to other psychiatric disorder than the offspring of Major or Minor Depressive spouses. Our results confirm that the spouses of bipolar manic depressives are liable to depressions, but they suggest that the depressions are usually precipitated rather than primary. Furthermore, the presence of either a primary or a precipitated Major Depression in the spouses of bipolar manic-depressives may be associated with a stronger family history of affective disorder in only those spouses, and is significantly associated with an increased risk to major affective disorder (Bipolar, Major Depression) in their offspring. However this latter finding is simply a reaffirmation of the phenomenon of dual mating for major affective disorder and its consequences for the offspring are the same as has been reported by others (Slater and Cowie 1971; Fischer 1980; Fischer and Gottesman 1980). The results may have been biased by the selection of intact marriages, however we are not aware of data which suggests that broken marriages of manic depressives show a preponderance of spousal affective disorder. The scanty available data suggest that the marriages of manic-depressives are the same qualitatively as those of the rest of the population (Frank et al. 1981). The sample size in this study is small and we did not do a psychiatric assessment on the controls because of this. However, we believe that the design is sound and that it points the way for larger, methodologically, more sound studies which will provide definitive answers on the as yet unresolved question of assortative mating for major affective disorders.
References Baron, M., Mendlewicz, J., Gruen, R., et al., Assortatlve matmg in affectwe disorders, J. Aff DIS.. 3 (1981) 167-171. Bhshen, B.R. and McRoberts, H.A., A revised socloecononuc mdex for occupations m Canada, Can Rev. Sot. Anthrop., 13 (1976) 71-80. Dunner, D.L., Flelss, J.L., Addonizlo, G., et al., Assortatlve matmg m primary affectwe disorder, Blol. Psychat., 11(1976) 43-51 Fischer, M., Twm studies and dual mating studies m defmmg mama. In: R. Belmaker and H. Van Praag (Eds.), Mama - An Evolving Concept, Spectrum Pubhcatlons, Holhswood, NY, 1980, pp. 43-60.
17 Fischer, M. and Gottesman, I.I., A study of offspring of parents both hospitahzed for psychiatric disorders. In: L.N. Robms, P.J. Clayton and J.W Wmg (Eds.), The Social Consequences of Psychiatric Illness, Brunner-Mazel, New York, 1980, pp. 75-90. Fowler, R.C. and Tsuang, M.T, Spouses of schrzophremcs - A bhnd comparative study, Compr. Psychiat., 16 (1975) 339-342. Frank, E., Targum, S., Gershon, ES., et al., Annual Meetmg, American Psychiatric Association, May 1981. Gershon, E.S., Dunner, D.L., Sturt, L. et al., Assortative mating m the affective disorders, Biol. Psychiat., 7 (1973) 63-74. Gershon, E.S., Mark, A., Cohen, N., et al., Transmitted factors in the morbid risk of affective disorders - A controlled study, J Psychrat. Res., 12 (1975) 283-299. Hagnell, 0. and Krettman, N., Mental illness m married pans m a total population, Brit. J. Psychiat., 125 (1974) 293-302. Kreitman, N., The patients spouse, Brit. J. Psychiat., 110 (1964) 159-173. Mendlewicz, J., Fleiss, J.L., Catlado, M., et al., The accuracy of the family history method m studies of affective illness, Arch Gen. Psychiat., 32 (1975) 309-314. Negro, F., Melica, A.M., Zuliam, R , et al., Assortative mating and affective disorders, J. Affect, Dis., I (1979) 247-253. Perris, C., Abnormahty on paternal and maternal sides - Observation in bipolar (mamc-depressive) and umpolar depressive psychoses, Brit. J. Psychiat., 118 ( 197 1) 207-2 10. Petterson, U., Manic-depressive illness - Investigation of social factors, Acta Psychiat. Stand., Suppl. 269 (1977) 43-54. Rice, J., Clonmger, CR. and Reich, T., Multifactorial inheritance with cultural transmission and assortative mating, Part 1 (Descriptive and basic properties of the unitary models), Amer. J. Hum. Genet., 30 (1978) 618-643. Slater, E. and Cowie, V., The Genetics of Mental Drsorders, Oxford University Press, London, 1971. Slater, E., Maxwell, J. and Price, I.S., Distribution of ancestral secondary cases in bipolar affective disorders, Brit. J. Psychiat , 118 (1971) 215-218. Spitzer, R.L. and Endicott, J , Family History - Research Diagnostic Criteria, Biometrics Research, New York, 1977. Spitzer, R.L., Endicott. J. and Robins, E., Schizophrenia and affective disorders schedule, life-time version, Biometrics Research, New York, 1977. Spitzer, R.L., Endicott, J. and Robins, E., Research diagnostic criteria - Rationale and reliabrhty, Arch. Gen. Psychiat., 35 (1978) 773-782. Stevens, B.C., Marriage and Fertility of Women Suffering from Schizophrenia or Affective Disorders (Institute of Psychiatry, Maudsley Monograph No. 19). Oxford Umversity Press, London, 1969. Weissman, M.M. and Myers, J.K., Affective disorders m a U.S. urban commumty, Arch. Gen. Psychiat., 35 (1978) 1304-1311.