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Offspring of Patients with Affective Disorders: II
Offspring of Patients with Affective Disorders: II LEON CYTRYN, M.D., DONALD H. McKNEW, JR., M.D., JOHN J. BARTKO, PH.D., MARTINE LAMOUR, M.D., AND JOELLE HAMOVITT, M.S.W. Nineteen children, aged 5 to 15, of 13 manic-depressive parents and 21 children aged 5 to 15 of 13 normal parents were evaluated for affective disorder using blind ratings and interviewers and employing both the Weinberg Criteria and the DSM·III. Significantly more index families had depressed children than normal families as measured by Weinberg and DSM-III Criteria. The presence of depression in the children did not correlate with I:ge or sex and no manic or psychotic children were seen. Journal of the American Academy of Child Psychiatry, 21, 4:389-391, 1982.
In a previous open study (McKnew et al., 1979) 30 children (aged 5 to 15) of 16 parents hospitalized with a major effective disorder were assessed for the pres· ence of affective illness in two structured interviews, at 4-month intervals, on the basis of the Weinberg Criteria (Weinberg et al., 1973). Of the 30 children, 9 were depressed on both interviews and 16 were depressed on one interview. There was no significant correlation between the presence of depression and the age or sex of the children. None of the children was manic or psychotic. The present study was undertaken in order to validate the above preliminary findings by the use of blind interviewers and raters, as well as the inclusion of a control group.
All the children were white, save for one black child in each group, and all were the biological offspring of the parents. The control group was matched with the index group on the following parameters: (a) age, within a 2-year span; (b) sex; and (c) socioeconomic status according to the Hollingshead-Redlich Scale, within a one-point span. All the parents in both groups were assessed by the Life Schedule of Affective Disorders and Schizophrenia (L-SADS) and diagnosed using the Research Diagnostic Criteria (RDC) as modified by Gershon (Leckman et al., 1977; Spitzer et al., 1977). All children whose IQ was below 90 or who had a chronic physical illness were excluded. The matching of the children, the screening and interviewing of the parents, as well as the random scheduling of the children for interviews, were done by an independent colleague in order to maintain the blindness. All the children were interviewed by a member of our team who was blind as to the purpose of the study and who had no knowledge of the origin of any given child. The two interviews at 4-month intervals were structured according to a previously developed format which elicits all types of childhood psychopathology. The interviews lasted approximately 45 minutes. At the end of each interview, the children were rated independently by the child interviewer on the following rating scales: (a) the Children's Psychiatric Rating Scale (CPRS) of the ECDEU, and (b) the Children's Affective Rating Scale (CARS). The interviews were observed through a one-way mirror by two other team members who rated the child on the same scales. The nature of the structured interview, as well as the interrater reliability on the CARS and CPRS has been reported elsewhere (McKnew et al., 1979). Based on these ratings, their observations, and any other available information from parents and/or school, the above-mentioned investigators who were blind as to the origin of each patient, diagnosed the child by consensus as depressed if he met the Weinberg Criteria (Weinberg et al., 1973).
Methods We studied two groups of children, ages 5 to 15: A. Nineteen children of 13 consecutive patients hospitalized in the National Institute of Mental Health with the diagnosis of Major Affective Disorder. (Mean age 11, 10 boys, 9 girls, Hollingshead-Redlich Scale-2.7.) B. Twenty-one control children of 13 parents who were free of major physical or mental illness. (Mean age 11.1, 13 boys, 8 girls, HollingsheadRedlich Scale-2.1). Drs. Cytryn and McKnew are staff psychiatrists in the Unit on Childhood Mental Illness of the Biological Psychiatry Branch, and the Laboratory of Developmental Psychology, N.I.M.H. They
are also with the George Washington University School of Medicine, where Dr. Cytryn is CliniccLl Professor and Dr. McKnew is Clinical Associate Professor, Department of Psychiatry and Behavioral Sciences and Child Health and Development. Dr. Bartko is a mathematical statistician, Division of Biometry and Epidemiology, N.I.M.H. Dr. Lamour and Ms. Hamovit are with the Unit on Childhood Mental Illness, N.I.M.H. Dr. Lamour is supported by a fellowship from the "Foundation pour la recherche medicale francaise." Reprints may be requested from Dr. Cytryn, National Institute of Mental Health, Building 10, Room 2N21O, Bethesda, MD 20205. 0002-7138/82/2104-0389 $02.00/0 © 1982 by the American Academy of Child Psychiatry. 389
390
CYTRYN ET AL.
