Abnormalities of EEG Microstates In Drug-Naïve, First-Episode Schizophrenia

Abstract Objective: Microstate analysis is a powerful tool to probe the brain functions, and changes in microstates under electroencephalography (EEG) have been repeatedly reported in patients with schizophrenia. This study aimed to investigate the dynamics of EEG microstates in drug-naïve, first-episode schizophrenia (FE-SCH) and to test the relationship between EEG microstates and clinical symptoms.Methods: Resting-state EEG were recorded for 23 patients with FE-SCH and 23 healthy controls using a 64-channel cap. Three parameters, i.e., contribution, duration, and occurrence, of the four microstate classes were calculated. Group differences in EEG microstates and their clinical symptoms (assessed using the Positive and Negative Syndrome Scale) were analyzed.Results: Compared with healthy controls, patients with FE-SCH showed increased duration, occurrence and contribution of microstate class C and decreased contribution and occurrence of microstate class D. In addition, the score of positive symptoms in PANSS was negatively correlated with the occurrence of microstate D.Conclusions: Our findings showed abnormal patterns of EEG microstates in drug-naïve, first-episode schizophrenia, which might help distinguish individuals with schizophrenia in the early stage and develop early intervention strategies.

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Duration Mismatch Negativity Predicts Remission in First-Episode Schizophrenia Patients

Frontiers in Psychiatry ◽

10.3389/fpsyt.2021.777378 ◽

2021 ◽

Vol 12 ◽

Author(s):

Suguru Nakajima ◽

Yuko Higuchi ◽

Takahiro Tateno ◽

Daiki Sasabayashi ◽

Yuko Mizukami ◽

...

Keyword(s):

Social Functioning ◽

Mismatch Negativity ◽

Rating Scale ◽

Clinical Symptoms ◽

First Episode ◽

Healthy Controls ◽

Brief Assessment ◽

Syndrome Scale ◽

Symptomatic Remission ◽

First Episode Schizophrenia

Objective: Remission in schizophrenia patients is associated with neurocognitive, social, and role functioning during both the early and chronic stages of schizophrenia. It is well-established that the amplitudes of duration mismatch negativity (dMMN) and frequency MMN (fMMN) are reduced in schizophrenia patients. However, the potential link between MMN and remission has not been established. In this study, we investigated the relationship between MMNs and remission in first-episode schizophrenia (FES) and their association with neurocognitive and social functioning.Method: dMMN and fMMN were measured in 30 patients with FES and 22 healthy controls at baseline and after a mean of 3 years. Clinical symptoms and cognitive and social functioning in the patients were assessed at the time of MMN measurements by using the Positive and Negative Syndrome Scale (PANSS), modified Global Assessment of Functioning (mGAF), Schizophrenia Cognition Rating Scale (SCoRS), and the Brief Assessment of Cognition in Schizophrenia (BACS). Remission of the patients was defined using the criteria by the Remission in Schizophrenia Working Group; of the 30 patients with FES, 14 achieved remission and 16 did not.Results: Baseline dMMN amplitude was reduced in FES compared to healthy controls. Further, baseline dMMN in the non-remitters had decreased amplitude and prolonged latency compared to the remitters. MMN did not change during follow-up period regardless of parameters, diagnosis, or remission status. Baseline dMMN amplitude in FES was correlated with future SCoRS and PANSS total scores. Logistic regression analysis revealed that dMMN amplitude at baseline was a significant predictor of remission.Conclusions: Our findings suggest that dMMN amplitude may be a useful biomarker for predicting symptomatic remission and improvement of cognitive and social functions in FES.

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The Role of Butyric Acid in Treatment Response in Drug-Naïve First Episode Schizophrenia

Frontiers in Psychiatry ◽

10.3389/fpsyt.2021.724664 ◽

2021 ◽

Vol 12 ◽

Author(s):

Xue Li ◽

Xiaoduo Fan ◽

Xiuxia Yuan ◽

Lijuan Pang ◽

Shaohua Hu ◽

...

