Higher socioeconomic status and less parental psychopathology improve prognosis in youths with bipolar disorder.

BACKGROUND: To identify prospectively ascertained individual and family factors that are associated with improvement in Bipolar Disorder (BD) among youths who initially presented with poor course. METHODS: 82 youths with BD with persistent poor mood symptomatology ("predominantly ill course") were compared to 70 youths with BD who at intake had poor course, but showed improvement during the follow-up ("ill with improving course"), (ages 12.3 ± 3.3, vs. 11.7 ± 3.3 years old, at intake). Improvement was measured by the percentage of time euthymic during a mean follow-up of 12.8 years. Youths and parents were interviewed to assess psychopathology, functioning, treatment, and familial functioning and psychopathology. RESULTS: Compared to the ill group, since intake, the improving group showed significantly lower subthreshold depression and hypo/mania, Attention Deficit Hyperactivity Disorder, and Disruptive Behavior Disorders. Parental Socioeconomic Status (SES) remained unchanged over time in the ill group, but progressively increased in the improving group. Importantly, the change in SES predated the improvement in the mood trajectory. The most influential variables that predicted improvement were higher SES, and absence of parental BD and Substance Use Disorder (SUD). Parental SUD also negatively affected the parental SES, which was directly associated with worse mood course. LIMITATIONS: Predominantly self-reported White samples may limit generalizability; other factors potentially associated with outcome (e.g., treatment adherence), were not ascertained. CONCLUSIONS: In addition to treating mood/comorbid psychopathology in symptomatic BD youths, to improve their prognosis, it is crucial to address their parent's BD and SUD and promote parental education/employment.

Validation of the youth mood recurrences risk calculator in an adult sample with bipolar disorder.

BACKGROUND: The ability to predict an individual's risk of mood episode recurrence can facilitate personalized medicine in bipolar disorder (BD). We sought to externally validate, in an adult sample, a risk calculator of mood episode recurrence developed in youth/young adults with BD from the Course and Outcome of Bipolar Youth (COBY) study. METHODS: Adult participants from the National Institute of Mental Health Collaborative Depression Study (CDS; N=258; mean(SD) age=35.5(12.0) years; mean follow-up=24.9 years) were utilized as a sample to validate the youth COBY risk calculator for onset of depressive, manic, or any mood episodes. RESULTS: In this older validation sample, the risk calculator predicted recurrence of any episode over 1, 2, 3, or 5-year follow-up intervals, with Area Under the Curves (AUCs) approximating 0.77. The AUC for prediction of depressive episodes was about 0.81 for each of the time windows, which was higher than for manic or hypomanic episodes (AUC=0.72). While the risk calculator was well-calibrated across the range of risk scores, it systematically underestimated risk in the CDS sample by about 20%. The length of current remission was a highly significant predictor of recurrence risk in the CDS sample. LIMITATIONS: Predominantly self-reported White samples may limit generalizability; the risk calculator does not assess more proximal risk (e.g., 1 month). CONCLUSIONS: Risk of mood episode recurrence can be predicted with good accuracy in youth and adults with BD in remission. The risk calculators may help identify higher risk BD subgroups for treatment and research.

Generalizing the Prediction of Bipolar Disorder Onset Across High-Risk Populations.

OBJECTIVE: Risk calculators (RC) to predict clinical outcomes are gaining interest. An RC to estimate risk of bipolar spectrum disorders (BPSD) could help reduce the duration of undiagnosed BPSD and improve outcomes. Our objective was to adapt an RC previously validated in the Pittsburgh Bipolar Offspring Study (BIOS) sample to achieve adequate predictive ability in both familial high-risk and clinical high-risk youths. METHOD: Participants (aged 6-12 years at baseline) from the Longitudinal Assessment of Manic Symptoms (LAMS) study (N = 473) were evaluated semi-annually. Evaluations included a Kiddie Schedule for Affective Disorders (K-SADS) interview. After testing an RC that closely approximated the original, we made modifications to improve model prediction. Models were trained in the BIOS data, which included biennial K-SADS assessments, and tested in LAMS. The final model was then trained in LAMS participants, including family history of BPSD as a predictor, and tested in the familial high-risk sample. RESULTS: Over follow-up, 65 youths newly met criteria for BPSD. The original RC identified youths who developed BPSD only moderately well (area under the curve [AUC] = 0.67). Eliminating predictors other than the K-SADS screening items for mania and depression improved accuracy (AUC = 0.73) and generalizability. The model trained in LAMS, including family history as a predictor, performed well in the BIOS sample (AUC = 0.74). CONCLUSION: The clinical circumstances under which the assessment of symptoms occurs affects RC accuracy; focusing on symptoms related to the onset of BPSD improved generalizability. Validation of the RC under clinically realistic circumstances will be an important next step.

