Demographic and clinical characteristics of the sample are presented in . Eighty percent of the BP-I probands are male.There were small but statistically significant differences in the ethnic and socio-economic backgrounds of the families. The control had had higher SES and the BP-I families had more ethnic diversity. Accordingly, all subsequent tests were adjusted for SES and race. There were no differences in the age or sex of the BP-I, ADHD, and control probands (by design, see methods above). The BP-I probands were more impaired than both ADHD and control children according to past and current global assessment of functioning (GAF) score (). There were no meaningful demographic characteristics differences between the parents or siblings of the BP-I, ADHD, and control probands, but relatives of BP-I probands were more impaired according to both lifetime and current GAF scores than the relatives of both the ADHD and control relatives.
Clinical and Demographic Characteristics
The clinical presentation of BP-I disorder in probands was characterized by early onset (5.8±3.4 years), rapid cycling (22.4±61.6 episodes) and a chronic course (3.6±3.3 years in duration). As shown in , BP-I in probands was predominantly mixed with co-occurring depression (N=131, 83%) and probands with BP-I were at increased risk of multiple (≥2) anxiety disorders, disruptive behavior disorders, and substance use disorder relative to both the ADHD and control probands. Although statistical comparisons could not be made between these groups for ADHD or psychosis due to the inclusion/exclusion criteria of the ADHD family studies, both of these disorders were overrepresented in BP-I probands.
Psychiatric Comorbidity in Proband Children
The age-dependant cumulative morbid risk of BP-I disorder in relatives is illustrated in Figures and . The risk of BP-I disorder in relatives of BP-I probands was statistically significantly higher compared with the relatives of both the ADHD (Hazard Ratio (HR)=3.1 (1.8-5.5); p<0.0001) and the healthy control probands (HR=3.3; (1.9-5.5); p<0.0001). In contrast, the relatives of ADHD probands were not at increased risk of BP-I compared with relatives of control probands (HR=1.0; (0.5-1.9); p=0.9). In this context, the HR indexes the relative risk for a disorder in the relative given the proband diagnoses. For example, the HR for BP-I in relatives of BP-I vs relatives of ADHD probands was 3.6, which means that there was an, age corrected 3.6 fold increase of BP-I among the relatives of BP-I probands compared with relatives of ADHD probands. Controlling for psychiatric comorbidity in probands (ODD, conduct disorder, major depression, multiple anxiety disorders, and substance use disorder) did not impact the statistical significance or magnitude of the hazards ratios comparing the relatives of BP-I probands with relatives of ADHD (corrected HR=3.8 (1.9-7.6, p<0.0001) or control (corrected HR=4.0 (1.6-10.1, p<0.0001) probands.
Familial risk of bipolar-I (BP-I) disorder in first-degree relatives. ADHD, attention deficit hyperactivity disorder.
Bipolar-I (BP-I) disorder in first-degree relatives.
The morbid risk of additional psychiatric disorders in the 1st degree relatives of BP-I, ADHD, and control probands are presented in . Relatives of BP-I probands were at increased risk of psychosis, major depression, multiple anxiety disorders, substance use disorders, ADHD, Oppositional Defiant Disorder (ODD) and antisocial (Conduct Disorder [CD] or Antisocial Personality Disorder [ASPD]) compared with relatives of Control probands. In addition, in comparison with relatives of ADHD probands, relatives of BP-I probands were also at increased risk of major depression, multiple anxiety disorders, substance use disorders and ODD (). However, in models adjusting for the same psychiatric comorbidity in probands, the relatives of BP-I probands were no longer at increased risk for ODD nor for CD/ASPD compared with relatives of Control probands, nor for ODD and CD/ASPD compared with relatives of ADHD probands (all p’s >0.05). Thus, BP-I in probands was independently associated with major depression, multiple anxiety disorders substance use disorders and ADHD in comparison with controls. Relatives of BP-I probands were at statistically significant increased risk of psychosis, multiple anxiety disorders and substance use disorder compared with relatives of ADHD probands independently of the psychiatric comorbidity with these disorders in probands.
Psychiatric Morbidity in 1st Degree Relatives of Pediatric BPD, ADHD and Control Probands
To determine if our findings of familial transmission were moderated by age, we augmented our statistical models by adding the interaction of age (12 and under vs. older) by proband group. We found no statistically significant interactions, which indicates that the magnitude of familial transmission was not moderated by age group.