scholarly journals Cognitive deficits and white matter abnormalities in never-treated first-episode schizophrenia

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Mi Yang ◽  
Shan Gao ◽  
Xiangyang Zhang

Abstract Cognitive impairment is viewed as a core symptom of schizophrenia (SCZ), but its pathophysiological mechanism remains unclear. White matter (WM) disruption is considered to be a central abnormality that may contribute to cognitive impairment in SCZ patients. However, few studies have addressed the association between cognition and WM integrity in never-treated first-episode (NTFE) patients with SCZ. In this study, we used the MATRICS Consensus Cognitive Battery (MCCB) to evaluate cognitive function in NTFE patients (n = 39) and healthy controls (n = 30), and associated it with whole-brain fractional anisotropy (FA) values obtained via voxel-based diffusion tensor imaging. We found that FA was lower in five brain areas of SCZ patients, including the cingulate gyrus, internal capsule, corpus callosum, cerebellum, and brainstem. Compared with the healthy control group, the MCCB’s total score and 8 out of 10 subscores were significantly lower in NTFE patients (all p < 0.001). Moreover, in patients but not healthy controls, the performance in the Trail Making Test was negatively correlated with the FA value in the left cingulate. Our findings provide evidence that WM disconnection is involved in some cognitive impairment in the early course of SCZ.

2007 ◽  
Vol 38 (6) ◽  
pp. 877-885 ◽  
Author(s):  
V. Cheung ◽  
C. Cheung ◽  
G. M. McAlonan ◽  
Y. Deng ◽  
J. G. Wong ◽  
...  

BackgroundDiffusion tensor imaging (DTI) can be used to investigate cerebral structural connectivity in never-medicated individuals with first-episode schizophrenia.MethodSubjects with first-episode schizophrenia according to DSM-IV-R who had never been exposed to antipsychotic medication (n=25) and healthy controls (n=26) were recruited. Groups were matched for age, gender, best parental socio-economic status and ethnicity. All subjects underwent DTI and structural magnetic resonance imaging (MRI) scans. Voxel-based analysis was performed to investigate brain regions where fractional anisotropy (FA) values differed significantly between groups. A confirmatory region-of-interest (ROI) analysis of FA scores was performed in which regions were placed blind to group membership.ResultsIn patients, FA values significantly lower than those in healthy controls were located in the left fronto-occipital fasciculus, left inferior longitudinal fasciculus, white matter adjacent to right precuneus, splenium of corpus callosum, right posterior limb of internal capsule, white matter adjacent to right substantia nigra, and left cerebral peduncle. ROI analysis of the corpus callosum confirmed that the patient group had significantly lower mean FA values than the controls in the splenium but not in the genu. The intra-class correlation coefficient (ICC) for independent ROI measurements was 0.90 (genu) and 0.90 (splenium). There were no regions where FA values were significantly higher in the patients than in the healthy controls.ConclusionsWidespread structural dysconnectivity, including the subcortical region, is already present in neuroleptic-naive patients in their first episode of illness.


2008 ◽  
Vol 39 (3) ◽  
pp. 371-379 ◽  
Author(s):  
P. A. Thomann ◽  
T. Wüstenberg ◽  
V. Dos Santos ◽  
S. Bachmann ◽  
M. Essig ◽  
...  

BackgroundAlthough minor motor and sensory deficits, or neurological soft signs (NSS), are a well-established finding in schizophrenia, the cerebral changes underlying these signs are only partly understood. We therefore investigated the cerebral correlates of NSS by using magnetic resonance imaging (MRI) in patients with schizophrenia and healthy controls.MethodForty-two patients, all receiving atypical neuroleptics, with first-episode schizophrenia or schizophreniform disorder and 22 healthy controls matched for age and gender were included. NSS were examined on the Heidelberg Scale after remission of the acute symptoms before discharge and correlated to density values by using optimized voxel-based morphometry (VBM).ResultsNSS scores were significantly higher in patients than healthy controls. Within the patient group NSS were significantly associated with reduced grey or white-matter densities in the pre- and post-central gyrus, pre-motor area, middle and inferior frontal gyri, cerebellum, caudate nucleus and thalamus. These associations did not apply for the control group, in whom only the associations between NSS and reduced frontal gyri densities could be confirmed.ConclusionsThe pattern of cerebral changes associated with NSS clearly supports the model of ‘cognitive dysmetria’ with a disrupted cortico-cerebellar-thalamic-cortical circuit in schizophrenia. The variety of sites may correspond with the clinical diversity of NSS, which comprises both motor and sensory signs, and with the putative heterogeneity of the pathogenetic changes involved. That the respective associations did not apply for the healthy control group indicates that NSS in patients and controls refer to different pathogenetic factors.


