Towards precision dosing of aripiprazole in children and adolescents with autism spectrum disorder: Linking blood levels to weight gain and effectiveness.

AIMS: Aripiprazole is one of the most commonly prescribed antipsychotic drugs to children and adolescents worldwide, but it is associated with serious side-effects, including weight gain. This study assessed the population pharmacokinetics of aripiprazole and its active metabolite and investigated the relationship between pharmacokinetic parameters and body mass index (BMI) in children and adolescents with autism spectrum disorder (ASD) and behavioural problems. Secondary outcomes were metabolic, endocrine, extrapyramidal and cardiac side-effects and drug effectiveness. METHODS: Twenty-four children and adolescents (15 males, 9 females) aged 6-18 years were included in a 24-week prospective observational trial. Drug plasma concentrations, side-effects and drug effectiveness were measured at several time points during follow-up. Relevant pharmacokinetic covariates, including CYP2D6, CYP3A4, CYP3A5 and P-glycoprotein (ABCB1) genotypes, were determined. Nonlinear mixed-effects modelling (NONMEM®) was used for a population pharmacokinetic analysis with 92 aripiprazole and 91 dehydro-aripiprazole concentrations. Subsequently, model-based trough concentrations, maximum concentrations and 24-h area under the curves (AUCs) were analysed to predict outcomes using generalized and linear mixed-effects models. RESULTS: For both aripiprazole and dehydro-aripiprazole, one-compartment models best described the measured concentrations, with albumin and BMI as significant covariates. Of all the pharmacokinetic parameters, higher sum (aripiprazole plus dehydro-aripiprazole) trough concentrations best predicted higher BMI z-scores (P < .001) and higher Hb1Ac levels (P = .03) during follow-up. No significant association was found between sum concentrations and effectiveness. CONCLUSIONS: Our results indicate a threshold with regard to safety, which suggests that therapeutic drug monitoring of aripiprazole could potentially increase safety in children and adolescents with ASD and behavioural problems.

Risperidone plasma concentrations are associated with side effects and effectiveness in children and adolescents with autism spectrum disorder.

AIM: Risperidone is the most commonly prescribed antipsychotic drug to children and adolescents worldwide, but it is associated with serious side effects, including weight gain. This study assessed the relationship of risperidone and 9-hydroxyrisperidone trough concentrations, maximum concentrations and 24-hour area under the curves (AUCs) with body mass index (BMI) z-scores in children and adolescents with autism spectrum disorder (ASD) and behavioural problems. Secondary outcomes were metabolic, endocrine, extrapyramidal and cardiac side effects and effectiveness. METHODS: Forty-two children and adolescents (32 males) aged 6-18 years were included in a 24-week prospective observational trial. Drug plasma concentrations, side effects and effectiveness were measured at several time points during follow-up. Relevant pharmacokinetic covariates, including medication adherence and CYP2D6, CYP3A4, CYP3A5 and P-glycoprotein (ABCB1) genotypes, were measured. Nonlinear mixed-effects modelling (NONMEM®) was used for a population pharmacokinetic analysis with 205 risperidone and 205 9-hydroxyrisperidone concentrations. Subsequently, model-based trough concentrations, maximum concentrations and 24-hour AUCs were analysed to predict outcomes using generalized and linear mixed-effects models. RESULTS: A risperidone two-compartment model combined with a 9-hydroxyrisperidone one-compartment model best described the measured concentrations. Of all the pharmacokinetic parameters, higher risperidone sum trough concentrations best predicted higher BMI z-scores during follow-up (P < .001). Higher sum trough concentrations also predicted more sedation (P < .05), higher prolactin levels (P < .001) and more effectiveness measured with Aberrant Behavior Checklist irritability score (P < .01). CONCLUSION: Our results indicate a therapeutic window exists, which suggests that therapeutic drug monitoring of risperidone might increase safety and effectiveness in children and adolescents with ASD and behavioural problems.

Risk factors and pattern of weight gain in youths using antipsychotic drugs.

Antipsychotic-induced weight gain is a major health concern in children and adolescents. The aim of this study was to identify risk factors for weight gain during short-, middle- and long-term treatment with antipsychotic drugs in this young population. We analysed a combined prospective and a retrospective observational cohort of Dutch children and adolescents, starting with risperidone, aripiprazole or pipamperone treatment. Linear mixed models were used to test whether sex, age, baseline body-mass-index (BMI) z score, type of antipsychotic, dose equivalent/kg, duration of use, previous antipsychotic use, ethnicity, physical exercise, IQ, concomitant medication, and psychiatric classification predicted the BMI z score for a follow-up of < 15 weeks, 15-52 weeks or > 52 weeks. A total of 144 patients were included with a median [interquartile range ([IQR)] age of 9 (4) years and median follow-up of 30 (73) weeks. During the complete follow-up, the median (IQR) weight gain was 0.37 (0.95) BMI z score points. Antipsychotic-induced weight gain was found to be most pronounced during the first 15 weeks of use (BMI z score increase per week ß = 0.02, 95% CI 0.01-0.03, p = 0.002). A higher baseline BMI z score and the absence of stimulant use were associated with a higher BMI z score during the entire follow-up and after 15 weeks, respectively. Previous treatment with an antipsychotic drug was associated with less weight gain during the first 15 weeks of treatment. Our findings underscore the importance of close patient monitoring during the first weeks of antipsychotic treatment with a focus on patients with a high baseline BMI z score.

