Altered white matter integrity in individuals with cognitive vulnerability to depression: a tract-based spatial statistics study.
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ABSTRACT:
SUBMITTER: Xiao J
PROVIDER: S-EPMC4434894 | biostudies-other | 2015
REPOSITORIES: biostudies-other
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Project description:ObjectiveHuman immunodeficiency virus (HIV) infection has been known to damage the microstructural integrity of white matter (WM). However, only a few studies have assessed the brain regions in HIV-associated neurocognitive disorders (HAND) with diffusion tensor imaging (DTI). Therefore, we sought to compare the DTI data between HIV patients with and without HAND using tract-based spatial statistics (TBSS).Materials and methodsTwenty-two HIV-infected patients (10 with HAND and 12 without HAND) and 11 healthy controls (HC) were enrolled in this study. A whole-brain analysis of fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity was performed with TBSS and a subsequent 20 tract-specific region-of-interest (ROI)-based analysis to localize and compare altered WM integrity in all group contrasts.ResultsCompared with HC, patients with HAND showed decreased FA in the right frontoparietal WM including the upper corticospinal tract (CST) and increased MD and RD in the bilateral frontoparietal WM, corpus callosum, bilateral CSTs and bilateral cerebellar peduncles. The DTI values did not significantly differ between HIV patients with and without HAND or between HIV patients without HAND and HC. In the ROI-based analysis, decreased FA was observed in the right superior longitudinal fasciculus and was significantly correlated with decreased information processing speed, memory, executive function, and fine motor function in HIV patients.ConclusionThese results suggest that altered integrity of the frontoparietal WM contributes to cognitive dysfunction in HIV patients.
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Project description:Altered brain connectivity has been widely considered as a genetic risk mechanism for schizophrenia. Of the many susceptibility genes identified so far, ZNF804A (rs1344706) is the first common genetic variant associated with schizophrenia on a genome-wide level. Previous fMRI studies have found that carriers of rs1344706 exhibit altered functional connectivity. However, the relationship between ZNF804A and white matter structural connectivity in patients of schizophrenia remains unknown. In this study, 100 patients with schizophrenia and 69 healthy controls were genotyped at the single nucleotide polymorphism rs1344706. Diffusion tensor imaging (DTI) was conducted and analyzed with tract-based spatial statistics. Systematic statistical analysis was conducted on multiple diffusion indices, including fractional anisotropy, axial diffusivity, radial diffusivity, and mean diffusivity. Unpaired two-sample t-test revealed significant differences in fractional anisotropy and diffusivity between schizophrenia and control groups. A two-way ANOVA analysis was conducted to assess the main effects of and the interaction between schizophrenia and ZNF804A. Although significant main effects of the diagnosis of schizophrenia were found on radial diffusivity, no association between the ZNF804A (rs1344706) and white matter connectivity was found in the entire group of subjects or in a selected subgroup of age-matched subjects (n=72).
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Project description:Increasing evidence is emerging for sexual dimorphism in the trajectory of white matter development in children assessed using volumetric magnetic resonance imaging (MRI) and more recently diffusion MRI. Recent studies using diffusion MRI have examined cohorts with a wide age range (typically between 5 and 30 years) showing focal regions of differential diffusivity and fractional anisotropy (FA) and have implicated puberty as a possible contributory factor. To further investigate possible dimorphic trajectories in a young cohort, presumably closer to the expected onset of puberty, we used tract-based spatial statistics to investigate diffusion metrics. The cohort consisted of 23 males and 30 females between the ages of 8 and 16 years. Differences in diffusion metrics were corrected for age, total brain volume, and full scale IQ. In contrast to previous studies showing focal differences between males and females, widespread sexually dimorphic trajectories in structural white matter development were observed. These differences were characterized by more advanced development in females compared to males indicated by lower mean diffusivity, radial and axial diffusivity, and higher FA in females. This difference appeared to be larger at lower ages (8-9 years) with diffusion measures from males and females tending to converge between 10 and 14 years of age. Males showed a steeper slope for age-diffusion metric correlations compared to females, who either did not correlate with age or correlated in fewer regions. Further studies are now warranted to determine the role of hormones on the observed differences, particularly in 8-9-year-old children.