2021 ◽  
pp. 1-8
Author(s):  
Yi-Bin Xi ◽  
Xu-Sha Wu ◽  
Long-Biao Cui ◽  
Li-Jun Bai ◽  
Shuo-Qiu Gan ◽  
...  

Background Neuroimaging- and machine-learning-based brain-age prediction of schizophrenia is well established. However, the diagnostic significance and the effect of early medication on first-episode schizophrenia remains unclear. Aims To explore whether predicted brain age can be used as a biomarker for schizophrenia diagnosis, and the relationship between clinical characteristics and brain-predicted age difference (PAD), and the effects of early medication on predicted brain age. Method The predicted model was built on 523 diffusion tensor imaging magnetic resonance imaging scans from healthy controls. First, the brain-PAD of 60 patients with first-episode schizophrenia, 60 healthy controls and 21 follow-up patients from the principal data-set and 40 pairs of individuals in the replication data-set were calculated. Next, the brain-PAD between groups were compared and the correlations between brain-PAD and clinical measurements were analysed. Results The patients showed a significant increase in brain-PAD compared with healthy controls. After early medication, the brain-PAD of patients decreased significantly compared with baseline (P < 0.001). The fractional anisotropy value of 31/33 white matter tract features, which related to the brain-PAD scores, had significantly statistical differences before and after measurements (P < 0.05, false discovery rate corrected). Correlation analysis showed that the age gap was negatively associated with the positive score on the Positive and Negative Syndrome Scale in the principal data-set (r = −0.326, P = 0.014). Conclusions The brain age of patients with first-episode schizophrenia may be older than their chronological age. Early medication holds promise for improving the patient's brain ageing. Neuroimaging-based brain-age prediction can provide novel insights into the understanding of schizophrenia.


2012 ◽  
Vol 24 (9) ◽  
pp. 1483-1493 ◽  
Author(s):  
Senthil Thillainadesan ◽  
Wei Wen ◽  
Lin Zhuang ◽  
John Crawford ◽  
Nicole Kochan ◽  
...  

ABSTRACTBackground: Previous studies using diffusion tensor imaging (DTI) have observed microstructural abnormalities in white matter regions in both Alzheimer's disease and mild cognitive impairment (MCI). The aim of this work was to examine the abnormalities in white matter and subcortical regions of MCI and its subtypes in a large, community-dwelling older aged cohortMethods: A community-based sample of 396 individuals without dementia underwent medical assessment, neuropsychiatric testing, and neuroimaging. Of these, 158 subjects were classified as MCI and 238 as cognitively normal (controls) based on international MCI consensus criteria. Regional fractional anisotropy (FA) and mean diffusivity (MD) measures were calculated from the DTI and compared between groups. The false discovery rate correction was applied for multiple testing.Results: Subjects with MCI did not have significant differences in FA compared with controls after correction for multiple testing, but had increased MD in the right putamen, right anterior limb of the internal capsule, genu and splenium of the corpus callosum, right posterior cingulate gyrus, left superior frontal gyrus, and right and left corona radiata. When compared with controls, changes in left anterior cingulate, left superior frontal gyrus, and right corona radiata were associated with amnestic MCI (aMCI), whereas changes in the right putamen, right anterior limb of the internal capsule, and the right corona radiata were associated with non-amnestic MCI (naMCI). On logistic regression, the FA values in the left superior gyrus and MD values in the anterior cingulate distinguished aMCI from naMCI.Conclusions: MCI is associated with changes in white matter and subcortical regions as seen on DTI. Changes in some anterior brain regions distinguish aMCI from naMCI.


