NO ONE PSYCHIATRIC diagnostic profile characterizes abused children. As several recent reviews have highlighted, child maltreatment is associated with a wide array of clinical outcomes (Green, 1993; Kashani, Daniel, Dandoy, & Holcomb, 1992; Kendall-Tackett, Williams, & Finkel- hor, 1993; Kolko, 1996; Malinosky-Rummell & Hansen, 1993). Little is known, however, about the factors that predispose abused children to develop particular forms of psychopathology.
Major Depressive Disorder (MDD) is a clinical syndrome which is frequently diagnosed in abused children. Rates of MDD in maltreated children and adolescents have been estimated at 18% and 40% (Kaufman, 1991; Pelcovitz et al., 1994), respectively. The rise in rates of depression from childhood to adolescence is consistent with trends observed in epidemiological studies. However,
This study was supported by two interlocking grants from the National Institute of Mental Health: 5K21 MH 01022 (P.I. Joan Kaufman, Ph.D.) and PO5 MH 41712 (P.I. Neal Ryan, M.D.).
Received for publication May 12, 1997; final revision received August 13, 1997; accepted August 13, 1997.
Reprint requests should be addressed to Joan Kaufman, Department of Psychology, Yale University, P.O. Box 208205, New Haven, CT 06520-8205.
171
172 J. Kaufman, B. Birmaher, D. Brent, R. Dahl, J. Bridge, and N. D. Ryan
the rates of MDD reported in abused cohorts are eight to nine times the prevalence rates reported in children and adolescents in the general population (Birmaher et al., 1996).
Increased rates of MDD have also been reported in the parents of maltreated children. In studies of parents recruited from protective services case loads, approximately one-third of the parents have been found to meet criteria for depression (Famularo, Kinscherff, & Fenton, 1992; Kaplan, Pelkovitz, Saltzinger, & Ganeles, 1983; Taylor et al., 1991). Similar findings have been reported in epidemiological samples which avoid the referral biases inherent to the study of protective services cases. In these studies, even after controlling for the effects of age, gender, and socio- economic status, individuals who report physically abusing a child have been found to be two to five times more likely than other adults to meet criteria for a major mood disorder (Bland & Orn, 1986; Dinwiddle & Bucholz, 1993; Egami, Ford, Greenfield, & Crum, 1996).
There is a plethora of evidence to suggest that MDD is familial. Twin and adoption studies suggest that genetic factors account for at least 50% of the variance in the transmission of mood disorders (McGuffin, Katz, & Rutherford, 1991). "Top down" studies also suggest that offspring of affectively ill adults are at increased risk for depression, with rates of MDD in the children of depressed parents estimated to range from 15% to 45% (Hammen, Burge, Burney, & Adrian, 1990; Orvaschel, Walsh-Allis, & Yei, 1988; Weissman et al., 1987). In "bottom up" studies, lifetime rates of depression in the first-degree relatives of depressed children have also been found to be significantly elevated (Kutcher & Marton, 1991; Puig-Antich et al., 1989; Todd, Neuman, Geller, Fox, & Hickok 1993; Williamson et al., 1995).
In addition to increased rates of major depression, the relatives of depressed children have also been found to have increased rates of disorders associated with the subtype of affective illness known as Depression Spectrum Disease (DSD) (Puig-Antich et al., 1989). DSD is associated with increased familial loading for unipolar depression together with increased risk for alcoholism, substance abuse, and/or antisocial personality disorder (Winokur, 1979; Winokur & Coryell, 1992). Increased rates of these same disorders have also been found in clinical (Famularo et al., 1992; Kaplan et al., 1983) and epidemiological (Bland & Orn, 1986; Dinwiddle & Bucholz, 1993; Egami et al., 1996) samples of adults who abuse their children, and are likely notably increased in the families of depressed abused children.
