Functional brain networks in never-treated and treated long-term Ill schizophrenia patients

Yao, Li; Li, Fēi; Liu, Jieke; Liao, Wei; Li, Xiaojing; Li, Mingli; Meng, Yajing; Liang, Siming; Zhang, Chengcheng; Yang, Xiao; Wang, Qiang; Ma, Xiaoyan; Guo, Wanjun; Sweeney, John A.; Gong, Qiyong; Lui, Su; Deng, Wei; Li, Tao

doi:10.1038/s41386-019-0428-2

Cited by 15 publications

(12 citation statements)

References 70 publications

(78 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%

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%

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

et al. 2020

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“…The observed reduction in centrality across core hubs with a smaller magnitude of increase in centrality in other regions is also consistent with many prior observations of reduced degree centrality 29 – 31 , though Tang et al 32 reported no centrality reductions in schizophrenia. Tang and colleagues studied a relatively younger age group of subjects with >50% medicated for an unspecified amount of time; and considered only positive values of functional connectivity to quantify centrality.…”

Section: Discussionsupporting

confidence: 89%

Conceptual disorganization and redistribution of resting-state cortical hubs in untreated first-episode psychosis: A 7T study

et al. 2021

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Network-level dysconnectivity has been studied in positive and negative symptoms of schizophrenia. Conceptual disorganization (CD) is a symptom subtype that predicts impaired real-world functioning in psychosis. Systematic reviews have reported aberrant connectivity in formal thought disorder, a construct related to CD. However, no studies have investigated whole-brain functional correlates of CD in psychosis. We sought to investigate brain regions explaining the severity of CD in patients with first-episode psychosis (FEPs) compared with healthy controls (HCs). We computed whole-brain binarized degree centrality maps of 31 FEPs, 25 HCs, and characterized the patterns of network connectivity in the 2 groups. In FEPs, we related these findings to the severity of CD. We also studied the effect of positive and negative symptoms on altered network connectivity. Compared to HCs, reduced centrality of a right superior temporal gyrus (rSTG) cluster was observed in the FEPs. In patients exhibiting high CD, increased centrality of a medial superior parietal (mSPL) cluster was observed, compared to patients exhibiting low CD. This cluster was strongly correlated with CD scores but not with other symptom scores. Our observations are congruent with previous findings of reduced but not increased centrality. We observed increased centrality of mSPL suggesting that cortical reorganization occurs to provide alternate routes for information transfer. These findings provide insight into the underlying neural processes mediating the presentation of symptoms in untreated FEP. Longitudinal tracking of the symptom course will be useful to assess the mechanisms underlying these compensatory changes.

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“…Both increased ( Reis Marques et al, 2014 ) and decreased FA ( Wang et al, 2013 ; Szeszko et al, 2014 ) as well as no evidence for whiter matter changes ( Kraguljac et al, 2019 ) after short-term (6–12 weeks) antipsychotic treatment have been reported. Clinical studies on long-term antipsychotic treatment, including our previous studies ( Xiao et al, 2018 ; Yao et al, 2019 ), suggest that antipsychotic medications may have beneficial effects on the brain’s structure and function. In contrast, studies on non-human primate models have suggested adverse effects of antipsychotics by reporting associations between chronic exposure to antipsychotics with reduced brain volume and glial cell numbers ( Dorph-Petersen et al, 2005 ; Konopaske et al, 2007 ).…”

Section: Discussionmentioning

confidence: 78%

“…This suggests that long-term antipsychotic treatment does not adversely affect the brain’s structure over the longer term course of illness and may even confer some benefits ( Xiao et al, 2018 ). The potential beneficial effects of long-term antipsychotic treatment are additionally supported by functional brain imaging data ( Yao et al, 2019 ). However, previous studies reporting brain structure alterations in antipsychotic-treated patients were limited by very diverse antipsychotic treatments, which did not allow specific conclusions about specific effects of individual agents on white matter brain structure ( Bartzokis et al, 2007 , 2009 ; Vita et al, 2015 ; Leroux et al, 2018 ).…”

Section: Introductionmentioning

confidence: 99%

Characteristics of White Matter Structural Networks in Chronic Schizophrenia Treated With Clozapine or Risperidone and Those Never Treated

Chen

Lencer

et al. 2020

International Journal of Neuropsychopharmacology

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Background Despite its benefits, a major concern regarding antipsychotic treatment is its possible impact on the brain’s structure and function. This study sought to explore the characteristics of white matter structural networks in chronic never treated schizophrenia and those treated with clozapine or risperidone, and its potential association with cognitive function. Methods Diffusion tensor imaging was performed on a unique sample of 34 schizophrenia patients treated with antipsychotic monotherapy for over five years (17 treated with clozapine and 17 treated with risperidone), 17 never-treated schizophrenia patients with illness duration over five years, and 27 healthy control subjects. Graph theory and network-based statistic (NBS) approaches were employed. Results We observed a disrupted organization of white matter structural networks as well as decreased nodal and connectivity characteristics across the schizophrenia groups, mainly involving thalamus, prefrontal and occipital regions. Alterations in nodal and connectivity characteristics were relatively milder in risperidone-treated patients than clozapine-treated patients and never-treated patients. Altered global network measures were significantly associated with cognitive performance levels. Structural connectivity as reflected by NBS mediated the difference in cognitive performance levels between clozapine-treated and risperidone-treated patients. Limitations Those results are constrained by the lack of random assignment to different types of antipsychotic treatment. Conclusion These findings provide insight into the white matter structural network deficits in patients with chronic schizophrenia, either being treated or untreated, and suggest white matter structural networks supporting cognitive function may benefit from antipsychotic treatment, especially in those treated with risperidone.

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Functional brain networks in never-treated and treated long-term Ill schizophrenia patients

Cited by 15 publications

References 70 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

Conceptual disorganization and redistribution of resting-state cortical hubs in untreated first-episode psychosis: A 7T study

Characteristics of White Matter Structural Networks in Chronic Schizophrenia Treated With Clozapine or Risperidone and Those Never Treated

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