Cognitive functioning in children with internalising, externalising and dysregulation problems: a population-based study.

Psychiatric symptoms in childhood are closely related to neurocognitive deficits. However, it is unclear whether internalising and externalising symptoms are associated with general or distinct cognitive problems. We examined the relation between different types of psychiatric symptoms and neurocognitive functioning in a population-based sample of 1177 school-aged children. Internalising and externalising behaviour was studied both continuously and categorically. For continuous, variable-centred analyses, broadband scores of internalising and externalising symptoms were used. However, these measures are strongly correlated, which may prevent identification of distinct cognitive patterns. To distinguish groups of children with relatively homogeneous symptom patterns, a latent profile analysis of symptoms at age 6 yielded four exclusive groups of children: a class of children with predominantly internalising symptoms, a class with externalising symptoms, a class with co-occurring internalising and externalising symptoms, that resembles the CBCL dysregulation profile and a class with no problems. Five domains of neurocognitive ability were tested: attention/executive functioning, language, memory and learning, sensorimotor functioning, and visuospatial processing. Consistently, these two different modelling approaches demonstrated that children with internalising and externalising symptoms show distinct cognitive profiles. Children with more externalising symptoms performed lower in the attention/executive functioning domain, while children with more internalising symptoms showed impairment in verbal fluency and memory. In the most severely affected class of children with internalising and externalising symptoms, we found specific impairment in the sensorimotor domain. This study illustrates the specific interrelation of internalising and externalising symptoms and cognition in young children.

Signs of a higher prevalence of autoimmune thyroiditis in female offspring of bipolar parents.

BACKGROUND: Studies are inconsistent as to whether patients with bipolar disorder are more frequently affected by autoimmune thyroiditis. AIM: To study the prevalence of autoimmune thyroiditis in offspring of bipolar patients. METHOD: In 1998 140 children (age 12-21 years) of bipolar parents were evaluated psychiatrically using the K-SADS-PL and blood was drawn to determine thyroperoxidase antibodies (TPO-Abs) and serum TSH. Blood samples of high school students (aged 12-19 years, n=77) and young adults (aged 20-35 years, n=52) were used as comparisons. At follow-up the offspring were psychiatrically evaluated and tested for TPO-Abs and TSH twice (14 months and 55 months after enrollment). RESULTS: TPO-Abs were predominantly found in female bipolar offspring, who had a significantly higher prevalence of positive TPO-Ab titers (9 out of 57 female offspring subjects) as compared to the female high school and young adult comparisons (4 out of 103 female control subjects). In TPO-Ab positive offspring (n=11) a raised prevalence of 55% of thyroid failure (i.e. a raised serum TSH or l-thyroxine treatment) was evident. TPO-Ab positive offspring did not show a raised prevalence of mood disorders (or any psychopathology) as compared to the TPO-Ab negative offspring. CONCLUSION: Our study suggests that bipolar offspring are more vulnerable to develop thyroid autoimmunity independently from the vulnerability to develop psychiatric disorders.

Social functioning of bipolar offspring.

BACKGROUND: Bipolar patients have impaired social functioning compared to people in the general population. It has been suggested that children of bipolar patients also have impaired social functioning. The objective of this study was to compare social functioning of adolescent and young adult offspring of bipolar parents with social functioning of adolescents and young adults in the general population. METHOD: Subjects were 140 offspring of bipolar parents and 1122 adolescents and 1175 young adults from the general population. Parent, teacher and self-report ratings were used to assess social functioning. RESULTS: Analyses revealed no differences in scores on social functioning for offspring aged 11 to 18 years, and few differences for ages 18 to 26 years compared to same aged individuals from the general population. Offspring with a DSM-IV disorder showed a lower level of social functioning compared to Dutch subjects from the general population in the same age range. LIMITATIONS: The limitations of this study are lack of information on the representativeness of the sample and use of one measure for social functioning. CONCLUSIONS: Bipolar offspring in the adolescent age range have good overall level of social functioning. Social functioning in offspring aged 18 years or older with a bipolar or other mood disorder is impaired.

Categorical and dimensional psychopathology in Dutch and US offspring of parents with bipolar disorder: A preliminary cross-national comparison.