In this study, familial loading for psychopathology is examined in depressed abused, depressed nonabused, and normal control children. It is hypothesized that the type of symptomatology abused children manifest is related to family history of psychopathology. Specifically, relatives of depressed abused children are expected to have increased rates of MDD and depressive spectrum disorders when compared to relatives of normal controls. Rates of MDD in the relatives of depressed abused and depressed nonabused children are expected to be comparable. Rates of depressive spectrum disorders (e.g., alcoholism, substance abuse, antisocial personality disorder), however, are expected to be somewhat elevated in the relatives of depressed abused children.
METHODS
Probands: Sample and Methodology
Proband samples. Family psychiatric history data were collected on the first- and second-degree relatives of 53 children: 13 depressed abused (MDD-AB), 13 depressed nonabused (MDD-NA), and 27 normal control (NC) children. The children included in the two depressed groups were participants in a larger study examining the psychobiological correlates of abuse (Kaufman et al., in press). As nonaffected offspring of adults with depression have been found to have some of the psychobiological abnormalities typical of patients with depression (Giles et al., 1989), inclusion in the normal control cohort of the larger study was contingent on low family history of affective
Caucasian Gender (Female/Male) Socioeconomic Status
Note. Means with different subscripts are statistically different fi'om one another, p < .05.
illness (e.g., no first- or second-degree relative with recurrent MDD). It would therefore not be appropriate to compare the lifetime rates of psychopathology in the relatives of the depressed children to the rates in the relatives of the low- risk normal controls recruited for the psychobio- logical studies. Consequently, the normal controls included in this report represent a previously published sample (Puig-Antich et al., 1989).
Recruitment. Abused and nonabused depressed children were recruited from the inpatient and outpatient clinics at Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center. Normal controls were recruited by random sampling of third, fourth, and fifth graders in an urban elementary school (Puig-Antich et al., 1989). Informed consent to participate in the study was obtained in accordance with Institutional Review Board guidelines.
Inclusion criteria. As many of the normal controls in the family history study conducted by Puig-Antich and colleagues (1989) also participated in interlocking psychobiological investiga- tions, the inclusion and exclusion criteria for all subjects were similar. Inclusion criteria common to all subjects included: (1) 7-13 years of age; (2) Tanner Stage I - I I indicating prepubertal sexual developmental status; and (3) not adopted. Children in both depressed cohorts were required to meet RDC criteria for MDD, and children in the depressed abused cohort were additionally required to have a lifetime history of maltreatment (e.g., physical abuse, sexual abuse, and/or exposure to extreme marital violence). For the normal controls, an additional inclusion criteria included no lifetime history of any psychiatric disorder.
Exclusion criteria. Exclusion criteria for all groups included: (1) significant medical illnesses; (2) medications (except Acetaminophen) within 2 weeks of the study; (3) inordinate fear of needles; (4) obesity (weight greater than 150% of ideal body weight) or severe growth failure (weight or height less than 3% of the National Health Statistic Curve); and (5) mental retardation (IQ < 70) or the presence of a specific learning disability. Additional exclusion criteria for the MDD cohorts only included: (1) concurrent D S M - I I I - R diagnosis of anorexia nervosa, bulimia nervosa, autism, schizoaffective disorder, or schizophrenia; and (2) MDD chronologically secondary to conduct disorder, as children with this specific comorbid condition have been found to have different familial correlates and course of disorder than depressed children without a pre-existing conduct disorder (Harrington, Fudge, Rutter, Pickels, & Hill, 1990; Puig-Antich et al., 1989).
Demographic" characteristics of the proband samples. The demographic characteristics of the depressed abused (MDD-AB), depressed nonabused (MDD-NA), and normal control (NC) cohorts are outlined in Table 1. The mean age of the sample was approximately 10 years of age, 45% were female, and 58% were of minority heritage (39% African American, 19% Hispanic). There were no differences among the groups in terms of age or gender distribution. As all the Hispanic children in the study were from the normal control group, the race distribution of the normal control cohort
174 J. Kaufman, B. Birmaher, D. Brent, R. Dahl, J. Bridge, and N. D. Ryan
differed significantly from the race distribution of the two depressed cohorts. This difference is consistent with the ethnic compositions of New York and Pittsburgh, the two cities where the normal control and depressed subjects were recruited, respectively. The groups also differed in terms of socioeconomic status (SES), with the depressed abused children having lower SES than the MDD-NA group. The SES of the normal control children was intermediate and not significantly different than the SES of either the MDD-AB or MDD-NA children.
