The Disruptive Behavioral Disorder in Children and Adolescents: Comorbidity and Clinical Course

The Disruptive Behavioral Disorder in Children and Adolescents: Comorbidity and Clinical Course

The Disruptive Behavioral Disorder in Children and Adolescents: Comorbidity and Clinical Course MARTIN B. KELLER, M.D., PHILIP W. LAVORl, Ph.D., WILLI...

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The Disruptive Behavioral Disorder in Children and Adolescents: Comorbidity and Clinical Course MARTIN B. KELLER, M.D., PHILIP W. LAVORl, Ph.D., WILLIAM R. BEARDSLEE, M.D., JOANNE WUNDER, B.A., CARL E. SCHWARTZ, M.D., JOAN ROTH, B.S., AND JOSEPH BIEDERMAN, M.D.

Abstract. Comorbidity, time to recovery, rate of chronicity, and probability of recurrence following recovery were studied in 51 children diagnosed with attention deficit disorder, conduct disorder, and oppositional defiant disorder. Thirty-three percent of the children had two of the above diagnoses, and one child had all three diagnoses. The mean duration of attention deficit disorder was 8 years up to the time of the interview; the mean duration of oppositional defiant disorder was 4.5 years, and the mean duration of conduct disorder was 3 years. Life-table estimates showed that 14% of the children would not have recovered 15 years after the onset of their disorder. Rates of recurrence were high following recovery from each of these disorders. I. Am. Acad. Child Adolesc. Psychiatry, 1992,31,2:204-209. Key Words: disruptive behavioral disorder, children, adolescents. Since 1980, attention deficit disorders (ADD) have received much recognition in the literature and the classification of these disorders has evolved considerably. In DSM-III-R (American Psychiatric Association, 1987), these disorders were classified as attention deficit hyperactivity disorder (ADHD). ADHD manifests itself in early childhood as brief attention span, impulsiveness, distractibility, excitability, and poor academic functioning. Epidemiological studies have reported rates of attention deficit disorder in children ranging from 5 to 20%, and male/female ratio ranges from 4:1 to 9:1 (Shekim et aI., 1985). DSM-III-R lists conduct disorder (CD) and oppositional defiant disorder (ODD) as complications or additional diagnoses that are often present in children diagnosed as having ADHD, although they are also frequently diagnosed in the absence of ADHD. Conduct disorder is manifested by delinquency and behavior that violates the rights of others, as well as impulsivity and poor school performance. ODD is characterized by disobedient behavior and opposition to authority figures that persist even when they are destructive to the child's interests or well being.

Accepted September 9, 1991. Drs. Keller and Lavori, Ms. Wunder, and Ms. Roth are with the Department of Psychiatry and Human Behavior, Brown University, Providence, Rhode Island. Dr. Beardslee is with the Department of Psychiatry, The Children's Hospital, Boston, Massachusetts. Dr. Schwartz is with the Massachusetts Mental Health Center, Boston. Dr. Biederman is with the Massachusetts General Hospital, Boston. This research was supported by the William T. Grant Foundation, the National Institute ofMental Health through a grant entitled' 'Children at Risk for Affective Disorder" (Grant RO-I-MH34780-3) in conjunction with the Boston center of the National Institute of Mental Health-Clinical Research Branch, Collaborative Psychobiology of Depression Study (Grant 2-U02-MH25475-09), the Harris Trust through Harvard University, the Overseas Shipholding Group, and the George P. Harrington Trust. The authors gratefully acknowledge the assistance ofDeborah Drs, B.A., Sarah Ackerman, B.A., and Deborah Offner, B.A., in the editing and preparation of this manuscript. Reprint requests to Dr. Keller, Department of Psychiatry and Human Behavior, Brown University, Providence, RI029/2. 0890-8567/92/31 02-0204$03.00/0© 1992 by the American Academy of Child and Adolescent Psychiatry.