When the DSM-III criteria became available in final form, our recorded structured interviews and ratings allowed us to rediagnose the children, using those criteria. Thus, each child received two diagnoses, Weinberg and DSM-III. A child was diagnosed as depressed if he or she met the DSM-III Criteria for Major Depressive Disorder or Dysthymic Disorder. Our diagnostic assessment of the children, focused on their present status and recent past. Lifetime diagnoses were not made since no appropriate instruments were available at the time of the study. The 40 children in our study come from 26 families. Since the hypothesis in this study is that child and adult depressions aggregate in families and this hypothesis has received considerable support from other studies (Puig-Antich, 1980), we decided to make the family the unit of analysis as children in the same family will share the same risk to develop the disorder. The statistics used were the Fisher Exact Test and the l test (Siegel, 1956).
Results Of the 13 index families, 11 had one or more children who were depressed on at least one interview as measured by the Weinberg criteria while two families had no children who satisfied the Weinberg criteria on any interview. In contrast, of the 13 control group families, 10 had children who were all Weinberg negative and 3 families had children who satisfied the Weinberg Criteria. This difference is statistically significant l = 7.58 (p = 0.01). Using the DSM-III criteria, the following results were obtained. In the index group, 9 families had at least one depressed child, while 4 families had none. In the control group 3 families had at least one depressed child, while 10 had none. This difference is again statistically significant l = 3.87 (p = 0.05). In the index group, 3 families had children with Major Depressive Disorder while 1 control family had a child with such a disorder. The remaining children with affective illness in both groups had Dysthymic Disorder. In addition to affective disorders, the DSM-III diagnoses of Overanxious Disorder were made in the children of 2 proband families and in one of the control families. Another index family had a child with a Simple Phobia. No child had manic or psychotic symptoms. According to RDC criteria, two spouses of the index parents had Depressive Personality, three spouses had minor Depression, one had General Anxiety and one had a Phobic Reaction. Six spouses were free of psychopathology. A comparison of the offspring of families with two affectively ill parents did not show that the former are at any greater risk for having an affec-
tive illness. There was also no significant correlation between the diagnosis of the index parent (Bipolar, Unipolar, and Schizo-Affective) or the age or sex of the child and the frequency of an affective illness in the children. However, we found that the frequency of affective disorders in the children was significantly higher if the child and the index parent were of opposite sex (Fisher Exact p = 0.03).
