White matter correlates of cognitive flexibility in youth with bipolar disorder and typically developing children and adolescents.
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ABSTRACT:
SUBMITTER: Radoeva PD
PROVIDER: S-EPMC8015187 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Altered white matter (WM) microstructure likely occurs in children with bipolar disorder (BD) with impulsivity representing one of the core features. However, altered WM microstructures and their age-related trendlines in children with BD and those at high-risk of developing BD, as well as correlations of WM microstructures with impulsivity, have been poorly investigated. In this study, diffusion MRI, cognitive, and impulsivity assessments were obtained from children/adolescents diagnosed with BD, offspring of individuals with BD (high-risk BD) and age-matched healthy controls. A novel atlas-based WM skeleton measurement approach was used to quantify WM microstructural integrity with all diffusion-tensor-imaging (DTI) metrics including fractional anisotropy, axial, mean and radial diffusivity to survey entire WM tracts and ameliorate partial volume effects. Among all DTI-derived metric measures, radial diffusivity quantifying WM myelination was found significantly higher primarily in corpus callosum and in the corona radiata in children with BD compared to controls. Distinguished from age-related progressively decreasing diffusivities and increasing fractional anisotropy in healthy controls, flattened age-related trendlines were found in BD group, and intermediate developmental rates were observed in high-risk group. Larger radial diffusivity in the corpus callosum and corona radiata significantly correlated with shorter response times to affective words that indicate higher impulsivity in the BD group, whereas no such correlation was found in the healthy control group. This work corroborates the progressive nature of pediatric BD and suggests that WM microstructural disruption involved in affective regulation and sensitive to impulsivity may serve as a biomarker of pediatric BD progression.
| S-EPMC9898209 | biostudies-literature
Project description:OBJECTIVES:Bipolar disorder (BD) and familial risk for BD have been associated with aberrant white matter (WM) microstructure in the corpus callosum and fronto-limbic pathways. These abnormalities might constitute trait or state marker and have been suggested to result from aberrant maturation and to relate to difficulties in emotion regulation. METHODS:To determine whether WM alterations represent a trait, disease or resilience marker, we compared youth at risk for BD (n = 36 first-degree relatives, REL) to youth with BD (n = 36) and healthy volunteers (n = 36, HV) using diffusion tensor imaging. RESULTS:Individuals with BD and REL did not differ from each other in WM microstructure and, compared to HV, showed similar aberrations in the superior corona radiata (SCR)/corticospinal tract (CST) and the body of the corpus callosum. WM microstructure of the anterior CC showed reduced age-related in-creases in BD compared to REL and HV. Further, individuals with BD and REL showed in-creased difficulties in emotion regulation, which were associated with the microstructure of the anterior thalamic radiation. DISCUSSION:Alterations in the SCR/CST and the body of the corpus callosum appear to represent a trait marker of BD, whereas changes in other WM tracts seem to be a disease state marker. Our findings also support the role of aberrant developmental trajectories of WM microstructure in the risk architecture of BD, although longitudinal studies are needed to confirm this association. Finally, our findings show the relevance of WM microstructure for difficulties in emotion regulation-a core characteristic of BD.
| S-EPMC7155105 | biostudies-literature
Project description:Few studies have examined multiple measures of white matter (WM) differences in youth with familial risk for bipolar disorder (FR-BD). To investigate WM in the FR-BD group, we used three measures of WM structure and two methods of analysis. We used fractional anisotropy (FA), axial diffusivity (AD), and radial diffusivity (RD) to analyze diffusion tensor imaging (DTI) findings in 25 youth with familial risk for bipolar disorder, defined as having both a parent with BD and mood dysregulation, and 16 sex-, age-, and IQ-matched healthy controls. We conducted a whole brain voxelwise analysis using tract based spatial statistics (TBSS). Subsequently, we conducted a complementary atlas-based, region-of-interest analysis using Diffeomap to confirm results seen in TBSS. When TBSS was used, significant widespread between-group differences were found showing increased FA, increased AD, and decreased RD in the FR-BD group in the bilateral uncinate fasciculus, cingulum, cingulate, superior fronto-occipital fasciculus (SFOF), superior longitudinal fasciculus (SLF), inferior longitudinal fasciculus, and corpus callosum. Atlas-based analysis confirmed significant between-group differences, with increased FA and decreased RD in the FR-BD group in the SLF, cingulum, and SFOF. We found significant widespread WM tract aberrations in youth with familial risk for BD using two complementary methods of DTI analysis.
| S-EPMC6147249 | biostudies-literature
Project description:Frontotemporal neural systems are highly implicated in the emotional dysregulation characteristic of bipolar disorder (BD). Convergent genetic, postmortem, behavioral and neuroimaging evidence suggests abnormalities in the development of frontotemporal white matter (WM) in the pathophysiology of BD. This review discusses evidence for the involvement of abnormal WM development in BD during adolescence, with a focus on frontotemporal WM. Findings from diffusion tensor imaging (DTI) studies in adults and adolescents are reviewed to explore possible progressive WM abnormalities in the disorder. Intra- and interhemispheric frontotemporal abnormalities were reported in adults with BD. Although evidence in children and adolescents with BD to date has been limited, similar intrahemispheric and interhemispheric findings have also been reported. The findings in youths suggest that these abnormalities may represent a trait marker present early in the course of BD. Functional connectivity studies, demonstrating a relationship between WM abnormalities and frontotemporal dysfunction in BD, and DTI studies of vulnerability in first-degree relatives of individuals with BD, are discussed. Together, findings suggest the involvement of abnormal frontotemporal WM development in the pathophysiology of BD and that these abnormalities may be early trait markers of vulnerability; however, more studies are critically needed.
