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

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 deficits and white matter abnormalities in never-treated first-episode schizophrenia

Translational Psychiatry ◽

10.1038/s41398-020-01049-0 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Mi Yang ◽

Shan Gao ◽

Xiangyang Zhang

Keyword(s):

Cognitive Impairment ◽

White Matter ◽

Diffusion Tensor ◽

Internal Capsule ◽

First Episode ◽

Control Group ◽

Pathophysiological Mechanism ◽

Healthy Controls ◽

Healthy Control ◽

First Episode Schizophrenia

Abstract Cognitive impairment is viewed as a core symptom of schizophrenia (SCZ), but its pathophysiological mechanism remains unclear. White matter (WM) disruption is considered to be a central abnormality that may contribute to cognitive impairment in SCZ patients. However, few studies have addressed the association between cognition and WM integrity in never-treated first-episode (NTFE) patients with SCZ. In this study, we used the MATRICS Consensus Cognitive Battery (MCCB) to evaluate cognitive function in NTFE patients (n = 39) and healthy controls (n = 30), and associated it with whole-brain fractional anisotropy (FA) values obtained via voxel-based diffusion tensor imaging. We found that FA was lower in five brain areas of SCZ patients, including the cingulate gyrus, internal capsule, corpus callosum, cerebellum, and brainstem. Compared with the healthy control group, the MCCB’s total score and 8 out of 10 subscores were significantly lower in NTFE patients (all p < 0.001). Moreover, in patients but not healthy controls, the performance in the Trail Making Test was negatively correlated with the FA value in the left cingulate. Our findings provide evidence that WM disconnection is involved in some cognitive impairment in the early course of SCZ.

Download Full-text

Diffusion tensor imaging study of the fornix in first episode schizophrenia and in healthy controls

Schizophrenia Research ◽

10.1016/j.schres.2014.04.022 ◽

2014 ◽

Vol 156 (2-3) ◽

pp. 157-160 ◽

Cited By ~ 19

Author(s):

J. Fitzsimmons ◽

H.M. Hamoda ◽

T. Swisher ◽

D. Terry ◽

G. Rosenberger ◽

...

Keyword(s):

Diffusion Tensor Imaging ◽

Diffusion Tensor ◽

Imaging Study ◽

First Episode ◽

Healthy Controls ◽

First Episode Schizophrenia ◽

Diffusion Tensor Imaging Study

Download Full-text

A diffusion tensor imaging study of structural dysconnectivity in never-medicated, first-episode schizophrenia

Psychological Medicine ◽

10.1017/s0033291707001808 ◽

2007 ◽

Vol 38 (6) ◽

pp. 877-885 ◽

Cited By ~ 143

Author(s):

V. Cheung ◽

C. Cheung ◽

G. M. McAlonan ◽

Y. Deng ◽

J. G. Wong ◽

...

Keyword(s):

Diffusion Tensor Imaging ◽

White Matter ◽

Corpus Callosum ◽

Diffusion Tensor ◽

Structural Connectivity ◽

First Episode ◽

Cerebral Peduncle ◽

Healthy Controls ◽

Subcortical Region ◽

First Episode Schizophrenia

BackgroundDiffusion tensor imaging (DTI) can be used to investigate cerebral structural connectivity in never-medicated individuals with first-episode schizophrenia.MethodSubjects with first-episode schizophrenia according to DSM-IV-R who had never been exposed to antipsychotic medication (n=25) and healthy controls (n=26) were recruited. Groups were matched for age, gender, best parental socio-economic status and ethnicity. All subjects underwent DTI and structural magnetic resonance imaging (MRI) scans. Voxel-based analysis was performed to investigate brain regions where fractional anisotropy (FA) values differed significantly between groups. A confirmatory region-of-interest (ROI) analysis of FA scores was performed in which regions were placed blind to group membership.ResultsIn patients, FA values significantly lower than those in healthy controls were located in the left fronto-occipital fasciculus, left inferior longitudinal fasciculus, white matter adjacent to right precuneus, splenium of corpus callosum, right posterior limb of internal capsule, white matter adjacent to right substantia nigra, and left cerebral peduncle. ROI analysis of the corpus callosum confirmed that the patient group had significantly lower mean FA values than the controls in the splenium but not in the genu. The intra-class correlation coefficient (ICC) for independent ROI measurements was 0.90 (genu) and 0.90 (splenium). There were no regions where FA values were significantly higher in the patients than in the healthy controls.ConclusionsWidespread structural dysconnectivity, including the subcortical region, is already present in neuroleptic-naive patients in their first episode of illness.

Download Full-text

Brain age prediction reveals aberrant brain white matter in schizophrenia and bipolar disorder: A multi-sample diffusion tensor imaging study

10.1101/607754 ◽

2019 ◽

Cited By ~ 1

Author(s):

Siren Tønnesen ◽

Tobias Kaufmann ◽

Ann-Marie de Lange ◽

Genevieve Richard ◽

Nhat Trung Doan ◽

...

Keyword(s):

Diffusion Tensor Imaging ◽

White Matter ◽

Diffusion Tensor ◽

Imaging Study ◽

Brain Maturation ◽

Group Differences ◽

Healthy Controls ◽

Brain White Matter ◽

Brain Age ◽

Age Prediction

AbstractBackgroundSchizophrenia (SZ) and bipolar disorders (BD) share substantial neurodevelopmental components affecting brain maturation and architecture. This necessitates a dynamic lifespan perspective in which brain aberrations are inferred from deviations from expected lifespan trajectories. We applied machine learning to diffusion tensor imaging (DTI) indices of white matter structure and organization to estimate and compare brain age between patients with SZ, BD, and healthy controls across 10 cohorts.MethodsWe trained six cross-validated models using different combinations of DTI data from 927 healthy controls (HC, 18-94 years), and applied the models to the test sets including 648 SZ (18-66 years) patients, 185 BD patients (18-64 years), and 990 HC (17-68 years), estimating brain age for each participant. Group differences were assessed using linear models, accounting for age, sex, and scanner. A meta-analytic framework was applied to assess the heterogeneity and generalizability of the results.Results10-fold cross-validation revealed high accuracy for all models. Compared to controls, the model including all feature sets significantly over-estimated the age of patients with SZ (d=-.29) and BD (d=.18), with similar effects for the other models. The meta-analysis converged on the same findings. Fractional anisotropy (FA) based models showed larger group differences than the models based on other DTI-derived metrics.ConclusionsBrain age prediction based on DTI provides informative and robust proxies for brain white matter integrity. Our results further suggest that white matter aberrations in SZ and BD primarily consist of anatomically distributed deviations from expected lifespan trajectories that generalize across cohorts and scanners.

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