Psychosocial variables in children and teens of extended families identified through bipolar affective disorder probands

Objectives: This multi‐site study investigated the frequency of risk‐related variables for developing an affective disorder using a within‐pedigree control group. We wished to determine the effect of life events, social relationships, self‐perceived competence, and aspects of home environment for youngsters from extended families with loading for bipolar disorder. Using a within‐family contrast group, we address the following two issues: (1) Do offspring or their parents from families who do and do not have an affected parent report differences (i) in home environment? (ii) in frequency and type of offspring life events? and (iii) in social relations and self‐perception? and (2) Do children or their parents who do or do not have an affective disorder report differently on these areas? Methods: Juvenile offspring (n = 50) and their parents from 14 bipolar pedigrees were assessed. Structured interviews and self‐ or parent‐reported instruments were used to compare offspring with an affected first‐degree relative to those without and to compare offspring with or without an affective disorder. Results: Only one significant psychosocial difference was found between offspring with or without a parent with an affective disorder but several were found between offspring who themselves did or did not have an affective disorder. These differences are in the areas of the need for discipline, social support, and dependent negative life events. Conclusions: The findings identify potential early psychosocial markers for affective disorder in high risk offspring.     

A controlled family history study of prepubertal major depressive disorder

First-degree (N = 195) and second-degree (N = 785) adult relatives of prepubertal children with major depression (N = 48), children with nonaffective psychiatric disorders (N = 20), and normal children (N = 27) were assessed by the Family History-Research Diagnostic Criteria method (FH-RDC), except for the adult informant (usually the mother), who was directly interviewed. Compared with normal controls, prepubertal children with major depressive disorder (MDD) had significantly higher familial rates of psychiatric disorders in both first- and second-degree relatives, especially MDD, alcoholism, and "other" (mostly anxiety) diagnoses. Relatives of children in the nonaffective psychiatric control (PC) group had low rates of alcoholism, high rates of other (anxiety) disorder diagnoses, and intermediate rates of MDD (accounted for by those children with separation anxiety). This suggests that prepubertal onset of major depression may be especially likely in families with a high aggregation of affective disorders when these families also have a high prevalence of alcoholism, and that a proportion of children without affective disorder but with separation anxiety disorder in this study were at high risk for the development of affective illness later in life. These results support the validity of prepubertal-onset depressive illness as a diagnostic category, and are consistent with high familial rates of MDD and other psychiatric disorders found in family studies of adolescent and early-onset adult probands with major affective disorders, and with studies of the offspring of parents with major affective disorders. Within the child MDD group substantial heterogeneity was found. Low familial rates of MDD were associated with suicidality and comorbid conduct disorder in the child probands. The highest familial rates of MDD, approximately threefold those in the normal controls, and all the bipolar relatives, were found in the families of prepubertal probands with MDD who never had a concrete suicidal plan or act and who were without comorbid conduct disorder. A useful nosological continuum in which to classify prepubertal MDD may be to place at one end those patients with comorbid conduct disorder and at the other end those patients with manifestations related to bipolarity, including hypomania, mania, and psychotic subtype.     

Social competence and positive and negative symptoms: a longitudinal study of children and adolescents at risk for schizophrenia and affective disorder

OBJECTIVE: The authors longitudinally examined social competence and positive and negative symptoms in children at risk for schizophrenia, children at risk for affective disorder, and matched normal subjects. METHOD: The subjects were offspring of parents with schizophrenia or affective disorder and normal comparison subjects matched on age, sex, and socioeconomic status. Ratings of social competence (Premorbid Adjustment Scale), affective flattening and poverty of speech (Scale for the Assessment of Negative Symptoms), and positive formal thought disorder (Scale for the Assessment of Positive Symptoms) were based on videotaped psychiatric interviews conducted in childhood (N = 144), early adolescence (N = 127), and adolescence (N = 106). RESULTS: In childhood, there were no significant group differences. In early adolescence, the subjects at risk for schizophrenia had poorer social competence than those at risk for affective disorder and the normal subjects. In early adolescence, the subjects at risk for schizophrenia also had greater positive thought disorder than those at risk for affective disorder but did not differ significantly from the normal subjects; there were no differences in negative symptoms. In adolescence, the subjects at risk for schizophrenia had poorer social competence and greater positive and negative symptoms than the adolescents at risk for affective disorder and the normal subjects. CONCLUSIONS: During early adolescence and adolescence, poor social competence may be more characteristic of children at risk for schizophrenia than those at risk for affective disorder. Higher levels of positive and negative symptoms may also be specific to subjects at risk for schizophrenia, but only during adolescence.     

