Specificity in etiology of subtypes of bipolar disorder: Evidence from a Swedish population-based family study

Objectives: The discrete boundaries between current diagnostic classifications of psychiatric disorders have been increasingly challenged by emerging evidences of shared genetic determinants between disorders (1). This... [ view full abstract ]

Objectives: The discrete boundaries between current diagnostic classifications of psychiatric disorders have been increasingly challenged by emerging evidences of shared genetic determinants between disorders (1). This challenge is particularly relevant for subtypes of mood disorders. To examine whether bipolar I disorder (BDI) and bipolar II disorder (BDII) have etiological differences, we used a population-based sample to assess the familial aggregation for each subtype and co-aggregation between them. Furthermore, we explored their correlations with schizophrenia, depression, attention-deficit/hyperactivity disorder, eating disorders, autism spectrum disorders, substance use disorders, anxiety disorders and personality disorders.

Methods: By linking Swedish national registers we established a population-based cohort (N=15,685,511) and identified relatives with different biological relationships. Odds ratios (ORs) were used to measure the risk of disorders in relatives of individuals diagnosed with BDI (N=4,309) and BDII (N=4,178). The heritabilities for BDI and BDII and the genetic correlation across psychiatric disorders were estimated by variance decomposition analysis.

Results: Compared with the general population, the OR of BDI was 17.0 (95% confidence interval (CI) 13.1-22.0) in first-degree relatives of BDI patients, higher than that of BDII patients (OR 9.8, 95% CI 7.7-12.5). By contrast, the ORs of BDII were 13.6 (95%CI 10.2-18.2) in first-degree relatives of BDII patients and 9.8 (95%CI 7.7-12.4) in first-degree relatives of BDI patients. The heritabilities for BDI and BDII were estimated as 0.60 (95%CI 0.33-0.82) and 0.41 (95%CI 0.13-0.65), respectively, with a substantial genetic correlation between them (0.69, 95 %CI 0.34-0.98). The familial co-aggregation with other psychiatric disorders, in particular schizophrenia, showed different patterns for BDI and BDII.

Conclusions: Our results suggest a distinction between BDI and BDII in etiology, partly due to genetic differences.

References

1. Cross-Disorder Group of the PGC, Identification of risk loci with shared effects on five major psychiatric disorders: a genome-wide analysis. Lancet. 2013; 381:1371-9.