Interaction between genetic vulnerability and familv environment: the Finnish adoptive family study of schizophrenia J
Tienari P. Interaction between genetic vulnerability and family environment: the Finnish adoptive family study of schizophrenia. Acta Psychiatr Scand 1991: 84: 460-465. A nationwide Finnish sample of schizophrenics’ offspring given up for adoption was compared blindly with matched controls, that is, adopted-away offspring of nonschizophrenic biologic parents. The adoptive families were investigated thoroughly by joint and individual interviews and psychologic tests. Biologic parents were also interviewed and tested. Among the 144 index and 178 control offspring, the percentage of both psychoses and other severe diagnoses (borderline syndrome and severe personality disorder) was significantly higher in the index adoptees than in the matched control adoptees. Of the 15 psychotic adoptees in the total sample to date, 13 are offspring of schizophrenics and 2 are control offspring. Both global clinical ratings and test data for the adoptive, rearing parents also correlate with the symptomatic status of the adoptees. A prospective, longitudinal study of adoptees at risk is being undertaken to explore the direction of effects between adoptees and adoptive parents.
A major goal in the Finnish adoptive family study is to evaluate both genetic and family-rearing contributions to schizophrenia and other psychopathology. We are interested in assessing to what extent genetic variables and family relationship variables jointly contribute to psychopathology of the adoptees. We would like to elucidate whether the genetic risk may be counteracted, and resilience promoted, by a healthy, possibly protective, family environment. We also would like to know whether the direction of effects between genetic and family environment factors can be clarified through a prospective, longitudinal study of adoptees at risk. Material and methods Selection of index cases
A nationwide sample was collected of all the women in Finland who have been hospitalized because of schizophrenia. The sample includes both the inpatient population on January 1, 1960 and later consecutive admissions for schizophrenia through 1979, making a total of 19,447 schizophrenic women. Information supplied by local civil and parish popu-
* In collaboration with Mikko Naarala, Anneli Sorri, Juha Moring, Ilpo Lahti, Kristian Laksy, Merja Kaleva, Karl-Erik Wahlberg, Pirjo Keskitalo, Helja Anias-Tanner, Pekka Koistinen, Taneli Tarvainen and Tuula Ronkko (University of Oulu, Finland) and Lyman C. Wynne (University of Rochester, USA). 460
P. Tienari * Department of Psychiatry, University of Oulu, Finland
Key words: schizophrenia; adoption; genetics: family environment
P. Tienari, University of Oulu, Department of Psychiatry, SF-902 1 0 Oulu, Finland Accepted for publication June 1, 199 1
lation registers showed which of these women had babies and gave them up for adoption. Through these registers, it was found that 264 of these mothers had given up 291 offspring for adoption. Of these offspring, 94 were excluded from the field study for various reasons, especially being adopted by a relative, adopted abroad or adopted after the age of 4 years. During the field work, 18 more cases were excluded, including 7 biologic mothers whose personal interview did not confirm the diagnosis of schizophrenia. A total of 179 offspring of 164 index schizophrenic women comprised the final sample of index cases. These children were adopted-away offspring of schizophrenic mothers and had been placed in adoptive families with Finnish nonrelatives during their first 4 years of life. The index cases were initially identified by a hospital diagnosis of schizophrenia (or paranoid psychosis) for the biologic, adopting-away mother. Paranoid psychoses were included because we expected that the boundaries between schizophrenia and paranoid psychosis would be unclear and would be checked later. Two experienced psychiatrists reviewed the records to confirm the diagnosis of schizophrenia by using the diagnostic criteria that are traditional in Finland (and correspond closely to Langfeldt’s criteria). Two additional raters applied the Research Diagnostic Criteria (RDC) to the hos-
Genes and family in schizophrenia