| S-EPMC4449671 | biostudies-literature
Project description:This study investigated the relationship between white matter microstructure and the development of morphosyntax in a spoken narrative in typically developing children (TD) and in children with high functioning autism (HFA). Autism is characterized by language and communication impairments, yet the relationship between morphosyntactic development in spontaneous discourse contexts and neural development is not well understood in either this population or typical development. Diffusion tensor imaging (DTI) was used to assess multiple parameters of diffusivity as indicators of white matter tract integrity in language-related tracts in children between 6 and 13 years of age. Children were asked to spontaneously tell a story about at time when someone made them sad, mad, or angry. The story was evaluated for morphological accuracy and syntactic complexity. Analysis of the relationship between white matter microstructure and language performance in TD children showed that diffusivity correlated with morphosyntax production in the superior longitudinal fasciculus (SLF), a fiber tract traditionally associated with language. At the anatomical level, the HFA group showed abnormal diffusivity in the right inferior longitudinal fasciculus (ILF) relative to the TD group. Within the HFA group, children with greater white matter integrity in the right ILF displayed greater morphological accuracy during their spoken narrative. Overall, the current study shows an association between white matter structure in a traditional language pathway and narrative performance in TD children. In the autism group, associations were only found in the ILF, suggesting that during real world language use, children with HFA rely less on typical pathways and more on alternative ventral pathways that possibly mediate visual elements of language.
| S-EPMC4457301 | biostudies-literature
Project description:Oxidative stress is associated with white matter diffusion metrics in adults with bipolar disorder (BD). We examined the association of single-nucleotide polymorphisms in the oxidative stress system, superoxide dismutase-2 (SOD2) rs4880 and glutathione peroxidase-3 (GPX3) rs3792797 with fractional anisotropy (FA) and radial diffusivity (RD) in youth with BD. Participants included 104 youth (age 17.5 ± 1.7 years; 58 BD, 46 healthy controls). Saliva samples were obtained for genotyping, and diffusion tensor imaging was acquired. Voxel-wise whole-brain white matter diffusion analyses controlled for age, sex, and race. There were significant diagnosis-by-SOD2 rs4880 interaction effects for FA and RD in major white matter tracts. Within BD, the group with two copies of the G-allele (GG) showed lower FA and higher RD than A-allele carriers. Whereas within the control group, the GG group showed higher FA and lower RD than A-allele carriers. Additionally, FA was higher and RD was lower within the control GG group compared to the BD GG group. No significant findings were observed for GPX3 rs3793797. The current study revealed that, within matter tracts known to differ in BD, associations of SOD2 rs4880 GG genotype with both FA and RD differed between BD vs healthy control youth. The SOD2 enzyme encoded by the G-allele, has higher antioxidant capacity than the enzyme encoded by the A-allele. We speculate that the current findings of lower FA and higher RD of the BD GG group compared to the other groups reflects attenuation of the salutary antioxidant effects of GG genotype on white matter integrity in youth with BD, in part due to predisposition to oxidative stress. Future studies incorporating other genetic markers and oxidative stress biomarkers are warranted.
| S-EPMC9729619 | biostudies-literature
Project description:There is a gap in knowledge regarding the polygenic underpinnings of brain anomalies observed in youth bipolar disorder (BD). This study examined the association of a polygenic risk score for BD (BD-PRS) with grey matter structure and white matter integrity in youth with and without BD. 113 participants were included in the analyses, including 78 participants with both T1-weighted and diffusion-weighted MRI images, 32 participants with T1-weighted images only, and 3 participants with diffusion-weighted images only. BD-PRS was calculated using PRS-CS-auto and was based on independent adult genome-wide summary statistics. Vertex- and voxel-wise analyses examined the associations of BD-PRS with grey matter metrics (cortical volume [CV], cortical surface area [CSA], cortical thickness [CTh]) and fractional anisotropy [FA] in the combined sample, and separately in BD and HC. In the combined sample of participants with T1-weighted images (n = 110, 66 BD, 44 HC), higher BD-PRS was associated with smaller grey matter metrics in frontal and temporal regions. In within-group analyses, higher BD-PRS was associated with lower CTh of frontal, temporal, and fusiform gyrus in BD, and with lower CV and CSA of superior frontal gyrus in HC. In the combined sample of participants with diffusion-weighted images (n = 81, 49 BD, 32 HC), higher BD-PRS was associated with lower FA in widespread white matter regions. In summary, BD-PRS calculated based on adult genetic data was negatively associated with grey matter structure and FA in youth in regions implicated in BD, which may suggest neuroimaging markers of vulnerability to BD. Future longitudinal studies are needed to examine whether BD-PRS predicts neurodevelopmental changes in BD vs. HC and its interaction with course of illness and long-term medication use.