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Project description:Although significant changes in both gray and white matter have been noted in late-life depression (LLD), the pathophysiology of implicated white-matter tracts has not been fully described. In this study we examined the integrity of specific white-matter tracts in LLD versus healthy controls (HC).Participants aged ?60 years were recruited from the community. The sample included 23 clinically diagnosed individuals with LLD and 23 HC. White-matter integrity metrics [fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD)] were calculated in the bilateral cingulum and uncinate fasciculus. Depression severity was measured using the Center for Epidemiological Studies Depression Scale (CESD). Composite scores for learning and memory and executive function were created using standardized neuropsychological assessments.White-matter integrity was lower in LLD versus HC in the bilateral cingulum and right uncinate fasciculus (p?0.05). In the whole sample, depression severity correlated with integrity in the bilateral cingulum and right uncinate fasciculus (p ?0.05). In patients, depression severity correlated with the integrity of the left uncinate fasciculus (p = 0.03); this tract also correlated with executive function (p = 0.02). Among HC, tract integrity did not correlate with depression scores; however, learning and memory correlated with integrity of the bilateral uncinate fasciculus and bilateral cingulum; executive function correlated with the right uncinate and left cingulum (p ?0.05).White-matter tract integrity was lower in LLD than in HC and was associated with depression severity across all participants. Tract integrity was associated with cognition in both groups but more robustly among HC.
| S-EPMC4310501 | biostudies-literature
Project description:Post-mortem and imaging studies have observed that white matter (WM) degenerates in a pattern inverse to myelin development, suggesting preferential regional vulnerabilities influencing cognitive decline in AD. This study applied novel WM tract integrity (WMTI) metrics derived from diffusional kurtosis imaging (DKI) to examine WM tissue properties in AD within this framework. Using data from amnestic mild cognitive impairment (aMCI, n = 12), AD (n = 14), and normal control (NC; n = 15) subjects, mixed models revealed interaction effects: specific WMTI metrics of axonal density and myelin integrity (i.e. axonal water fraction, radial extra-axonal diffusivity) in late-myelinating tracts (i.e. superior and inferior longitudinal fasciculi) changed in the course of disease, but were stable in the initial stages for early-myelinating tracts (i.e. posterior limb of the internal capsule, cerebral peduncles). WMTI metrics in late-myelinating tracts correlated with semantic verbal fluency, a cognitive function known to decline in AD. These findings corroborate the preferential vulnerability of late-myelinating tracts, and illustrate an application of WMTI metrics to characterizing the regional course of WM changes in AD.
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Project description:Several strands of evidence reported a significant overlapping, in terms of clinical symptoms, epidemiology and treatment response, between the two major psychotic disorders-Schizophrenia (SCZ) and Bipolar Disorder (BD). Nevertheless, the shared neurobiological correlates of these two disorders are far from conclusive. This study aims toward a better understanding of possible common microstructural brain alterations in SCZ and BD. Magnetic Resonance Diffusion data of 33 patients with BD, 19 with SCZ and 35 healthy controls were acquired. Diffusion indexes were calculated, then analyzed using Tract-Based Spatial Statistics (TBSS). We tested correlations with clinical and psychological variables. In both patient groups mean diffusion (MD), volume ratio (VR) and radial diffusivity (RD) showed a significant increase, while fractional anisotropy (FA) and mode (MO) decreased compared to the healthy group. Changes in diffusion were located, for both diseases, in the fronto-temporal and callosal networks. Finally, no significant differences were identified between patient groups, and a significant correlations between length of disease and FA and VR within the corpus callosum, corona radiata and thalamic radiation were observed in bipolar disorder. To our knowledge, this is the first study applying TBSS on all the DTI indexes at the same time in both patient groups showing that they share similar impairments in microstructural connectivity, with particular regards to fronto-temporal and callosal communication, which are likely to worsen over time. Such features may represent neural common underpinnings characterizing major psychoses and confirm the central role of white matter pathology in schizophrenia and bipolar disorder.
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Project description:OBJECTIVES:Patients with bipolar disorder spend the most time in the depressed phase, and that phase is associated with the most morbidity and mortality. Treatment of bipolar depression lacks a test to determine who will respond to treatment. White matter disruptions have been found in bipolar disorder. Previous reports suggest that white matter disruptions may be associated with resistance to antidepressant medication, but this has never been investigated in a prospective study using a Food and Drug Administration (FDA)-approved medication. METHODS:Eighteen subjects with bipolar disorder who were in a major depressive episode and off all medications were recruited. Magnetic resonance imaging was acquired using a 64-direction diffusion tensor imaging sequence on a 3T scanner. Subjects were treated with 8 weeks of open-label lurasidone. The Montgomrey-Asberg Depression Rating Scale (MADRS) was completed weekly. Tract-Based Spatial Statistics were utilized to perform a regression analysis of fractional anisotropy (FA) data with treatment outcome as assessed by percent change in MADRS as a regressor while controlling for age and sex, using a threshold of P (threshold-free cluster enhancement-corrected) <.05. RESULTS:FA was positively correlated with antidepressant treatment response in multiple regions of the mean FA skeleton bilaterally, including tracts in the frontal and parietal lobes. CONCLUSIONS:Greater disruptions in the white matter tracts in bipolar disorder were associated with poorer antidepressant response to lurasidone. The disruptions may potentially indicate treatment with a different antidepressant medication class. These results are limited by the open-label study design, sample size and lack of a healthy control group.