pita1 records of the biologic mothers. The biologic index mothers have been personally interviewed and tested when possible and, to date, 118 have been interviewed. These psychiatric interviews include a modified Present State Examination (with added items that facilitate DSM-111-R and RDC diagnoses), a 10-card Rorschach, Minnesota Multiphasic Personality Inventory (MMPI) and information on the biologic fathers. In as much detail as possible, data also are obtained on the psychiatric hospitalizations, symptoms, and personal characteristics of the biologic relatives of both the biologic and control parents, including formal diagnoses and information on personal eccentricities, patterns of adjustment and major somatic illnesses. We also interviewed all available biologic index fathers and biologic control parents to evaluate whether the psychiatric diagnoses of the biologic fathers add to the risk of the offspring. All the interviews and tests were tape-recorded. This makes it possible to carry out blind ratings, reliability checks and reclassifications by other investigators in the phase of the project that is now underway. Selection of matched controls
These index offspring and their adoptive families have been blindly compared with matched controls, that is, adoptive families with adopted-away offspring of biologic parents who have not been hospitalized because of psychosis. Pairwise matching was done outside our department by persons who were given the criteria and who independently carried out the case-by-case matching. The criteria for matching the control and index cases are described elsewhere (1). Biologic control parents were excluded only if they have been treated for psychosis. Hence, some of the biologic parents in the control series have received psychiatric help for reasons other than psychosis. The adoptive index and control series were numbered randomly so that the 4 psychiatrists conducting the personal interviews were blind as to whether the case in question was an index or a control family. Assessment of adoptive families and individuals
The adoptive index and control families were investigated in their homes directly and intensively with procedures that usually take 2 d (14-16 h). The family relationships are studied through family and couple interviews, as well as the consensus Rorschach (2) and the interpersonal perception method (3). Both of the adoptive parents and the offspring are individually interviewed to assess their current psychiatric status and past history. Individual Ror-
schachs were given after the consensus Rorschach. In the adoptive families, the MMPI was given only to the adoptive offspring (4). When the collection of data from the adoptive families was begun in 1977, a classification system was used that provided the basis for the present, preliminary data analysis. A 6-point scale for the severity of illness was combined with qualitative diagnoses, collapsed into 4 diagnostic levels for this report. Level 6 (psychosis) includes schizophrenia, paranoid psychosis and affective psychoses; these Finnish diagnoses appear to be similar to those in DSM-111-R. Level 5 (borderline syndrome) and level 4 (severe personality disorders) are combined in Tables 1-5 of this report. Further specification will be carried out with the DSM-111-R criteria. Levels 4 and 5 together presumptively include the schizotypal and paranoid personality disorders diagnosed with criteria similar to those of DSM-111-R, as well as what used to be called latent schizophrenia and pseudoneurotic schizophrenia. Additionally, and to be sorted out in future rediagnosis, these levels include borderline and narcissistic personality disorders and some cases of severely dysfunctional, egosyntonic character disorders. Level 3 (neurosis) includes the disorders with moderate and mild symptoms as well as the less severe personality disorders. Levels 1 and 2 (no diagnosis) are combined and include healthy individuals and those with mild eccentricities or symptoms that fall short of meeting criteria for a mental disorder. Family mental health ratings
The total interview material has also been used for global ratings of the mental health of the families, as obtained from interviews of entire families and parental couples. These global ratings represent clinical assessments by the research psychiatrists based upon the 2-d interviews of each adoptive family. Because of rules imposed by the adoption agency, only one investigator was permitted to visit each family. Therefore, a possible bias was present when the same person interviewed and rated first the adoptive family and later the adoptee. As a partial check on this source of bias, the 4 interviewers conducted interrater reliability studies from audiotapes, independently rating the conjoint family interviews. They have also developed a 33-item family rating scale that dimensionalizes the initial, more global ratings of the adoptive families. For this report, data from 3 levels of globally rated family functioning have been obtained. These levels have been collapsed from the five levels described in more detail elsewhere (4): healthy (levels 1 and 2 combined) denotes families in which conflicts are transient or rare, psychologic boundaries between 46 1