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Outcome studies of children with a diagnosis of ADD have shown that 26% of the children exhibit serious delinquency between the ages of 7 and 13 (Mendelson et aI., 1971), and as many as 25% are institutionalized for delinquency between the ages of 14 and 21 (Satterfield et aI., 1982). Children with ADD show poorer social adjustment, truancy, and more arrests than children with no diagnosis of ADD (Howell et aI., 1985). Using the retrospective case history method, Tarter et ai. (1977) and Wood et ai. (1983) found that a high proportion of male alcoholics had symptoms of ADD as children. In a prospective follow-up study, it was found that 23 to 55% of children with conduct disorders developed antisocial personality disorder as adults (Graham and Rutter, 1973; Kelso and Stewart, 1986; Robins and Ratcliff, 1979). Given the poor psychopathological prognosis, the legal difficulties, academic deficits, and alcoholic complications, it is important to study the course of these disorders to better understand their pathogenesis and to develop early detection and prevention strategies. This research expands upon work done to date by sampling from a population of children who were not referred for any psychiatric treatment or juvenile programs and were not seeking help or being referred for medical or psychiatric treatment as part of the process of their intake into the study. This manuscript reports on the comorbidity and the course of psychopathology of these disorders specifying the time to recovery, time to recurrence for children who recover, and rates of chronicity.

Methods and Subjects Design

The impact of a range of parental illness on children was studied by recruiting parents with affective illness and nonaffective illness and comparison groups and then assessing their children with extensive tests. Families were recruited in which a parent had an affective illness and was seeking treatment for this condition, families in which a parent had an affective illness but was not seeking treatment for it, and families with no affective illness. Inclusion criteria for the study required that the parents be Caucasian, that the mother speak English, that information be obtainable about I. Am. A cad. Child Adolesc. Psychiatry, 31:2, March 1992

DISRUPTIVE BEHAVIORAL DISORDER

both biological parents, that the biological mother and her children be living together and available to be interviewed in person, and that the family had at least one child between the ages of 6 and 19 (Beardslee et aI., 1988). The findings reported here arose from a comprehensive study of all psychopathology and impaired functioning in children after the parents were carefully assessed with structured clinical interviews and criterion based diagnoses were made. The study was naturalistic, and therefore children were not assigned to any treatment groups, although they may have sought treatment in the community. Subjects

The 275 children in the initial sample were obtained when their parents were recruited in one of five ways: (1) The "Collaborative Depression Study proband" group (Katz and Klerman, 1979) is a sample of 16 families (28 children) with one parent from the Adult Collaborative Depression Study, who had children in the age range 6 to 19. These families had a parent with an affective illness of sufficient severity to cause the parent to seek treatment at an inpatient or outpatient facility at a university medical center. (2) The "relatives" group (11 families; 24 children) consists of first degree relatives of other probands from the Collaborative Depression Study. They are not relatives of the probands who were selected for the "proband" group. (3) The "acquaintances" group (12 families; 21 children) was selected from the larger Collaborative Depression Study group of acquaintances of relatives of probands. As in the "relatives," these families were selected only by having children in the appropriate age range (6-19), without regard to the affective status of the parents. (4) The "community" group (23 families; 49 children) was chosen from the same neighborhoods or neighborhoods similar to those from which the affectively ill parents in the "proband" group had been selected and were recruited by contacting every third residence in the neighborhood. (5) By randomly selecting (using computer-generated random numbers) from the families enrolled in a health maintenance organization (HMO), the Harvard Community Health Plan (81 families; 153 children), the authors provided an internal "comparison" group to maintain the blindness of the child interviewers to parental status, and diversify the reference population to include a broad range of demographics and severity of illness in the families, paralleling the general population. Fifty-one of the 275 children initially interviewed received at least one of the three diagnoses (ADD, CD, or ODD). Fourteen (27%) of the children were from the "proband" ascertainment group (selected for having at least one parent with an affective disorder), and seven (14%) were from the "relative" group (selected for having a first degree relative with affective disorder). The remaining children were from the unselected groups: four children (8%) from the "community" group, one (2%) from the "acquaintance" group, and 25 (49%) from the HMO group. Because of this frequent comorbidity of ADD, CD, and ODD and their similarity as behavioral disorders in children, the authors analyzed course and outcome by pooling children who fell into one or more of these three categories J. Am. Acad. Child Adolesc. Psychiatry, 31:2, March 1992

together, and then separately analyzed and compared the course of individuals who had only one of these three diagnoses. Assessments

Current and past psychiatric illness in the biological parent was assessed with the Schedule of Affective Disorders and Schizophrenia, Life-Time Version (SADS-L) (Spitzer and Endicott, 1978), which yields Research Diagnostic Criteria diagnoses. Past and present psychopathology in the child was assessed in a face-to-face interview with the child using the Diagnostic Interview of Children and Adolescents (DICA) (Herjanic and Reich, 1982), which yields DSM-lII (American Psychiatric Association, 1980) diagnoses (in use at the time of the study). A parental report about the child was obtained using the Diagnostic Interview of Children and Adolescents for Parents (DICA-P) (Reich et aI., 1982). The DICA-P has the same form and content as the children's version, but the mother is used as the informant about the child. Procedures