OBJECTIVE: Accumulating evidence suggests cross-national differences in adults with bipolar disorder (BD), but also in the susceptibility of their offspring (bipolar offspring). This study aims to explore and clarify cross-national variation in the prevalence of categorical and dimensional psychopathology between bipolar offspring in the US and The Netherlands. METHODS: We compared levels of psychopathology in offspring of the Pittsburgh Bipolar Offspring Study (n=224) and the Dutch Bipolar Offspring Study (n=136) (age 10-18). Categorical psychopathology was ascertained through interviews using the Schedule for Affective Disorders and Schizophrenia for School Age Children (K-SADS-PL), dimensional psychopathology by parental reports using the Child Behavior Checklist (CBCL). RESULTS: Higher rates of categorical psychopathology were observed in the US versus the Dutch samples (66% versus 44%). We found no differences in the overall prevalence of mood disorders, including BD-I or -II, but more comorbidity in mood disorders in US versus Dutch offspring (80% versus 34%). The strongest predictors of categorical psychopathology were maternal BD (OR: 1.72, p<.05), older age of the offspring (OR: 1.19, p<.05), and country of origin (US; OR: 2.17, p<.001). Regarding comorbidity, only country of origin (OR: 7.84, p<.001) was a significant predictor. In general, we found no differences in dimensional psychopathology based on CBCL reports. LIMITATIONS: Preliminary measure of inter-site reliability. CONCLUSIONS: We found cross-national differences in prevalence of categorical diagnoses of non-mood disorders in bipolar offspring, but not in mood disorder diagnoses nor in parent-reported dimensional psychopathology. Cross-national variation was only partially explained by between-sample differences. Cultural and methodological explanations for these findings warrant further study.

Stressful life events and onset of mood disorders in children of bipolar parents during 14-month follow-up.

BACKGROUND: Although multiple studies have examined the association between stressful life events (SLEs) and the development of mood disorders, the exact nature of the association and the degree to which it is independent from familial loading (FL) and gender-specific are still not fully elucidated. AIMS: To study the association between person-independent and -dependent SLEs and first onset or recurrence of a DSM-IV mood disorder episode (MDE) in offspring of bipolar parents. To examine interaction effects of SLEs with familial loading and gender. METHOD: Offspring of bipolar parents (N=132) were assessed with the K-LEDS, the FHRDC and the K-SADS. Logistic regression analysis was used to examine main and interaction effects of various operationalizations of SLEs, familial loading and gender. RESULTS: Dependent SLEs were more likely to occur before onset among the 13 offspring who had a MDE onset during the 14-month follow-up (39%) than in a comparable period among the 67 controls without any lifetime diagnosis (10%). Associations were slightly stronger for first onsets than for recurrences. The association between SLEs and MDE onset/recurrence was independent of socio-demographic characteristics and familial loading, but disappeared when adjusted for baseline anxious/depressive symptoms. Gender and familial loading did not modify the influence of any SLE measure on the development of mood disorders. CONCLUSIONS: In this sample of bipolar offspring dependent stressful SLEs triggered the onset of MDEs, but this association disappeared after adjustment of prior anxious/depressive symptoms, indicating that the association between SLEs and MDE is probably a spurious association. No interaction was found between SLE and FL and gender. Prior anxious/depressive symptoms seem to increase the risk for both occurrence of dependent SLEs and MDE onset or recurrence. LIMITATIONS: Limited statistical power due to small number of MDE onsets.

The use of the GBI as predictor of bipolar disorder in a population of adolescent offspring of parents with a bipolar disorder.

OBJECTIVE: To assess the usefulness of the General Behavior Inventory (GBI) to predict the development of mood disorders in the offspring of parents with bipolar disorder. METHOD: The GBI and the K-SADS (first measurement) and the SCID (last measurement) were used to assess psychopathology among 129 adolescent and young adult offspring of a bipolar parent with an interval of 5 years. Based on the SCID results at the last measurement, the offspring were assigned to one of four groups: with bipolar mood disorder, with unipolar mood disorders, with non-mood disorders and without disorders and GBI-scores at the first measurement were compared across the four groups. RESULTS: The scores on the Depression scale of the GBI for the offspring who later developed a bipolar or any mood disorder were significantly higher than for the offspring who did not develop a mood disorder across a 5-year interval. For the offspring with a unipolar mood disorder at the first measurement, the scores on the Depression scale were significantly higher for those who switched to bipolar disorder versus those who remained unipolar. CONCLUSIONS: The GBI can be used in a high-risk sample of offspring of parents with bipolar disorder as a self-report measure as an aid to detect those who will develop bipolar disorder across a 5-year interval.

Child and adolescent antecedents of adult mood disorders.