2013 ◽  
Vol 43 (11) ◽  
pp. 2301-2309 ◽  
Author(s):  
Q. Wang ◽  
C. Cheung ◽  
W. Deng ◽  
M. Li ◽  
C. Huang ◽  
...  

BackgroundIt is not clear whether the progressive changes in brain microstructural deficits documented in previous longitudinal magnetic resonance imaging (MRI) studies might be due to the disease process or to other factors such as medication. It is important to explore the longitudinal alterations in white-matter (WM) microstructure in antipsychotic-naive patients with first-episode schizophrenia during the very early phase of treatment when relatively ‘free’ from chronicity.MethodThirty-five patients with first-episode schizophrenia and 22 healthy volunteers were recruited. High-resolution diffusion tensor imaging (DTI) was obtained from participants at baseline and after 6 weeks of treatment. A ‘difference map’ for each individual was calculated from the 6-week follow-up fractional anisotropy (FA) of DTI minus the baseline FA. Differences in Positive and Negative Syndrome Scale (PANSS) scores and Global Assessment of Functioning (GAF) scores between baseline and 6 weeks were also evaluated and expressed as a 6-week/baseline ratio.ResultsCompared to healthy controls, there was a significant decrease in absolute FA of WM around the bilateral anterior cingulate gyrus and the right anterior corona radiata of the frontal lobe in first-episode drug-naive patients with schizophrenia following 6 weeks of treatment. Clinical symptoms improved during this period but the change in FA did not correlate with the changes in clinical symptoms or the dose of antipsychotic medication.ConclusionsDuring the early phase of treatment, there is an acute reduction in WM FA that may be due to the effects of antipsychotic medications. However, it is not possible to entirely exclude the effects of underlying progression of illness.


2014 ◽  
Vol 156 (2-3) ◽  
pp. 157-160 ◽  
Author(s):  
J. Fitzsimmons ◽  
H.M. Hamoda ◽  
T. Swisher ◽  
D. Terry ◽  
G. Rosenberger ◽  
...  

2018 ◽  
Vol 17 (3) ◽  
pp. 737-746 ◽  
Author(s):  
Yingchun Zeng ◽  
Andy S. K. Cheng ◽  
Ting Song ◽  
Xiujie Sheng ◽  
Shaojing Wang ◽  
...  

Background: Among women in China, gynecological cancers are the second most common cancers after breast cancer. Cancer-related cognitive impairment (CRCI) has emerged as a significant problem affecting gynecological cancer survivors. While acupuncture has been used in different aspects of cancer care, the possible positive effects of acupuncture on cognitive impairment have received little attention. This study hypothesized that patients would demonstrate lower neurocognitive performance and lower structural connectivity compared to healthy controls. This pilot study also hypothesized that acupuncture may potentially be effective in treating CRCI of cancer patients by increasing brain structural connectivity and integrity. Methods: This prospective cohort study consisted of 3 stages: the first stage included a group of gynecological cancer patients and a group of age-matched healthy controls. This baseline stage used a core set of neurocognitive tests to screen patients with cognitive impairment and used a multimodal approach of brain magnetic resonance imaging (MRI) to explore the possible neurobiological mechanism of cognitive impairment in cancer patients, comparing the results with a group of noncancer controls. The second stage involved assigning CRCI patients into the acupuncture intervention group, while patients without CRCI were assigned into the cancer control group. The third stage was a postintervention assessment of neurocognitive function by the same set of neurocognitive tests at baseline. To explore the possible neurobiological basis of acupuncture for treating CRCI, this study also used a multimodal MRI approach to assess changes in brain structural connectivity, and neurochemical properties in patients at pre- and postacupuncture intervention. Results: This study found that the prevalence of cognitive impairment in Chinese gynecological cancer patients at diagnosis was 26.67%. When investigating the microstructural white matter in the brain, diffusion tensor imaging data in this study indicated that premorbid cognitive functioning (before clinical manifestations become evident) has already existed, as the global and local connectome properties in the entire patient group were lower than in the healthy control group. Using magnetic resonance spectroscopy, this study indicated there was a significant reduction of relative concentration of NAA ( N-acetyl aspartate) in the left hippocampus, comparing these results with healthy controls. Regarding the effects of acupuncture on reducing CRCI, patients in the acupuncture group reported better neurocognitive test performance after matching for age, menopausal status, cancer stage, and chemotherapy regimen dosage. On a microstructural level, acupuncture’s ability to reduce CRCI may be attributed to a reduction in demyelination and an enhancement of the neuronal viability of white matter in the hippocampus. Conclusion: This pilot study indicates that acupuncture is a promising intervention in treating CRCI in gynecological cancer patients undergoing chemotherapy; however, it requires evaluation in larger randomized controlled studies to definitively assess its benefit. By using a multimodal imaging approach, this pilot study also provides novel insights into the neurobiological basis of cognitive impairment on the human brain that has been induced by cancer and/or its treatment.


