scholarly journals A Multimodal Fusion Analysis of Pretreatment Anatomical and Functional Cortical Abnormalities in Responsive and Non-responsive Schizophrenia

2021 ◽  
Vol 12 ◽  
Author(s):  
Chenyang Yao ◽  
Na Hu ◽  
Hengyi Cao ◽  
Biqiu Tang ◽  
Wenjing Zhang ◽  
...  
Keyword(s):  
Multimodal Fusion ◽  
First Episode ◽  
Antipsychotic Treatment ◽  
Pathophysiological Mechanism ◽  
Multimodal Features ◽  
Significant Difference ◽  
Postcentral Gyrus ◽  
Functional Features ◽  
Fusion Analysis ◽  
The Right

Background: Antipsychotic medications provide limited long-term benefit to ~30% of schizophrenia patients. Multimodal magnetic resonance imaging (MRI) data have been used to investigate brain features between responders and nonresponders to antipsychotic treatment; however, these analytical techniques are unable to weigh the interrelationships between modalities. Here, we used multiset canonical correlation and joint independent component analysis (mCCA + jICA) to fuse MRI data to examine the shared and specific multimodal features between the patients and healthy controls (HCs) and between the responders and non-responders.Method: Resting-state functional and structural MRI data were collected from 55 patients with drug-naïve first-episode schizophrenia (FES) and demographically matched HCs. Based on the decrease in Positive and Negative Syndrome Scale scores from baseline to the 1-year follow-up, FES patients were divided into a responder group (RG) and a non-responder group (NRG). Gray matter volume (GMV), fractional amplitude of low-frequency fluctuation (fALFF), and regional homogeneity (ReHo) maps were used as features in mCCA + jICA.Results: Between FES patients and HCs, there were three modality-specific discriminative independent components (ICs) showing the difference in mixing coefficients (GMV-IC7, GMV-IC8, and fALFF-IC5). The fusion analysis indicated one modality-shared IC (GMV-IC2 and ReHo-IC2) and three modality-specific ICs (GMV-IC1, GMV-IC3, and GMV-IC6) between the RG and NRG. The right postcentral gyrus showed a significant difference in GMV features between FES patients and HCs and modality-shared features (GMV and ReHo) between responders and nonresponders. The modality-shared component findings were highlighted by GMV, mainly in the bilateral temporal gyrus and the right cerebellum associated with ReHo in the right postcentral gyrus.Conclusions: This study suggests that joint anatomical and functional features of the cortices may reflect an early pathophysiological mechanism that is related to a 1-year treatment response.

Early striatal hypertrophy in first-episode psychosis within 3 weeks of initiating antipsychotic drug treatment

2008 ◽  
Vol 39 (5) ◽  
pp. 793-800 ◽  
Author(s):  
S. E. Chua ◽  
Y. Deng ◽  
E. Y. H. Chen ◽  
C. W. Law ◽  
C. P. Y. Chiu ◽  
...  
Keyword(s):  
Antipsychotic Medication ◽  
Grey Matter ◽  
Economic Status ◽  
Region Of Interest ◽  
Brain Morphology ◽  
Group Differences ◽  
First Episode ◽  
Antipsychotic Treatment ◽  
Caudate Nuclei ◽  
The Right

BackgroundWe and others have reported that patients experiencing their first episode of psychosis already have significant structural brain abnormalities. Antipsychotics seem to reverse subcortical volume deficits after months of treatment. However, the early impact of medication on brain morphology is not known.MethodForty-eight individuals in their first episode of psychosis underwent magnetic resonance imaging (MRI) brain scanning. Twenty-six were antipsychotic naive and 22 were newly treated with antipsychotic medication for a median period of 3 weeks. In each group, 80% of subjects received a diagnosis of schizophrenia. The two groups were balanced for age, sex, handedness, ethnicity, height, years of education, paternal socio-economic status (SES) and Positive and Negative Syndrome Scale (PANSS) score. Group differences in whole-brain grey matter were compared voxel by voxel, using Brain Activation and Morphological Mapping (BAMM) software. We also conducted testing of group differences with region-of-interest (ROI) measurements of the caudate nucleus.ResultsRelative to the untreated group, those receiving antipsychotic medication for 3–4 weeks had significantly greater grey-matter volumes in the bilateral caudate and cingulate gyri, extending to the left medial frontal gyrus. ROI analysis confirmed that, in treated patients, the right and left caudate nuclei were significantly larger by 10% (p<0.039, two-tailed) and 9% (p<0.048, two-tailed) respectively.ConclusionsEarly striatal grey-matter enlargement may occur within the first 3–4 weeks of antipsychotic treatment. Possible reasons for putative striatal hypertrophy and its implications are discussed.

scholarly journals Antipsychotic drugs increase Neuregulin1b1 serum levels in first-episode drug-naïve patients and chronic schizophrenia with suggestions for improving the treatment of psychotic symptoms