the family members and between the family and the outside world are well defined, anxiety and depression are mild, and role functioning is appropriate to the stage of the family life cycle and external circumstances of the family. Moderately disturbed (level 3) denotes families in which unresolved conflicts of mild or moderate severity are present, psychological boundaries are clear, and reality testing is good; but the family roles are somewhat inappropriate for the ages or capabilities of the members, as well as somewhat constricted and repetitive. Severely disturbed (levels 4 and 5 combined) denotes families that either are maladaptive because of major unresolved and unacknowledged conflicts or are openly chaotic; their psychological boundaries are either rigid or unclear and stable, and family roles do not change flexibly in response to the major life events and transitions in the family life cycle. Follow-up assessment
The adoptive families were interviewed by telephone 5-7 years after the initial assessment. In addition, the later morbidity of adoptees, adoptive parents and biologic parents was checked through registers of the National Health Insurance Scheme in Finland. These follow-ups of adoptees have revealed 3 cases of schizophrenia, 1 bipolar manic psychosis and 2 suicides. In these cases, the family evaluations had taken place prospectively before the onset of the adoptee’s illness. We also plan to invite all the offspring to face-to-face assessments at follow-up that will include standardized interviews, re-testing, and possibly videotaping. Some preliminary results
By April 1991,361 adoptive families (index and control combined) had been contacted for field study, with data from 337 partially scored and 24 refused so far. We must point out that all the results still are preliminary because not all families have been interviewed, and because some diagnoses and family ratings need to be confirmed with reliability checks. Table 1 presents results from the initial assessment using matched groups from 322 offspring (index and control). There is a significant difference between index offspring with biologic schizophrenic mothers and the control offspring (Table 1). The offspring of schizophrenics are more disturbed than offspring of controls. When telephone follow-up data are included, the adoptee outcomes reveal a total of 15 psychotic adoptees, 13 index and 2 controls (1 1 identified in direct initial assessment and 4 through follow-up telephone interview). Of the 13 index adoptees, 7 are schizophrenics, two schizophreniform psychoses, 2
Table 1. The mental health ratings of adoptees at initial assessment: offspring of biologic, schizophrenic mothers vs offspring of control mothers Adoptee ratings’ Biologic mothers Schizophrenic Control Total
1t2
3
4t5
6
Total
68 92
35 59
31 26
10 1
144 178
160
94
57
11
322
Total spectrum (4, 5, 6)x2=8.1131, df=3, P=0.004. *Ratings: 1 t2=healthy; 3 =neurotic; 4 t 5=severe personalitydisorders and borderline syndrome; 6= psychotic.
delusional (paranoid) disorders and 2 manic depressive psychotics. Both of the control subjects are schizophrenics. Both biologic mothers of the 2 schizophrenic control adoptees had been interviewed personally and had never been mentally ill. Individually adoptive parent rating
In addition to making global family ratings, the adoptive family interviewers made individual diagnostic assessments of the adoptive parents. In Table 2 the individual adoptee ratings are correlated with the adoptive parents’ ratings (both adoptive parents combined). There is relatively little severe psychopathology in the adoptees if both the adoptive parents are healthy (ratings one or two). The difference between the index and control adoptees is statistically nonsignificant. However, if one or Table 2. The mental health ratings of the adoptees in relation to the ratings of their adoptive parents Healthy adoptive parents (1t 2 ) (both parents healthy) Adoptee ratings*
Biologic mothers Schizophrenic Control Total
Healthy 1-2
Neurotic 3
19 29 48
13 19
6
Severet psychotic 4-6 4 3
1
Total 29 45 14
x2=3.570, df=3, NS. Disturbed adoptive parents (3-6) (one or both disturbed) Adoptee ratings* Biologic mothers
1-2
3
4-6
Total
Schizophrenic Control Total
39 46 85
23 38 61
30 21 51
92 105 197
x2=8.986, df=3, P 0 . 0 3 . *Ratings: 1 +2=healthy; 3=neurotic; 4t5=severe personality disorders and borderline syndrome; 6 =psychotic.