Pipamperone Population Pharmacokinetics Related to Effectiveness and Side Effects in Children and Adolescents.

BACKGROUND: Pipamperone is a frequently prescribed antipsychotic in children and adolescents in the Netherlands, Belgium, and Germany. However, pediatric pharmacokinetics and the relationship with side effects and efficacy are unknown. Currently, divergent pediatric dosing recommendations exist. OBJECTIVES: The objective of this study was to describe the population pharmacokinetics of pipamperone in children and adolescents; to correlate measured and predicted pipamperone trough concentrations and predicted 24-h area under the curves with effectiveness, extrapyramidal symptoms, and sedation; and to propose dose recommendations based on simulations. METHODS: Pipamperone concentrations were collected from Dutch pediatric patients in a prospective naturalistic trial (n = 8), and German pediatric patients in a therapeutic drug monitoring service (n = 22). A total of 70 pipamperone concentrations were used to develop a population pharmacokinetic model with non-linear mixed-effects modeling (NONMEM®). Additionally, an additional random sample of 21 German patients with 33 pipamperone concentrations from the same therapeutic drug monitoring service was used for external validation. Pharmacokinetic parameters were related to clinical improvement, sedation, and extrapyramidal symptoms. Simulations were performed to determine optimal dosages. RESULTS: In a one-compartment model, the apparent volume of distribution was 416 L/70 kg and the apparent clearance was 22.1 L/h/70 kg. Allometric scaling was used to correct for differences in bodyweight. The model was successfully externally validated. The median [25th-75th percentile] measured pipamperone trough concentrations were numerically higher in responders (98.0 µg/L [56.0-180.5 µg/L]) than in non-responders (58.0 µg/L [14.9-105.5 µg/L]), although non-significant (p = 0.14). A twice-daily 0.6-mg/kg dosage was better than a fixed dosage to attain the concentration range observed in responders. CONCLUSIONS: Our findings suggest that pipamperone therapeutic reference ranges may be lower for children with behavioral problems than recommended for adults with psychotic symptoms (100-400 µg/L). When dosing pipamperone in children and adolescents, bodyweight should be taken into account.

The Leiden Family Lab study on Social Anxiety Disorder: A multiplex, multigenerational family study on neurocognitive endophenotypes.

OBJECTIVES: Social anxiety disorder (SAD) is a serious and prevalent psychiatric condition, with a heritable component. However, little is known about the characteristics that are associated with the genetic component of SAD, the so-called "endophenotypes". These endophenotypes could advance our insight in the genetic susceptibility to SAD, as they are on the pathway from genotype to phenotype. The Leiden Family Lab study on Social Anxiety Disorder (LFLSAD) is the first multiplex, multigenerational study aimed to identify neurocognitive endophenotypes of social anxiety. METHODS: The LFLSAD is characterized by a multidisciplinary approach and encompasses a variety of measurements, including a clinical interview, functional and structural magnetic resonance imaging and an electroencephalography experiment. Participants are family members from 2 generations, from families genetically enriched for SAD. RESULTS: The sample (n = 132 participants, from 9 families) was characterized by a high prevalence of SAD, in both generations (prevalence (sub)clinical SAD: 38.3%). Furthermore, (sub)clinical SAD was positively related to self-reported social anxiety, fear of negative evaluation, trait anxiety, behavioral inhibition, negative affect, and the level of depressive symptoms. CONCLUSIONS: By the multidimensional character of the measurements and thorough characterization of the sample, the LFLSAD offers unique opportunities to investigate candidate neurocognitive endophenotypes of SAD.

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.

Parents' perceptions on offspring risk and prevention of anxiety and depression: a qualitative study.