Clinical assessment of probands. In the depressed cohorts, current and past psychiatric history information was obtained by administering both the Present Episode (K-SADS-P; Chambers et al., 1985) and Epidemiological (K-SADS-E, Orvaschel & Puig-Antich, 1987) versions of the semi- structured diagnostic interview, the Schedule for Affective Disorders and Schizophrenia for School-Aged Children. Normal controls were only administered the K-SADS-E, as the K-SADS-P contains detailed ratings scales of clinical symptomatology, and is not typically administered to normal controls. The K-SADS interviews were administered by research assistants with extensive training and experience. Comparable procedures were utilized in administering the K-SADS to depressed and normal control cohorts. The K-SADS were administered to parent(s) first, then to the children. Interviews with both informants were completed by the same interviewer, with summary DSM-III-R diagnoses assigned utilizing clinical judgement to synthesize the data provided by both sources. The diagnosis of MDD was made using Research Diagnostic Criteria (RDC; Spitzer, Endicott, & Robins, 1978), with the presence of all positive symptoms confirmed by a child psychiatrist or psychologist.
Clinical characteristics of the proband samples. In terms of clinical characteristics, the MDD-AB and MDD-NA groups were comparable in terms of duration (MDD-AB: 44.0 -+ 37.0 weeks; MDD-NA: 43.5 _+ 53.6 weeks, F(1, 25) = .01, ns) and 12-item K-SADS-P severity rating of current episode of depression (MDD-AB: 34.4 _+ 4.6; MDD-NA: 33.0 + 6.8, F(1, 25) = .02, ns). The two groups were also comparable in terms of proportion of children with comorbid Overanx- ious (31%), Oppositional Defiant (23%), Attention Deficit Hyperactivity (19%), and Separation Anxiety (8%) disorders. Depressed abused children, however, were significantly more likely than the depressed nonabused children to meet criteria for Posttraumatic Stress Disorder (PTSD; 8 vs. 0, Fisher's Exact p < .001) and somewhat more likely to meet criteria for comorbid Dysthymia (6 vs. 2, Fisher's Exact, p < .09).
Abuse histor3' assessment. Abuse history data was only available for children in the two depressed cohorts. Information about abuse was derived by completing the Psychosocial Schedule for School Aged Children (PSS; Kaufman, Brent, & Ryan, 1993; Lukens et al., 1983). The PSS is a semi-structured interview which was designed to obtain information about functional impairment, family environment, and abuse history. Both parents and children were used as informants in collecting this data. Supplemental abuse history data was obtained by reviewing children's medical records, with this information integrated with the information obtained using the PSS to obtain a "best estimate" of children's lifetime abuse experiences (Kaufman, Jones, Stieglitz, Vitulano, & Mannarino, 1994). The majority of the depressed abused children in the study experienced more than one type of abuse. Ten (77%) children had a history of sexual abuse; five (38%) had a history of physical abuse; and l0 (77%) had a history of emotional maltreatment (e.g., exposure to severe domestic violence; verbal rejection and hostile degradation; repeated ignoring of active attempts from the child to engage the parent; terrorizing).
Relatives: Sample and Methodology
Number and demographic characteristics of relatives. The number and demographic characteristics of the relatives included in the study are outlined in Table 2. Consistent with the methodology
Psychopathology in relatives
Table 2. Demographic Characteristics of Adult Relatives
= 117, NC = 259) relatives. The mean number of relatives per proband studied was comparable
for the three groups of children. The three groups were also comparable in terms of gender
distribution mad age of first-degree relatives. The second-degree relatives of the normal controls,
however, were approximately 5 to 6 years younger than the second-degree relatives of the two
depressed cohorts.
