White Matter Microstructure in Individuals With and At Risk for Bipolar Disorder: Evidence for an Endophenotype From a Voxel-Based Meta-analysis

Hu, Rebecca; Stavish, Caitlin; Leibenluft, Ellen; Linke, Julia

doi:10.1016/j.bpsc.2020.06.007

Cited by 25 publications

(42 citation statements)

References 69 publications

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“…This provides further evidence that the effect of these two types of psychotropic medication is circuit-specific, and that these circuitry do not entail the UF. In contrast to prior meta-analyses 13,22 , age and sex did not explain heterogeneity in UF findings across studies. Further, differences in the DTI processing pipeline did not explain variability of the findings.…”

Section: Do Demographic and Clinical Characteristics Explain Interstudy Heterogeneity?contrasting

confidence: 99%

“…First, we integrate evidence from published reports that used a region-of-interest (ROI) approach to specifically investigate the microstructure of the UF. Prior meta-analyses either included only whole-brain studies, which might be relatively insensitive to effects in a small tract like the UF [12][13][14] , or focused on data from the ENIGMA consortium (Favre et al, 2019). Second, aside from fractional anisotropy (FA), a diffusion tensor imaging (DTI) metric that has been positively associated with the directionality and coherence of WM tracts 15 , we also investigate radial diffusivity (RD), a metric negatively associated with the myelination of WM tracts 16 .…”

Section: Introductionmentioning

confidence: 99%

“…The microstructure of the UF is highly heritable, with familial effects explaining 71-80% of variance in FA of the UF 20,21 , but it is unclear whether the remaining endophenotype criteria apply. Prior meta-analyses have consistently reported FA reductions in the genu of the corpus callosum in individuals with BD [12][13][14]22 ; however, findings in the UF have varied, with reports of lower 12,22 or no FA alterations in the UF in individuals with BD 13,14 . Additionally, previous studies have reported higher, lower, or no FA aberrations in the left or right UF in individuals with BD or AR (Supplementary Tables S1-S2).…”

Section: Introductionmentioning

confidence: 99%

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

Nguyen

et al. 2021

Preprint

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BackgroundBipolar 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.MethodsUsing 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).ResultsWe included 32 studies (nBD=1186, nHV=2001; nAR=289, nHV=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).ConclusionComparable 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.

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Section: Do Demographic and Clinical Characteristics Explain Interstudy Heterogeneity?contrasting

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Nguyen

et al. 2021

Preprint

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“…To identify local differences in white matter between patients and controls, we performed a voxel-wise analysis of the DTI/DKI metrics. The FA map of each subject was registered with Elastix (https://elastix.lumc.nl, RRID:SCR_009619) 37 to the 1×1×1mm 3 FA template of the FMRIB, which is part of FSL. 29 To achieve fine voxel-wise alignment, each subject was registered with a combination of rigid, affine and b-spline transformations.…”

Section: Methodsmentioning

confidence: 99%

“…2 Moreover, diffusion MRI (dMRI) studies have often reported observations of white matter abnormalities in BD. 3,4…”

Section: Introductionmentioning

confidence: 99%

Diffusion kurtosis imaging of white matter in bipolar disorder

Goghari

Kusi

Shakeel

et al. 2021

Preprint

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Objectives: White matter pathology is thought to contribute to the pathogenesis of bipolar disorder (BD). However, most studies of white matter in BD have used the simple diffusion tensor imaging (DTI) model, which has several limitations. DTI studies have reported heterogenous results, leading to a lack of consensus about the extent and location of white matter alterations. Here, we applied two advanced diffusion magnetic resonance imaging (MRI) techniques to investigate white matter microstructure in BD. Methods: Twenty-five patients with BD and 24 controls comparable for age and sex were included in the study. Whole-brain voxel-based analysis (VBA) and a network-based connectivity approach using constrained spherical deconvolution (CSD)-tractography were used to assess group differences in diffusion kurtosis imaging (DKI) and DTI metrics. Results: VBA showed lower mean kurtosis in the corona radiata and posterior association fibers in BD following threshold-free cluster enhancement. Regional differences in connectivity were indicated by lower mean kurtosis and kurtosis anisotropy in streamlines traversing the temporal and occipital lobes, and lower mean axial kurtosis in the right cerebellar, thalamo-subcortical pathways in BD. Significant differences were not seen in the DTI metrics following FDR-correction. Conclusions: Differences between BD and controls were observed in DKI metrics in multiple brain regions, indicating altered connectivity across cortical, subcortical and cerebellar areas. DKI was more sensitive than DTI at detecting these differences, suggesting that DKI is useful for investigating white matter in BD.

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Structural connectivity associated with familial risk for mental illness: A meta‐analysis of diffusion tensor imaging studies in relatives of patients with severe mental disorders

Zhang

Hochwalt

et al. 2022

Human Brain Mapping

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Schizophrenia (SCZ), bipolar disorder (BD), and major depressive disorder (MDD) are heritable conditions with overlapping genetic liability. Transdiagnostic and disorderspecific brain changes associated with familial risk for developing these disorders remain poorly understood. We carried out a meta-analysis of diffusion tensor imaging (DTI) studies to investigate white matter microstructure abnormalities in relatives that might correspond to shared and discrete biomarkers of familial risk for psychotic or mood disorders. A systematic search of PubMed and Embase was performed to identify DTI studies in relatives of SCZ, BD, and MDD patients. Seed-based d Mapping software was used to investigate global differences in fractional anisotropy (FA) between overall and disorder-specific relatives and healthy controls (HC). Our search identified 25 studies that met full inclusion criteria. A total of 1,144 relatives and 1,238 HC were included in the meta-analysis. The overall relatives exhibited decreased FA in the genu and splenium of corpus callosum (CC) compared with HC. This finding was found highly replicable in jack-knife analysis and subgroup analyses. In disorder-specific analysis, compared to HC, relatives of SCZ patients exhibited the same changes while those of BD showed reduced FA in the left inferior longitudinal fasciculus (ILF). The present study showed decreased FA in the genu and splenium of CC in relatives of SCZ, BD, and MDD patients, which might represent a shared familial vulnerability marker of severe mental illness. The white matter abnormalities in the left ILF might represent a specific familial risk for bipolar disorder.

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White Matter Microstructure in Individuals With and At Risk for Bipolar Disorder: Evidence for an Endophenotype From a Voxel-Based Meta-analysis

Cited by 25 publications

References 69 publications

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

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

Diffusion kurtosis imaging of white matter in bipolar disorder

Structural connectivity associated with familial risk for mental illness: A meta‐analysis of diffusion tensor imaging studies in relatives of patients with severe mental disorders

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