Patterns of psychopathology and dysfunction in high-risk children of parents with panic disorder and major depression

OBJECTIVE: The purpose of the study was to evaluate 1) whether an underlying familial predisposition is shared by all anxiety disorders or whether specific risks are associated with specific disorders, and 2) whether panic disorder and major depression have a familial link. METHOD: The study compared four groups of children: 1) offspring of parents with panic disorder and comorbid major depression (N=179), 2) offspring of parents with panic disorder without comorbid major depression (N=29), 3) offspring of parents with major depression without comorbid panic disorder (N=59), and 4) offspring of parents with neither panic disorder nor major depression (N=113). RESULTS: Parental panic disorder, regardless of comorbidity with major depression, was associated with an increased risk for panic disorder and agoraphobia in offspring. Parental major depression, regardless of comorbidity with panic disorder, was associated with increased risks for social phobia, major depression, disruptive behavior disorders, and poorer social functioning in offspring. Both parental panic disorder and parental major depression, individually or comorbidly, were associated with increased risk for separation anxiety disorder and multiple (two or more) anxiety disorders in offspring. CONCLUSIONS: These findings confirm and extend previous results documenting significant associations between the presence of panic disorder and major depression in parents and patterns of psychopathology and dysfunction in their offspring.     

A controlled study of behavioral inhibition in children of parents with panic disorder and depression

OBJECTIVE: "Behavioral inhibition to the unfamiliar" has been proposed as a precursor to anxiety disorders. Children with behavioral inhibition are cautious, quiet, introverted, and shy in unfamiliar situations. Several lines of evidence suggest that behavioral inhibition is an index of anxiety proneness. The authors sought to replicate prior findings and examine the specificity of the association between behavioral inhibition and anxiety. METHOD: Laboratory-based behavioral observations were used to assess behavioral inhibition in 129 young children of parents with panic disorder and major depression, 22 children of parents with panic disorder without major depression, 49 children of parents with major depression without panic disorder, and 84 children of parents without anxiety disorders or major depression (comparison group). A standard definition of behavioral inhibition based on previous research ("dichotomous behavioral inhibition") was compared with two other definitions. RESULTS: Dichotomous behavioral inhibition was most frequent among the children of parents with panic disorder plus major depression (29% versus 12% in comparison subjects). For all definitions, the univariate effects of parental major depression were significant (conferring a twofold risk for behavioral inhibition), and for most definitions the effects of parental panic disorder conferred a twofold risk as well. CONCLUSIONS: These results suggest that the comorbidity of panic disorder and major depression accounts for much of the observed familial link between parental panic disorder and childhood behavioral inhibition. Further work is needed to elucidate the role of parental major depression in conferring risk for behavioral inhibition in children.     

Psychopathology in the young offspring of parents with bipolar disorder: a controlled pilot study

Studies have suggested that the offspring of parents with bipolar disorder are at risk for a spectrum of psychopathology, but few have focused on children in the youngest age ranges or examined the impact of comorbid parental disorders. We utilized a pre-existing sample of young (mean age: 6.8 years) offspring of parents with bipolar disorder (n=34), of parents with panic or major depression (n=179), and of parents with neither mood or anxiety disorder (n=95). Children were assessed blindly to parental diagnoses using the Schedule for Affective Disorders and Schizophrenia-Epidemiologic version (K-SADS-E). Offspring of bipolar parents had significantly higher rates of disruptive behavior and anxiety disorders than offspring from both of the comparison groups, accounted for by elevated rates of ADHD and overanxious disorder. These comparisons were significant even when lifetime histories of the corresponding categories of comorbid disorders in the parents (disruptive behavior disorders and anxiety disorders) were covaried. In addition, offspring of bipolar parents had increased rates of bipolar I disorder, compared with psychiatric controls. Results support the hypotheses of elevated behavior, anxiety, and mood disorders among offspring at risk for bipolar disorder, and suggest that this psychopathology is already evident in early childhood.     

Parental Mental Disorders and Suicidal Behavior in the Nigerian Survey of Mental Health and Well-Being

The objective of this study was to determine which parental mental disorders predict offspring suicidal behavior in a general adult population sample of a sub-Saharan African country. The World Health Organization Composite International Diagnostic Interview, version 3 was used to assess respondents' suicidal behaviors as well as psychopathology in their parents. The effects of parental disorders in predicting offspring suicide ideation and attempts were examined in a series of bivariate and multivariate models. Sections on suicidality were administered to the entire sample (n = 6752), but associations with parental psychopathology were examined in a subsample of respondents (n = 2143). Lifetime prevalence (95% confidence interval) of suicide ideation, plans, and attempts was 3.2% (1.4–6.5), 1.0% (0.4–7.5), and 0.7% (0.5–1.0) respectively. Parental panic disorder and substance abuse were associated with suicide ideation in offspring, but only parental panic disorder was linked to suicide attempts. Parental panic disorder predicted the onset and persistence of suicide ideation and attempts and also which persons with suicide ideation go on to make a suicide attempt. This study further affirms findings from previous studies of the role of disorders characterized by anxiety and impulse control in suicide attempts and as being a probable link in the transmission of suicidal behavior to offspring.     