2021 ◽  
Author(s):  
Haidong Yang ◽  
Wen Pan ◽  
Wenhuan Xiao ◽  
Man Yang ◽  
Jianchun Xu ◽  
...  
Keyword(s):  
Antipsychotic Drugs ◽  
Chronic Schizophrenia ◽  
Serum Levels ◽  
Psychotic Symptoms ◽  
First Episode ◽  
Antipsychotic Treatment ◽  
Therapeutic Effects ◽  
Pathophysiological Mechanism ◽  
Healthy Controls ◽  
Drug Naïve

Abstract Background: Neuregulin1 (NRG1) plays a role in neuronal migration, regulation of synaptic plasticity, and neural survival, and has been considered to be among the candidate genes for schizophrenia. This study focused on the variations in serum NRG1b1 levels following antipsychotic treatment and the relationship between NRG1b1 level and improvements in psychotic symptoms in first-episode drug-naïve (FEDN) patients and chronic schizophrenia.Methods: A total of 100 patients with schizophrenia were recruited and compared with 79 matched healthy controls. All patients had been drug-naïve for at least four weeks. Serum NRG1b1 levels and positive and negative syndrome scale (PANSS) scores were measured at the baseline and after four weeks. Serum NRG1b1 levels were measured using sandwich enzyme-linked immunosorbent assays (ELISA).Results: Baseline NRG1b1 levels were significantly lower in the patients with schizophrenia compared with the healthy controls. NRG1b1 levels increased significantly following antipsychotic treatment. NRG1b1 levels gradually increased with declining PANSS scores and its three subscales during antipsychotic therapy. The levels of NRG1b1 increased significantly in responders after four weeks of treatment, although non-responders showed no such effect. Correlation analyses showed that the levels of NRG1b1 were negatively correlated with the duration of illness and positively correlated with improvement in symptoms.Conclusion: The levels of serum NRG1b1 and the therapeutic effects gradually increased following treatment, indicating that NRG1b1 may be an indicator of therapy, and that it may also be associated with the pathophysiological mechanism causing schizophrenia, although this possible pathway requires further investigation. Antipsychotic drugs increase Neuregulin1b1 serum levels in first-episode drug-naïve patients and chronic schizophrenia with suggestions for improving the treatment of psychotic symptoms

Sexual Dysfunction in Unmedicated Patients with Schizophrenia and in Healthy Controls

2018 ◽  
Vol 51 (06) ◽  
pp. 251-256 ◽  
Author(s):  
Theresa Dembler-Stamm ◽  
Jana Fiebig ◽  
Andreas Heinz ◽  
Jürgen Gallinat
Keyword(s):  
Sexual Dysfunction ◽  
Gender Effects ◽  
First Episode ◽  
Antipsychotic Treatment ◽  
Healthy Controls ◽  
Cross Sectional ◽  
Sexual Activities ◽  
Medication Effects ◽  
Significant Difference ◽  
And Gender

Abstract Introduction Sexual dysfunction figures prominently in patients with schizophrenia; however, medication effects may play a role. The objective of this case control study was to assess differences in the presence of sexual dysfunction in unmedicated patients with schizophrenia versus healthy controls. Methods Sexual dysfunction was assessed using the Derogatis Inventory for Sexual Function self-rating in a cross-sectional design controlling for age and gender effects. A brief sexual anamnesis was applied to describe the psychosocial background of the mostly male sample further. Results Results show a significant difference with patients reporting more problems in most domains and with a significant correlation between severity of psychosis (Positive and Negative Syndrome Scale total scores) and the impairment of orgasm experience. The study revealed reduced sexual activities and less pleasure during sexual activities of patients. Discussion This study implies that schizophrenia has an impact on the presence of sexual dysfunction and that sexual dysfunction is partly independent of antipsychotic treatment. Since the sample consisted mostly of first-episode males, conclusions might only be valid for this subgroup.

scholarly journals Changes in Brain Structure, Function, and Network Properties in Patients With First-Episode Schizophrenia Treated With Antipsychotics

2021 ◽  
Vol 12 ◽  
Author(s):  
Ping Yin ◽  
Chao Zhao ◽  
Yang Li ◽  
Xiaoyi Liu ◽  
Lei Chen ◽  
...  
Keyword(s):  
Structure Function ◽  
Clinical Symptoms ◽  
First Episode ◽  
Antipsychotic Treatment ◽  
Precentral Gyrus ◽  
Inferior Parietal Lobule ◽  
Network Properties ◽  
Parietal Lobule ◽  
The Right ◽  
First Episode Schizophrenia