Discussion The high incidence of depressive disorders in the offspring of affectively ill parents which we reported in our first open study has been confirmed by this controlled study using the offspring of normal parents. Similarly confirmed were the findings of no correlation of depressive diagnosis in the children with age and sex, as well as the absence of mania and psychosis. The Weinberg Criteria were used for two reasons. (1) At the beginning of this study, the DSM-III Criteria were only in a formative stage and the use of RDC in children had not yet been published. (2) Our first offspring study (McKnew et al., 1979) used the Weinberg Criteria and it seemed essential to use the same standards as a basis for comparison. The discrepancy in this study between the Weinberg Criteria and the DSM-III Criteria in the proband group has also been noted by several authors (Apter et al., 1981; Carlson and Cantwell, 1980). Both groups found that the Weinberg Criteria are often overinclusive and sometimes underinclusive, as compared with DSM-III Criteria. In addition, it should be noted that Carlson et al. were comparing Weinberg Criteria only to Major Depressive Disorder while Apter et al. and we included Dysthymic Disorders as well. The high incidence of depression in the children of the index group can be due to many factors such as: (1) the hardship of having a parent with any chronic illness which requires hospitalization (Rutter, 1966), (2) genetic vulnerability, and (3) the impact of living with a mentally ill parent. The curious finding of a significantly increased incidence of affective illness in the opposite sex offspring of a manic depressive proband cannot be generalized because of our small sample. However, the potential significance of this finding warrants further investigation. References APTER, A., BORENGASSER, M. A., HAMOVIT, J., BARTKO, J., CYTRYN, L. & McKNEW, D. R., JR. (1981), A four-year follow-up of depressed children. J. Prevent. Psychiat. (in press). CARLSON, G. A. & CANTWELL, D. P. (1980), Diagnosis of Childhood Depression-A Comparison of the Weinberg and DSM-III Criteria. Presented at the Annual Meeting of the American Psychiatric Association, San Francisco. LECKMAN, J. F., GERSHON, E., NICHOLS, A. S. & MURPHY, D. L.
OFFSPRING OF PATIENTS WITH AFFECTIVE DISORDERS: II (1977), Reduced MAO activity in first degree relatives of individuals with bipolar affective disorders. Arch. Gen Psychiat., 34:601606. McKNEW, D. H., CYTRYN, L., EFRON, A. M., GERSHON, E. S. & BUNNEY, W. E., JR. (1979), Offspring of patients with affective disorders. Brit. J. Psychiat.• 134:148-152. PUIG-ANTICH. K. (1980). Affective disorders in children; an overview. Psychiatr. Clin. N. Amer., 3:403-424. RUTrER. M. (1966), Children of Sick Parents. Oxford: Oxford University Press.
391
SIEGEL. S. (1956), Nonparametic Tests for the Behavioral Sciences. New York: McGraw-Hill. SPITZER, R. L., ENDICOTr, J. & ROBINS, E. (1977), Research Diag· nostic Criteria, Ed. 3. Bionetics Research, New York State Psychiatric Institute, 722 W. 168th Street, New York. NY 10032. WEINBERG, W. A., RUTMAN. J., SULLIVAN, L., PENICK, E. C. & DIETZ, S. G. (1973). Depression in children referred to an educational diagnostic center; diagnosis and treatment. J. Pediatr.• 83:1065-1972.
In a previous open study (McKnew et al., 1979) 30 children (aged 5 to 15) of 16 parents hospitalized with a major effective disorder were assessed for the pres· ence of affective illness in two structured interviews, at 4-month intervals, on the basis of the Weinberg Criteria (Weinberg et al., 1973). Of the 30 children, 9 were depressed on both interviews and 16 were depressed on one interview. There was no significant correlation between the presence of depression and the age or sex of the children. None of the children was manic or psychotic. The present study was undertaken in order to validate the above preliminary findings by the use of blind interviewers and raters, as well as the inclusion of a control group.
All the children were white, save for one black child in each group, and all were the biological offspring of the parents. The control group was matched with the index group on the following parameters: (a) age, within a 2-year span; (b) sex; and (c) socioeconomic status according to the Hollingshead-Redlich Scale, within a one-point span. All the parents in both groups were assessed by the Life Schedule of Affective Disorders and Schizophrenia (L-SADS) and diagnosed using the Research Diagnostic Criteria (RDC) as modified by Gershon (Leckman et al., 1977; Spitzer et al., 1977). All children whose IQ was below 90 or who had a chronic physical illness were excluded. The matching of the children, the screening and interviewing of the parents, as well as the random scheduling of the children for interviews, were done by an independent colleague in order to maintain the blindness. All the children were interviewed by a member of our team who was blind as to the purpose of the study and who had no knowledge of the origin of any given child. The two interviews at 4-month intervals were structured according to a previously developed format which elicits all types of childhood psychopathology. The interviews lasted approximately 45 minutes. At the end of each interview, the children were rated independently by the child interviewer on the following rating scales: (a) the Children's Psychiatric Rating Scale (CPRS) of the ECDEU, and (b) the Children's Affective Rating Scale (CARS). The interviews were observed through a one-way mirror by two other team members who rated the child on the same scales. The nature of the structured interview, as well as the interrater reliability on the CARS and CPRS has been reported elsewhere (McKnew et al., 1979). Based on these ratings, their observations, and any other available information from parents and/or school, the above-mentioned investigators who were blind as to the origin of each patient, diagnosed the child by consensus as depressed if he met the Weinberg Criteria (Weinberg et al., 1973).
