Families at high and low risk for depression: a 3-generation study

BACKGROUND: The familial nature of early-onset major depressive disorder (MDD) has been documented in numerous family studies of adults and is supported by studies of offspring of parents with MDD, for whom the risk is more than 3-fold. None of the published high-risk studies have gone beyond 2 generations, and few have a longitudinal design. We report results of an approximately 20-year follow-up of families at high and low risk for depression. The first 2 generations were interviewed 4 times during this period. The offspring from the second generation are now adults and have children of their own, the third generation of the original cohort. OBJECTIVE: To examine the familial aggregation of psychiatric disorders and functioning in grandchildren by their parents' and grandparents' depression status. DESIGN: Longitudinal, retrospective cohort, family study. PARTICIPANTS: One hundred sixty-one grandchildren and their parents and grandparents. MAIN OUTCOME MEASURES: Lifetime rate of psychiatric disorder and functioning in grandchildren, stratified by parental and by grandparental depression status, collected by clinicians blind to diagnoses of previous generations and to previous interviews. RESULTS: There were high rates of psychiatric disorders, particularly anxiety disorders, in the grandchildren with 2 generations of major depression, with 59.2% of these grandchildren (mean age, 12 years) already having a psychiatric disorder. The effect of parental depression on grandchildren's outcomes differed significantly with grandparental depression status. Among families with a depressed grandparent, increased risk of anxiety (relative risk, 5.17; 95% confidence interval, 1.4-18.7; P = .01) and increased risk of any disorder (relative risk, 5.52; 95% confidence interval, 2.0-15.4; P = .002) were observed in grandchildren with a depressed parent as compared with those with nondepressed parents. The severity of parental depression, as measured by impairment, significantly increased the rate of a mood disorder in these grandchildren (relative risk, 2.44; 95% confidence interval, 1.1-5.5; P = .03). In contrast, among grandchildren with nonfamilial depression, ie, depressed parents with no depressed grandparents, there was no significant effect of parental MDD on grandchildren diagnoses. However, parental MDD, regardless of whether families had a depressed grandparent, had a significant impact on the grandchildren's overall functioning. Potential confounding variables did not affect the strength of the association with parental and grandparental depression. CONCLUSIONS: The association between parental MDD and child diagnosis is moderated by grandparental MDD status. The rates of psychopathology are highest in grandchildren of parents and grandparents with a moderately to severely impairing depression. Anxiety disorders are the early sign of psychopathology in the young grandchildren. Early interventions in the offspring of 2 generations affected with moderately to severely impairing MDD seem warranted. This familial group may be the target for neuroimaging, genetic, and other biological studies.     

Family factors contributing to emotional and behavioral problems in Korean adolescents with epilepsy

PurposeWe aimed to determine whether different aspects of family functioning are associated with emotional and behavioral problems in adolescents with epilepsy and, if not, to document any indirect associations mediated by other family factors.MethodsThis was a cross-sectional, multicenter study. A total of 297 adolescents with epilepsy and their parents participated. Adolescent psychopathology was measured using the Youth Self-Report. Family factors were classified into proximal (parent–child interaction), distal (parent characteristics), and contextual factors (family characteristics) in accordance to their level of proximity to the adolescent's everyday life. Regression analyses were used to analyze the unique and combined predictive power of family factors in relation to psychopathology.ResultsIn total, 44 (14.8%) and 51 (17.2%) adolescents with epilepsy scored above the borderline cutoff (T-score ≥ 60) of internalizing and externalizing problems, respectively. Proximal and distal factors were independently associated with both internalizing and externalizing problems. High levels of parental depressive mood and parental overcontrol were the strongest factors contributing to internalizing and externalizing problems, respectively. Contextual factors were indirectly associated with both internalizing and externalizing problems through more proximal factors.ConclusionsBoth proximal and distal family factors affect psychopathology in Korean adolescents with epilepsy. Parental feelings of depression and parental overcontrol are the strongest factors contributing to internalizing and externalizing problems, respectively.     