High rate of affective disorders in probands with attention deficit disorder and in their relatives: a controlled family study

In a controlled family study of attention deficit disorder, data were collected on first-degree relatives of 22 children with attention deficit disorder and 20 normal children. The rate of major affective disorder was significantly higher in the attention deficit disorder probands (32%) and their relatives (27%) than in the normal control subjects (0%) and their relatives (6%). The findings indicate that attention deficit disorder is associated with higher risk for affective disorder and suggest that probands who have both disorders may represent a distinct subgroup.     

Comorbidity of attention deficit hyperactivity disorder with early- and late-onset bipolar disorder

OBJECTIVE: The relationship between attention deficit hyperactivity disorder (ADHD) and earlier age at onset of affective illness was examined in probands with a history of bipolar disorder. METHOD: The authors assessed 56 adult bipolar subjects. Those with a history of childhood ADHD (N=8) were age and sex matched with bipolar subjects without a history of childhood ADHD (N=8). RESULTS: The age at onset of the first affective episode was lower for the subjects with bipolar disorder and a history of childhood ADHD (mean=12.1 years, SD=4.6) than for those without a history of childhood ADHD (mean=20. 0 years, SD=11.3). CONCLUSIONS: ADHD in children of bipolar probands might identify children at highest risk for development of bipolar disorder.     

Lithium in children of lithium-responding parents

Six offspring of manic-depressive patients, whose parents were lithium responders, were selected on the basis of their incapacitating psychopathology for treatment with lithium. The children ranged in age from 6 to 12. A double-blind, crossover design was used over 16–18 weeks. Weekly ratings were done, and average evoked potentials (EPs) were measured at each crossover. Two children diagnosed as having a bipolar affective disorder had a clear-cut response to lithium and were strong augmenters on the EP. This, taken together with the similarity of the EP changes on lithium to those occurring in adult patients treated with lithium, supports a physiological parallel between bipolar affective illness in adults and children.     

The Munich vulnerability study on affective disorders: premorbid psychometric profile of affected individuals

OBJECTIVE: We conducted a longitudinal high-risk study to identify psychometric vulnerability markers for affective disorders. METHOD: We examined 82 healthy subjects [high-risk probands (HRPs)] with at least one first-degree relative suffering from an affective disorder. The premorbid psychometric profile of 20 HRPs who developed a psychiatric disorder during follow-up was compared with the profile of control subjects without personal and family history of psychiatric disorders matched for age and gender. RESULTS: Somatization, complaints (vegetative lability), and perception of strain are increased in HRPs who developed a psychiatric disorder. These alterations were not influenced by the time interval until the onset of the disorder. CONCLUSION: The premorbid psychometric profile in subjects at high risk for affective disorders is characterized by somatization, complaints, and elevated perception of strain. Together with previous findings our results suggest that these alterations can be regarded as potential vulnerability markers for affective disorders.     

Behavioral inhibition in children of parents with panic disorder and agoraphobia. A controlled study

To investigate the role of "behavioral inhibition to the unfamiliar" as an early temperamental characteristic of children at risk for adult panic disorder and agoraphobia (PDAG), we compared children of parents with PDAG with those from psychiatric comparison groups. Fifty-six children aged 2 to 7 years, matched for age, socioeconomic status, ethnic background, and ordinal position, were blindly evaluated at the Harvard Infant Study laboratory, Cambridge, Mass. The rates of behavioral inhibition in children of probands with PDAG, with or without comorbid major depressive disorder (MDD), were significantly higher than for our comparison group without PDAG. Further, the data suggest a progression of increasing rates of inhibition from the comparison group without MDD (15.4%), to MDD (50.0%), and to comorbid PDAG and MDD (70%) and PDAG (84.6%). In contrast, the rate of behavioral inhibition in children of probands with MDD did not meaningfully differ from the comparison group without MDD. Behavioral inhibition to the unfamiliar, as defined and measured in the previous work of the Harvard Infant Study program, is highly prevalent in the offspring of adults in treatment for PDAG. These children appear to be at risk for distress and disability in childhood and also perhaps for development of psychiatric disorder in later childhood and aulthood.     