Methods We studied two groups of children, ages 5 to 15: A. Nineteen children of 13 consecutive patients hospitalized in the National Institute of Mental Health with the diagnosis of Major Affective Disorder. (Mean age 11, 10 boys, 9 girls, Hollingshead-Redlich Scale-2.7.) B. Twenty-one control children of 13 parents who were free of major physical or mental illness. (Mean age 11.1, 13 boys, 8 girls, HollingsheadRedlich Scale-2.1). Drs. Cytryn and McKnew are staff psychiatrists in the Unit on Childhood Mental Illness of the Biological Psychiatry Branch, and the Laboratory of Developmental Psychology, N.I.M.H. They
are also with the George Washington University School of Medicine, where Dr. Cytryn is CliniccLl Professor and Dr. McKnew is Clinical Associate Professor, Department of Psychiatry and Behavioral Sciences and Child Health and Development. Dr. Bartko is a mathematical statistician, Division of Biometry and Epidemiology, N.I.M.H. Dr. Lamour and Ms. Hamovit are with the Unit on Childhood Mental Illness, N.I.M.H. Dr. Lamour is supported by a fellowship from the "Foundation pour la recherche medicale francaise." Reprints may be requested from Dr. Cytryn, National Institute of Mental Health, Building 10, Room 2N21O, Bethesda, MD 20205. 0002-7138/82/2104-0389 $02.00/0 © 1982 by the American Academy of Child Psychiatry. 389
390
CYTRYN ET AL.
When the DSM-III criteria became available in final form, our recorded structured interviews and ratings allowed us to rediagnose the children, using those criteria. Thus, each child received two diagnoses, Weinberg and DSM-III. A child was diagnosed as depressed if he or she met the DSM-III Criteria for Major Depressive Disorder or Dysthymic Disorder. Our diagnostic assessment of the children, focused on their present status and recent past. Lifetime diagnoses were not made since no appropriate instruments were available at the time of the study. The 40 children in our study come from 26 families. Since the hypothesis in this study is that child and adult depressions aggregate in families and this hypothesis has received considerable support from other studies (Puig-Antich, 1980), we decided to make the family the unit of analysis as children in the same family will share the same risk to develop the disorder. The statistics used were the Fisher Exact Test and the l test (Siegel, 1956).
Results Of the 13 index families, 11 had one or more children who were depressed on at least one interview as measured by the Weinberg criteria while two families had no children who satisfied the Weinberg criteria on any interview. In contrast, of the 13 control group families, 10 had children who were all Weinberg negative and 3 families had children who satisfied the Weinberg Criteria. This difference is statistically significant l = 7.58 (p = 0.01). Using the DSM-III criteria, the following results were obtained. In the index group, 9 families had at least one depressed child, while 4 families had none. In the control group 3 families had at least one depressed child, while 10 had none. This difference is again statistically significant l = 3.87 (p = 0.05). In the index group, 3 families had children with Major Depressive Disorder while 1 control family had a child with such a disorder. The remaining children with affective illness in both groups had Dysthymic Disorder. In addition to affective disorders, the DSM-III diagnoses of Overanxious Disorder were made in the children of 2 proband families and in one of the control families. Another index family had a child with a Simple Phobia. No child had manic or psychotic symptoms. According to RDC criteria, two spouses of the index parents had Depressive Personality, three spouses had minor Depression, one had General Anxiety and one had a Phobic Reaction. Six spouses were free of psychopathology. A comparison of the offspring of families with two affectively ill parents did not show that the former are at any greater risk for having an affec-
tive illness. There was also no significant correlation between the diagnosis of the index parent (Bipolar, Unipolar, and Schizo-Affective) or the age or sex of the child and the frequency of an affective illness in the children. However, we found that the frequency of affective disorders in the children was significantly higher if the child and the index parent were of opposite sex (Fisher Exact p = 0.03).