Nephron ◽  
2020 ◽  
Vol 145 (1) ◽  
pp. 35-43
Author(s):  
Wesley T. Richerson ◽  
Laura G. Umfleet ◽  
Brian D. Schmit ◽  
Dawn F. Wolfgram

<b><i>Introduction:</i></b> Patients on hemodialysis (HD) have a significant burden of cognitive impairment. Characterizing the cerebral structural changes in HD patients compared to healthy controls and evaluating the relationship of cerebral structural integrity with cognitive performance in HD patients can help clarify the pathophysiology of the cognitive impairment in HD patients. <b><i>Methods:</i></b> In this cross-sectional study, in-center HD patients ≥50 years of age underwent brain structural and diffusion MRIs and cognitive assessment using the NIH Toolbox cognition battery. The cerebral imaging measures of the HD participants were compared to imaging from age-matched controls. Gray matter volume, white matter volume, and white matter integrity determined by diffusion tensor imaging parameters (including fractional anisotropy [FA]) were measured in both cohorts to determine differences in the cerebral structure between HD participants and healthy controls. The association between cognitive performance on the NIH Toolbox cognition battery and cerebral structural integrity was evaluated using multiple linear regression models. <b><i>Results:</i></b> We compared imaging measures form 23 HD participants and 15 age-matched controls. The HD participants had decreased gray matter volumes (526.8 vs. 589.5 cm<sup>3</sup>, <i>p</i> &#x3c; 0.01) and worsened white matter integrity overall (FA values of 0.2864 vs. 0.3441, <i>p</i> &#x3c; 0.01) within major white matter tracts compared to healthy controls. Decreases in white matter integrity in the left superior longitudinal fasciculus was associated with lower executive function scores (<i>r</i><sup><i>2</i></sup> = 0.24, <i>p</i> = 0.02) and inferior longitudinal fasciculus with lower memory scores (<i>r</i> = 0.25 and <i>p</i> = 0.03 for left and <i>r</i><sup>2</sup> = 0.21 and <i>p</i> = 0.03 for right). <b><i>Conclusions:</i></b> HD patients have a pattern of decreased white matter integrity and gray matter atrophy compared to controls. Decreases in white matter integrity were associated with decreased cognitive performance in the HD population.


2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Jibiao Zhang ◽  
Junling Gao ◽  
Huqing Shi ◽  
Bingsheng Huang ◽  
Xiang Wang ◽  
...  

Conduct disorder (CD) is one of the most common behavior disorders in adolescents, such as impulsivity, aggression, and running from school. Males are more likely to develop CD than females, and two previous diffusion tensor imaging (DTI) studies have demonstrated abnormal microstructural integrity in the uncinate fasciculus (UF) in boys with CD compared to a healthy control group. However, little is known about changes in the UF in females with CD. In this study, the UF was illustrated by tractography; then, the fractional anisotropy (FA), axial diffusivity, mean diffusion, radial diffusivity (RD), and the length and number of the UF fiber bundles were compared between male and female patients with CD and between female patients with CD and female healthy controls, as well as between males with CD and healthy males. We found that males with CD showed significantly higher FA of the bilateral UF and significantly lower RD of the left UF when comparing with females with CD. Meanwhile, significantly higher FA and lower RD of the bilateral UF were also found in boys with CD relative to the male healthy controls. Our results replicated previous reports that the microstructural integrity of the UF was abnormal in boys with CD. Additionally, our results demonstrated significant gender effects on the UF of patients with CD, which may indicate why boys have higher rates of conduct problems than girls.


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