To promote interrater reliability, these interviewers were rigorously trained to conduct the SADS-L, DICA, and DICA-P interviews through vignettes, role plays, videos of sample interviews, and attendance at others' interviews. It should be noted that as part of the training, each interviewer, after satisfactorily completing formal classroom training, went through a process of' 'hands-on" training. This process involved watching several interviews without participating, cointerviewing several subjects with an experienced interviewer, and then interviewing with an experienced interviewer present. Ongoing supervision was maintained primarily through an extensive editing process in which each report was carefully reviewed to check for diagnostically sound data. Three interviewers were used for each subject. The interviewer for the parents did not have any information regarding the children, and the two interviewers for the children were blind to parental information. One of the child interviewers obtained information from the child, while the other gained information from the mother about the child. These two child interviewers met in conference with the study's child psychiatrist (W.R.B.) to come to an "all sources" consensus diagnosis. Predetermined rules were used for resolving any discrepancies between parental and child reports (Keller et aI., 1986). Statistical Methods

The authors wanted to be able to take into account diagnoses that were ongoing at the time of interview. The cumulative probability of recovery as a function of time from entry into the study was estimated by the Kaplan-Meier method. The Kaplan-Meier method is a way of extending the lifetable method to censored data. The method takes account of varying times of follow-up (Keller et aI., 1982). Results

Fifty-one of the 275 children (19%) in the sample were 205

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diagnosed with a disruptive behavioral disorder. Sixty-seven percent (N = 34 of 51) were males and 33% (N = 17 of 51) were females. Thirty-three percent (N = 17 of 51) received two of the above diagnoses and one (2%) received all three diagnoses. Fifty percent (N = 14 of 28) ofthe entire sample of all children in the high risk "proband" group (those with a parent from the Adult COllaborative Depression Study) were diagnosed with a disruptive behavioral disorder, and 29% (N = 7 of 24) of the children in the relative group were diagnosed with one of these disorders. These rates are much higher than the rates of disorder in the unselected groups: 8% (N = 4 of 49) of the community group, 5% (N = 1 of 21) of the acquaintance group, and 16% (N = 25 of the 153) of the HMO group were diagnosed with a disruptive behavioral disorder. Comorbidity of the Disruptive Behavioral Disorders Thirty-five percent (N = 18 of 51) of the children received more than one of the target diagnoses (i.e., ADD, CD, ODD). The mean age of onset for the diagnosis with the first onset was age seven, and the mean duration of this diagnosis was 6 years. Seventeen percent (N = 3 of 18) of the children with a diagnosis of ADD received an additional diagnosis of CD, 39% (N = 7 of 18) of the children with a diagnosis of ADD received an additional diagnosis of ODD, 39% (N = 7 of 18) of the children with a diagnosis of CD received a diagnosis of ODD, and one of these children received two diagnoses of CD. One child received all three diagnoses. In 39% (N = 7 of 18) of these cases, ADD was the diagnosis of first onset; 22% (N = 4 of 18) of the children had ODD as first onset. Seventeen percent (N = 3 of 18) of the children received a diagnosis of ODD and CD with the same age of onset and 22% (N = 4 of 18) received a diagnosis of ODD and CD at the same time. All but one of the children with more than one diagnosis of ADD, CD, or ODD had one or more additional psychiatric diagnoses. Twenty-two percent (N = 4 of 18) of the children had anxiety symptoms, and 50% (N = 9 of 18) of the children had depressive symptoms, with six of the children meeting definite criteria for major depression. Forty-four percent (N = 8 of 18) of the children received diagnoses of substance use. Comorbidity of Additional Psychiatric Disorders Twenty-four percent (N = 8 of 33) of the children with only one target diagnosis received no additional psychiatric diagnoses, 27% (N = 9 of 33) received one additional diagnosis, 18% (N = 6 of33) received two additional diagnoses, 12% (N = 4 of 33) received three additional diagnoses, and 18% (N = 6 of 33) received four additional diagnoses. Of the 17 children with two target diagnoses, only one received no additional psychiatric diagnoses. Thirty-five percent (N = 6 of 17) received one additional diagnosis, 24% (N = 4 of 17) received two additional diagnoses, and 35% (N = 6 of 17) received three additional diagnoses. The one child who received all three target diagnoses-ADD, CD, and ODD-also received two additional psychiatric diagnoses. The most common' 'additional" diagnosis given was substance use disorder. Twenty-five percent (N = 13 of 51) of the children received this diagnosis, with five of the children