BACKGROUND: Offspring of patients with anxiety or depression are at high risk for developing anxiety or depression. Despite the positive findings regarding effectiveness of prevention programs, recruitment for prevention activities and trials is notoriously difficult. Our randomized controlled prevention trial was terminated due to lack of patient inclusion. Research on mentally-ill parents' perceptions of offspring's risk and need for preventive intervention may shed light on this issue, and may enhance family participation in prevention activities and trials. METHODS: Qualitative data were collected through semi-structured interviews with 24 parents (patients with anxiety or depression, or their partners). An inductive content analysis of the data was performed. Five research questions were investigated regarding parents' perceptions of anxiety, depression, and offspring risk; anxiety, depression, and parenting; the need for offspring intervention and prevention; and barriers to and experiences with participation in preventive research. RESULTS: Parental perceptions of the impact of parental anxiety and depression on offspring greatly differed. Parents articulated concerns about children's symptomatology, however, most parents did not perceive a direct link between parent symptoms and offspring quality of life. They experienced an influence of parental symptoms on family quality of life, but chose not to discuss that with their children in order to protect them. Parents were not well aware of the possibilities regarding professional help for offspring and preferred parent-focused rather than offspring-focused interventions such as parent psycho-education. Important barriers to participation in preventive research included parental overburden, shame and stigma, and perceived lack of necessity for intervention. CONCLUSIONS: This study highlights the importance of educating parents in adult health care. Providing psycho-education regarding offspring risk, communication in the family, and parenting in order to increase parental knowledge and parent-child communication, and decrease guilt and shame are important first steps in motivating parents to participate in preventive treatment.

Temperament and parenting predicting anxiety change in cognitive behavioral therapy: the role of mothers, fathers, and children.

OBJECTIVE: A considerable amount of children with anxiety disorders do not benefit sufficiently from cognitive behavioral treatment. The present study examines the predictive role of child temperament, parent temperament and parenting style in the context of treatment outcome. METHOD: Participants were 145 children and adolescents (ages 8-18) with DSM-IV-TR anxiety disorders who received a 12-session CBT program and were assessed at pretreatment, posttreatment and three months follow-up. Multiple-regression analyses were used to evaluate the following pretreatment and posttreatment variables as potential predictors of treatment response at follow-up: baseline level of anxiety symptoms, child reported maternal and paternal rearing style (emotional warmth, rejection, and overprotection), parent reported child temperament traits (negative affect, effortful control, and extraversion), and mothers' and fathers' self-report temperament traits. RESULTS: More maternal negative affect and less emotional warmth as perceived by the child before treatment were related to less favorable treatment outcome (accounting for 29% of the variance in anxiety at follow-up). Furthermore, maternal negative affect and children's extraversion measured after treatment also predicted anxiety at follow-up (together accounting for 19% of the variance). Paternal temperament and parenting style were unrelated to treatment outcome, as were children's pretreatment temperament traits. CONCLUSION: The results suggest that tailoring intervention to include strategies to reduce maternal negative affect and promote an emotional warm rearing style may improve treatment outcome.

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.

Preventing mood and anxiety disorders in youth: a multi-centre RCT in the high risk offspring of depressed and anxious patients.

BACKGROUND: Anxiety and mood disorders are highly prevalent and pose a huge burden on patients. Their offspring is at increased risk of developing these disorders as well, indicating a clear need for prevention of psychopathology in this group. Given high comorbidity and non-specificity of intergenerational transmission of disorders, prevention programs should target both anxiety and depression. Further, while the indication for preventive interventions is often elevated symptoms, offspring with other high risk profiles may also benefit from resilience-based prevention programs. METHOD/DESIGN: The current STERK-study (Screening and Training: Enhancing Resilience in Kids) is a randomized controlled clinical trial combining selected and indicated prevention: it is targeted at both high risk individuals without symptoms and at those with subsyndromal symptoms. Individuals without symptoms meet two of three criteria of the High Risk Index (HRI; female gender, both parents affected, history of a parental suicide (attempt). This index was developed in an earlier study and corresponds with elevated risk in offspring of depressed patients. Children aged 8-17 years (n = 204) with subthreshold symptoms or meeting the criteria on the HRI are randomised to one of two treatment conditions, namely (a) 10 weekly individual child CBT sessions and 2 parent sessions or (b) minimal information. Assessments are held at pre-test, post-test and at 12 and 24 months follow-up. Primary outcome is the time to onset of a mood or anxiety disorder in the offspring. Secondary outcome measures include number of days with depression or anxiety, child and parent symptom levels, quality of life, and cost-effectiveness. Based on models of aetiology of mood and anxiety disorders as well as mechanisms of change during interventions, we selected potential mediators and moderators of treatment outcome, namely coping, parent-child interaction, self-associations, optimism/pessimism, temperament, and emotion processing. DISCUSSION: The current intervention trial aims to significantly reduce the risk of intergenerational transmission of mood and anxiety disorders with a short and well targeted intervention that is directed at strengthening the resilience in potentially vulnerable children. We plan to evaluate the effectiveness and cost-effectiveness of such an intervention and to identify mechanisms of change. TRIAL REGISTRATION: NTR2888.

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.

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.

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.

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.

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.

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.

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.

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.

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.