Increased plasma level of kynurenic acid in drug-free patients with first-episode schizophrenia compared to patients with chronic schizophrenia and healthy controls: preliminary data

Mismatch negativity (MMN) to deviant stimuli is robustly smaller in individuals with chronic schizophrenia compared with healthy controls (Cohen’s d > 1.0 or more), leading to the possibility of MMN being used as a biomarker for schizophrenia. However, there is some debate in the literature as to whether MMN is reliably reduced in first-episode schizophrenia patients. For the biomarker to be used as a predictive marker for schizophrenia, it should be reduced in the majority of cases known to have the disease, particularly at disease onset. We conducted a meta-analysis on the fourteen studies that measured MMN to pitch or duration deviants in healthy controls and patients within 12 months of their first episode of schizophrenia. The overall effect size showed no MMN reduction in first-episode patients to pitch-deviants (Cohen’s d < 0.04), and a small-to-medium reduction to duration-deviants (Cohen’s d = 0.47). Together, this indicates that pitch-deviant MMN is not a candidate biomarker for schizophrenia prediction, while duration-deviant MMN may hold some promise, albeit nearly a third as large an effect as in chronic schizophrenia. Potential causes for discrepancies between studies are discussed.

Download Full-text

Neuroimaging-based brain-age prediction of first-episode schizophrenia and the alteration of brain age after early medication

The British Journal of Psychiatry ◽

10.1192/bjp.2021.169 ◽

2021 ◽

pp. 1-8

Author(s):

Yi-Bin Xi ◽

Xu-Sha Wu ◽

Long-Biao Cui ◽

Li-Jun Bai ◽

Shuo-Qiu Gan ◽

...

Keyword(s):

Diffusion Tensor ◽

First Episode ◽

Age Difference ◽

Healthy Controls ◽

Data Set ◽

Brain Ageing ◽

First Episode Schizophrenia ◽

Brain Age ◽

The Brain ◽

Age Prediction

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.

Download Full-text

Cognitive heterogeneity in first-episode schizophrenia

The British Journal of Psychiatry ◽

10.1192/bjp.187.6.516 ◽

2005 ◽

Vol 187 (6) ◽

pp. 516-522 ◽

Cited By ~ 79

Author(s):

Eileen M. Joyce ◽

Sam B. Hutton ◽

Stanley H. Mutsatsa ◽

Thomas R. E. Barnes

Keyword(s):

Working Memory ◽

Cognitive Decline ◽

Spatial Working Memory ◽

Age At Onset ◽

Chronic Schizophrenia ◽

First Episode ◽

Entire Group ◽

Illness Onset ◽

Cognitive Heterogeneity ◽

First Episode Schizophrenia

BackgroundStudies of chronic schizophrenia suggest that there are subgroups with different profiles of cognitive impairment.AimsTo determine whether such heterogeneity is present at illness onset and any relationship to clinical variables.MethodNinety-three community patients with first-episode schizophrenia and 50 healthy volunteers were assessed for premorbid (Revised National Adult Reading Test) and current IQ, memory and executive function.ResultsHalf of those with schizophrenia had preserved IQ in the normal range but there was evidence of a specific impairment in spatial working memory even in those with high/average IQ; 37 out of 93 (40%) had generalised cognitive decline. Those with low premorbid IQ were significantly younger at illness onset. For the entire group, age at onset correlated positively with premorbid but not current IQ.ConclusionsAt illness onset, cognitive heterogeneity is present in people with schizophrenia, with a high proportion having undergone general cognitive decline. However, working memory impairment may be a common feature. Lower premorbid IQ is a risk factor for an earlier onset.

Download Full-text

An fMRI study of face encoding and recognition in first-episode schizophrenia

Acta Neuropsychiatrica ◽

10.1111/j.1601-5215.2008.00280.x ◽

2008 ◽

Vol 20 (3) ◽

pp. 129-138 ◽

Cited By ~ 10

Author(s):

Anantha P. P. Anilkumar ◽

Veena Kumari ◽

Ravi Mehrotra ◽

Ingrid Aasen ◽

Martina T. Mitterschiffthaler ◽

...