Genes and family in schizophrenia
both of the adoptive parents are mentally disturbed (ratings 3, 4, 5 or 6) the likelihood of the adoptees to get a serious rating increases. There is also a statistically significant difference between the index and control cases ( P = 0.03). This is in accordance with the hypothesis that the offspring of schizophrenics are more sensitive if the rearing parents suffer from mental disturbance. Global adoptive family ratings
If we look at the relationship between the global mental health ratings of the adoptive families and the diagnostic ratings of the offspring, we see that in healthy rearing families the adoptees have little serious mental illness, whether or not their biologic mothers were schizophrenic. In contrast, when the index or control adoptive rearing families are disturbed, the adoptees are much more disturbed, but more so in the index cases with biologic schizophrenic mothers than in control cases (Table 3). The disturbed adoptive families show much more serious ratings (in 46% in index and 24% in controls). The difference between the index and control groups is significant (P= 0.003). The results are consistent with the hypothesis that healthy families have possibly protected the vulnerable child, whereas in disturbed families the vulnerable children have been more sensitive to dysfunctional rearing.
Table 3. The mental health ratings of the adoptees in relation to global ratings of adoptive families Healthy adoptive families (1 t 2 ) *
Dimensionalized family ratings
The 4 psychiatrists who conducted the interviews of adoptive families and their testing have made a reliability study, listening blindly to each others’ audiotapes of family interviews. They have also developed a 33-item family rating scale (OPAS) that attempts to dimensionalize the initial, more global ratings of adoptive families. The reliability study gave rather satisfactory results even though the interviewers rated each others’ interviews blindly from audiotapes only. Only 4 items of 33 gave poor reliability. Table 4 presents the 12 items for which the reliability was between 0.68 and 0.84, which is quite satisfactory. These independent ratings of the adoptive families correlated significantly with individual diagnoses of the offspring (from personal interviews). Also, most of the specific family dimensions, such as degree of empathy and communication in the family, make sense clinically. Test ratings of adoptive families An important methodologic difficulty with the preceding clinical ratings of the adoptive families is that the same interviewer who interviewed the adoptive families also made the individual parents’ ratings and adoptee ratings. To check the halo effect or bias that may have resulted, independently rated tests, especially the MMPI and Rorschach, were obtained for both the adoptive parents and adoptees. MMPI adoptee ratings
MMPI ratings were assessed blindly by a psychologist who was not aware of either the clinical data
Adoptee ratings Table 4. Dimensions of adoptive family functioning and adoptee mental health ratings (4 levels) [indextcontrols: n= 1651
Healthy
Neurotic
Severet psychotic
Biologic mothers
1-2
3
4-6
Total
Schizophrenic Control Total
44 45 89
8 21 29
3 2 5
55 68 123
~
x2=5.933, df=3, P=0.1149. Disturbed adoptive families (3-5) Adoptee ratings Biologic mothers
1-2
3
4-6
Total
Schizophrenic Control Total
20 38 58
25 38 63
38 24 62
83 100 183
~~
Relation to adoptee ratings Family dimensions Congruence of family and interviewer views of family Communication, disrupted Acknowledgment Family hierarchy, rigid Empathy Conflict between parents and offspring Expelling relation to offspring Criticism Expressed satisfaction with family Mood and tone Communication, constricted Affect, flat
Pearson 1‘
P
98.2 73.0 72.6 69.3 61.3 57.2 52.5 49.4 39.0 31.0 22.5 20.8
0.0001 0.0001 0.0001 0.0001 0.0001 0.0001 0.0001 0.0001 0.0001 0.0003 0.0074 0.0138
~
f=13 959, df=3, P=OOO3, *Ratings of families: 1 t 2 healthy, 3 neurotic, 4 t 5 seriously dysfunctional
Family dimensions with ICC reliabilities of 0.68-0.84, rated on 5-point scale: Pearson chi-square 4X 5.