Clinical assessment of relatives. All diagnostic interviews with relatives were completed by
research assistants blind to the proband 's diagnoses and abuse status. Psychiatric data on the chi ld 's
mother and/or father was collected by direct interview. The Schedule for Affective Disorders and
Schizophrenia (SADS, Spitzer & Endicott, 1978), a semi-structured diagnostic interview for adults was used to assess psychopathology in parents. Family His tory- -Research Diagnostic Criteria
(FH-RDC, Andreasen, Endicott, Spitzer, & Winokur, 1977) method of diagnosis and pedigree data
acquisition was used to determine lifetime psychiatric history of second degree relatives, with the
proband 's parent(s) used as informants in reporting this data on relatives. The FH-RDC system-
atically surveys symptoms associated with the different diagnostic categories for each relative.
Information about psychiatric hospitalizations, types of treatment received, and functional impair- ment are also obtained to facilitate diagnostic formulations.
ANALYSES
Data available on the normal control cohort included: summary statistics describing the demo- graphic characteristics of the normal control children; summary statistics describing the demo-
graphic characteristics of their first- and second-degree relatives; and rates of disorder for the major
diagnostic classifications. The Mantel-Haenszel procedure was utilized to calculate odds ratios to compare rates of disorder in the relatives of the MDD-AB, MDD-NA, and NC children. All statistical tests of significance were two-tailed. Within the depressed cohorts, logistic regression analyses with maximum likelihood estimates were also conducted, and the effect of variables that were different in these two groups were found to have no significant impact on rates of disorder (e.g., SES, comorbid PTSD).
176 J. Kaufman, B. Birmaher, D. Brent, R. Dahl, J. Bridge, and N. D. Ryan
RESULTS
Lifetime Rates qf Psychopathology in First-Degree Relatives
Table 3 outlines the lifetime rates of psychopathology in first- and second-degree relatives of depressed abused (MDD-AB), depressed nonabused (MDD-NA), and normal control (NC) chil- dren. There were no significant differences in the rates of disorder in the relatives of the MDD-AB and MDD-NA children. When compared to the first-degree relatives of the NC children, however, the first-degree relatives of both the MDD-AB and MDD-NA children bad significantly increased lifetime rates of MDD, Substance Dependence, and Any Psychiatric Disorder. The first-degree relatives of the MDD-AB children also showed a trend toward increased lifetime rates of Antisocial Personality Disorder and Alcohol Dependence when compared to the relatives of the normal controls. Since no first-degree relatives of the normal controls had attempted suicide, it was not possible to calculate odds ratios comparing suicide rates in the relatives of normal control and depressed children. It is noteworthy, however, that a substantial number of the first-degree relatives of the MDD-AB children (28%) and MDD-NA children (17%) had made suicide attempts.
Lifetime Rates qf Psychopathology in Second-Degree Relatives
The second-degree relatives of both the MDD-AB and MDD-NA children had significantly elevated lifetime rates of suicide and any psychiatric disorder when compared to the second-degree relatives of the NC children. The second-degree relatives of the MDD-AB children also had significantly elevated rates of MDD, Alcohol Dependence, and Substance Dependence when compared to the second-degree relatives of the NC children. The second-degree relatives of the MDD-AB children had significantly greater rates of Substance Dependence and a trend toward elevated rates of MDD when compared to the second-degree relatives of the MDD-NA children. The rates of all other disorders were comparable in the second-degree relatives of the MDD-AB and MDD-NA children.
DISCUSSION
The results of this study confirm hypotheses regarding differences in rates of disorder in the relatives of depressed abused (MDD-AB) and normal control (NC) children. When compared to the relatives of NC children, the relatives of the MDD-AB children had significantly elevated rates of MDD. This was true for both first- and second-degree relatives, with the first-degree relatives of the depressed abused children approximately nine times more likely to have a lifetime history of MDD than the first-degree relatives of the normal control children. The relatives of the MDD-AB children also had elevated rates of depressive spectrum disorders (e.g., alcoholism, substance dependence disorders, antisocial personality disorder), and increased rates of suicide attempts. Twenty-eight percent of the first-degree relatives of the MDD-AB children had made a suicide attempt, compared to 0% of the relatives of the normal control children.