Keyword(s):

Face Recognition ◽

Brain Activity ◽

Chronic Schizophrenia ◽

First Episode ◽

Functional Magnetic Resonance ◽

Resonance Imaging ◽

Social Situations ◽

Fmri Study ◽

On Line ◽

First Episode Schizophrenia

Background:Schizophrenia has been associated with limited abilities to interact effectively in social situations. Face perception and ability to recognise familiar faces are critical for social interaction. Patients with chronic schizophrenia are known to show impaired face recognition. Studying first-episode (FE) patients allows the exclusion of confounding effects of chronicity, medication and institutionalisation in this deficit.Objective:To determine brain (dys)functions during a face encoding and recognition paradigm in FE schizophrenia.Methods:Thirteen antipsychotic-naïve FE schizophrenia patients and 13 age- and sex-matched healthy controls underwent functional magnetic resonance imaging during a face encoding and recognition paradigm. Behavioural responses were recorded on line.Results:Patients recognised significantly fewer of previously presented faces than the controls (p = 0.008). At the neural level, both groups activated a network of regions including the fusiform area, occipital, temporal and frontal regions. In brain activity, the two groups did not differ in any region during encoding or recognition conditions (p > 0.05, corrected or uncorrected).Conclusions:Our findings show impaired face recognition without a significant alteration of related brain activity in FE schizophrenia patients. It is possible that neural changes become more strongly evident with progression of the illness, and manifest themselves as behavioural impairments during the early course.

Download Full-text

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

10.21203/rs.3.rs-1042706/v1 ◽

2021 ◽

Author(s):

Qiaoling Sun ◽

Linlin Zhao ◽

Liwen Tan

Keyword(s):

Clinical Symptoms ◽

Early Stage ◽

First Episode ◽

Healthy Controls ◽

Brain Functions ◽

Class D ◽

Syndrome Scale ◽

Drug Naïve ◽

Microstate Analysis ◽

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.

Download Full-text

Serum Levels of HCY, MIF, and hs-CRP Correlate with Glycolipid Metabolism in Adults with Never-Medicated First-Episode Schizophrenia

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2021/7394699 ◽

2021 ◽

Vol 2021 ◽

pp. 1-9

Author(s):

Xiao Zhong ◽

Qin Ao ◽

Fei Xing

Keyword(s):

Waist Circumference ◽

Rating Scale ◽

Serum Levels ◽

First Episode ◽

Healthy Controls ◽

Glycolipid Metabolism ◽

Hs Crp ◽

Positive Correlations ◽

First Episode Schizophrenia ◽

Negative Syndrome

Objective. It has been reported that the prevalence of metabolic syndrome (MS) in multiepisode patients with schizophrenia is 35.3%, which is 2- to 4-fold higher than in the general population. The study is designed to compare the glycolipid metabolism in patients with first-episode schizophrenia (FES) with sex- and age-matched healthy controls to investigate changes in serum levels of homocysteine (Hcy), macrophage migration inhibitory factor (MIF), and high-sensitive C-reactive protein (hs-CRP) and their relationships with the glycolipid metabolism in patients with FES. Methods. His case-control study included 88 patients diagnosed with FES and 88 sex- and age-matched healthy controls. Patient psychopathology was assessed using the Positive and Negative Syndrome Scale (PANSS), Young Mania Rating Scale (YMRS), and 17-item Hamilton Rating Scale for Depression (HAMD-17). Patients with FES were classified into MS and non-MS groups. Results. There were significant differences in the education level, body mass index (BMI), and waist circumference between the patients with FES and healthy controls (all p > 0.05 ). The patients with FES had higher levels of FPG and blood glucose at the oral glucose tolerance test (OGTT) (2 h glucose) concomitant with higher proportion of impaired glucose tolerance (IGT) and homeostasis model assessment of insulin resistance (HOMA2-IR) than healthy controls (all p < 0.001 ). It was revealed that the patients with FES showed higher serum levels of Hcy, MIF, and hs-CRP than healthy controls (all p < 0.001 ). The serum level of Hcy shared positive correlations with the score of PANSS totals (r = 0.551) and the negative syndrome of the PANSS scale (r = 0.494). The serum levels of MIF and hs-CRP was only positively correlated with the negative syndrome of the PANSS scale (r = 0.320 and r = 0.446). The level of Hcy shared positive correlations with the levels of FPG, 2 h glucose, and HOMA2-IR; the level of MIF was only positively correlated with the level of HOMA2-IR; the level of hs-CRP had a positive correlation with both levels of FPG and 2 h glucose (all p < 0.001 ). The levels of Hcy, MIF, and hs-CRP all shared positive correlations with the TG level and negative correlations with the HDL-C level (all p < 0.001 ). There were remarkable differences between the MS and non-MS groups with regard to BMI, waist circumference, negative subscale of the PANSS scale, FPG, TG, and HDL-C (all p < 0.05 ). Elevated levels of Hcy, MIF, and hs-CRP were detected in the MS group compared to the non-MS group (all p < 0.05 ). Conclusion. These findings suggest that increased concentrations of HCY, MIF, and hs-CRP may contribute to the abnormal glycolipid metabolism in the context of schizophrenia.