The continuity of psychopathology from early childhood to preadolescence

Objective To study the continuity of psychopathology from the age of 3–12 years. Methods In a population-based birth cohort, children’s emotional and behavioral problems were assessed at age 3 using the Child Behavior Checklist 2–3 (CBCL 2–3), and at age 12 by parents using the CBCL 11–18, and the Youth Self Report (YSR) completed by the children. Behavioral ratings were obtained from 800 subjects at both time points. Results externalizing problems at age 3 predicted both externalizing and internalizing problems among both genders in preadolescence. In girls, internalizing behavior at age 3 predicted parent-reported internalizing behavior, and associated negatively with externalizing behavior in self-reports at age 12. Aggressive behavior was found to be remarkably stable, and both aggressive and destructive behavior independently predicted a wide range of later externalizing and internalizing problems. Parent ratings of withdrawal showed stability from early childhood to preadolescence in both genders. Somatic complaints of 3-year-old girls independently predicted both externalizing and internalizing problems. Conclusions The results show the complexity of pathways in psychopathology from early childhood to preadolescence. In particular, aggressive and destructive behaviors in very early childhood predict later problems and necessitate early recognition and possible intervention at an early age. An instrument like the CBCL 2–3 is valuable in the early detection of children at risk of long-term problems.     

Self-reported emotional and behavioral symptoms,parent-adolescent bonding and family functioning in clinically referred adolescent offspring of Croatian PTSD war veterans

The presence of posttraumatic stress disorder (PTSD) in male war veterans has been linked with family dysfunction and psychopathology in their children [1, 2]. This study aimed to evaluate self-reported emotional and behavioral symptoms, parent–adolescent bonding and family functioning in clinically referred adolescent offspring of Croatian PTSD war veterans and determine the degree that parent–child bonding and family functioning contributed to adolescent behavior problems. Internalizing and externalizing behavior problems, parent–child bonding and family functioning were assessed in a sample of clinically referred Croatian PTSD veterans adolescent offspring (N = 122) and non-PTSD veteran adolescent offspring (N = 122) matched for age, sex, educational level, family income, parental employment status, ethnicity, and residential area. Youth Self-Report, Parental Bonding Instrument, Family Assessment Device were used. Adolescent offspring of PTSD veterans reported having significantly more internalizing and externalizing problems than non-PTSD veteran offspring, and also more difficulties in their family functioning, lower levels of maternal and paternal care, and more impaired mother–child and father–child bonding than control subjects. Internalizing symptoms were associated with family dysfunction, while externalizing symptoms were associated with paternal overcontrol/overprotection, and low maternal and paternal care. In conclusion, the increase in internalizing and externalizing symptoms as well as family and parental dysfunction among clinically referred adolescent offspring of PTSD veterans compared to their non-PTSD veteran counterparts indicates a need for early detection and interventions targeting both adolescent psychopathology and family relationships.     

Suicide attempts and externalizing psychopathology in a nationally representative sample

Suicide is most often associated with internalizing disorders such as depression; however, recent evidence suggests that externalizing psychopathology (substance dependence disorders, antisocial personality disorder) may have an independent relationship with suicidal behavior. The aim in the present study was to examine the relationship between lifetime suicide attempts and lifetime externalizing psychopathology in the US National Comorbidity Survey data set (n = 5877). First, hierarchical regression was performed to explore the associations between internalizing and externalizing disorders and suicide attempts. Externalizing psychopathology was significantly associated with lifetime suicide attempts (adjusted odds ratio = 3.47; P < .001) and significantly improved the model beyond that including only the sociodemographic variables and internalizing psychopathology (chi(2) difference = 73.12; df = 1; P < .001). A second logistic regression was used to investigate the association between specific patterns of psychopathology and suicidality. Externalizing disorders were significantly associated with suicide attempts even in the absence of internalizing disorders (adjusted odds ratio = 5.98; 95% confidence interval = 3.07-11.67; P < .001). These findings add to the growing literature that suggests that externalizing psychopathology is an important psychiatric correlate of suicidal behavior.     

Relations Between Parent Psychopathology, Family Functioning, and Adolescent Problems In Substance-Abusing Families: Disaggregating the Effects of Parent Gender