It was initially hypothesized that rates of MDD would be comparable in the relatives of MDD-AB and MDD-NA children, and that rates of depressive spectrum disorders (e.g., alcohol- ism, substance dependence, antisocial personality disorder) would be greater in the relatives of the MDD-AB children. While there were no significant differences in the rates of any disorders among the first-degree relatives of the MDD-AB and MDD-NA children, the second-degree relatives of the MDD-AB children had somewhat elevated rates of MDD. This finding is consistent with several studies in adults which have reported higher rates of MDD in the relatives of adults with depressions associated with adverse life events versus adults with depressions independent of life events (Coryell et al., 1994; Zimmerman, Pfohl, Stangl, & Coryell, 1985). The second-degree
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178 J. Kaufman, B. Birmaher, D. Brent, R. Dahl, J. Bridge, and N. D. Ryan
relatives of the MDD-AB children also had significantly higher rates of substance dependence disorders, consistent with initial hypotheses based on prior clinical (Famularo et al., 1992; Kaplan et al., 1983; Taylor et al., 1991) and epidemiological (Bland & Orn, 1986; Dinwiddle & Bucholz, 1993; Egami et al., 1996) studies. To detect greater differences in the familial loading for psychopathology in the relatives of MDD-AB and MDD-NA children, the use of larger samples and more refined methodology, including direct psychiatric interviews with both first- and second- degree relatives, may be required.
There were a number of limitations to the present study. They include:
1. small number of probands; 2. utilization of data on normal controls published almost 10 years ago introducing possible secular
trend confounds (Ryan et al., 1992); 3. use of indirect interviews (e.g., family history method.) to assess psychopathology in second-
degree relatives (Andreasen, Rice, Endicott, Reich, & Coryell, 1986); 4. recruitment of depressed children from a clinic setting introducing a referral bias in subject
selection (Pauls & Kidd, 1982); 5. absence of a no-depression abuse control group.
The findings of the present study were not likely significantly compromised by the last two limitations, since a previous study of a representative sample of abused children recruited from child protective services caseloads which included a no-depression abuse cohort found similar results. In that study, mothers of abused children who met criteria for MDD were found to have significantly greater current depressive symptomatology than mothers of nondepressed abused children (Kaufman, 1991). The present study extends the findings of the prior report by obtaining lifetime and family history psychiatric assessments, and including a no-abuse normal control cohort. The two studies together highlight the importance of familial vulnerability factors in determining type of symptomatology manifest in maltreated children.
Familial vulnerability factors alone, however, do not explain the etiology of depressive disorders in maltreated children. Recent research suggests that individuals at high genetic risk for affective illness are more sensitive to adverse environmental effects than individuals at low genetic risk (Kendler et al., 1995). It appears to be the interaction among inherent vulnerabilities and life stressors that produces depression in predisposed individuals, with both positive and negative factors influencing the likelihood of vulnerable children developing a depressive disorder. For example, in the study cited previously (Kaufman, 1991), in addition to having higher familial loading for depression, abused children who met criteria for a depressive disorder had more severe abuse histories, a greater number of out-of-home placements, and fewer available positive supports than nondepressed abused children.
While many of the early writings in the area of child maltreatment were heavily influenced by psychiatric formulations (e.g., Steele & Pollack, 1968), over the past two decades psychiatric models have been minimized (e.g., Gelles, 1973, 1993). In two recent prospective longitudinal studies, however, the presence of parental depression at initial assessment predicted new cases of abuse at 1 year follow-up, even after controlling for multiple social factors (Chaffin, Kelleher, & Hollenberg, 1996; Kotch et al., 1995). These and other studies highlight the importance of including psychiatric assessments in studies on the etiology, prevention, treatment, and sequelae of child abuse. The results also highlight the importance of assessing depression in parents of abused children, and inquiring about the child rearing practices of depressed adults. Appropriate interven- tions should then be provided as needed.
Numerous child, family, social, and abuse-related factors have been identified which influence symptom presentation in abused children (Berliner & Elliot, 1996; Kaufman, 1996). More research is required to understand how inherent vulnerability factors interact with these risk and protective factors to produce psychopathology in abused children. Such studies will help to enhance our
Psychopathology in relatives 179
understanding of the sequelae of abuse, and infbrm the development of more efficacious multi- modal treatment interventions.