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receiving a diagnosis of substance use disorder for more than one psychoactive substance. Of the eight children with only one diagnosis of substance use disorder, two abused alcohol, five abused drugs, and one was dependent on alcohol. Of the five children with multiple diagnoses of substance use disorder, three abused alcohol, marijuana, and a drug in the "other" category, and one was dependent on both alcohol and an "other" drug. The mean age of onset of these substance use disorders was 14.5 years, and the mean duration up to the time of the interview was 110 weeks. Anxiety disorders were the next most common category of diagnosis (two of these children were diagnosed as having more than one anxiety disorder). Depressive disorders were also quite common in this category. Twenty-five percent (N = 13 of 51) of the children were diagnosed with major depressive disorder, and 18% (N = 9 of 51) of the children had a diagnosis of dysthymia. Parental History of Psychopathology Twenty percent (N = 10 of 51) of the children had one parent with a history of psychiatric illness and 67% (N = 34 of 51) had two parents with psychiatric diagnoses, leaving only 14% (N = 7 of 51) who had parents who did not meet DSM-III criteria for a psychiatric disorder. In the assessment of parental psychopathology, it was found that 12% (N = 6 of 51) of the children had at least one parent with a history of alcoholism, 29% (N = 15 of 51) had a parent with a diagnosis of major depressive disorder, 39% (N = 20 of 51) had parents with a history of both alcoholism and major depressive disorder, and 12% (N = 6 of 51) of the children had a father with a diagnosis of antisocial personality. Seventy-five percent (N = 15 of 20) of the children who were diagnosed with major depression or dysthymia had a parent with major depression. Of the 13 children diagnosed with substance use disorders, 92% (N = 12) had a parent who had a history of alcoholism. Twenty-nine percent (N = 15 of 51) of the children had experienced parental separation or divorce before the onset of their illness. Remission, Recurrence, and Comorbidity in Children with a Diagnosis of ADD Only Twenty-seven percent (N = 14 of 51) of the children received a diagnosis of ADD only (with or without hyperactivity). The mean age of onset was 4 and the mean duration (up to the time of the interview) was 8 years. Fifty percent (N = 7 of 14) of the children had remitted from this disorder, and 71 % (N = 5 of 7) of the remitted children experienced some form of DSM-IlI defined psychopathology after remission (Table 1). Life-table estimates indicate that 9 years after onset, 54% of the children will still be ill (Fig. 1). Fortythree percent (N = 6 of 14) of the children with ADD only also had a history of depressive symptoms, with 21 % (N = 3 of 14) receiving a diagnosis of major depression. Seven percent (N = 1 of 14) of the children also received a diagnosis of substance use disorder. Remission, Recurrence, and Comorbidity in Children with a Diagnosis of CD Only Sixteen percent (N = 8 of 51) of the children received a J. Am. Acad. Child Adolesc. Psychiatry, 31 :2, March 1992

DISRUPTIVE BEHAVIORAL DISORDER 100

TABLE 1. Probability of Relapse and Duration of Episode for

Patients with Attention Deficit, Conduct, and Oppositional Disorder

Probability of Relapse into DSM-lII Episodes(% )a

Diagnosis

N

Mean Duration (yrs)

Attention deficit disorder Conduct disorder Oppositional disorder

14 8

8 3

71 80

11

4

67

80

I....

diagnosis of CD only, with a mean age of onset of 11 years. The mean duration of the disorder was 3 years and 3 months. Sixty-three percent (N = 5 of 8) had remitted, and of these children 50% (N = 4 of 8) experienced psychopathology after remission (Table 1). Life-table estimates indicate that 4 years after onset, 35% of the children will still be ill (Fig. 2). One (13%) of these children remitted from a diagnosis of nonsocialized aggressive conduct disorder and had a subsequent episode of socialized nonaggressive conduct disorder. Thirty-eight percent (N = 3 of 8) of the children received a diagnosis of substance use and 63% (N = 5 of 8) had depressive symptoms, with three of these children meeting criteria for major depression. Remission, Recurrence, and Comorbidity in Children with a Diagnosis of ODD Only Twenty-two percent (N = 11 of 51) of the children received a diagnosis of ODD only. The mean age of onset was 12 and the mean duration of episodes was 4 years. Twenty-seven percent (N = 3 of 11) of these children had remitted and 18% (N = 2 of 11) experienced subsequent psychopathology. Life-table estimates indicate that 8 years after onset, 39% of the children will still be ill (Fig. 3). One of the 11 children (9%) also met criteria for major depression, and two of the children (18%) received a diagnosis of substance use. Pooled Analyses of the Disruptive Behavioral Disorders The mean age of onset for all diagnoses was 8 years. The 100

