Tract-specific analysis of white matter integrity disruption in schizophrenia

Department of Diagnostic Radiology, Toranomon Hospital, 2-2-2 Toranomon, Minato-ku, Tokyo, Japan.
Psychiatry Research (Impact Factor: 2.47). 03/2012; 201(2):136-43. DOI: 10.1016/j.pscychresns.2011.07.010
Source: PubMed


Several studies have suggested that white matter integrity is disrupted in some brain regions in patients with schizophrenia. The purpose of this study was to assess the white matter integrity of the cingulum, uncinate fasciculus, fornix, and corpus callosum using diffusion tensor imaging (DTI). Participants comprised 39 patients with schizophrenia (19 males and 20 females) and 40 age-matched normal controls (20 males and 20 females). We quantitatively assessed the fractional anisotropy (FA) and apparent diffusion coefficient (ADC) of the anterior cingulum, body of the cingulum, uncinate fasciculus, fornix, and corpus callosum on a tract-specific basis using diffusion tensor tractography (DTT). Group differences in FA and ADC between the patients and normal controls were sought. Additional exploratory analyses of the relationship between the FA or ADC and four clinical parameters (i.e., illness duration, positive symptom scores, negative symptom scores, and medication dosage) were performed. Results were analyzed in gender-combined and gender-separated group comparisons. FA was significantly lower on both sides of the anterior cingulum, uncinate fasciculus, and fornix in the schizophrenia patients irrespective of gender group separation. In the gender-combined analyses, significantly higher ADC values were demonstrated in the schizophrenia patients in both sides of the anterior cingulum, body of the cingulum and uncinate fasciculus, the left fornix, and the corpus callosum, compared with those of the normal controls. In the gender-separated analyses, the male patients showed higher ADC in the left anterior cingulum, the bilateral cingulum bodies, and the bilateral uncinate fasciculi. The female patients showed higher ADC in the right anterior cingulum, the left fornix, and the bilateral uncinate fasciculus. In correlation analyses, a significant negative correlation was found between illness duration and ADC in the right anterior cingulum in the gender-combined analyses. The gender-separated analyses found that the male patients had a significant negative correlation between negative symptom scores and FA in the right fornix, a positive correlation between illness duration and FA in the right anterior cingulum, and a negative correlation between illness duration and FA in the left uncinate fasciculus. Our DTI study showed that the integrity of white matter is disrupted in patients with schizophrenia. The results of our sub-analyses suggest that changes in FA and ADC may be related to negative symptom scores or illness duration.