PURPOSE OF REVIEW: Developmental information such as childhood risk factors and childhood precursors of adult mood disorders may have implications for etiologic theory, clinical practice and preventive intervention. From a developmental point of view, mood disorders are of particular interest because of the complex interplay of psychological, social and biological components across time. Identifying different developmental trajectories of mood disorders may yield insights that are relevant to the etiology. RECENT FINDINGS: Findings demonstrate a clear association between early mood problems and onset of mood disorders in adult life. Childhood environmental risks are associated with increased risk of depression in adulthood. There is a lack of studies that have tested the role of gene-environment correlation and the role of gene-environment interaction in the development of depression from childhood into adulthood. A promising line of research comes from studies looking into the biological modifications of the developing brain as a result of early adverse experiences, especially alterations in the corticotropin-releasing factor system, which may lead to increased responsiveness to stress. SUMMARY: To better understand the complex interplay between nature and nurture in the development of mood disorders in adults, future studies should ideally consider well measured risk environments in genetic sensitive designs. It is equally important that future studies should also consider both age differences in causal processes and gender differences in effects. Such an approach calls for research in which (molecular) genetic and psychosocial research is well integrated in prospective epidemiological strategies.

Impact of birth weight and genetic liability on psychopathology in children of bipolar parents.

OBJECTIVE: To test different models for ways in which birth weight and familial loading influence the risk for psychopathology in bipolar offspring. METHOD: DSM-IV diagnoses of 140 bipolar offspring (12-21 years of age) were assessed with the K-SADS-PL. Parents were interviewed using the Family History-Research Diagnostic Criteria to determine familial loading of mood and substance use disorders. Parents reported the birth weight of their offspring. Age- and sex-adjusted hazard ratios were calculated. RESULTS: Low birth weight was associated with mood and non-mood disorders in bipolar offspring (hazard ratio = 0.6, confidence interval = 0.4-0.8), even after controlling for familial loading of unipolar disorder, bipolar disorder, or substance use disorder. There were no significant interactions between birth weight and familial loading of unipolar disorder, familial loading of bipolar disorder, and familial loading of substance use disorder. CONCLUSIONS: Birth weight is associated with mood as well as non-mood disorders. This association is independent from the association of familial loading of mood and substance use disorder with mood- and non-mood disorders in bipolar offspring.

Psychopathology in the adolescent offspring of bipolar parents.

BACKGROUND: The aim of this study was to determine the prevalence and 14-months incidence of psychopathology in adolescent offspring of a bipolar parent. METHOD: Parent, teacher and self-report rating scales and Kiddie-SADS were used to assess 132 13-23-year-old offspring of bipolar parents. RESULTS: Compared to the general population, there were few differences between rating scale scores for bipolar offspring and problem scores for normative adolescents. Of the sample 49% had a lifetime psychiatric disorder, most commonly (33%) a mood disorder. LIMITATIONS: There was no suitable control group and there are no comparison data for psychiatric diagnoses (DSM-IV), based on semi-structured interviews in the adolescent age group in the Netherlands. CONCLUSIONS: The overall level of psychopathology of bipolar offspring was not particularly elevated, but when there were more problems, they tended to be mood disorders.

The use of the GBI in a population of adolescent offspring of parents with a bipolar disorder.

OBJECTIVE: To assess the psychometric properties and the usefulness of the General Behavior Inventory (GBI) in the adolescent age range. METHOD: The GBI, the Schedule for Affective Disorders and Schizophrenia for School Age Children, Kiddie-SADS-Present and Lifetime Version (K-SADS-PL) and the Youth Self-Report (YSR) were used to assess 117 adolescents of a bipolar parent twice with an interval of 14 months. Based on the K-SADS results, the bipolar offspring were assigned to one of three groups: with mood disorders, with non-mood disorders, and with no disorders. RESULTS: Principal component analyses resulted in the same two-factor solution as reported for adults. The Depression scale of the GBI discriminated between adolescents with a DSM-IV mood disorder, a non-mood disorder and no disorder on Axis I. Significant correlations between GBI scales and the corresponding Internalizing and Externalizing scales of the YSR showed convergent validity. CONCLUSIONS: The GBI can be used in the adolescent age range as a self-report to discriminate mood disorders from non-mood disorders or no disorders.

The Dutch bipolar offspring study: 12-year follow-up.