Further evidence of association between behavioral inhibition and social anxiety in children

OBJECTIVE: The authors sought to examine psychopathological correlates of behavioral inhibition in young offspring of parents with panic disorder and/or major depression. METHOD: Behavioral inhibition, determined by using standard laboratory observations, was assessed in four groups of children (age 2-6 years): 129 children of parents with both panic disorder and major depression, 22 children of parents with panic disorder alone, 49 children of parents with major depression alone, and 84 comparison children of parents with neither panic disorder nor major depression. Psychopathology in children > or =5 years was compared between children with behavioral inhibition (N=64) and without (N=152). RESULTS: Social anxiety disorder (social phobia or avoidant disorder) was significantly more likely to be found in the children with behavioral inhibition (17%) than in those without (5%). Noninhibited children were significantly more likely than inhibited children to have disruptive behavior disorders (20% versus 6%, respectively) and had higher scores on the attention problems scale of the Child Behavior Checklist (mean=52.1 versus 50.8). CONCLUSIONS: This study adds to the growing literature suggesting an association between behavioral inhibition and social anxiety disorder and an inverse relationship between inhibition and disruptive behavior disorders.     

Comorbidity of parental anxiety disorders as risk for childhood-onset anxiety in inhibited children.

OBJECTIVE: Previous work suggested that children of parents with panic disorder and agoraphobia were likely to be classified as behaviorally inhibited and that behaviorally inhibited children were likely to develop anxiety disorders. However, the factors determining which inhibited children were at risk for childhood onset of anxiety disorders remained unknown. The authors of this study hypothesized that greater anxiety loading in parents would increase the risk for anxiety disorders in children with behavioral inhibition. METHOD: Using DSM-III structured interviews, the authors examined patterns of aggregation of anxiety disorders in parents of two existing cohorts of children, one cross-sectional and clinically derived (31 children, 60 parents) and the other epidemiologically derived and longitudinal (40 children, 75 parents). Within each cohort, parents were stratified into three groups based on the presence (behavioral inhibition and anxiety) or absence (behavioral inhibition only, no behavioral inhibition and no anxiety) of behavioral inhibition and two or more anxiety disorders in their child. RESULTS: Parents of children with behavioral inhibition and anxiety, from both the clinical and nonclinical cohorts, had significantly higher rates of two or more anxiety disorders than did parents of children with behavioral inhibition only and parents of children with no behavioral inhibition and no anxiety. CONCLUSIONS: These results indicate that the presence of parental loading for anxiety disorders may help to identify the subgroup of inhibited children at very high risk for developing childhood-onset anxiety disorders.     

Psychiatric correlates of behavioral inhibition in young children of parents with and without psychiatric disorders

Behavioral inhibition is a laboratory-based temperamental category by the tendency to constrict behavior in unfamiliar situations and assumed to reflect low thresholds of limbic arousal. We previously found behavioral inhibition prevalent in the offspring of parents with panic disorder and agoraphobia. In this report, we examined the psychiatric correlates of behavioral inhibition by evaluating the sample of offspring of parents with panic disorder and agoraphobia, previously dichotomized as inhibited and not inhibited, and an existing epidemiologically derived sample of children, followed by Kagan and colleagues and originally identified at 21 months of age as inhibited or uninhibited. A third group of healthy children was added for comparison. Our findings indicate that inhibited children had increased risk for multiple anxiety, overanxious, and phobic disorders. It is suggested that behavioral inhibition may be associated with risk for anxiety disorders in children.     

The child behavior checklist broad-band scales predict subsequent psychopathology: A 5-year follow-up

OBJECTIVE: To evaluate the utility of the Child Behavior Check list (CBCL) for identifying children of parents with panic disorder or major depression at high-risk for future psychopathology. METHODS: Baseline Internalizing and Externalizing CBCL T-scores were used to predict subsequent depressive, anxiety, and disruptive behavior disorders at a 5-year follow-up in children of parents with panic disorder, major depression, or neither disorder. RESULTS: The Internalizing scale predicted subsequent agoraphobia, generalized anxiety disorder, separation anxiety disorder, and social phobia. In contrast, the Externalizing scale predicted subsequent disruptive behavior disorders and major depression. CONCLUSIONS: The convergence of these results with previous findings based on structured diagnostic interviews suggests that the CBCL broad-band scales can inexpensively and efficiently help identify children at high risk for future psychopathology within a population of children already at risk by virtue of parental psychopathology.     