| S-EPMC10584947 | biostudies-literature
Project description:BackgroundDistinguishing pediatric bipolar disorder (BD) from attention-deficit hyperactivity disorder (ADHD) can be challenging. Hyperactivity is a core feature of both disorders, but severely disturbed sleep and circadian dysregulation are more characteristic of BD, at least in adults. We tested the hypothesis that objective measures of activity, sleep, and circadian rhythms would help differentiate pediatric subjects with BD from ADHD and typically developing controls.MethodsUnmedicated youths (N = 155, 97 males, age 5-18) were diagnosed using DSM-IV criteria with Kiddie-SADS PL/E. BD youths (n = 48) were compared to typically developing controls (n = 42) and children with ADHD (n = 44) or ADHD plus comorbid depressive disorders (n = 21). Three-to-five days of minute-to-minute belt-worn actigraph data (Ambulatory Monitoring Inc.), collected during the school week, were processed to yield 28 metrics per subject, and assessed for group differences with analysis of covariance. Cross-validated machine learning algorithms were used to determine the predictive accuracy of a four-parameter model, with measures reflecting sleep, hyperactivity, and circadian dysregulation, plus Indic's bipolar vulnerability index (VI).ResultsThere were prominent group differences in several activity measures, notably mean 5 lowest hours of activity, skewness of diurnal activity, relative circadian amplitude, and VI. A predictive support vector machine model discriminated bipolar from non-bipolar with mean accuracy of 83.1 ± 5.4%, ROC area of 0.781 ± 0.071, kappa of 0.587 ± 0.136, specificity of 91.7 ± 5.3%, and sensitivity of 64.4 ± 13.6%.ConclusionsObjective measures of sleep, circadian rhythmicity, and hyperactivity were abnormal in BD. Wearable sensor technology may provide bio-behavioral markers that can help differentiate children with BD from ADHD and healthy controls.
| S-EPMC4873411 | biostudies-literature
Project description:Bipolar disorder (BD) patients show aberrant white matter microstructure compared to healthy controls but little is known about the relation with clinical characteristics. We therefore investigated the relation of white matter microstructure with the main pharmacological treatments as well its relation with IQ. Patients with BD (N = 257) and controls (N = 167) underwent diffusion tensor imaging (DTI) and comprehensive clinically assessments including IQ estimates. DTI images were analyzed using tract-based spatial statistics. Fractional anisotropy (FA) and Mean Diffusivity (MD) were determined. Patients had significantly lower FA and higher MD values throughout the white matter skeleton compared to controls. Within the BD patients, lithium use was associated with higher FA and lower MD. Antipsychotic medication use in the BD patients was not associated with FA but, in contrast to lithium, was associated with higher MD. IQ was significantly positively correlated with FA and negatively with MD in patients as well as in controls. In this large DTI study we found evidence for marked differences in FA and MD particularly in (but not restricted to) corpus callosum, between BD patients and controls. This effect was most pronounced in lithium-free patients, implicating that lithium affects white matter microstructure and attenuates differences associated with bipolar disorder. Effects of antipsychotic medication intake were absent in FA and only subtle in MD relative to those of lithium. The abnormal white matter microstructure was associated with IQ but not specifically for either group.
| S-EPMC6008233 | biostudies-literature
Project description:Abnormalities in white-matter (WM) microstructure, as lower fractional anisotropy (FA), have been reported in adolescent-onset bipolar disorder and in youth at familial risk for bipolarity. We sought to determine whether healthy adolescents with subthreshold bipolar symptoms (SBP) would have early WM microstructural alterations and whether those alterations would be associated with differences in gray-matter (GM) volumes. Forty-two adolescents with three core manic symptoms and no psychiatric diagnosis, and 126 adolescents matched by age and sex, with no psychiatric diagnosis or symptoms, were identified after screening the IMAGEN database of 2223 young adolescents recruited from the general population. After image quality control, voxel-wise statistics were performed on the diffusion parameters using tract-based spatial statistics in 25 SBP adolescents and 77 controls, and on GM and WM images using voxel-based morphometry in 30 SBP adolescents and 106 controls. As compared with healthy controls, adolescents with SBP displayed lower FA values in a number of WM tracts, particularly in the corpus callosum, cingulum, bilateral superior and inferior longitudinal fasciculi, uncinate fasciculi and corticospinal tracts. Radial diffusivity was mainly higher in posterior parts of bilateral superior and inferior longitudinal fasciculi, inferior fronto-occipital fasciculi and right cingulum. As compared with controls, SBP adolescents had lower GM volume in the left anterior cingulate region. This is the first study to investigate WM microstructure and GM morphometric variations in adolescents with SBP. The widespread FA alterations in association and projection tracts, associated with GM changes in regions involved in mood disorders, suggest altered structural connectivity in those adolescents.
| S-EPMC3965837 | biostudies-other