Download Full-text

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.

Download Full-text

Connectome-Based Patterns of First-Episode Medication-Naïve Patients With Schizophrenia

Schizophrenia Bulletin ◽

10.1093/schbul/sbz014 ◽

2019 ◽

Vol 45 (6) ◽

pp. 1291-1299 ◽

Cited By ~ 13

Author(s):

Long-Biao Cui ◽

Yongbin Wei ◽

Yi-Bin Xi ◽

Alessandra Griffa ◽

Siemon C De Lange ◽

...

Keyword(s):

Network Architecture ◽

Functional Neuroimaging ◽

Brain Network ◽

First Episode ◽

Healthy Controls ◽

Cross Sectional ◽

Rich Club ◽

Functional Dynamics ◽

Neuroimaging Study ◽

First Episode Schizophrenia

Abstract Emerging evidence indicates that a disruption in brain network organization may play an important role in the pathophysiology of schizophrenia. The neuroimaging fingerprint reflecting the pathophysiology of first-episode schizophrenia remains to be identified. Here, we aimed at characterizing the connectome organization of first-episode medication-naïve patients with schizophrenia. A cross-sectional structural and functional neuroimaging study using two independent samples (principal dataset including 42 medication-naïve, previously untreated patients and 48 healthy controls; replication dataset including 39 first-episode patients [10 untreated patients] and 66 healthy controls) was performed. Brain network architecture was assessed by means of white matter fiber integrity measures derived from diffusion-weighted imaging (DWI) and by means of structural-functional (SC-FC) coupling measured by combining DWI and resting-state functional magnetic resonance imaging. Connectome rich club organization was found to be significantly disrupted in medication-naïve patients as compared with healthy controls (P = .012, uncorrected), with rich club connection strength (P = .032, uncorrected) and SC-FC coupling (P < .001, corrected for false discovery rate) decreased in patients. Similar results were found in the replication dataset. Our findings suggest that a disruption of rich club organization and functional dynamics may reflect an early feature of schizophrenia pathophysiology. These findings add to our understanding of the neuropathological mechanisms of schizophrenia and provide new insights into the early stages of the disorder.

Download Full-text

Morphology of the corpus callosum at different stages of schizophrenia: Cross-sectional study in first-episode and chronic illness

The British Journal of Psychiatry ◽

10.1192/bjp.bp.107.041251 ◽

2008 ◽

Vol 192 (6) ◽

pp. 429-434 ◽

Cited By ~ 56

Author(s):

Mark Walterfang ◽

Amanda G. Wood ◽

David C. Reutens ◽

Stephen J. Wood ◽

Jian Chen ◽

...

Keyword(s):

Corpus Callosum ◽

Chronic Schizophrenia ◽

Cross Sectional Study ◽

First Episode ◽

Schizophrenia Spectrum Disorders ◽

Cross Sectional ◽

Size And Shape ◽

Schizophrenia Spectrum ◽

First Episode Schizophrenia ◽

Parietal Cortices

BackgroundThe shape of the corpus callosum may differ in schizophrenia, although no study has compared first-episode with established illness.AimsTo investigate the size and shape of the corpus callosum in a large sample of people with first-episode and established schizophrenia.MethodCallosal size and shape were determined using highresolution magnetic resonance imaging on 76 patients with first-episode schizophrenia-spectrum disorders, 86 patients with established schizophrenia and 55 healthy participants.ResultsThere were no significant differences in total area across groups. Reductions in callosal width were seen in the region of the anterior genu in first-episode disorder (P<0.005). Similar reductions were seen in the chronic schizophrenia group in the anterior genu, but also in the posterior genu and isthmus (P = 0.0005).ConclusionsReductions in anterior callosal regions connecting frontal cortex are present at the onset of schizophrenia, and in established illness are accompanied by changes in other regions of the callosum connecting cingulate, temporal and parietal cortices.

Download Full-text