Laboratory-observed behavioral disinhibition in the young offspring of parents with bipolar disorder: a high-risk pilot study

OBJECTIVE: This study tested whether behavioral disinhibition is more prevalent among offspring of parents with bipolar disorder than among offspring of parents without bipolar disorder. METHOD: The authors conducted a secondary analysis of data from a preexisting high-risk study of offspring at risk for panic disorder and depression (N=278) that had included some children with parents who had bipolar disorder (N=34). Children (ages 2-6) had been classified as behaviorally inhibited, disinhibited, or neither in laboratory assessments. RESULTS: Offspring of bipolar parents had significantly higher rates of behavioral disinhibition than offspring of parents without bipolar disorder. Behavioral inhibition did not differ between groups. Differences were not accounted for by parental panic disorder or major depression or by parental history of attention deficit hyperactivity disorder, conduct disorder, antisocial personality, or substance use disorders. CONCLUSIONS: Results suggest a familial link between bipolar disorder in parents and behavioral disinhibition in their offspring. Behavioral disinhibition may be a familially transmitted predisposing factor for dysregulatory distress later in life.     

Influence of parental concordance for psychiatric disorders on psychopathology in offspring

OBJECTIVE: To examine the influence of parental mating types for substance abuse and anxiety/affective disorders on the risk of psychopathology among child and adolescent offspring. METHOD: Emotional and behavioral disorders were assessed in offspring, aged 7 to 17 years, of male and female parents who served as probands from a family study of comorbidity of substance abuse and anxiety disorders. RESULTS: The findings indicated that (1) patterns of psychopathology among offspring were similar for mothers and fathers; (2) spouse concordance for psychopathology was greater among parents with substance abuse than among those with anxiety, particularly among female substance abusers; (3) there was a direct relationship between the number of affected parents and the magnitude of psychopathology in children, particularly with respect to the anxiety disorders; and (4) by contrast, rates of conduct disorder were elevated only among offspring of dually affected parents, irrespective of the specific parental disorders. CONCLUSIONS: These findings underscore the importance of the contribution of both mothers and fathers, particularly those with concordance for psychiatric disorders, to the development of psychopathology in offspring.     

Behavioral inhibition

Over the past 25 years, our understanding of the risks conferred by "behavioral inhibition to the unfamiliar" (BI) has grown tremendously, yet many questions remain. BI represents the persistent tendency to show extreme reticence, fearfulness, or avoidance in novel situations or with unfamiliar people. Prospective studies of high-risk offspring, selected community children, and unselected epidemiologic samples converge to suggest that BI confers specific risk for social anxiety disorder in early and middle childhood and adolescence. Later outcomes are less clear, with some studies suggesting associations with depression or panic disorder. Studies that find broad associations between BI and anxiety proneness in general may be limited by the absence of information about parental psychopathology (an important potential confound associated with both BI and anxiety disorders in offspring). A critical area for further inquiry is the degree to which BI confers risk for social anxiety disorder in the absence of family history of anxiety disorders. Additionally, although progress has been made in identifying risk factors, protective factors, and treatments that may influence the course of BI and associated anxiety, more work is needed. Also, several exciting inroads have been made into the genetic and neurobiologic underpinnings of BI, and future studies promise greater elucidation of these areas. For now, the clinical take-home message is that preschool-age children presenting with extreme and persistent BI are at elevated risk for social anxiety disorder and possibly for other future disorders; preliminary evidence suggests that these children may be helped by early cognitive-behavioral intervention.     

