Special review articleAssociation of increased genotypes risk for bipolar disorder with brain white matter integrity investigated with tract-based spatial statistics: Special Section on “Translational and Neuroscience Studies in Affective Disorders”.

- Diffusion tensor imaging investigates non-invasively brain tissue integrity in-vivo.
- ANK3 and ZNF804A genes associate with brain integrity indexes in bipolar disorder.
- Current studies are limited by SNPs and chronically treated patients investigation.

BackgroundDiffusion tensor imaging (DTI) studies, which allow the in-vivo investigation of brain tissue integrity, have shown that bipolar disorder (BD) patients present signs of white matter dysconnectivity. In parallel, genome-wide association studies (GWAS) identified several risk genetic variants for BD. IMethodsIn this mini-review, we summarized DTI studies coupling tract-based spatial statistics (TBSS), a reliable technique exploring white matter axon bundles, and genetics in BD. We performed a bibliographic search on PUBMED, using the search terms “TBSS”, “genetics”, “genome”, “genes”, “polymorphism”, “bipolar disorder”.ResultsTen studies met these inclusion criteria. ANK3 and ZNF804A polymorphisms have shown the most consistent results, with the risk alleles showing abnormal white matter integrity in patients with BD.LimitationsCurrent studies are limited by the investigation of single SNPs in small and chronically treated samples.ConclusionsMost considered TBSS-DTI studies found associations between decreased white matter integrity and genetic risk variants. These results suggest an involvement of dysmyelination in the pathogenesis of BD. The combination of TBSS with genotyping can be powerful to unveil the role of white matter in BD, in conjunction with risk genes. Future DTI studies should combine TBSS and GWAS in large populations of drug-free or minimally treated patients with BD at the onset of the disease.