The role of the uncinate fasciculus in the risk-architecture of bipolar disorders: A meta-analysis

Background: Bipolar disorder (BD) is a severe mental disorder, characterized by prominent mood swings and emotion regulation (ER) deficits. The uncinate fasciculus (UF), a white matter tract connecting the amygdala and the ventral prefrontal cortex, has been implicated in ER. Aberrancies in UF microstructure may be an endophenotype associated with increased risk for BD. However, findings in individuals with BD and at familial risk for BD (AR) have yielded inconsistent findings. This meta-analysis takes a region-of-interest approach to consolidate the available evidence and elucidate the role of the UF in the risk-architecture of BD. Methods: Using web-based search engines, we identified diffusion tensor imaging studies focusing on the left and right UF and conducted meta-analyses comparing fractional anisotropy (FA) and radial diffusivity (RD) between BD or AR to healthy volunteers (HV). Results: We included 32 studies (BD: n=1186, HV: n=2001; AR: n=289, HV-AR: n=314). Compared to HV, individuals with BD showed lower FA in the right (p<.0001) and left UF (p=.010), and higher RD in the right UF (p=.009). We found no significant differences between AR and HV. In the right but not the left UF, AR individuals showed higher FA than BD (p=.043). Conclusion: Comparable UF microstructure between AR and HV and higher FA in the right UF in AR compared to BD suggest that aberrancies in UF microstructure is not an endophenotype for BD. Longitudinal studies are needed to determine when UF abnormalities emerge in the context of BD.