Family discord, parental depression, and psychopathology in offspring: 20-year follow-up

OBJECTIVE: To determine the independent effects of parental depression and family discord on offspring psychopathology among children at high and low risk of depression. METHOD: Family discord factors were assessed when subjects were approximately 17 years old, and offspring diagnoses were assessed about 20 years later. Parental and offspring psychopathology was assessed by interviewers blind to parents' clinical status. The following dimensions of family discord were assessed: poor marital adjustment, parent child discord, low family cohesion, affectionless control, and parental divorce. RESULTS: Most family discord factors were associated with parental depression. Among children of depressed parents, none of the measures of family discord had a statistically significant association with offspring major depressive disorder or anxiety disorders. Among children of nondepressed parents, parental affectionless control was associated with an almost fivefold increased risk of major depressive disorder (odds ratio [OR] = 4.8; p < or = .05) and with more than a 14-fold increased risk of substance use disorders (OR = 14.3; p < or = .01). CONCLUSIONS: Parental depression is associated with family discord and is a consistent risk factor for offspring major depressive disorder and anxiety disorders, as shown over a 20-year follow-up of offspring of depressed and nondepressed parents. Family discord factors may be a risk factor for major depressive disorder and substance use disorders in offspring of nondepressed parents.     

Developmental trajectories of anxiety disorders in offspring at high risk for panic disorder and major depression

The objective of this study was to evaluate the longitudinal course of psychiatric disorders in children of parents with and without panic disorder and major depression as they transition through the period of risk from early to late childhood. Over a 5-year follow-up, we compared the course of psychiatric disorders in offspring of parents with panic disorder, major depression, or neither disorder. Subjects consisted of 233 offspring (from 151 families) with baseline and follow-up assessments. Subjects were comprehensively assessed with structured diagnostic interviews. Anxiety disorders at baseline were used to predict anxiety disorders and major depression at follow-up using stepwise logistic regression. Separation anxiety disorder significantly increased the risk for the subsequent development of specific phobia, agoraphobia, panic disorder, and major depression, even after parental panic and depression were covaried. Agoraphobia significantly increased the risk for subsequent generalized anxiety disorder. These findings suggest that separation anxiety disorder is a major antecedent disorder for the development of panic disorder and a wide range of other psychopathological outcomes, and that it increases the risk for subsequent psychopathology even among children already at high familial risk for anxiety or mood disorder.     

Family adversity in DSM-IV ADHD combined and inattentive subtypes and associated disruptive behavior problems

OBJECTIVE: This study evaluated the relationship between a family adversity index and DSM-IV attention-deficit/hyperactivity disorder (ADHD) subtypes and associated behavior problems. The relationship of family adversity to symptoms and subtypes of ADHD was examined. METHOD: Parents and 206 children aged 7-13 completed diagnostic interviews and rating scales about socioeconomic status, parental lifetime psychiatric disorders, marital conflict, and stressful life events. RESULTS: Children with ADHD combined type experienced more risk factors than community controls (p = .002) or children with ADHD predominantly inattentive type (p = .02). The families of children with ADHD combined type described more risk factors associated with family adversity than the families of children with ADHD inattentive type and the control group. Parent-rated symptoms of child inattention/disorganization were related uniquely to the adversity index score independently of conduct disorder symptoms. Children's perceptions of marital conflict were independently related to inattention and hyperactivity behaviors as rated by parents and teachers after control of all other risk factors. Oppositional defiant symptoms were independently related to marital conflict and maternal psychopathology, whereas conduct disorder symptoms were uniquely related to low socioeconomic status and maternal psychopathology. CONCLUSIONS: Family adversity is related to ADHD combined type in children and may be related specifically to ADHD symptoms in addition to conduct disorder symptoms.     

Stress responsivity and HPA axis activity in juveniles: results from a home-based CO2 inhalation study

OBJECTIVE: A previous laboratory-based study found elevated cortisol levels in anxious children susceptible to CO(2)-induced panic, but the effects of parent diagnosis were not considered. The current home-based study tested the hypothesis that parental panic disorder and offspring response to CO(2) are associated with elevated cortisol levels in juvenile offspring. METHOD: A total of 131 offspring (ages 9-19) of parents with panic disorder, major depression, and no mental disorder underwent CO(2) inhalation. Parent and child diagnoses were assessed. Salivary cortisol was assayed before and after CO(2) inhalation. RESULTS: Neither parents with panic disorder, parents with major depression, or offspring anxiety predicted offspring cortisol levels. Independent of parent and child diagnoses, anxiety response to CO(2) predicted elevated cortisol levels in offspring. CONCLUSIONS: As in adults, anxiety response to CO(2) in juveniles is associated with elevated cortisol levels, but elevated cortisol levels are not related to parent or child diagnoses.     

