ZNF804A rs1344706 is associated with cortical thickness, surface area, and cortical volume of the unmedicated first episode schizophrenia and healthy controls

BackgroundReduced cortical gray-matter volume is commonly observed in patients with psychosis. Cortical volume is a composite measure that includes surface area, thickness and gyrification. These three indices show distinct maturational patterns and may be differentially affected by early adverse events. The study goal was to determine the impact of two distinct obstetrical complications (OCs) on cortical morphology.MethodA detailed birth history and MRI scans were obtained for 36 patients with first-episode psychosis and 16 healthy volunteers.ResultsPerinatal hypoxia and slow fetal growth were associated with cortical volume (Cohen's d = 0.76 and d = 0.89, respectively) in patients. However, the pattern of associations differed across the three components of cortical volume. Both hypoxia and fetal growth were associated with cortical surface area (d = 0.88 and d = 0.72, respectively), neither of these two OCs was related to cortical thickness, and hypoxia but not fetal growth was associated with gyrification (d = 0.85). No significant associations were found within the control sample.ConclusionsCortical dysmorphology was associated with OCs. The use of a global measure of cortical morphology or a global measure of OCs obscured important relationships between these measures. Gyrification is complete before 2 years and its strong relationship with hypoxia suggests an early disruption to brain development. Cortical thickness matures later and, consistent with previous research, we found no association between thickness and OCs. Finally, cortical surface area is largely complete by puberty and the present results suggest that events during childhood do not fully compensate for the effects of early disruptive events.

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Cortical Volume, Thickness, and Surface Area in the Motoric Cognitive Risk Syndrome

Journal of Alzheimer s Disease ◽

10.3233/jad-201576 ◽

2021 ◽

pp. 1-14

Author(s):

Helena M. Blumen ◽

Emily Schwartz ◽

Gilles Allali ◽

Olivier Beauchet ◽

Michele Callisaya ◽

...

Keyword(s):

Surface Area ◽

Sex Education ◽

Cortical Thickness ◽

Clinical Stage ◽

White Matter Lesions ◽

Cortical Atrophy ◽

Intracranial Volume ◽

Cortical Volume ◽

Cognitive Risk ◽

Cognitive Complaint

Background: The motoric cognitive risk (MCR) syndrome is a pre-clinical stage of dementia characterized by slow gait and cognitive complaint. Yet, the brain substrates of MCR are not well established. Objective: To examine cortical thickness, volume, and surface area associated with MCR in the MCR-Neuroimaging Consortium, which harmonizes image processing/analysis of multiple cohorts. Methods: Two-hundred MRIs (M age 72.62 years; 47.74%female; 33.17%MCR) from four different cohorts (50 each) were first processed with FreeSurfer 6.0, and then analyzed using multivariate and univariate general linear models with 1,000 bootstrapped samples (n-1; with resampling). All models adjusted for age, sex, education, white matter lesions, total intracranial volume, and study site. Results: Overall, cortical thickness was lower in individuals with MCR than in those without MCR. There was a trend in the same direction for cortical volume (p = 0.051). Regional cortical thickness was also lower among individuals with MCR than individuals without MCR in prefrontal, insular, temporal, and parietal regions. Conclusion: Cortical atrophy in MCR is pervasive, and include regions previously associated with human locomotion, but also social, cognitive, affective, and motor functions. Cortical atrophy in MCR is easier to detect in cortical thickness than volume and surface area because thickness is more affected by healthy and pathological aging.

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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.

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GREATER CORTICAL THICKNESS IN PATIENTS WITH FIRST-EPISODE SCHIZOPHRENIA WHO ARE RESPONSIVE TO ATYPICAL ANTIPSYCHOTICS

Schizophrenia Research ◽

10.1016/s0920-9964(08)70015-x ◽

2008 ◽

Vol 102 (1-3) ◽

pp. 5

Author(s):

Philip R. Szeszko ◽

Catherine L. Narr ◽

Owen R. Phillips ◽

Joanne McCormack ◽

Serge Sevy ◽

...

Keyword(s):

Cortical Thickness ◽

Atypical Antipsychotics ◽

First Episode ◽

First Episode Schizophrenia

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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.

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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.

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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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Cortical thickness and surface area correlates with cognitive dysfunction among first-episode psychosis patients

Psychological Medicine ◽

10.1017/s0033291716000684 ◽

2016 ◽

Vol 46 (10) ◽

pp. 2145-2155 ◽

Cited By ~ 8

Author(s):

L. Haring ◽

A. Müürsepp ◽

R. Mõttus ◽

P. Ilves ◽

K. Koch ◽

...

Keyword(s):

Structure Function ◽

Surface Area ◽

Cortical Thickness ◽

Brain Structure ◽

Brain Mri ◽

Brain Regions ◽

First Episode Psychosis ◽

First Episode ◽

Neurocognitive Performance ◽

Episode Psychosis

BackgroundIn studies using magnetic resonance imaging (MRI), some have reported specific brain structure–function relationships among first-episode psychosis (FEP) patients, but findings are inconsistent. We aimed to localize the brain regions where cortical thickness (CTh) and surface area (cortical area; CA) relate to neurocognition, by performing an MRI on participants and measuring their neurocognitive performance using the Cambridge Neuropsychological Test Automated Battery (CANTAB), in order to investigate any significant differences between FEP patients and control subjects (CS).MethodExploration of potential correlations between specific cognitive functions and brain structure was performed using CANTAB computer-based neurocognitive testing and a vertex-by-vertex whole-brain MRI analysis of 63 FEP patients and 30 CS.ResultsSignificant correlations were found between cortical parameters in the frontal, temporal, cingular and occipital brain regions and performance in set-shifting, working memory manipulation, strategy usage and sustained attention tests. These correlations were significantly dissimilar between FEP patients and CS.ConclusionsSignificant correlations between CTh and CA with neurocognitive performance were localized in brain areas known to be involved in cognition. The results also suggested a disrupted structure–function relationship in FEP patients compared with CS.

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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.

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