The present study: (1) examined relations between parent psychopathology and adolescent internalizing problems, externalizing problems, and substance use in substance-abusing families; and (2) tested family functioning problems as mediators of these relations. Structural equation modeling was used to estimate the independent effects of parent psychopathology and family functioning problems by parent gender. Participants included 242 parents in treatment for substance abuse and/or dependence and 59 of their coparents (16.9% in treatment for substance-abuse/dependence) from middle income households (SES: M = 4.7; SD = 2.1). Ratings were obtained for 325 adolescents (48% female; 27.8% non-Caucasian) between the ages of 10 and 18 years (M = 13.5 years; SD = 2.5 years). Parent psychopathology, family functioning problems, and adolescent problems were assessed with parent and coparent ratings on the Symptom Checklist (SCL-90)/Brief Symptom Inventory (BSI), the Family Relationship Measure, and the Child Behavior Checklist, respectively. Results indicated that maternal psychopathology was directly related to adolescent internalizing problems and substance use, but maternal perceptions of family functioning problems failed to mediate relations between maternal psychopathology and adolescent problems. By contrast, paternal perceptions of family functioning problems uniquely mediated relations between paternal psychopathology and adolescent externalizing problems. Findings underscore the importance of examining how mothers and fathers may differentially impact adolescent problems in substance-abusing families.     

Early preschool predictors of preadolescent internalizing and externalizing DSM-IV diagnoses

OBJECTIVE: To investigate the independent predictive value of parent-reported psychopathology and family risk factors in early preschool in relation to parent-reported internalizing and externalizing psychopathology in preadolescence. METHOD: Subjects were participants in a longitudinal study of 420 two- to three-year-olds from the general population of Zuid-Holland, the Netherlands, which started in 1989. At a second follow-up 8 years later (ages 10-11 years), 358 children participated. For this study, 332 children were included for whom DSM-IV diagnoses (derived from the Diagnostic Interview Schedule for Children-Version 4-Parent Version) were obtained at age 10 to 11 years. Preschool risk factors were obtained through the Child Behavior Checklist for ages 2 to 3 years and a parent interview. RESULTS: Early preschool internalizing and externalizing problems were predictive of their DSM-IV counterparts 8 years later, independent of the influence of early parent-reported family risk factors. Preschool child physical problems were independently predictive of both internalizing and externalizing diagnoses in preadolescence. Of the environmental risk factors, only stressful life events contributed independently to the prediction of later externalizing problems. CONCLUSION: Early adverse family circumstances and parenting characteristics do not contribute to the prediction of later psychopathology once child characteristics are accounted for.     

Suicide attempts associated with externalizing psychopathology in an epidemiological sample

OBJECTIVE: Borrowing from recent dimensional models of psychopathology, the authors conducted analyses that optimized the common variance shared by internalizing (depression, anxiety) and externalizing (antisocial personality, substance dependence) disorders in statistically predicting suicidal behaviors. These relationships were analyzed in a large epidemiological sample, thus allowing for the examination of gender differences in risk for suicide attempts associated with psychopathology. METHOD: The data were obtained from the Colorado Social Health Survey. Participants (N=4,745) were a community sample recruited by household address. Structured clinical interviews were used to obtain lifetime diagnostic and symptom count information. Symptom counts were included in a factor analysis that yielded two main dimensions of psychopathology: internalizing and externalizing. These factors were used in hierarchical logistic regression analyses to predict history of suicide attempts associated with the presence of internalizing symptoms, externalizing symptoms, and comorbid internalizing and externalizing symptoms. RESULTS: After the investigators controlled for the presence of internalizing symptoms and the comorbidity of internalizing and externalizing symptoms, externalizing symptoms were related to suicidal behavior in both men and women, although comorbidity was most predictive of suicide attempts among women, compared to men. CONCLUSIONS: Suicidal behavior among individuals with externalizing symptoms is not necessarily a result of comorbid depressive or other internalizing disorder. Thus, persons exhibiting antisocial behaviors should receive rigorous assessment for suicidal ideation and behavior.     

HPA-axis activity and externalizing behavior problems in early adolescents from the general population: the role of comorbidity and gender The TRAILS study