Acknowledgement~he authors would like to thank the staff, children, and families whose efforts made this study possible.
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RI~SUMI~
Objectif: DEterminer si le type de sympt6mes que manifestent les enfents maltraitEs est lie b~ l'anamnEse psycho- pathologique de leur famille. M~thode: On a retenu 26 pr6-adolescents dont 13 6taient maltraitEs et dEprimEs (groupe MDD-AB) et 13 qui 6taient dEOrimEs mais non abuses (groupe MDD-NA). Le taux de dEsordre mental des membres de leurs families a 6tE compare au tuax de psychopathologie de 27 enfants normaux dans un groupe contr61e (groupe NC). On a recueilli des donnEes sur 104 membres immEdiats de leurs famille (25 du groupe MDD-AB; 29 du groupe MDD-NA; et 50 du groupe NC) et sur 503 membres distants de la famille (127 du groupe MDD-AB; 117 du groupe MDD-NA et 259 du groupe NC). Pour 6valuer la psychopathologie des parents on s'est servi du Schedule for Affective Disorders and Schizophrenia. Pour recueillir des donnEes sur la santE mentale pour le reste des membres de la famille, on a eu recours h l'anamnbse familiale. R~sultats: ComparEs aux membres imm~diats de la famille du groupe contr61e, ceux du groupe MDD-AB Etaient neuf fois plus aptes h vivre une depression importante et entre 3 et 9 lois plus aptes ~ connaitre des difficultEs qu'on associe aux maladies dites. "Depression Spectrum Diseases" (maladies dans la gamme de depression, telles que la presonnalitE anti-sociale et la dependance sur l'alcool et les substances psychoactives). On a note des constats semblables chez les membres plus distants de la famille et aussi lorsqu'on a compare les membres de la famille des groupes MDD-NA et NC. Conclusions: Les constats s'accordent avec des recherches antErieures et (1) portent h croire qu'il existe des facteurs de
Psychopathology in relatives 181
vuln6rabilit6 familiale qui influence le profil symptomatique des enfants maltrait6s et (2) soulignent l'importance d'inclure des formulations psychiatriques dans des mod61es pluridisciplinaires de recherches qui traitent des mauvais traitements et des programmes de traitement.
R E S U M E N
Objectivo: Determinar si el tipo de sintomatolog/a que manifiestan los nifios abusados estfi relacionada con una historia familiar de psicopatologia. M~todo: Se evaluaron la historia de psicopatolog/a en la vida de los familiares de 26 preadolescentes--13 nifios abusados depresivios (MDD-AB) y 13 nifios depresivos no abusados (MDD-NA). Se obtuvieron datos de parientes de primer grado, (MDD-AB = 127, MDD-NA 29, NC = 50 y 503 parientes de segundo grado (MDD-AB = 127, MDD-N 117, NC - 259). Para evaluar la psicopatologia en los padres se us6 el Inventario de los Des6rdenes Afectivos y Esquizofrenia, y el m6todo de la Historia Familiar se utiliz6 para obtener datos psiquifitricos de la vida de todos los otros parientes. Resultados: AI compararse con parientes de primer grado de nifios NC, los parientes de primer grado de nifios MDD-AB tenfan aproximadamente nueve veces mayor riesg de depresi6n mayor, y de tres a nueve veces mayor riesgo de otros des6rdenes asociados con el subtipo familiar de enfermedad afectiva conocida como Spectrum de la Enfermedad Depresiva (e.g. personalidad antisocial, dependencia del alcohol y sustancias). Se reportaron hallazgos similares en parientes de segundo grado, y las comparaciones entre los parientes de nifios MDD-NA y nifios NC. Conelusiones: Los hallazgos extienden los resultados de investigaciones anteriores y 1) sugieren que factores de vulnerabilidad familiar influyen el perfil sintomfitico de los nifios abusados: y 2) resaltan el valor de incorporar consid- eraciones psiquifitricas en los modelos multidisciplinarios de investigaciones y programas de tratamiento del abuso a los nifios.