463
Tienari
for the biologic or adoptive parents or the mental health ratings of the adoptees. The MMPI ratings of the offspring were correlated ( P < 0.001) with clinical ratings made of them independently ( 5 ) . The paranoia and schizophrenia scale ratings of the MMPI correlated significantly with the clinical ratings of the offspring (unpublished data). Furthermore, the offspring classified as severely disturbed in their MMPIs had been reared significantly more often in adoptive families clinically rated as severely disturbed. This confirms the relationship found between the clinical ratings of the adoptees and the clinical ratings of the adoptive families. Rorschach adoptee ratings
The individual Rorschach protocols ( n = 529) were also scored blindly with psychopathology ratings by 5 psychologists after a training and reliability check period. The weighted kappa reliability varied between different pairs of psychologists: from 0.529 (P
Tienari P. Interaction between genetic vulnerability and family environment: the Finnish adoptive family study of schizophrenia. Acta Psychiatr Scand 1991: 84: 460-465. A nationwide Finnish sample of schizophrenics’ offspring given up for adoption was compared blindly with matched controls, that is, adopted-away offspring of nonschizophrenic biologic parents. The adoptive families were investigated thoroughly by joint and individual interviews and psychologic tests. Biologic parents were also interviewed and tested. Among the 144 index and 178 control offspring, the percentage of both psychoses and other severe diagnoses (borderline syndrome and severe personality disorder) was significantly higher in the index adoptees than in the matched control adoptees. Of the 15 psychotic adoptees in the total sample to date, 13 are offspring of schizophrenics and 2 are control offspring. Both global clinical ratings and test data for the adoptive, rearing parents also correlate with the symptomatic status of the adoptees. A prospective, longitudinal study of adoptees at risk is being undertaken to explore the direction of effects between adoptees and adoptive parents.
A major goal in the Finnish adoptive family study is to evaluate both genetic and family-rearing contributions to schizophrenia and other psychopathology. We are interested in assessing to what extent genetic variables and family relationship variables jointly contribute to psychopathology of the adoptees. We would like to elucidate whether the genetic risk may be counteracted, and resilience promoted, by a healthy, possibly protective, family environment. We also would like to know whether the direction of effects between genetic and family environment factors can be clarified through a prospective, longitudinal study of adoptees at risk. Material and methods Selection of index cases
A nationwide sample was collected of all the women in Finland who have been hospitalized because of schizophrenia. The sample includes both the inpatient population on January 1, 1960 and later consecutive admissions for schizophrenia through 1979, making a total of 19,447 schizophrenic women. Information supplied by local civil and parish popu-
* In collaboration with Mikko Naarala, Anneli Sorri, Juha Moring, Ilpo Lahti, Kristian Laksy, Merja Kaleva, Karl-Erik Wahlberg, Pirjo Keskitalo, Helja Anias-Tanner, Pekka Koistinen, Taneli Tarvainen and Tuula Ronkko (University of Oulu, Finland) and Lyman C. Wynne (University of Rochester, USA). 460
P. Tienari * Department of Psychiatry, University of Oulu, Finland
Key words: schizophrenia; adoption; genetics: family environment
P. Tienari, University of Oulu, Department of Psychiatry, SF-902 1 0 Oulu, Finland Accepted for publication June 1, 199 1
lation registers showed which of these women had babies and gave them up for adoption. Through these registers, it was found that 264 of these mothers had given up 291 offspring for adoption. Of these offspring, 94 were excluded from the field study for various reasons, especially being adopted by a relative, adopted abroad or adopted after the age of 4 years. During the field work, 18 more cases were excluded, including 7 biologic mothers whose personal interview did not confirm the diagnosis of schizophrenia. A total of 179 offspring of 164 index schizophrenic women comprised the final sample of index cases. These children were adopted-away offspring of schizophrenic mothers and had been placed in adoptive families with Finnish nonrelatives during their first 4 years of life. The index cases were initially identified by a hospital diagnosis of schizophrenia (or paranoid psychosis) for the biologic, adopting-away mother. Paranoid psychoses were included because we expected that the boundaries between schizophrenia and paranoid psychosis would be unclear and would be checked later. Two experienced psychiatrists reviewed the records to confirm the diagnosis of schizophrenia by using the diagnostic criteria that are traditional in Finland (and correspond closely to Langfeldt’s criteria). Two additional raters applied the Research Diagnostic Criteria (RDC) to the hos-
Genes and family in schizophrenia
