Abstract
BackgroundMajor contributors to the global burden of bipolar disorders (BD) are the early age at onset (AAO) and the co-occurrence of non-mood disorders before and after the onset of BD. Using data from two independent cohorts from Europe and the USA, we investigated whether the trajectories of BD-I onset and patterns of psychiatric comorbidities differed in (a) individuals with or without a family history (FH) of BD, or (b) probands and parents who both had BD-I.MethodsFirst, we estimated cumulative probabilities and AAO of comorbid mental disorders in familial and non-familial cases of BD-I (Europe, n = 573), and sex-matched proband-parent pairs of BD-I cases (USA, n = 194). Then we used time to onset analyses to compare overall AAO of BD-I and AAO according to onset polarity. Next, we examined associations between AAO and polarity of onset of BD-I according to individual experiences of comorbidities. This included analysis of the density of antecedent events (defined as the number of antecedent comorbidities per year of exposure to mental illness per individual) and time trend analysis of trajectory paths plotted for the subgroups included in each cohort (using R2 goodness of fit analysis).ResultsEarlier AAO of BD-I was found in FH versus non-FH cases (log rank test = 7.63; p = 0.006) and in probands versus parents with BD-I (log rank test = 15.31; p = 0.001). In the European cohort, AAO of BD-I was significantly associated with factors such as: FH of BD (hazard ratio [HR]: 0.60), earlier AAO of first non-mood disorder (HR: 0.93) and greater number of comorbidities (HR: 0.74). In the USA cohort, probands with BD-I had an earlier AAO for depressive and manic episodes and AAO was also associated with e.g., number of comorbidities (HR: 0.65) and year of birth (HR: 2.44). Trajectory path analysis indicated significant differences in density of antecedents between subgroups within each cohort. However, the time trend R2 analysis was significantly different for the European cohort only.ConclusionsEstimating density of antecedent events and comparing trajectory plots for different BD subgroups are informative adjuncts to established statistical approaches and may offer additional insights that enhance understanding of the evolution of BD-I.
Highlights
Major contributors to the global burden of bipolar disorders (BD) are the early age at onset (AAO) and the co-occurrence of non-mood disorders before and after the onset of BD
It was clear that more intriguing findings emerged when analyses are extended to consider the overall burden of comorbidities and whether the total exposure and/or timing of exposures to comorbidities is associated with AAO of BD
We found that most family history (FH) and PRB cases experience ≥ 1 non-mood disorder prior to the onset of BD, and that the increased illness burden associated with all comorbidities appears to be due to incremental differences in the cumulative probability and/or AAO in these two subgroups compared with the other study groups
Summary
Major contributors to the global burden of bipolar disorders (BD) are the early age at onset (AAO) and the co-occurrence of non-mood disorders before and after the onset of BD. Key reasons for the substantial morbidity are that 75% of BD onsets occur at age < 30, and that BD is highly comorbid (Angst et al 2002; Merikangas et al 2007; Merikangas et al 2008) These issues are amplified in individuals with a family history (FH) of BD who have an increased risk of developing BD, to experience an earlier age at onset (AAO) of BD, and to report high rates of mood and non-mood disorders during childhood and adolescence compared with control populations (e.g., Duffy et al 2019; Hafeman et al 2017; Lau et al 2018). The findings suggest that, for example, most anxiety disorders may occur earlier than mood problems and precede substance misuse (Lau et al 2018)
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