Keyword(s):

Treatment Response ◽

Butyric Acid ◽

Serum Levels ◽

First Episode ◽

Healthy Controls ◽

Significant Difference ◽

Drug Naïve ◽

First Episode Schizophrenia ◽

Risperidone Treatment

Background: Butyric acid, a major short-chain fatty acid (SCFA), has an important role in the microbiota–gut–brain axis and brain function. This study investigated the role of butyric acid in treatment response in drug-naïve first episode schizophrenia.Methods: The study recruited 56 Chinese Han schizophrenia inpatients with normal body weight and 35 healthy controls. Serum levels of butyric acid were measured using Gas Chromatography-Mass Spectrometer (GC-MS) analysis at baseline (for all participants) and 24 weeks after risperidone treatment (for patients). Clinical symptoms were measured using the Positive and Negative Syndrome Scale (PANSS) for patients at both time points.Results: At baseline, there was no significant difference in serum levels of butyric acid between patients and healthy controls (p = 0.206). However, there was a significant increase in serum levels of butyric acid in schizophrenia patients after 24-week risperidone treatment (p = 0.030). The PANSS total and subscale scores were decreased significantly after 24-week risperidone treatment (p's < 0.001). There were positive associations between baseline serum levels of butyric acid and the reduction ratio of the PANSS total and subscale scores after controlling for age, sex, education, and duration of illness (p's < 0.05). Further, there was a positive association between the increase in serum levels of butyric acid and the reduction of the PANSS positive symptoms subscale scores (r = 0.38, p = 0.019) after controlling for potential confounding factors.Conclusions: Increased serum levels of butyric acid might be associated with a favorable treatment response in drug-naïve, first episode schizophrenia. The clinical implications of our findings were discussed.

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White-matter microstructure in previously drug-naive patients with schizophrenia after 6 weeks of treatment

Psychological Medicine ◽

10.1017/s0033291713000238 ◽

2013 ◽

Vol 43 (11) ◽

pp. 2301-2309 ◽

Cited By ~ 55

Author(s):

Q. Wang ◽

C. Cheung ◽

W. Deng ◽

M. Li ◽

C. Huang ◽

...

Keyword(s):

White Matter ◽

Early Phase ◽

Clinical Symptoms ◽

Diffusion Tensor ◽

Disease Process ◽

Anterior Cingulate ◽

First Episode ◽

Drug Naïve ◽

The Right ◽

First Episode Schizophrenia

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.

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The comparison of glycometabolism parameters and lipid profiles between drug-naïve, first-episode schizophrenia patients and healthy controls

Schizophrenia Research ◽

10.1016/j.schres.2013.07.051 ◽

2013 ◽

Vol 150 (1) ◽

pp. 157-162 ◽

Cited By ~ 47

Author(s):

Xiaoli Wu ◽

Zeping Huang ◽

Renrong Wu ◽

Zhiyong Zhong ◽

Qinling Wei ◽

...

Keyword(s):

Lipid Profiles ◽

First Episode ◽

Healthy Controls ◽

Drug Naïve ◽

First Episode Schizophrenia

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Reducedγ-Aminobutyric Acid and Glutamate+Glutamine Levels in Drug-Naïve Patients with First-Episode Schizophrenia but Not in Those at Ultrahigh Risk

Neural Plasticity ◽

10.1155/2016/3915703 ◽

2016 ◽

Vol 2016 ◽

pp. 1-9 ◽

Cited By ~ 13

Author(s):

Junjie Wang ◽

Yingying Tang ◽

Tianhong Zhang ◽

Huiru Cui ◽

Lihua Xu ◽

...

