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Review
. 2022 Jan 15:297:208-216.
doi: 10.1016/j.jad.2021.10.045. Epub 2021 Oct 24.

The uncinate fasciculus in individuals with and at risk for bipolar disorder: A meta-analysis

Ellie Xu  1 , Lynn Nguyen  1 , Rebecca Hu  1 , Caitlin M Stavish  1 , Ellen Leibenluft  1 , Julia O Linke  1
Affiliations
Review

The uncinate fasciculus in individuals with and at risk for bipolar disorder: A meta-analysis

Ellie Xu et al. J Affect Disord. .

Abstract

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, studies in individuals with BD and their first-degree relatives (REL) 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 (DTI) studies focusing on the left and right UF and conducted meta-analyses comparing fractional anisotropy (FA) and radial diffusivity (RD) between BD or REL and healthy control participants (HC).

Results: We included 32 studies (nBD=1186, nREL=289, nHC=2315). Compared to HC, individuals with BD showed lower FA in the right (WMD=-0.31, p<0.0001) and left UF (WMD=-0.21, p = 0.010), and higher RD in the right UF (WMD=0.32, p = 0.009). We found no significant differences between REL and HC. In the right but not left UF, REL showed higher FA than BD (p = 0.043).

Conclusion: Our findings support aberrant UF microstructure, potentially related to alterations in myelination, as a mechanism, but not as an endophenotype of BD. However, given the limited power in the REL subsample, the latter finding must be considered preliminary. Studies examining the role of the UF in individuals at familial risk for BD are warranted.

Keywords: At-risk relatives; Bipolar disorder; Endophenotype; Uncinate fasciculus; White matter.

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Conflict of interest statement

Declarations of interest

None.

Figures

Figure 1.
Figure 1.. Flow chart of the literature search process.
Abbreviations: BD, bipolar disorder; FA, fractional anisotropy; HC, healthy control participants; REL, first-degree relatives; ROI, region-of-interest; UF, uncinate fasciculus; NOS, Newcastle-Ottawa Assessment Scale. a Final study count does not include one outlier.
Figure 2.
Figure 2.. Funnel plots depicting standardized mean differences of fractional anisotropy (FA) and radial diffusivity (RD) between study groups. Funnel plots are scatter plots that represent each study’s reported effect size (x-axis) plotted against its size (y-axis). Asymmetric funnel plots may suggest publication bias.
(A) Funnel plot of FA in the left and right uncinate fasciculus (UF) of individuals with bipolar disorder (BD) versus healthy control participants (HC). (B) Funnel plot of FA in the left and right UF of at-risk relatives (REL) versus HC. (C) Funnel plot of RD in the left and right UF of BD versus HC groups.
Figure 3.
Figure 3.. Forest plot of fractional anisotropy in the left uncinate fasciculus of individuals with bipolar disorder versus healthy control participants.
Abbreviations: CI, confidence interval; RE model, random-effect model.
Figure 4.
Figure 4.. Forest plot of fractional anisotropy in the right uncinate fasciculus of individuals with bipolar disorder versus healthy control participants.
Abbreviations: CI, confidence interval; RE model, random-effect model.
Figure 5.
Figure 5.. Forest plot of radial diffusivity in the right uncinate fasciculus of individuals with bipolar disorder versus healthy control participants.
Abbreviations: CI, confidence interval; RE model, random-effect model.
See this image and copyright information in PMC

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