Abstract
Patients with Bipolar Disorder (BD) are associated with aberrant uncinate fasciculus (UF) that connects amygdala-ventral prefrontal cortex (vPFC) system, but the casual relationship is still uncertain. The research aimed to investigate the integrity of UF among offspring of patients with BD and investigate its potential causal association with subsequent declaration of BD. The fractional anisotropy (FA) and mean diffusivity (MD) of UF were compared in asymptomatic offspring (AO, n = 46) and symptomatic offspring (SO, n = 45) with a parent with BD, and age-matched healthy controls (HCs, n = 35). Logistic regressions were performed to assess the predictive effect of UF integrity on the onset of BD. The three groups did not differ at baseline in terms of FA and MD of the UF. Nine out of 45 SO developed BD over a follow-up period of 6 years, and the right UF FA predicted the onset of BD (p = 0.038, OR = 0.212, 95% CI = 0.049–0.917). The ROC curve revealed that the right UF FA predicted BD onset (area-under-curve = 0.859) with sensitivity of 88.9% and specificity of 77.3%. The complementary whole-brain tract-based spatial statistics (TBSS) showed that widespread increases of FA were found in the SO group compared with HCs, but were not associated with the onset of BD. Our data provide evidence supporting the causal relationship between the white matter structural integrity of the amygdala-vPFC system and the onset of BD in genetically at-risk offspring of BD patients.
Highlights
Bipolar disorder (BD) is a major disabling mental illness, afflicting approximately 1% of the general population and accounting for 0.4% of total DALYs in global burden[1,2]
We investigated whether baseline integrity measures of the uncinate fasciculus (UF) could predict the prognosis of a cohort of offspring of parents with BD over a follow-up period of 6 years
No significant difference in the Hamilton depression rating scale (HAMD), Hamilton anxiety rating scale (HAMA), orYMRS was found between the AO and the health controls (HCs) (p > 0.05)
Summary
Participants The data were derived from the recognition and early intervention on prodromal bipolar disorder (REI-PBD) project[25] that was launched in 2013, in which we followed-up a cohort of offspring of parents with BD. The project was approved by the Institutional Review Board of Guangzhou Brain Hospital All participants and their guardians (if aged under 18 years) provided written informed consent. After aligning each participant’s FA data into 1 × 1 × 1 mm[3] standard Montreal Neurological Institute (MNI152) space using non-linear registration[31,32], the mean FA was created and thinned to generate a mean FA skeleton which represented the centers of all the tracts derived from all participants. The above procedure was applied for the calculation of MD (https://fsl.fmrib.ox.ac.uk/fsl/fslwiki/TBSS/ UserGuide). Non-parametric permutation for voxel-wise statistics inference provided by FSL’s randomization procedure was conducted to detect the group difference. Statistical analyses were carried out using SPSS version 24.0
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