Genetic differences between bipolar disorder subtypes: A systematic review focused in bipolar disorder type II

Abstract

Background: The identification of bipolar disorder (BD) type II patients has both treatment and prognostic implications. Better understanding of its underlying genetics may yield useful diagnostic tools.

Methods: A systematic review on BDII genetics was done using articles published in 2009-2019, following PRISMA recommendations.

Results: The most studied polymorphism was BDNF Val66Met with several gene-gene interactions within the dopaminergic system. Associations were reported within the monoaminergic systems (DRD3, ADH1B and SLC6A4), calcium (CACNB2 and CACNG2) and cAMP (PDE1DA, PDE4B and DISC1) signal transduction pathways and the immune system (TNFα, IFNδ and IL-10). Chromosomes 2, 3 and 10 were associated with BDII and polygenic risk scores distinguished between BD subtypes and with major depressive disorder.

Conclusions: Research on BDII stems from BDI findings, however with a stronger contribution of gene-gene interactions and low-effect alleles on known neuroplasticity and monoaminergic system genes. Genome studies point to transdiagnostic backgrounds, with wider associations across bipolar spectrum disorders. Findings able to accurately differentiate BDII remain elusive, dependent on better phenotypic characterization and new research methods.

Keywords: Bipolar disorder type II; Bipolar spectrum disorders; Candidate-gene studies; Genome-wide association studies.