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    • "White matter integrity has previously been shown to be impaired in patients with more severe negative symptoms. For instance , Kunimatsu et al. found that patients with schizophrenia and a more severe severity of negative symptoms also had decreased FA in the right fornix (Kunimatsu et al., 2012). Similarly, decreased FA values in the right cingulum have been associated with greater severity of negative symptoms (Hazlett et al., 2011). "
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    ABSTRACT: Aberrant white matter structures in fronto-temporal regions have previously been identified in patients with schizophrenia. However, scant research has focused on white matter integrity in patients presenting with a first episode of psychosis (FEP) with persistent negative symptoms (PNS). This study aimed to explore microstructure in the neurocircuitry proposed to be involved in PNS, by using a region-of-interest approach. Secondly, the relationship between individual negative symptoms and white matter were explored. Fractional anisotropy (FA) was measured in the fornix and three other tracts bilaterally including the uncinate fasciculus, superior longitudinal fasciculus and the cingulum bundle. Twelve patients with PNS were compared to a non-PNS group (52) and a healthy control group (51). Results showed that the PNS group had significantly lower FA values in the fornix when compared to healthy controls and that the non-PNS group had significantly lower FA values in the right uncinate fasciculus compared to healthy controls. Significant correlations were observed between SANS global score for anhedonia-asociality and lower FA values in the right cingulum bundle. Our results suggest that fronto-temporal white matter might be more closely related to PNS and that this relationship may possibly be mediated by greater anhedonia in PNS patients. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
    Full-text · Article · Jul 2015 · Psychiatry Research: Neuroimaging
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    • "On the other hand, changes in WM integrity may be a fundamental pathophysiological mechanism underlying the clinical presentation of schizophrenia, present before the appearance of clinical symptoms. There are several studies supporting this hypothesis, proposing the change in WM as an endophenotypical feature of the disease (Davis et al., 2003; Camchong, 2009; Abdul-Rahman et al., 2011; Kunimatsu et al., 2012; Kuswanto et al., 2012; Scheel et al., 2012). Together, the data to date strongly suggests that there is an underlying abnormality in the WM tracts of patients with schizophrenia. "
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    ABSTRACT: Background: White matter abnormality has been recently proposed as a pathophysiological feature of schizophrenia (SZ). However, most of the data available has been gathered from chronic patients, and was therefore possibly confounded by factors such as duration of the disease, and treatment received. The extent and localization of these changes is also not clear. Methods: We examined a population of early stage SZ patients using diffusion tensor imaging (DTI). 77 SZ patients and 60 healthy controls (HCs) were included in the analysis using Tract-Based Spatial Statistics (TBSS). We have also analyzed 250 randomly created subsets of the original cohort, to investigate the relation between the result of TBSS analysis, and the size of the sample studied. Results: We have found a significant decrease in fractional anisotropy (FA) in the patient group. This change is present in most major white matter (WM) tracts including the corpus callosum, superior and inferior longitudinal fasciculi, inferior fronto-occipital fasciculus, and posterior thalamic radiation. Furthermore, we identified a clear trend towards an increase in the number and spatial extent of significant voxels reported, with an increasing number of subjects included in the analysis. Conclusion: Our study shows that FA is significantly decreased in patients at an early stage of schizophrenia, and that the extent of this finding is dependent on the size of studied sample; therefore underpowered studies might produce results with false spatial localization.
    Full-text · Article · Feb 2015 · Schizophrenia Research
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    • "Kanaan et al. [2005] suggested a tractography-based analysis (TBA) method [Kunimatsu et al., 2012; Wakana et al., 2004] that analyzes the integrity of a specific tract bundle based on diffusion tractography [Mori and van Zijl, 2002]. However, because the TBA approach invokes tractography , it is operator-dependent and prone to poor reproducibility when less efficient fiber tracking algorithm is used [Tensaouti et al., 2011]. "
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    ABSTRACT: Trait markers of schizophrenia aid the dissection of the heterogeneous phenotypes into distinct subtypes and facilitate the genetic underpinning of the disease. The microstructural integrity of the white matter tracts could serve as a trait marker of schizophrenia, and tractography-based analysis (TBA) is the current method of choice. Manual tractography is time-consuming and limits the analysis to preselected fiber tracts. Here, we sought to identify a trait marker of schizophrenia from among 74 fiber tracts across the whole brain using a novel automatic TBA method. Thirty-one patients with schizophrenia, 31 unaffected siblings and 31 healthy controls were recruited to undergo diffusion spectrum magnetic resonance imaging at 3T. Generalized fractional anisotropy (GFA), an index reflecting tract integrity, was computed for each tract and compared among the three groups. Ten tracts were found to exhibit significant differences between the groups with a linear, stepwise order from controls to siblings to patients; they included the right arcuate fasciculus, bilateral fornices, bilateral auditory tracts, left optic radiation, the genu of the corpus callosum, and the corpus callosum to the bilateral dorsolateral prefrontal cortices, bilateral temporal poles, and bilateral hippocampi. Posthoc between-group analyses revealed that the GFA of the right arcuate fasciculus was significantly decreased in both the patients and unaffected siblings compared to the controls. Furthermore, the GFA of the right arcuate fasciculus exhibited a trend toward positive symptom scores. In conclusion, the right arcuate fasciculus may be a candidate trait marker and deserves further study to verify any genetic association. Hum Brain Mapp, 2014. © 2014 Wiley Periodicals, Inc.
    Full-text · Article · Nov 2014 · Human Brain Mapping
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