pita1 records of the biologic mothers. The biologic index mothers have been personally interviewed and tested when possible and, to date, 118 have been interviewed. These psychiatric interviews include a modified Present State Examination (with added items that facilitate DSM-111-R and RDC diagnoses), a 10-card Rorschach, Minnesota Multiphasic Personality Inventory (MMPI) and information on the biologic fathers. In as much detail as possible, data also are obtained on the psychiatric hospitalizations, symptoms, and personal characteristics of the biologic relatives of both the biologic and control parents, including formal diagnoses and information on personal eccentricities, patterns of adjustment and major somatic illnesses. We also interviewed all available biologic index fathers and biologic control parents to evaluate whether the psychiatric diagnoses of the biologic fathers add to the risk of the offspring. All the interviews and tests were tape-recorded. This makes it possible to carry out blind ratings, reliability checks and reclassifications by other investigators in the phase of the project that is now underway. Selection of matched controls
These index offspring and their adoptive families have been blindly compared with matched controls, that is, adoptive families with adopted-away offspring of biologic parents who have not been hospitalized because of psychosis. Pairwise matching was done outside our department by persons who were given the criteria and who independently carried out the case-by-case matching. The criteria for matching the control and index cases are described elsewhere (1). Biologic control parents were excluded only if they have been treated for psychosis. Hence, some of the biologic parents in the control series have received psychiatric help for reasons other than psychosis. The adoptive index and control series were numbered randomly so that the 4 psychiatrists conducting the personal interviews were blind as to whether the case in question was an index or a control family. Assessment of adoptive families and individuals
The adoptive index and control families were investigated in their homes directly and intensively with procedures that usually take 2 d (14-16 h). The family relationships are studied through family and couple interviews, as well as the consensus Rorschach (2) and the interpersonal perception method (3). Both of the adoptive parents and the offspring are individually interviewed to assess their current psychiatric status and past history. Individual Ror-
schachs were given after the consensus Rorschach. In the adoptive families, the MMPI was given only to the adoptive offspring (4). When the collection of data from the adoptive families was begun in 1977, a classification system was used that provided the basis for the present, preliminary data analysis. A 6-point scale for the severity of illness was combined with qualitative diagnoses, collapsed into 4 diagnostic levels for this report. Level 6 (psychosis) includes schizophrenia, paranoid psychosis and affective psychoses; these Finnish diagnoses appear to be similar to those in DSM-111-R. Level 5 (borderline syndrome) and level 4 (severe personality disorders) are combined in Tables 1-5 of this report. Further specification will be carried out with the DSM-111-R criteria. Levels 4 and 5 together presumptively include the schizotypal and paranoid personality disorders diagnosed with criteria similar to those of DSM-111-R, as well as what used to be called latent schizophrenia and pseudoneurotic schizophrenia. Additionally, and to be sorted out in future rediagnosis, these levels include borderline and narcissistic personality disorders and some cases of severely dysfunctional, egosyntonic character disorders. Level 3 (neurosis) includes the disorders with moderate and mild symptoms as well as the less severe personality disorders. Levels 1 and 2 (no diagnosis) are combined and include healthy individuals and those with mild eccentricities or symptoms that fall short of meeting criteria for a mental disorder. Family mental health ratings
The total interview material has also been used for global ratings of the mental health of the families, as obtained from interviews of entire families and parental couples. These global ratings represent clinical assessments by the research psychiatrists based upon the 2-d interviews of each adoptive family. Because of rules imposed by the adoption agency, only one investigator was permitted to visit each family. Therefore, a possible bias was present when the same person interviewed and rated first the adoptive family and later the adoptee. As a partial check on this source of bias, the 4 interviewers conducted interrater reliability studies from audiotapes, independently rating the conjoint family interviews. They have also developed a 33-item family rating scale that dimensionalizes the initial, more global ratings of the adoptive families. For this report, data from 3 levels of globally rated family functioning have been obtained. These levels have been collapsed from the five levels described in more detail elsewhere (4): healthy (levels 1 and 2 combined) denotes families in which conflicts are transient or rare, psychologic boundaries between 46 1
