Toward the Definition of a Bipolar Prodrome: Dimensional Predictors of Bipolar Spectrum Disorders in At-Risk Youths

Abstract

Objective: The authors sought to assess dimensional symptomatic predictors of new-onset bipolar spectrum disorders in youths at familial risk of bipolar disorder ("at-risk" youths).

Method: Offspring 6-18 years old of parents with bipolar I or II disorder (N=359) and community comparison offspring (N=220) were recruited. At baseline, 8.4% of the offspring of bipolar parents had a bipolar spectrum disorder. Over 8 years, 14.7% of offspring for whom follow-up data were available (44/299) developed a new-onset bipolar spectrum disorder (15 with bipolar I or II disorder). Measures collected at baseline and follow-up were reduced using factor analyses, and factors (both at baseline and at the visit prior to conversion or last contact) were assessed as predictors of new-onset bipolar spectrum disorders.

Results: Relative to comparison offspring, at-risk and bipolar offspring had higher baseline levels of anxiety/depression, inattention/disinhibition, externalizing, subsyndromal manic, and affective lability symptoms. The strongest predictors of new-onset bipolar spectrum disorders were baseline anxiety/depression, baseline and proximal affective lability, and proximal subsyndromal manic symptoms (p<0.05). While affective lability and anxiety/depression were elevated throughout follow-up in those who later developed a bipolar spectrum disorder, manic symptoms increased up to the point of conversion. A path analysis supported the hypothesis that affective lability at baseline predicts a new-onset bipolar spectrum disorder in part through increased manic symptoms at the visit prior to conversion; earlier parental age at mood disorder onset was also significantly associated with an increased risk of conversion. While youths without anxiety/depression, affective lability, and mania (and with a parent with older age at mood disorder onset) had a 2% predicted chance of conversion to a bipolar spectrum disorder, those with all risk factors had a 49% predicted chance of conversion.

Conclusions: Dimensional measures of anxiety/depression, affective lability, and mania are important predictors of new-onset bipolar spectrum disorders in at-risk youths. These symptoms emerged from among numerous other candidates, underscoring the potential clinical and research utility of these findings.

Figure 1

Baseline Differences in each factor across groups, adjusting for demographics. All two-group comparisons are significant (p<.05) except for Sleep scores between at-risk and control offspring.

Figure 2

Trajectories for dimensions graphed up to final eligible visit (either the visit prior to conversion or the visit prior to right censorship). a. Parent-Reported Internalizing, b. Child-reported affective lability, c. manic rating scale.

Figure 3

Path analysis showing significant predictors of new-onset bipolar spectrum from baseline and proximal visits. Baseline history of depressive disorders, lifetime anxiety disorders, and co-parent with bipolar disorder were significant in individual models, but did not directly predict bipolar spectrum onset in the final probit model. Model is adjusted for age at proximal visit, a nuisance covariate in this analysis. Correlations and beta coefficients between variables are included. ***p<.001, **p<.01

Figure 4

Predicted probability of new-onset bipolar spectrum for risk profiles defined by significant predictors in the overall probit model. Predicted risk differed substantially between someone with no symptoms (baseline anxiety/depression, proximal affective lability, and proximal manic symptoms all 1 S.D. below the mean) vs. someone with all of these symptoms (1 S.D. above the mean). Predicted risk also differed according to parental age of mood disorder onset, looking in particular at an individual 1 S.D. below the mean (parent proband developed mood disorder at 11 years old) vs. 1 S.D. above the mean (parent proband developed mood disorder at 29 years old). Results are adjusted for age at proximal visit, a nuisance covariate in this analysis.