Keyword(s):

Prefrontal Cortex ◽

Proton Magnetic Resonance ◽

Proton Magnetic Resonance Spectroscopy ◽

Aminobutyric Acid ◽

First Episode ◽

Resonance Spectroscopy ◽

Healthy Controls ◽

Drug Naïve ◽

First Episode Schizophrenia

Alteredγ-aminobutyric acid (GABA), glutamate (Glu) levels, and an imbalance between GABAergic and glutamatergic neurotransmissions have been involved in the pathophysiology of schizophrenia. However, it remains unclear how these abnormalities impact the onset and course of psychosis. In the present study, 21 drug-naïve subjects at ultrahigh risk for psychosis (UHR), 16 drug-naïve patients with first-episode schizophrenia (FES), and 23 healthy controls (HC) were enrolled. In vivo GABA and glutamate+glutamine (Glx) levels in the medial prefrontal cortex were measured using proton magnetic resonance spectroscopy. Medial prefrontal GABA and Glx levels in FES patients were significantly lower than those in HC and UHR, respectively. GABA and Glx levels in UHR were comparable with those in HC. In each group, there was a positive correlation between GABA and Glx levels. Reduced medial prefrontal GABA and Glx levels thus may play an important role in the early stages of schizophrenia.

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Interrelationships Between BDNF, Superoxide Dismutase, and Cognitive Impairment in Drug-Naive First-Episode Patients With Schizophrenia

Schizophrenia Bulletin ◽

10.1093/schbul/sbaa062 ◽

2020 ◽

Vol 46 (6) ◽

pp. 1498-1510 ◽

Cited By ~ 3

Author(s):

Mei Hong Xiu ◽

Zezhi Li ◽

Da Chun Chen ◽

Song Chen ◽

Maile E Curbo ◽

...

Keyword(s):

Superoxide Dismutase ◽

Cognitive Impairment ◽

Clinical Symptoms ◽

Interactive Effect ◽

Redox System ◽

First Episode ◽

Sod Activity ◽

Neuropsychological Status ◽

Syndrome Scale ◽

Drug Naïve

Abstract The pathogenesis and etiology of schizophrenia (SCZ) remains unclear. Accumulating studies showed that complex interrelationships between brain-derived neurotrophic factor (BDNF) and an imbalanced redox system has a crucial role in the psychopathology of SCZ. However, the influence of the interrelationships of BDNF and superoxide dismutase (SOD) on cognitive impairment and clinical symptomatology in drug-naive first-episode (DNFE) SCZ patients has not been studied thoroughly. Serum BDNF levels, plasma total SOD, manganese-SOD (Mn-SOD), copper/zinc-containing SOD (CuZn-SOD) activities, and malondialdehyde (MDA) levels were measured in 327 DNFE patients with SCZ and 391 healthy controls. Cognitive functions were measured using the Repeatable Battery for the Assessment of Neuropsychological status (RBANS) and clinical symptoms were evaluated by the Positive and Negative Syndrome Scale (PANSS). Compared with the controls, the DNFE patients had increased activities of total SOD and CuZn-SOD, and reduced levels of BDNF and MDA. BDNF levels were positively correlated with CuZn-SOD activity in patients. In addition, we found that elevated Mn-SOD and CuZn-SOD activities were related to PANSS depression factor. Moreover, an interactive effect of BDNF levels and Mn-SOD activity was associated with attentional index score in the patients. Therefore, our findings suggested that interrelationships between BDNF and antioxidant mechanisms might underlie the pathological mechanisms of cognitive impairments and symptomatology in the DNFE patients with SCZ.

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NLRP3 Influences Cognitive Function in Schizophrenia in Han Chinese

Frontiers in Genetics ◽

10.3389/fgene.2021.781625 ◽

2021 ◽

Vol 12 ◽

Author(s):

Ruimei Liu ◽

Wei Tang ◽

Weiping Wang ◽

Feikang Xu ◽

Weixing Fan ◽

...