the family members and between the family and the outside world are well defined, anxiety and depression are mild, and role functioning is appropriate to the stage of the family life cycle and external circumstances of the family. Moderately disturbed (level 3) denotes families in which unresolved conflicts of mild or moderate severity are present, psychological boundaries are clear, and reality testing is good; but the family roles are somewhat inappropriate for the ages or capabilities of the members, as well as somewhat constricted and repetitive. Severely disturbed (levels 4 and 5 combined) denotes families that either are maladaptive because of major unresolved and unacknowledged conflicts or are openly chaotic; their psychological boundaries are either rigid or unclear and stable, and family roles do not change flexibly in response to the major life events and transitions in the family life cycle. Follow-up assessment
The adoptive families were interviewed by telephone 5-7 years after the initial assessment. In addition, the later morbidity of adoptees, adoptive parents and biologic parents was checked through registers of the National Health Insurance Scheme in Finland. These follow-ups of adoptees have revealed 3 cases of schizophrenia, 1 bipolar manic psychosis and 2 suicides. In these cases, the family evaluations had taken place prospectively before the onset of the adoptee’s illness. We also plan to invite all the offspring to face-to-face assessments at follow-up that will include standardized interviews, re-testing, and possibly videotaping. Some preliminary results
By April 1991,361 adoptive families (index and control combined) had been contacted for field study, with data from 337 partially scored and 24 refused so far. We must point out that all the results still are preliminary because not all families have been interviewed, and because some diagnoses and family ratings need to be confirmed with reliability checks. Table 1 presents results from the initial assessment using matched groups from 322 offspring (index and control). There is a significant difference between index offspring with biologic schizophrenic mothers and the control offspring (Table 1). The offspring of schizophrenics are more disturbed than offspring of controls. When telephone follow-up data are included, the adoptee outcomes reveal a total of 15 psychotic adoptees, 13 index and 2 controls (1 1 identified in direct initial assessment and 4 through follow-up telephone interview). Of the 13 index adoptees, 7 are schizophrenics, two schizophreniform psychoses, 2
Table 1. The mental health ratings of adoptees at initial assessment: offspring of biologic, schizophrenic mothers vs offspring of control mothers Adoptee ratings’ Biologic mothers Schizophrenic Control Total
1t2
3
4t5
6
Total
68 92
35 59
31 26
10 1
144 178
160
94
57
11
322
Total spectrum (4, 5, 6)x2=8.1131, df=3, P=0.004. *Ratings: 1 t2=healthy; 3 =neurotic; 4 t 5=severe personalitydisorders and borderline syndrome; 6= psychotic.
delusional (paranoid) disorders and 2 manic depressive psychotics. Both of the control subjects are schizophrenics. Both biologic mothers of the 2 schizophrenic control adoptees had been interviewed personally and had never been mentally ill. Individually adoptive parent rating
In addition to making global family ratings, the adoptive family interviewers made individual diagnostic assessments of the adoptive parents. In Table 2 the individual adoptee ratings are correlated with the adoptive parents’ ratings (both adoptive parents combined). There is relatively little severe psychopathology in the adoptees if both the adoptive parents are healthy (ratings one or two). The difference between the index and control adoptees is statistically nonsignificant. However, if one or Table 2. The mental health ratings of the adoptees in relation to the ratings of their adoptive parents Healthy adoptive parents (1t 2 ) (both parents healthy) Adoptee ratings*
Biologic mothers Schizophrenic Control Total
Healthy 1-2
Neurotic 3
19 29 48
13 19
6
Severet psychotic 4-6 4 3
1
Total 29 45 14
x2=3.570, df=3, NS. Disturbed adoptive parents (3-6) (one or both disturbed) Adoptee ratings* Biologic mothers
1-2
3
4-6
Total
Schizophrenic Control Total
39 46 85
23 38 61
30 21 51
92 105 197
x2=8.986, df=3, P 0 . 0 3 . *Ratings: 1 +2=healthy; 3=neurotic; 4t5=severe personality disorders and borderline syndrome; 6 =psychotic.
Genes and family in schizophrenia
both of the adoptive parents are mentally disturbed (ratings 3, 4, 5 or 6) the likelihood of the adoptees to get a serious rating increases. There is also a statistically significant difference between the index and control cases ( P = 0.03). This is in accordance with the hypothesis that the offspring of schizophrenics are more sensitive if the rearing parents suffer from mental disturbance. Global adoptive family ratings
If we look at the relationship between the global mental health ratings of the adoptive families and the diagnostic ratings of the offspring, we see that in healthy rearing families the adoptees have little serious mental illness, whether or not their biologic mothers were schizophrenic. In contrast, when the index or control adoptive rearing families are disturbed, the adoptees are much more disturbed, but more so in the index cases with biologic schizophrenic mothers than in control cases (Table 3). The disturbed adoptive families show much more serious ratings (in 46% in index and 24% in controls). The difference between the index and control groups is significant (P= 0.003). The results are consistent with the hypothesis that healthy families have possibly protected the vulnerable child, whereas in disturbed families the vulnerable children have been more sensitive to dysfunctional rearing.