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FIG. 3. Time to recovery in children with a diagnosis of oppositional defiant disorder only (N = II).

mean duration of the episodes up to the time of the interview was 6 years, and life-table estimates show that approximately 14% of the children will still be ill 15 years after onset of the disorder (Fig. 4). Although almost one-half (23 of 51 = 45%) of the children remitted from these disorders by the time of the initial assessment, 29% (N = 15 of 51) of the children developed psychopathology after remission, with many of them being diagnosed with more than one disorder. Discussion

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FrG. 1. Time to recovery in children with a diagnosis of attention deficit disorder only (N = 14). J. Am. Acad. Child Adolesc. Psychiatry, 31:2, March 1992

Several caveats need to be placed on these findings. The outcome of disruptive behavioral disorders was investigated in a high risk and a community sample of nonreferred children, and the clinical course of these disorders was analyzed separately and together. Because the authors' assessment of psychopathology was retrospective, it was hard to make differential diagnoses of ADD, CD, and ODD that may have had onsets more than 10 years before the assessment. This is especially true given that many clinicians and researchers believe that ODD may be an early manifestation of CD, and that CD may be a complication of ADD. Also, because many of the children studied had more than one of the 207

KELLER ET AL. 100

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FIG. 4. Time to recovery in all 51 children (N = 51).

disruptive behavioral disorders, it was at times difficult for interviewers to specifically delineate the course and outcome of these conditions even when using a structured clinical interview to obtain the psychiatric history. However, raters did have extensive training and were carefully supervised, all reports were carefully reviewed and edited by senior research assistants, and a reliability study done on the major affective disorder diagnosis demonstrated excellent reliability. A formal reliability study was not done on the diagnoses of disruptive behavioral disorders. Finally, as mentioned previously, attention should be paid to the fact that part of this group was recruited from the Collaborative Depression Study proband group (Keller et aI., 1982) and as such are generally at greater risk for psychopathology since their parents had sought treatment at university medical centers for a major affective disorder. The findings show a prevalence of ADD, CD, and ODD in this population, which is similar to that found in the reports of epidemiological studies of the general population (Anderson et aI., 1987; Cantwell, 1977; Shekim et al., 1985). In the total sample of 275 children, 19% received at least one of the above diagnoses, making a total of 51 subjects in this substudy. Many of the children received more than one of these diagnoses, which supports the DSM-III-R's association of these three disorders although also further complicating the ability to study the course of these disorders with clarity. The frequent coexistence of these conditions may contribute to the serious nature of the disorders, the risk of disruption in the child's academic performance, the interpersonal difficulties usually accompanying these conditions, the substance abuse, and the frequent legal difficulties. There were also high rates of other disorders in the children diagnosed as having disruptive behavioral disorders, with 84% of the children receiving at least one other diagnosis, and 27% (N = 14 of 51) receiving a total offive psychiatric diagnoses by the time of the assessment. This concurs with other reports that indicate the children diagnosed with attention deficit disorders have more emotional and personality problems than other children (Schulte-Befera and Barkley, 1985). The rates of comorbidity reported here are also 208