Discussion The high incidence of depressive disorders in the offspring of affectively ill parents which we reported in our first open study has been confirmed by this controlled study using the offspring of normal parents. Similarly confirmed were the findings of no correlation of depressive diagnosis in the children with age and sex, as well as the absence of mania and psychosis. The Weinberg Criteria were used for two reasons. (1) At the beginning of this study, the DSM-III Criteria were only in a formative stage and the use of RDC in children had not yet been published. (2) Our first offspring study (McKnew et al., 1979) used the Weinberg Criteria and it seemed essential to use the same standards as a basis for comparison. The discrepancy in this study between the Weinberg Criteria and the DSM-III Criteria in the proband group has also been noted by several authors (Apter et al., 1981; Carlson and Cantwell, 1980). Both groups found that the Weinberg Criteria are often overinclusive and sometimes underinclusive, as compared with DSM-III Criteria. In addition, it should be noted that Carlson et al. were comparing Weinberg Criteria only to Major Depressive Disorder while Apter et al. and we included Dysthymic Disorders as well. The high incidence of depression in the children of the index group can be due to many factors such as: (1) the hardship of having a parent with any chronic illness which requires hospitalization (Rutter, 1966), (2) genetic vulnerability, and (3) the impact of living with a mentally ill parent. The curious finding of a significantly increased incidence of affective illness in the opposite sex offspring of a manic depressive proband cannot be generalized because of our small sample. However, the potential significance of this finding warrants further investigation. References APTER, A., BORENGASSER, M. A., HAMOVIT, J., BARTKO, J., CYTRYN, L. & McKNEW, D. R., JR. (1981), A four-year follow-up of depressed children. J. Prevent. Psychiat. (in press). CARLSON, G. A. & CANTWELL, D. P. (1980), Diagnosis of Childhood Depression-A Comparison of the Weinberg and DSM-III Criteria. Presented at the Annual Meeting of the American Psychiatric Association, San Francisco. LECKMAN, J. F., GERSHON, E., NICHOLS, A. S. & MURPHY, D. L.
OFFSPRING OF PATIENTS WITH AFFECTIVE DISORDERS: II (1977), Reduced MAO activity in first degree relatives of individuals with bipolar affective disorders. Arch. Gen Psychiat., 34:601606. McKNEW, D. H., CYTRYN, L., EFRON, A. M., GERSHON, E. S. & BUNNEY, W. E., JR. (1979), Offspring of patients with affective disorders. Brit. J. Psychiat.• 134:148-152. PUIG-ANTICH. K. (1980). Affective disorders in children; an overview. Psychiatr. Clin. N. Amer., 3:403-424. RUTrER. M. (1966), Children of Sick Parents. Oxford: Oxford University Press.
391
SIEGEL. S. (1956), Nonparametic Tests for the Behavioral Sciences. New York: McGraw-Hill. SPITZER, R. L., ENDICOTr, J. & ROBINS, E. (1977), Research Diag· nostic Criteria, Ed. 3. Bionetics Research, New York State Psychiatric Institute, 722 W. 168th Street, New York. NY 10032. WEINBERG, W. A., RUTMAN. J., SULLIVAN, L., PENICK, E. C. & DIETZ, S. G. (1973). Depression in children referred to an educational diagnostic center; diagnosis and treatment. J. Pediatr.• 83:1065-1972.