Table 3. The mental health ratings of the adoptees in relation to global ratings of adoptive families Healthy adoptive families (1 t 2 ) *
Dimensionalized family ratings
The 4 psychiatrists who conducted the interviews of adoptive families and their testing have made a reliability study, listening blindly to each others’ audiotapes of family interviews. They have also developed a 33-item family rating scale (OPAS) that attempts to dimensionalize the initial, more global ratings of adoptive families. The reliability study gave rather satisfactory results even though the interviewers rated each others’ interviews blindly from audiotapes only. Only 4 items of 33 gave poor reliability. Table 4 presents the 12 items for which the reliability was between 0.68 and 0.84, which is quite satisfactory. These independent ratings of the adoptive families correlated significantly with individual diagnoses of the offspring (from personal interviews). Also, most of the specific family dimensions, such as degree of empathy and communication in the family, make sense clinically. Test ratings of adoptive families An important methodologic difficulty with the preceding clinical ratings of the adoptive families is that the same interviewer who interviewed the adoptive families also made the individual parents’ ratings and adoptee ratings. To check the halo effect or bias that may have resulted, independently rated tests, especially the MMPI and Rorschach, were obtained for both the adoptive parents and adoptees. MMPI adoptee ratings
MMPI ratings were assessed blindly by a psychologist who was not aware of either the clinical data
Adoptee ratings Table 4. Dimensions of adoptive family functioning and adoptee mental health ratings (4 levels) [indextcontrols: n= 1651
Healthy
Neurotic
Severet psychotic
Biologic mothers
1-2
3
4-6
Total
Schizophrenic Control Total
44 45 89
8 21 29
3 2 5
55 68 123
~
x2=5.933, df=3, P=0.1149. Disturbed adoptive families (3-5) Adoptee ratings Biologic mothers
1-2
3
4-6
Total
Schizophrenic Control Total
20 38 58
25 38 63
38 24 62
83 100 183
~~
Relation to adoptee ratings Family dimensions Congruence of family and interviewer views of family Communication, disrupted Acknowledgment Family hierarchy, rigid Empathy Conflict between parents and offspring Expelling relation to offspring Criticism Expressed satisfaction with family Mood and tone Communication, constricted Affect, flat
Pearson 1‘
P
98.2 73.0 72.6 69.3 61.3 57.2 52.5 49.4 39.0 31.0 22.5 20.8
0.0001 0.0001 0.0001 0.0001 0.0001 0.0001 0.0001 0.0001 0.0001 0.0003 0.0074 0.0138
~
f=13 959, df=3, P=OOO3, *Ratings of families: 1 t 2 healthy, 3 neurotic, 4 t 5 seriously dysfunctional
Family dimensions with ICC reliabilities of 0.68-0.84, rated on 5-point scale: Pearson chi-square 4X 5.
463
Tienari
for the biologic or adoptive parents or the mental health ratings of the adoptees. The MMPI ratings of the offspring were correlated ( P < 0.001) with clinical ratings made of them independently ( 5 ) . The paranoia and schizophrenia scale ratings of the MMPI correlated significantly with the clinical ratings of the offspring (unpublished data). Furthermore, the offspring classified as severely disturbed in their MMPIs had been reared significantly more often in adoptive families clinically rated as severely disturbed. This confirms the relationship found between the clinical ratings of the adoptees and the clinical ratings of the adoptive families. Rorschach adoptee ratings
The individual Rorschach protocols ( n = 529) were also scored blindly with psychopathology ratings by 5 psychologists after a training and reliability check period. The weighted kappa reliability varied between different pairs of psychologists: from 0.529 (P