Contradictory findings on the relationship between hypothalamus-pituitary-adrenal (HPA)-axis activity and externalizing behavior problems could be due to studies not accounting for issues of comorbidity and gender. In a population-based cohort of 1768 (10- to 12-year-old) early adolescents, we used a person-oriented approach and a variable-oriented approach to investigate whether comorbidity with internalizing behavior problems and gender moderate the relationship between HPA-axis activity (cortisol awakening response and evening cortisol levels) and externalizing behavior problems. We found that: (1) in early adolescents with pure externalizing behavior problems, there was a particularly strong effect of gender, in that girls showed significantly higher total cortisol levels after awakening (AUC(G) levels) and a significantly higher cortisol awakening response (AUC(I) levels) than boys. (2) Girls with pure externalizing behavior problems showed a significantly higher cortisol awakening response (AUC(I) levels) than girls without behavior problems or girls with comorbid internalizing behavior problems. This effect was absent in boys. (3) Externalizing behavior problems, in contrast to internalizing behavior problems, were associated with higher evening cortisol levels. This effect might, however, result from girls with externalizing behavior problems showing the highest evening cortisol levels. Overall, we were unable to find the expected relationships between comorbidity and HPA-axis activity, and found girls with pure externalizing behavior problems to form a distinct group with regard to their HPA-axis activity. There is need for prospective longitudinal studies of externalizing behavior problems in boys and girls in relation to their HPA-axis activity. It would be useful to consider how other risk factors such as life events and family and parenting factors as well as genetic risks affect the complex relationship between externalizing behavior problems and HPA-axis activity.     

Influence of adult domestic violence on children's internalizing and externalizing problems: an environmentally informative twin study

OBJECTIVE: Externalizing and internalizing problems may aggregate in families because (1) siblings share genetic risks for problem behaviors or (2) siblings are exposed to similar environmental risks. A genetically sensitive design was used to determine whether domestic violence accounted significantly for the variation and covariation of externalizing and internalizing problems, independent of additive genetic effects on these behavior problems. METHOD: Using the Achenbach family of instruments, mothers and teachers reported internalizing and externalizing problems for 1,116 monozygotic and dizygotic 5-year-old twin pairs in the United Kingdom (93% response rate). Mothers reported their experiences of domestic violence in the previous 5 years. Structural equation models were tested to determine the effect of mothers' experiences of domestic violence on children's emotional and conduct problems, controlling for latent genetic and environmental effects on these behaviors. RESULTS: A multivariate model showed that adult domestic violence accounted for 2% and 5% of the variation in children's internalizing and externalizing problems, respectively, independent of genetic effects. The co-occurrence of externalizing and internalizing scores was accounted for by genetic (62.6%) and shared environmental (29.2%) factors and by domestic violence (8%). CONCLUSIONS: Because domestic violence affects children's behavior problems beyond genetic influences, programs that successfully reduce domestic violence should also prevent children's psychopathology.     

Predicting internalizing and externalizing problems at five years by child and parental factors in infancy and toddlerhood

This study examined child and parental factors in infancy and toddlerhood predicting subclinical or clinical levels of internalizing and externalizing problems at 5 years of age. Ninety-six children and their families participated. They were assessed when the children were 4–10 weeks old (T1), 2 years (T2) and 5 years old (T3). Child risks (difficult temperament, health problems, early emotional and behavioral problems), parental risks (psychopathology, parenting stress and perception of the child) and family risks (socio-economic status, quality of marital relationship and family violence) were examined. At 5 years, internalizing problems were predicted by family violence during the child’s infancy and parenting stress at age 2. Externalizing problems were predicted by psychiatric problems of the mother before pregnancy and child’s externalizing problems at 2 years of age. When interventions aiming at preventing emotional and behavioral problems in children are considered, these issues should be recognized early and effective intervention initiated.     

The pathway of internalizing and externalizing problems from childhood to adolescence: a prospective study from age 7 to 14-16 in Korea

This study prospectively investigated developmental psychopathology pathway from the age of 7 to ages 14–16. The subjects (N = 1,857) were evaluated using the Korean version of the Child Behavior Checklist and reassessed using the Korean Youth Self Report. In path analyses, total problems, externalizing problems, and internalizing problems in childhood associated significantly with problems in adolescence. In particular, childhood externalizing problems associated with adolescent externalizing problems, for both genders. However, our results differ from those of previous studies in that internalizing problems showed a restrictive stability by gender and in that early externalizing problems correlated negatively with later internalizing problems for girls. In the syndrome scales analyses, we confirmed that some syndromes showed heterotypic pathways, despite the general continuity of the developmental psychopathology. The importance of Anxiety/Depression and Attention problems in childhood suggested that adolescent difficulties are a consequence of an accumulation of such risk factors.     

