White Matter Abnormalities in Never-Treated Patients With Long-Term Schizophrenia

Xiao, Yuan; Sun, Huaiqiang; Shi, Shulin; Jiang, Dan; Tao, Bo; Zhao, Youjin; Zhang, Wenjing; Gong, Qiyong; Sweeney, John A.; Lui, Su

doi:10.1176/appi.ajp.2018.17121402

Cited by 59 publications

(48 citation statements)

References 58 publications

(76 reference statements)

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“…It should be noted that unlike our previous findings that long-term untreated patients showed more severe deficits in the white matter 17 and functional networks 48 than treated patients, our findings revealed more regions with reduced GM in treated patients than untreated patients. One of the possible explanations is that the mechanism of antipsychotics may be associated with GM reductions and functional performance improvements.…”

Section: Discussioncontrasting

confidence: 99%

“…Previous studies have shown GM abnormalities in chronic schizophrenia [10][11][12][13][14][15] , but these studies have mostly been during the middle course of the illness. However, only two studies 16,17 reported GM alterations during a relatively later course of the illness. A cross-sectional brain structural study 16 found that, relative to healthy controls, schizophrenia patients with an untreated illness course of more than 20 years demonstrated less cortical thickness in the bilateral ventromedial prefrontal cortices, left superior temporal gyrus, and right pars triangularis and greater cortical thickness in the left superior parietal lobe.…”

Section: Introductionmentioning

confidence: 99%

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Characteristics of gray matter alterations in never-treated and treated chronic schizophrenia patients

et al. 2020

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Though gray matter deficits have been consistently revealed in chronic treated schizophrenia, it is still not clear whether there are different brain alterations between chronic never treated and treated patients. To explore the different patterns of gray matter alterations among chronic never treated patients and those treated with monotherapy, we recruited 35 never-treated chronic schizophrenia patients with illness durations ranging from 5 to 48 years, 20 illness duration-matched risperidone monotherapy and 20 clozapine monotherapy patients, and 55 healthy controls. GM (surface area, cortical thickness, and cortical volume) measures were extracted and compared using ANCOVA across the four groups followed by post hoc tests. Relative to controls, both treated and never-treated chronic schizophrenia patients showed reduced GM mainly involving the bilateral medial and rostral middle frontal, left banks superior temporal sulcus, left fusiform, and left pericalcarine cortex and increased in the left cuneus. Compared with the untreated patient group, the two treated groups showed reductions mainly in the bilateral prefrontal, temporal, and left inferior parietal lobules. The clozapine monotherapy patients demonstrated more severe decreases in the bilateral prefrontal cortex and left cuneus and less severe decreases in the left ventral temporal lobe than risperidone monotherapy patients. These findings provide new insights into the long-term effects of antipsychotic treatment on gray matter alterations in schizophrenia patients. Furthermore, the characteristic findings of reductions in the inferior parietal lobule might be specific for long-term antipsychotic treatment, which could be a possible target for medication development in the future.

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Section: Discussioncontrasting

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Characteristics of gray matter alterations in never-treated and treated chronic schizophrenia patients

et al. 2020

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“…Comparison of individuals with schizophrenia and healthy controls introduces an additional confounder of antipsychotic drug exposure, from which healthy controls are naïve. Antipsychotic drug exposure is correlated with a reduction in age-related FA decline in the corpus callosum in those with schizophrenia (Xiao et al, 2018), potentially via facilitation of oligodendrocyte regeneration and myelin repair following injury (Zhang et al, 2012). Although in the current study we found no correlation between chlorpromazine equivalents and corpus callosum FA, a comparison with healthy controls would likely suffer from some degree of interference from antipsychotic drugs.…”

Section: Discussioncontrasting

confidence: 77%

Differences in white matter connectivity between treatment-resistant and treatment-responsive subtypes of schizophrenia

McNabb

Kydd

Sundram

et al. 2018

Psychiatry Research: Neuroimaging

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Schizophrenia is a heterogeneous disorder exhibiting variable responsiveness to treatment between individuals. Previous work demonstrated that white matter abnormalities may relate to antipsychotic response but no study to date has examined differences between first-line treatment responders (FLR) and clozapine-eligible individuals receiving first-line antipsychotics. The current study aimed to establish whether differences in white matter structure exist between these two cohorts. Diffusionweighted images were acquired for 15 clozapine-eligible and 10 FLR participants. Measures of fractional anisotropy (FA), radial diffusivity (RD) and axial diffusivity (AD) were obtained and between-group ttests interrogating differences in FA were conducted. To investigate the neural basis of a decrease in FA, the significant cluster from FA analysis was masked and used to obtain mean RD and AD measures for that region. Those who were clozapine-eligible had significantly lower FA in the body of the corpus callosum (p<0.05), associated with a significant increase in mean RD compared with FLR (p<0.001). No difference in mean AD was observed for this region. These data reveal differences in diffusion measures between FLR and those eligible for clozapine and suggest that lower FA and greater RD in the corpus callosum could exist as a biomarker of treatment resistance in people with schizophrenia.

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“…Collectively, both functional and structural connectivities between the left PCC and ACC may be related to the severity of symptoms as represented by delusions. Additionally, Yuan et al revealed that patients with schizophrenia who had never been treated for a long term showed more sever white matter abnormalities in the left cingulum-hippocampus pathway compared with patients with schizophrenia who had been treated [ 49 ]. This finding supports our hypothesis that the persistent symptoms observed in patients with TRS may be associated with functional abnormalities in the left cingulate cortex.…”

Section: Discussionmentioning

confidence: 99%

Resting-State Isolated Effective Connectivity of the Cingulate Cortex as a Neurophysiological Biomarker in Patients with Severe Treatment-Resistant Schizophrenia

Wada

Nakajima

Tarumi

et al. 2020

JPM

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Background: The neural basis of treatment-resistant schizophrenia (TRS) remains unclear. Previous neuroimaging studies suggest that aberrant connectivity between the anterior cingulate cortex (ACC) and default mode network (DMN) may play a key role in the pathophysiology of TRS. Thus, we aimed to examine the connectivity between the ACC and posterior cingulate cortex (PCC), a hub of the DMN, computing isolated effective coherence (iCoh), which represents causal effective connectivity. Methods: Resting-state electroencephalogram with 19 channels was acquired from seventeen patients with TRS and thirty patients with non-TRS (nTRS). The iCoh values between the PCC and ACC were calculated using sLORETA software. We conducted four-way analyses of variance (ANOVAs) for iCoh values with group as a between-subject factor and frequency, directionality, and laterality as within-subject factors and post-hoc independent t-tests. Results: The ANOVA and post-hoc t-tests for the iCoh ratio of directionality from PCC to ACC showed significant findings in delta (t45 = 7.659, p = 0.008) and theta (t45 = 8.066, p = 0.007) bands in the left side (TRS < nTRS). Conclusion: Left delta and theta PCC and ACC iCoh ratio may represent a neurophysiological basis of TRS. Given the preliminary nature of this study, these results warrant further study to confirm the importance of iCoh as a clinical indicator for treatment-resistance.

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White Matter Abnormalities in Never-Treated Patients With Long-Term Schizophrenia

Cited by 59 publications

References 58 publications

Characteristics of gray matter alterations in never-treated and treated chronic schizophrenia patients

Characteristics of gray matter alterations in never-treated and treated chronic schizophrenia patients

Differences in white matter connectivity between treatment-resistant and treatment-responsive subtypes of schizophrenia

Resting-State Isolated Effective Connectivity of the Cingulate Cortex as a Neurophysiological Biomarker in Patients with Severe Treatment-Resistant Schizophrenia

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