similar to rates reported by Munir et al. (1987), who found that 96% of probands with ADD had one or more additional diagnoses, and 82% had three or more diagnoses. This high rate of disorder, coupled with the complications of ADD, CD, and ODD indicate a poor prognosis for these children as they enter adulthood. The finding that 39% of the children studied here received a diagnosis of an affective disorder is consistent with comorbidity findings from studies of probands with ADD (Biederman et aI., 1986, 1987). In particular, Biederman et aI. (1987) reported that 32% of a sample of children with ADD were also diagnosed with an affective disorder as were 27% of their relatives, whereas in the normal control group there was 0% of major affective disorders and 6% in their firstdegree relatives. Another study has suggested that depression and low self-esteem are associated with ADD and CD because of the academic deficits and resulting low achievement in these children (Cantwell, 1977). High rates of disruptive behavioral disorders were found in the groups of children selected for having a relative with affective disorder. Fifty percent of the entire "proband" group and 29% of the entire "relative" group were diagnosed with disruptive behavioral disorder, a finding that concurs with family studies that show higher rates of affective disorders in probands with ADD compared with normal controls (Biederman et aI., 1986). In studying 56 adults with adult ADHD, Shekim et aI. (1990) found that the majority of those who met Utah Criteria for adult ADHD had additional diagnoses, among which were 25% diagnosed with dysthymic disorder and 25% diagnosed with cyclothymic disorder. The high rates of alcoholism in the parents and the prevalence of substance use disorders in the children is consistent with findings about the high incidence of alcoholism in parents of children with ADD and CD (Cantwell, 1972), and the reports showing that a high percentage of adult alcoholics had symptoms of ADD as children (Wood et aI., 1983), pointing to the risk of alcoholism in children with ADD. In studying the biological parents of 86 outpatient children, Lahey et aI. (1988) found that both parents of children with conduct disorder had a greater tendency toward antisocial personality disorder. The fathers were more prone to exhibiting substance abuse problems whereas the mothers tended toward more depression along with antisocial personality disorder, substance abuse, or somatization disorder. In summary, these three disorders had a very early age of onset, a chronic course with 14% of the children not expected to recover 15 years after onset, and showed comorbidity and familial association with depression. This is consistent with other studies which found that ADDH may persist into adulthood (Gittelman et aI., 1985), CD may persist into adulthood with continued antisocial behavior (Kelso and Stewart, 1986; Satterfield et al., 1982), and ADD and depression aggregate in families (Biederman et aI., 1986, 1987). On the basis of these results, the authors conclude that a prospective, longitudinal follow-up of these children is warranted to determine in detail the course of recovery, recurrence, and chronicity of these disorders as children l. Am. Acad. Child Adolesc. Psychiatry, 31:2, March 1992

DISRUPTIVE BEHAVIORAL DISORDER

enter adulthood. Moreover, given the high proportion of children who have comorbid substance abuse disorders, it would be valuable to trace the temporal and possible causal associations between these conditions and substance abuse, as well as to make an in-depth assessment of other maladaptive and dysfunctional sequelae of these conditions. And sufficiently increased prevalence rates among first-degree relatives suggests the need for a comprehensive study of the familial association of ADD and depression. The implications of these findings for clinical practice point to the large role that early detection can play in the identification of adolescents who may be susceptible to comorbid substance abuse disorders and comorbid affective disorders. Although these data do not allow us to conclude that early intervention will significantly improve the longterm prognosis of disruptive behavioral disorders, the severity and chronicity of these conditions in adolescents is a matter of great concern. This suggests that early active intervention should be strongly considered by clinicians. More definitive treatments must be developed for these disorders. Until new therapeutic advances occur, it would be prudent to employ those treatments that are currently thought to be of value. Careful observation for the onset of affective disorders or of substance abuse should be made regularly by clinicians in patients with disruptive behavioral disorders. References American Psychiatric Association (1980), Diagnostic and Statistical Manual of Mental Disorders, Third Edition. Washington, DC: American Psychiatric Association Press. - - (1987), Diagnostic and Statistical Manual of Mental Disorders, Third Edition-Revised. Washington, DC: American Psychiatric Association Press. Anderson, J. c., Williams, S., McGee, R. & Silva, P. A. (1987), DSMIII disorders in preadolescent children: prevalence in a large sample from the general population. Arch. Gen. Psychiatry, 44:69-76. Beardslee, W. R., Keller, M. B., Lavori, P. W., Klerman, G. L., Dorer, D. J. & Samuelson, H. (1988), Psychiatric disorder in adolescent offspring of parents with affective disorders in a non-referred sample. J. Affective Disord., 313-322.16. Biederman, J., Munir, K, Knee, D. et al. (1986), A family study of patients with attention deficit disorder and normal controls. J. Psychiatr. Res., 20:263-274. - - - - - - et al. (1987), High rate of affective disorder in probands with attention deficit disorder and in their relatives: a controlled family study. Am. J. Psychiatry, 144:330-333. Cantwell, D. P. (1972), Psychiatric illness in the families of hyperactive children. Arch. Gen. Psychiatry, 27:414--417. - - (1977), Hyperkinetic syndrome. In: Child Psychiatry, Modern Approaches, eds. M. Rutter & L. Hersov. London: Blackwell Scientific. Gittleman, R., Mannuzza, S., Shenker, R. & Bonagura, N. (1985), Hyperactive boys almost grown up, 1. psychiatric status. Arch. Gen. Psychiatry, 42:937-947.

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