Examination of the structure of psychopathology using latent class analysis

Several recent studies using factor analytic methods find that the structure of psychopathology reflects broad internalizing and externalizing dimensions, with the internalizing dimension being further divided into fear and distress disorders. Although these variable-centered studies have provided important insights into the structure of psychopathology, they provide limited information about the classification of individual cases. The present study examines patterns of lifetime internalizing and externalizing psychopathology in participants from the Oregon Adolescent Depression Project using latent class analysis that classifies individuals rather than variables. A 4-class solution best fits the data. The largest class (62.5%) included individuals with relatively little psychopathology; 1 class (16.4%) was largely characterized by internalizing disorders, 1 class (16.9%), largely characterized by externalizing disorders; and the final class (4.2%), characterized by both internalizing and externalizing disorders. The validity of the classes was further examined using data on psychiatric morbidity, temperament, and family aggregation of psychopathology. Classes differed on indices of positive, negative, and disinhibited temperament in ways that were consistent with theoretical predictions. Patterns of familial aggregation of psychopathology demonstrated relative specificity of transmission of different disorders. Overall, the findings support conclusions from studies of dimensional models of internalizing and externalizing disorders, and extend them to person-centered approaches to classification.     

Exploring mediating factors in the association between parental psychological distress and psychosocial maladjustment in adolescence

Abstract  

Parental psychopathology is associated with increased psychosocial maladjustment in adolescents. We examined, from a psychosocial perspective, the association between parental psychological distress and psychosocial maladjustment in adolescents and assessed the mediating role of psychosocial covariates. This is a cross-sectional survey and the setting include representative sample of Quebec adolescents in 1999. The participants of the study include 13- and 16-year-old children (N = 2,346) in the Social and Health Survey of Quebec Children and Adolescents. The main outcome measures are internalizing disorders, externalizing disorders, substance use, and alcohol consumption. For statistical analysis, we used structural equation modeling to test for mediation. Internalizing and externalizing disorders were significantly associated with parental psychological distress, but not substance use or alcohol consumption. The higher the parental distress, the higher the risk of adolescent mental health disorders. The association between parental psychological distress and internalizing disorders was mediated by adolescent self-esteem, parental emotional support and extrafamilial social support. As for externalizing disorders, these variables only had an independent effect. In conclusion, A family’s well being is a necessary condition for psychosocial adjustment in adolescence. Beyond the psychiatric approach, psychosocial considerations need to be taken into consideration to prevent negative mental health outcomes in children living in homes with distressed parents.     

Depressive symptoms and associated psychopathology in urban adolescents: a cross-cultural study of three countries

The study aimed to compare cross-cultural trends of comorbid internalizing and externalizing psychopathology, prosocial beliefs, and perceptions of risk in adolescents with and without clinical levels of self-reported depressive symptoms. The Social and Health Assessment, a self-report survey, was conducted in a representative sample of 3309 adolescents 14 to 17 years old from urban communities in the United States (N = 1343), Belgium (N = 946), and Russia (N = 1009). In all three countries, girls reported higher levels of depressive symptoms than boys. The findings also demonstrate that in both genders, depressive symptoms were associated with increased levels of internalizing and externalizing problems, as well as lower levels of prosocial beliefs and low perceptions of harm from risk-taking behavior. Depressed boys had relatively higher levels of externalizing problems than depressed girls. Greater levels of internalizing problems observed in depressed youth, as compared with their nondepressed counterparts, were not gender-specific. Current findings suggest that the relationships between depression and comorbid psychopathology are not culture-specific and have similar patterns in different populations.     

Exploring the Effects of Parental Involvement on Broad and Specific Dimensions of Behavioral Problems in Adolescence

Few studies have differentiated the specificity from the generality of the associations between parental involvement and adolescent behavioral problems across levels of the psychopathology hierarchy. Among 537 adolescents aged 11–17 years, the current study considered the extent to which associations between mother- and father- involvement and behavioral problems (assessed via the parent-reported Child Behavior Checklist) were unique to a specific dimension or reflective of associations with higher-order factors. The hierarchical structure of behavioral problems fit well, with total problems at the top, internalizing and externalizing at the second level, and eight specific symptom dimensions at the third level. Mother and father involvement were protective factors for withdrawn/depressed symptoms and risk factors for anxious/depressed symptoms that were not accounted for by internalizing or total problems. Mother involvement was also a protective factor for rule-breaking behavior and a risk factor for social problems symptoms and aggressive behavior symptoms that were not accounted for by externalizing or total problems.