Lack of association between parental alcohol or drug addiction and behavioral inhibition in children

OBJECTIVE: "Behavioral inhibition to the unfamiliar" has been proposed as a precursor to anxiety. A recent study proposed that it may also be a precursor to alcoholism. The authors sought to replicate the latter finding through a secondary analysis of data from a large study of young children (age 2-6 years)-offspring of parents with panic and depressive disorders-who had been assessed for behavioral inhibition through laboratory-based observations. METHOD: The offspring were stratified on the basis of presence or absence of parental lifetime history of DSM-III-R alcohol dependence (N=115 versus N=166, respectively) or drug dependence (N=78 versus N=203). The rates of behavioral inhibition were then compared between groups. RESULTS: Despite adequate power to detect associations, neither parental alcohol dependence nor drug dependence was associated with a higher risk for behavioral inhibition in the offspring. CONCLUSIONS: These results are not consistent with the hypothesis linking behavioral inhibition to addictions.     

Family discord, parental depression, and psychopathology in offspring: ten-year follow-up

OBJECTIVE: To determine the independent effects of parental depression and family discord on psychopathology in offspring at high and low risk for major depression. METHOD: One hundred eighty-two offspring of depressed or nondepressed parents were followed over 10 years. In direct interviews, parents' and offspring's psychopathology was evaluated by raters blind to parents' clinical status. Five dimensions of family discord-poor marital adjustment, parent-child discord, low family cohesion, affectionless control, and parental divorce-were assessed. RESULTS: Offspring exposed to either parental depression or family discord had higher rates of psychopathology than their counterparts. High-risk offspring had few family discord measures associated with their psychopathology; in low-risk offspring, family discord was associated with all offspring diagnoses. Between the two risk factors, parental depression proved a more important predictor for offspring major depressive disorder (MDD) and anxiety disorder, whereas family discord was a more important predictor for substance use disorder. CONCLUSIONS: Parental depression is a strong and consistent risk factor for offspring MDD and anxiety disorder. Without parental depression, offspring have less exposure to family discord and lower rates of psychopathology. In the presence of family discord, rates of MDD, anxiety disorder and substance use disorder increased. When offspring matured into young adulthood, effects of parental depression and family discord persisted.     

Pregnancy complications associated with childhood anxiety disorders

To determine whether perinatal complications predict childhood anxiety disorders independently of parental psychopathology, we systematically assessed pregnancy and delivery complications and psychopathology in a sample of children (mean age=6.8 years) at high risk for anxiety disorders whose parents had panic disorder with (n=138) or without (n=26) major depression, and in contrast groups of offspring of parents with major depression alone (n=47), or no mood or anxiety disorders (n=95; total N=306). Psychopathology in the children was assessed by structured diagnostic interviews (K-SADS), and pregnancy and delivery complications were assessed using the developmental history module of the DICA-P. Number of pregnancy complications predicted multiple childhood anxiety disorders independently of parental diagnosis (odds ratio=1.6 [1.4-2.0]). This effect was accounted for by heavy bleeding requiring bed-rest, hypertension, illness requiring medical attention, and serious family problems. Associations remained significant when lifetime child mood and disruptive behavior disorders were covaried. Results suggest that prenatal stressors may increase a child's risk for anxiety disorders beyond the risk conferred by parental psychopathology alone.     

Associations of familial risk factors with social fears and social phobia: evidence for the continuum hypothesis in social anxiety disorder?

We examined parental psychopathology and family environment in subthreshold and DSM-IV threshold conditions of social anxiety disorder (SAD) in a representative cohort sample of 1,395 adolescents. Offspring and parental psychopathology was assessed using the DIA-X/M-CIDI; recalled parental rearing and family functioning via questionnaire. Diagnostic interviews in parents were supplemented by family history reports from offspring. The cumulative lifetime incidence was 23.07% for symptomatic SAD, and 18.38 and 7.41% for subthreshold and threshold SAD, respectively. The specific parent-to-offspring association for SAD occurred for threshold SAD only. For subthreshold and threshold SAD similar associations were found with other parental anxiety disorders, depression and substance use disorders. Parental rearing behaviour, but not family functioning, was associated with offspring threshold SAD, and although less strong and less consistent, also with subthreshold SAD. Results suggest a continued graded relationship between familial risk factors and offspring SAD. Parental psychopathology and negative parental styles may be used defining high-risk groups to assign individuals with already subthreshold conditions of SAD to early intervention programs.     

Children of parents with psychiatric disorder in the community

The relationship between parental psychopathology and risk for maladjustment in the offspring was investigated in a community sample. The children of 130 parents who met criteria for 12 DIS/DSM-III disorders were compared to the children of 235 normal parents. Significantly more children of disturbed parents were functionally impaired and had higher scores in the parent and youth Child Behavior Checklist total behavior scores as compared to children of normal parents. These associations were maintained even after accounting for an adverse family environment, suggesting a strong relationship between parental and childhood psychopathology as well as a mediating influence of environmental adversity.