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Project description:OBJECTIVE:Greater psychological resilience may protect against developing depression in a growing geriatric population. Identifying the neural correlates of resilience in geriatric depression could provide neurobiologic targets to inform clinical interventions. However, most prior neuroimaging studies have only considered the presence or absence of resilience and have not addressed the multifactorial nature of resilience. The current study aimed to establish the neural correlates of four factors of resilience in the depressed elderly. METHODS:White matter integrity was assessed using diffusion-weighted magnetic resonance imaging data collected from 70 older adults with major depressive disorder. We used four resilience factors previously derived in an exploratory factor analysis of the Connor-Davidson Resilience Scale in a large sample of depressed older adults: 1, grit; 2, active coping self-efficacy; 3, accommodative coping self-efficacy; and 4, spirituality. RESULTS:The resilience factor "grit" was positively associated with fractional anisotropy in the callosal region connecting prefrontal cortex and fractional anisotropy in cingulum fibers; however, the latter did not survive correction for multiple comparisons. CONCLUSION:Structural integrity of major white matter pathways implicated in cognitive control and emotion regulation (i.e., connecting prefrontal cortex) was positively associated with the resilience factor "grit" in our sample of older adults with depression. Prospective studies are needed to determine the utility of the structural integrity of these pathways as a biomarker in predicting risk for depression and treatment response.
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Project description:Purpose: The aim of this study was to evaluate microstructural changes of major white matter (WM) tracts in patients with vascular cognitive impairment (VCI). Method: Diffusion tensor imaging (DTI) data were obtained from 24 subjects with subcortical ischemic vascular disease (SIVD), including 13 subjects with VCI-no dementia (VCIND) and 11 subjects with normal cognition (as a control group). A tract-based spatial statistics approach was performed to investigate WM microstructure in VCIND by integrating multiple indices including fractional anisotropy (FA) and mean diffusivity (MD), which are intra-voxel metrics, and local diffusion homogeneity (LDH), which is an inter-voxel metric. Results: The VCIND group had decreased FA and increased MD values throughout widespread WM areas predominately in the corpus callosum, bilateral internal capsule/corona radiata/posterior thalamic radiation/inferior fronto-occipital fasciculus and right inferior/superior longitudinal fasciculus. There was a slight discrepancy between the distribution of areas with decreased FA and LDH. The FA, MD and LDH values were significantly correlated with cognitive test results. According to a WM tract atlas, 10 major tracts were identified as tracts of interest in which three diffusion metrics simultaneously differed between groups, including bilateral anterior thalamic radiation, forceps minor, right corticospinal tract, bilateral inferior fronto-occipital fasciculus, left inferior and superior longitudinal fasciculus, and bilateral uncinate fasciculus. Receiver operating characteristic (ROC) analysis demonstrated the feasibility of using diffusion metrics along the forceps minor and left anterior thalamic radiation for separating two groups. Conclusion: The results suggest WM microstructural abnormalities contribute to cognitive impairments in SIVD patients. DTI parameters may be potential biomarkers for detecting VCIND from SIVD.
| S-EPMC6028522 | biostudies-literature
Project description:BackgroundNearly all persons with Down syndrome will show pathology of Alzheimer's disease in their 40s. There is a critical need for studies to identify early biomarkers of these various pathological changes of Alzheimer's disease in the Down syndrome population and understand the relationship of these biomarkers to cognitive symptoms in order to inform clinical trials. Although Alzheimer's disease is often considered a disease of gray matter, white matter degeneration has been documented during the preclinical stage of Alzheimer's disease. The current study examined the association between diffusion tensor imaging (DTI) measures of white matter microstructure and episodic memory performance in 52 adults with Down syndrome.MethodsSeventy (N = 70) participants (M = 40.13, SD = 7.77 years) received baseline scans as part of the Neurodegeneration in Aging Down Syndrome (NiAD) study at two imaging facilities (36 at the University of Wisconsin-Madison [UW-Madison] and 34 at the University of Pittsburgh Medical Center [UPMC]). All participants had genetically confirmed trisomy 21. Fifty-two (N = 52) participants remained after QC. The DTI measures, fractional anisotropy (FA) and mean diffusivity (MD), were calculated for each participant. A combined measure of episodic memory was generated by summing the z-scores of (1) Free and Cued Recall test and (2) Rivermead Behavioural Memory Test for Children Picture Recognition. The DTI data were projected onto a population-derived FA skeleton and tract-based spatial statistics analysis was conducted using the FSL tool PALM to calculate Pearson's r values between FA and MD with episodic memory.ResultsA positive correlation of episodic memory with FA and a negative correlation of episodic memory and MD in the major association white matter tracts were observed. Results were significant (p < 0.05) after correction for chronological age, imaging site, and premorbid cognitive ability.ConclusionThese findings suggest that white matter degeneration may be implicated in early episodic memory declines prior to the onset of dementia in adults with Down syndrome. Further, our findings suggest a coupling of episodic memory and white matter microstructure independent of chronological age.
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