Inventory identification of cyclothymia. IX. Validation in offspring of bipolar I patients

We present the ninth in a series of validation studies that support the effectiveness of the General Behavior Inventory (GBI) in identifying cyclothymia. This study assessed the potential utility of the GBI in family and offspring studies by evaluating its ability to satisfy three prerequisites for use in such research: (1) identification of cyclothymia familially related to bipolar I disorder, (2) use with young adolescents, and (3) "insensitivity" to the effects of nonaffective psychopathology and parental nonaffective disorder in the offspring of control probands. The GBI and a blind, structured diagnostic interview were administered to 37 offspring of bipolar I patients and 21 offspring of psychiatric control patients, Twenty-seven percent of the offspring of bipolar patients, but none of the control offspring, were found to have bipolar forms of affective disorder, primarily cyclothymia (24%). Concordance between the GBI and interview-derived diagnoses was 95% to 97%, with 98% specificity and 80% to 90% sensitivity, depending on cutting score location. Together with the results of previous studies, the findings suggest that the GBI holds promise for the identification of cyclothymia in several research and clinical contexts.     

Interrater reliability of the Structured Clinical Interview for DSM-III-R, Axis II: schizophrenia spectrum and affective spectrum disorders.

Three interviewers (second raters) blindly rated 15 audiotapes each of the Structured Clinical Interview for DSM-III-R, Axis II (SCID-II) administered to the first degree relatives of probands with either DSM-III-R schizophrenia, schizoaffective disorder, or bipolar disorder, for a total of 45 second ratings. Interrater reliability was determined using the intraclass correlation coefficient and ranged from 0.60 to 0.84. The previous studies of the reliability of structured interviews for diagnosing personality disorders are summarized and compared to the present findings. We conclude that the SCID-II can be reliably used to diagnose schizophrenia-spectrum and affective spectrum disorders in the first degree family members of probands with schizophrenic or bipolar affective disorders.     

Autistic social impairment in the siblings of children with pervasive developmental disorders

OBJECTIVE: Sibling recurrence risk in autism has been estimated to be approximately 10%. This study investigated subsyndromal autistic impairments among siblings of probands with pervasive developmental disorders. METHOD: The authors used the Social Responsiveness Scale to obtain quantitative assessments of autistic social impairment in three groups of proband-sibling pairs: 1) autistic children from multiple-incidence families and their closest in age nonautistic brothers (N=49 pairs); 2) children with any pervasive developmental disorder, including autism, and their closest-in-age brothers (N=100 pairs), and 3) children with psychopathology unrelated to autism and their closest-in-age brothers (N=45 pairs). RESULTS: Sibling Social Responsiveness Scale scores were continuously distributed and substantially elevated for both the autistic and pervasive developmental disorder groups. Highest scores (i.e., greatest impairment) were seen among siblings of autistic probands from multiple-incidence families, followed by siblings of probands with any pervasive developmental disorder, then siblings of probands with psychopathology unrelated to autism. CONCLUSIONS: Taken together with previous findings, these results support the notion that genetic susceptibility factors responsible for common, subsyndromal social impairments may be related to the causes of categorically defined pervasive developmental disorders.     

Children of parents with obsessive-compulsive disorder -- a 2-year follow-up study

OBJECTIVE: To examine the association between parental obsessive-compulsive disorder (OCD) and emotional and behavioural disorders in offspring. METHOD: Demographic, clinical, and diagnostic data were collected from parents with OCD, control subjects, and their respective offspring. Offspring were reassessed at a 2-year follow-up. RESULTS: Probands with OCD and controls were relatively well matched for age, gender, race, educational rating, and marital status. Offspring of OCD probands were at greater risk than offspring of controls for dimensionally measured anxiety, depression, somatization, and social problems. OCD offspring were significantly more likely than control offspring to have lifetime overanxious disorder, separation anxiety disorder, OCD, or 'any anxiety disorder'. Female gender in the parent with OCD, evidence of family dysfunction, and high symptom levels in offspring were predictive of broadly defined OCD at follow-up. CONCLUSION: Children having a parent with OCD are more likely than control offspring to have social, emotional, and behavioural disorders.     

Avoidant disorder and social phobia in children and adolescents.

