Further Evidence for Robust Familiality of Pediatric Bipolar I Disorder

Abstract

Objective To determine the risk for BP-I disorder in first-degree relatives of children with DSM-IV bipolar-I disorder (BP-I) via meta-analysis and expanded controlled study. Data Sources and Extraction Meta-Analysis We searched the Pubmed database for scientific articles published in the world literature in the English language through 2011. The key words searched were: bipolar disorder, first-degree relatives, family study, control. All online abstracts were reviewed and relevant full manuscripts were collected and reviewed. Citations were also examined for other potential relevant articles. We included only controlled family studies that examined rates of bipolar-I disorder in all first-degree relatives (parents and siblings) of pediatric bipolar-I probands and included only studies that had age and sex matched controls. Family history studies were excluded. Also excluded were studies that were not in English, did not report the rates of all first-degree relatives, and reported only bipolar spectrum rates. We also excluded family studies that included only adult probands. We conducted a meta-analysis of the five controlled family studies of pediatric BP-I probands that met our search criteria using the random effects model of DerSimonian and Laird. Method Family Study We greatly expanded our previous sample of DSM-IV BP-I probands using structured diagnostic interviews. Our new study included 239 children satisfying full with DSM-IV diagnostic criteria for BP-I (n=726 first-degree relatives), 162 ADHD (without BP-I) probands (n=511 first-degree relatives), and 136 healthy control (without ADHD or BP-I) probands (n=411 first-degree relatives). We used the Kaplan-Meier cumulative failure function to calculate survival curves and cumulative, lifetime risk in relatives. Cox proportional hazard models were used to calculate the risk of BP-I in relatives. Results The pooled odds ratio for BP-I disorder in relatives was estimated to be 6.96 (95% Confidence Interval (CI): 4.8 to 10.1). We also found first-degree relatives of BP-I probands to be significantly more likely than first-degree relatives of both ADHD (Hazards Ratio: 3.02; 95% CI: 1.85 to 4.93; p<0.001) and control probands (HR: 2.83; 1.65 to 4.84; p<0.001) to have bipolar-I disorder. Conclusion Our results document an increased familial risk for BP-I disorder in relatives of pediatric probands with DSM-IV BP-I.

Further evidence that severe scores in the aggression/anxiety-depression/attention subscales of child behavior checklist (severe dysregulation profile) can screen for bipolar disorder symptomatology: a conditional probability analysis

“…Detailed study methods have been previously described (Wozniak et al, 2012). Briefly, children with BP-I disorder 6 to 17 years of age of both sexes were assessed at the Clinical and Research Program in Pediatric Psychopharmacology at the Massachusetts General Hospital (Wozniak et al, 2005; Wozniak et al, 2010).…”

Does sex moderate the clinical correlates of pediatric bipolar-I disorder? Results from a large controlled family-genetic study

“…To the best of our knowledge, this is the first report examining sex effects of familiality of pediatric BP-I disorder. This finding is particularly noteworthy considering that familiality is a useful external validator of complicated diagnostic entities such as pediatric BP-I disorder (Wozniak et al, 2012). …”

“…Family and other studies document robust patterns of familiality (Schulze et al, 2006, Wozniak et al, 2010, Wozniak et al, 2012), a protracted course (Wozniak et al, 2011) and selective responsivity to antimanic agents (Smith et al, 2007, Correll et al, 2010, Liu et al, 2011). While it clearly affects both sexes, very few studies have addressed whether the sex of the proband influences the clinical presentation of pediatric bipolar disorder.…”

Attention Deficits in a Comorbidity-Free Sample of Euthymic Pediatric Bipolar Disorder

“…Impairments in attention have been demonstrated across symptomatic (1–3) and euthymic (4–7) phases in adult bipolar disorder (BD) patients and to variable degrees, in populations at higher risk for BD (4, 7–9). Further, naturalistic longitudinal study examining cognitive functioning in adult BD patients found that while cognitive function in BD varied significantly over time, a deficit in attention remained stable (5).…”