OBJECTIVE: Offspring of bipolar parents have a genetically increased risk of developing mood disorders. In a longitudinal study, the authors followed a bipolar offspring cohort from adolescence into adulthood to determine the onset, prevalence, and early course of mood disorders and other psychopathology. METHOD: The Dutch bipolar offspring cohort is a fixed cohort initiated in 1997 (N=140; age range at baseline, 12-21 years). Bipolar offspring were psychiatrically evaluated at baseline and at 1-, 5-, and 12-year follow-ups. Of the original sample, 77% (N=108) were followed for the full 12 years. RESULTS: Overall, 72% of the bipolar offspring developed a lifetime DSM-IV axis I disorder, 54% a mood disorder, and 13% bipolar spectrum disorders. Only 3% met DSM-IV criteria for bipolar I disorder. In 88% of the offspring with a bipolar spectrum disorder, the illness started with a depressive episode. In total, 24% of offspring with a unipolar mood disorder developed a bipolar spectrum disorder over time. Mood disorders were often recurrent (31%), were complex (comorbidity rate, 67%), and started before age 25. CONCLUSIONS: Even after 12 years of follow-up, from adolescence into adulthood, bipolar I disorder was rare among bipolar offspring. Nevertheless, the risk of developing severe and recurrent mood disorders and other psychopathology was high. Future follow-up of this and other adult bipolar offspring cohorts is essential to determine whether recurrent mood disorders in bipolar offspring reflect the early stages of bipolar disorder.

Five-year prospective outcome of psychopathology in the adolescent offspring of bipolar parents.

OBJECTIVE: For nearly 5 years a prospective high risk cohort study was carried out in the Netherlands among adolescent offspring of parents with bipolar disorder (BD). The purpose of this study was to determine the prevalence of psychopathology, specifically mood disorders, in adolescents and young adults with a bipolar parent. METHOD: At first and second measurement 140 and 132 children of bipolar parents, respectively, were psychiatrically evaluated with a semi-structured psychiatric interview (K-SADS-PL). At follow up (third measurement), nearly 5 years later, lifetime DSM IV diagnoses were obtained from the SCID interview for 129 subjects (aged 16--26 years). RESULTS: Compared with the first measurement, the lifetime prevalence of BD increased from 3 to 10% at follow up. In addition, the lifetime prevalence of overall mood disorders increased to 40% and of overall psychopathology to 59%. All subjects except for one with BD, debuted with a unipolar mood disorder with a mean of 4.9 (SD 3.4) years prior to the first (hypo)manic episode. CONCLUSION: At follow up, we noticed an increase in BD onset, while a further increase could be expected. In addition, we found that a unipolar depression in bipolar offspring is a risk factor for, and at the same time the first sign of, the development of BD.

Impact of stressful life events, familial loading and their interaction on the onset of mood disorders: study in a high-risk cohort of adolescent offspring of parents with bipolar disorder.

BACKGROUND: Stressful life events are established as risk factors for the onset of mood disorders, but few studies have investigated their impact on the development of mood disorders in adolescents. AIMS: To study the effect of life events on the development of mood disorders in the offspring of parents with bipolar disorder, with respect to the possibility of a decay effect and modification by familial loading. METHOD: In a high-risk cohort of 140 Dutch adolescent offspring of parents with bipolar disorder, we assessed life events, current and past DSM-IV diagnoses and familial loading. To explore their interaction and impact on mood disorder onset, we constructed four different models and used a multivariate survival analysis with time-dependent covariates. RESULTS: The relationship between life events and mood disorder was described optimally with a model in which the effects of life events gradually decayed by 25% per year. The effect of life event load was not significantly stronger in the case of high familial loading. CONCLUSIONS: Independent of familial loading, life events increase the liability to mood disorders in children of patients with bipolar disorder but the effects slowly diminish with time.

Multiple dimensions of familial psychopathology affect risk of mood disorder in children of bipolar parents.

The aim of our study was to determine whether familial loading of unipolar disorder, bipolar disorder, and substance use disorder are associated with DSM-IV mood disorders in adolescents at risk for bipolar disorder. One hundred and forty adolescents aged 12-21 years of 86 bipolar parents participated in the study. Lifetime DSM-IV diagnoses of the bipolar offspring were assessed with the Schedule for Affective Disorders and Schizophrenia for School Age Children Kiddie-SADS-Present and Lifetime Version (SADS-PL). Parents were interviewed using the Family History Research Diagnostic Criteria (FH-RDC) which were used to calculate a continuous familial loading score (FL) for unipolar disorder, bipolar disorder, and for substance use disorder in first- and second-degree relatives of the adolescents. FL for unipolar disorder and substance use disorder were strong and independent predictors for lifetime mood disorders in the adolescents. The gender adjusted hazard ratios for mood disorders in the children were 1.5 (95% confidence interval (CI) = 1.2-2.0) for FL of unipolar disorder and 1.8 (95% CI = 1.3-2.4) for FL of substance use disorder. Expression of mood disorders in children of bipolar parents varies with the degree of additional FL of unipolar disorder and substance use disorder in the extended family.