Development of bipolar disorder and other comorbidity among youth with attention-deficit/hyperactivity disorder.

OBJECTIVE: To examine development of bipolar spectrum disorders (BPSD) and other disorders in prospectively followed children with attention-deficit/hyperactivity disorder (ADHD). METHOD: In the Longitudinal Assessment of Manic Symptoms (LAMS) study, 531 of 685 children age 6-12 (most selected for scores > 12 on General Behavior Inventory 10-item Mania scale) had ADHD, 112 with BPSD, and 419 without. With annual assessments for 8 years, retention averaged 6.2 years. Chi-square analyses compared rate of new BPSD and other comorbidity between those with versus without baseline ADHD and between retained versus resolved ADHD diagnosis. Cox regression tested factors influencing speed of BPSD onset. RESULTS: Of 419 with baseline ADHD but not BPSD, 52 (12.4%) developed BPSD, compared with 16 of 110 (14.5%) without either baseline diagnosis. Those who developed BPSD had more nonmood comorbidity over the follow-up than those who did not develop BPSD (p = .0001). Of 170 who still had ADHD at eight-year follow-up (and not baseline BPSD), 26 (15.3%) had developed BPSD, compared with 16 of 186 (8.6%) who had ADHD without BPSD at baseline but lost the ADHD diagnosis (χ2  = 3.82, p = .051). There was no statistical difference in whether ADHD persisted or not across new BPSD subtypes (χ2  = 1.62, p = .446). Of those who developed BPSD, speed of onset was not significantly related to baseline ADHD (p = .566), baseline anxiety (p = .121), baseline depression (p = .185), baseline disruptive behavior disorder (p = .184), age (B = -.11 p = .092), maternal mania (p = .389), or paternal mania (B = .73, p = .056). Those who started with both diagnoses had more severe symptoms/impairment than those with later developed BPSD and reported having ADHD first. CONCLUSIONS: In a cohort selected for symptoms of mania at age 6-12, baseline ADHD was not a significant prospective risk factor for developing BPSD. However, persistence of ADHD may marginally mediate risk of BPSD, and early comorbidity of both diagnoses increases severity/impairment.

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.

Anxiety Disorders in Caucasian and African American Children: A Comparison of Clinical Characteristics, Treatment Process Variables, and Treatment Outcomes.

This study examined racial differences in anxious youth using data from the Child/Adolescent Anxiety Multimodal Study (CAMS) [1]. Specifically, the study aims addressed whether African American (n = 44) versus Caucasian (n = 359) children varied on (1) baseline clinical characteristics, (2) treatment process variables, and (3) treatment outcomes. Participants were ages 7-17 and met DSM-IV-TR criteria for generalized anxiety disorder, social phobia, and/or separation anxiety disorder. Baseline data, as well as outcome data at 12 and 24 weeks, were obtained by independent evaluators. Weekly treatment process variables were collected by therapists. Results indicated no racial differences on baseline clinical characteristics. However, African American participants attended fewer psychotherapy and pharmacotherapy sessions, and were rated by therapists as less involved and compliant, in addition to showing lower mastery of CBT. Once these and other demographic factors were accounted for, race was not a significant predictor of response, remission, or relapse. Implications of these findings suggest African American and Caucasian youth are more similar than different with respect to the manifestations of anxiety and differences in outcomes are likely due to treatment barriers to session attendance and therapist engagement.