Keyword(s):

Cascade Reactions ◽

First Episode ◽

Eqtl Analysis ◽

Mrna Levels ◽

Healthy Controls ◽

Pyrin Domain ◽

Genotype Frequencies ◽

Significant Difference ◽

Drug Naïve ◽

First Episode Schizophrenia

It has been proposed that immune abnormalities may be implicated with pathophysiology of schizophrenia. The nod-like receptor pyrin domain-contraining protein 3 (NLRP3) can trigger immune-inflammatory cascade reactions. In this study, we intended to identify the role of gene encoding NLRP3 (NLRP3) in susceptibility to schizophrenia and its clinical features. For the NLRP3 mRNA expression analysis, 53 drug-naïve patients with first-episode schizophrenia and 56 healthy controls were enrolled. For the genetic study, a total of 823 schizophrenia patients and 859 controls were recruited. Among them, 239 drug-naïve patients with first-episode schizophrenia were enrolled for clinical evaluation. There is no significant difference in NLRP3 mRNA levels between patients with schizophrenia and healthy controls (p = 0.07). We did not observe any significant differences in allele and genotype frequencies of rs10754558 polymorphism between the schizophrenia and control groups. We noticed significant differences in the scores of RBANS attention and total scores between the patients with different genotypes of rs10754558 polymorphism (p = 0.001 and p < 0.01, respectively). Further eQTL analysis presented a significant association between the rs10754558 polymorphism and NLRP3 in frontal cortex (p = 0.0028, p = 0.028 after Bonferroni correction). Although our findings did not support NLRP3 confer susceptibility to schizophrenia, NLRP3 may be a risk factor for cognitive impairment, especially attention deficit in this disorder.

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Extensive White Matter Abnormalities and Clinical Symptoms in Drug-Naive Patients With First-Episode Schizophrenia

The Journal of Clinical Psychiatry ◽

10.4088/jcp.14m09374 ◽

2015 ◽

Vol 77 (02) ◽

pp. 205-211 ◽

Cited By ~ 20

Author(s):

Xiang Yang Zhang ◽

Feng-Mei Fan ◽

Da-Chun Chen ◽

Yun-Long Tan ◽

Shu-Ping Tan ◽

...

Keyword(s):

White Matter ◽

Clinical Symptoms ◽

First Episode ◽

White Matter Abnormalities ◽

Drug Naïve ◽

First Episode Schizophrenia

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Disrupted Sense of Agency as a State Marker of First-Episode Schizophrenia: A Large-Scale Follow-Up Study

Frontiers in Psychiatry ◽

10.3389/fpsyt.2020.570570 ◽

2020 ◽

Vol 11 ◽

Author(s):

Eva Kozáková ◽

Eduard Bakštein ◽

Ondřej Havlíček ◽

Ondřej Bečev ◽

Pavel Knytl ◽

...

Keyword(s):

Large Scale ◽

Clinical Symptoms ◽

Early Stage ◽

A Priori ◽

Sense Of Agency ◽

First Episode ◽

Dependent Manner ◽

Self Monitoring ◽

First Episode Schizophrenia

Background: Schizophrenia is often characterized by a general disruption of self-processing and self-demarcation. Previous studies have shown that self-monitoring and sense of agency (SoA, i.e., the ability to recognize one's own actions correctly) are altered in schizophrenia patients. However, research findings are inconclusive in regards to how SoA alterations are linked to clinical symptoms and their severity, or cognitive factors.Methods: In a longitudinal study, we examined 161 first-episode schizophrenia patients and 154 controls with a continuous-report SoA task and a control task testing general cognitive/sensorimotor processes. Clinical symptoms were assessed with the Positive and Negative Syndrome Scale (PANSS).Results: In comparison to controls, patients performed worse in terms of recognition of self-produced movements even when controlling for confounding factors. Patients' SoA score correlated with the severity of PANSS-derived “Disorganized” symptoms and with a priori defined symptoms related to self-disturbances. In the follow-up, the changes in the two subscales were significantly associated with the change in SoA performance.Conclusion: We corroborated previous findings of altered SoA already in the early stage of schizophrenia. Decreased ability to recognize self-produced actions was associated with the severity of symptoms in two complementary domains: self-disturbances and disorganization. While the involvement of the former might indicate impairment in self-monitoring, the latter suggests the role of higher cognitive processes such as information updating or cognitive flexibility. The SoA alterations in schizophrenia are associated, at least partially, with the intensity of respective symptoms in a state-dependent manner.

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