The diagnoses of avoidant disorder and social phobia in children have received little research attention. Although DSM-III-R describes avoidant disorder and social phobia as data are available to support this notion. The current study examined characteristics of avoidant disorder and social phobia by comparing outpatient youngsters with avoidant disorder, social phobia, and avoidant disorder plus social phobia on demographic variables and patterns of comorbidity. The psychiatric groups were compared with matched normal controls on symptom measures of depression and fear. Findings indicated that the three psychiatric groups were strikingly similar on all but one variable, age at intake. These findings question the notion of avoidant disorder and social phobia as distinct disorders in children and adolescents.     

A secular increase in child and adolescent onset affective disorder.

Both longitudinal and cross-sectional studies utilizing population and family study samples have found evidence for a secular increase in major affective disorders in adults. Applying techniques used in cross-sectional studies in adults to family study data of children and adolescents, the authors demonstrate evidence of a parallel secular increase for child and adolescent onset affective disorders. Normal and depressed prepubertal probands were identified. All full siblings were directly interviewed for lifetime episodes of affective disorder. Analysis of the siblings (probands not further analyzed in this article) by the Cox proportional hazards model demonstrates that the risk for affective disorder is higher in siblings born more recently.     

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.     

But are they cases? Validity of DSM-III major depression in children identified in a family study

The authors examine the validity of the diagnosis of major depression in nine children and adolescents assessed as part of a study of offspring of parents who had affective disorders. The authors conclude that these nine children were suffering from valid cases of affective disorder because disruptions in multiple domains of functioning accompanied the major depression. The seriousness of the impairment and the finding that few of these children received any treatment at all strongly suggest the need for a heightened awareness among clinicians about the seriousness of depression in children whose parents have affective disorders.     

A DSM-III family study of the nonschizophrenic psychotic disorders

The authors conducted a blind DSM-III family study based on probands diagnosed from long-term follow-up information as having schizophreniform disorder, schizoaffective disorder, or psychotic affective illness. The pattern of psychopathology in relatives of schizophreniform probands closely resembled that found previously in relatives of schizophrenic probands. Relatives of schizoaffective probands had an excess risk for schizophrenia, other psychoses, and bipolar illness. The pattern of illness found in relatives of the probands meeting Research Diagnostic Criteria for mainly schizophrenic schizoaffective disorder appeared indistinguishable from that of relatives of schizophrenic probands. Relatives of probands with psychotic affective disorder had an excess risk for schizophrenia and for unipolar and bipolar affective disorder.     

Differential effect of subtype of parental major affective disorder on children

Fifty offspring of patients with major affective disorder (MAD) were studied. The children and their parents were interviewed using a structured diagnostic instrument. The results supported previous studies that the children of patients with MAD endorse a variety of symptoms of psychopathology. In addition, when the sample was separated by subtype of parental MAD, few differences in the types of symptoms were reported, and the differences that were found may be spurious. The differences, as well as indications for future research, are discussed.     

DSM-III-R schizotypal personality traits in offspring of schizophrenic disorder, affective disorder, and normal control parents

The aggregation of disorder in families identified by a schizophrenic disorder proband (index case) has provided indirect clues to the question of diagnostic boundaries of schizophrenic spectrum categories. The Danish Adoption Studies provided quasi-experimental evidence for the range of expression of a putative schizophrenic spectrum disorder which was subsequently denoted schizotypal personality disorder (STPD) in DSM-III-R. It has been hypothesized that such schizophrenic spectrum categories bear a genetic relationship to schizophrenic disorder and thus are continuous with schizophrenia in terms of etiology and pathogenesis. For meaningful use of such spectrum categories in genetic analyses, i.e., linkage analysis, it is important that rates of spectrum traits and disorder in normal control and in psychiatric control populations are known. The rate of DSM-III-R schizotypal traits and disorder was assessed in three offspring groups (ages 18-29) defined by parental diagnoses, including schizophrenic disorder (N = 90), affective disorder (N = 79), and no parental disorder (N = 161). The assessment was conducted by trained social workers and psychologists by means of a direct interview (Personality Disorder Examination). The interviewers were blind to the parental status and to previous psychiatric assessments of these offspring. The rates of three, four and five schizotypal features were elevated in the offspring with parental psychiatric disorder in contrast to the offspring with no parental psychiatric disorder. However, the rates between the offspring of the schizophrenic disorder parental group and the offspring of the affective disorder parental group did not differ significantly, thus failing to support the assumption of diagnostic specificity.     

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.