     

Parents of children with psychopathology: psychiatric problems and the association with their child’s problems

Knowledge is lacking regarding current psychopathology in parents whose children are evaluated in a psychiatric outpatient clinic. This especially accounts for fathers. We provide insight into the prevalence rates of parental psychopathology and the association with their offspring psychopathology by analyzing data on psychiatric problems collected in 701 mothers and 530 fathers of 757 referred children. Prevalence rates of parental psychopathology were based on (sub)clinical scores on the adult self report. Parent–offspring associations were investigated in multivariate analyses taking into account co-morbidity. Around 20 % of the parents had a (sub)clinical score on internalizing problems and around 10 % on attention deficit hyperactivity (ADH) problems. Prevalence rates did not differ between mothers and fathers. Parent–offspring associations did not differ between girls and boys. Maternal anxiety was associated with all offspring problem scores. In addition, maternal ADH problems were associated with offspring ADH problems. Paternal anxiety and ADH problems scores were specifically associated with offspring internalizing and externalizing problem scores, respectively. Associations with offspring psychopathology were of similar magnitude for mothers and fathers and were not influenced by spousal resemblance. Our study shows that both fathers and mothers are at increased risk for psychiatric problems at the time of a child’s evaluation and that their problems are equally associated with their offspring problems. The results emphasize the need to screen mothers as well as fathers for psychiatric problems. Specific treatment programs should be developed for these families in especially high need.     

Maternal Pre-pregnancy Body Mass Index and Offspring Temperament and Behavior at 1 and 2 Years of Age

Recent research suggests that fetal exposure to increased maternal body mass index (BMI) during pregnancy may be associated with psychopathology later in life. When this link first emerges, and if it is due to intrauterine exposures or confounding variables is not known. We therefore assessed associations between maternal pre-pregnancy BMI and: (1) temperament at 1 year of age, and (2) Child Behavior Checklist internalizing and externalizing scales at age 2 in the 2900 mothers and infants enrolled in the Western Australian Pregnancy Study. Pre-pregnancy BMI was positively associated with externalizing scores (β = 0.131, 95 % CI 0.013–0.249) at age 2, even after adjustment for confounders, but not with internalizing scores or an increased risk of difficult temperament. These data suggest that fetal exposure to increased maternal BMI is associated with elevated levels of behavior problems as early as age 2, and that this may be linked to the intrauterine environment.     

Temperament Traits and Psychopathology in Young Clinically Referred Children Compared to a General Population Sample

Evidence from general population studies shows the contribution of various temperament traits to the development of child psychopathology. Little is known about which traits are associated with internalizing and externalizing problems in young clinically referred children. The current study assessed temperament and internalizing and externalizing problems in 216 referred children (M?=?4.35 years, SD 0.89, 81% boys). A comparison was made with an age and gender matched general population sample. Referred children showed less effortful control than general population children. Less effortful control and more negative affectivity were associated with more internalizing and externalizing problems across groups. Surgency, and specifically temperamental impulsivity, was more strongly associated with externalizing problems in referred children compared to general population. Less soothability, less inhibitory control and more frustration predicted (sub)clinical levels of comborbid internalizing and externalizing problems in referred children. The results can be used in diagnostic and treatment procedures in early childhood.     

Grandparents, parents, and grandchildren at high risk for depression: a three-generation study

OBJECTIVE: High-risk studies of psychiatric disorders in parents and offspring that include 3 generations are uncommon. Multigenerational studies can be clinically useful as they can provide information for risk prediction from one generation to another for the development of empirically based interventions. Using a high-risk design, this study examines the association of grandparent major depressive disorder (MDD) and parent MDD with psychopathology in grandchildren. METHOD: Using Cox proportional hazards in a sample of 90 grandchildren at high and low risk for depression by virtue of their grandparents' and parents' depression status, the authors examined the risk for offspring depression and anxiety. RESULTS: Grandparent and parent MDD were associated with grandchild anxiety (relative risk [RR] = 5.51 and R = 3.09, respectively). Grandchildren with both a depressed parent and grandparent had the highest risk for anxiety. Parental MDD is associated with an increased risk for grandchild disruptive disorder (RR = 10.77). Forty-nine percent of the grandchildren in families in which both the parent and grandparent were depressed had some form of psychopathology. The grandchildren from those families were the most impaired. CONCLUSIONS: Prepubertal-onset anxiety disorder is a risk factor for the later development of clinically significant recurrent MDD across several generations of families at high risk for depression. Parental impaired functioning increases the risk for disruptive disorders. Children in families with multiple generations of depression are at particularly high risk for some form of psychopathology.