Purpose: Comprehensive and longitudinal brain analysis is of great significance for understanding the pathological changes of antipsychotic drug treatment in patients with schizophrenia. This study aimed to investigate the changes of structure, function, and network properties in patients with first-episode schizophrenia (FES) after antipsychotic therapy and their relationship with clinical symptoms.Materials and Methods: A total of 30 patients diagnosed with FES and 30 healthy subjects matched for sex and age were enrolled in our study. Patients at baseline were labeled as antipsychotic-naive first-episode schizophrenia (AN-FES), and patients after antipsychotic treatment were labeled as antipsychotic treatment first-episode schizophrenia (AT-FES). The severity of illness was measured by using the PANSS and CGI score. Structural and functional MRI data were also performed. Differences in GMV, ALFF, and ReHo between the FES group and healthy control group were tested using a voxel-wise two-sample t-test, and the comparison of AN-FES group and AT-FES group was evaluated by paired-sample t-test.Results: After the 1-year follow-up, the FES patients showed increased GMV in the right cerebellum, right inferior temporal gyrus, left middle frontal gyrus, parahippocampal gyrus, bilateral inferior parietal lobule, and reduced GMV in the left occipital lobe, gyrus rectus, right orbital frontal cortex. The patients also showed increased ALFF in the medial superior frontal gyrus and right precentral gyrus. For network properties, the patients showed reduced characteristic path length and increased global efficiency. The GMV of the right inferior parietal lobule was negatively correlated with the clinical symptoms.Conclusions: Our study showed that the antipsychotic treatment contributed to the structural alteration and functional improvement, and the GMV alteration may be associated with the improvement of clinical symptoms.

scholarly journals Gut microbial biomarkers for the treatment response in first-episode, drug-naïve schizophrenia: a 24-week follow-up study

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Xiuxia Yuan ◽  
Yunpeng Wang ◽  
Xue Li ◽  
Jiajun Jiang ◽  
Yulin Kang ◽  
...  
Keyword(s):  
Treatment Response ◽  
First Episode ◽  
Antipsychotic Treatment ◽  
Follow Up Study ◽  
Α Diversity ◽  
Microbial Biomarkers ◽  
Significant Difference ◽  
Drug Naïve ◽  
Risperidone Treatment

AbstractPreclinical studies have shown that the gut microbiota can play a role in schizophrenia (SCH) pathogenesis via the gut-brain axis. However, its role in the antipsychotic treatment response is unclear. Here, we present a 24-week follow-up study to identify gut microbial biomarkers for SCH diagnosis and treatment response, using a sample of 107 first-episode, drug-naïve SCH patients, and 107 healthy controls (HCs). We collected biological samples at baseline (all participants) and follow-up time points after risperidone treatment (SCH patients). Treatment response was assessed using the Positive and Negative Symptoms Scale total (PANSS-T) score. False discovery rate was used to correct for multiple testing. We found that SCH patients showed lower α-diversity (the Shannon and Simpson’s indices) compared to HCs at baseline (p = 1.21 × 10−9, 1.23 × 10−8, respectively). We also found a significant difference in β-diversity between SCH patients and HCs (p = 0.001). At baseline, using microbes that showed different abundance between patients and controls as predictors, a prediction model can distinguish patients from HCs with an area under the curve (AUC) of 0.867. In SCH patients, after 24 weeks of risperidone treatment, we observed an increase of α-diversity toward the basal level of HCs. At the genus level, we observed decreased abundance of Lachnoclostridium (p = 0.019) and increased abundance Romboutsia (p = 0.067). Moreover, the treatment response in SCH patients was significantly associated with the basal levels of Lachnoclostridium and Romboutsia (p = 0.005 and 0.006, respectively). Our results suggest that SCH patients may present characteristic microbiota, and certain microbiota biomarkers may predict treatment response in this patient population.

Neurotrophic proteins and symptom profile in psychotic disorders

2011 ◽  
Vol 26 (S2) ◽  
pp. 1523-1523
Author(s):  
N. van de Kerkhof ◽  
D. Fekkes ◽  
F. van der Heijden ◽  
W.M.A. Verhoeven
Keyword(s):  
Treatment Effect ◽  
Psychotic Disorders ◽  
Serum Levels ◽  
First Episode Psychosis ◽  
Psychotic Symptoms ◽  
First Episode ◽  
Antipsychotic Treatment ◽  
Symptom Profile ◽  
Episode Psychosis ◽  
Significant Difference

BackgroundPsychotic disorders are highly prevalent and are treated with antipsychotics. There are no biological markers to predict or measure treatment effects. Research to neurotrophic proteins Brain Derived Neurotrophic Factor (BDNF) and S100B demonstrated association with psychotic symptoms and suggested association with treatment outcome and symptomatology.ObjectivesInvestigate the relevance of neurotrophic proteins BDNF and S100B in patients with psychotic disorders treated with antipsychotics.AimsPrimary objective is to investigate the relationship between serum levels of BDNF and S100B and symptomatology at baseline and after six weeks of treatment. Furthermore, a detailed evaluation of symptom profile and treatment effect is performed.Methods80 patients with acute and chronic psychotic disorder were evaluated during six weeks while receiving antipsychotic treatment of any kind. Symptomatology was assessed using CASH, PANSS and CGI-S/I. Biochemical parameters were determined at baseline and after six weeks. Symptomatology and treatment effect were related to biochemical results.ResultsPreliminary analyses show an overall treatment response of 19% (reduction of PANSS). A significant difference was found at baseline between patients with first-episode psychosis and patients with relapse or chronic psychosis (BDNF 12,4 vs. 21,7μg/l P ≤ 0,01, S100B 0,1055 vs. 0,05937 μg/l, P < 0,05). During treatment, serum levels of neurotrophic proteins returned to normal values in both groups.ConclusionsSix weeks of antipsychotic treatment results in a modest symptomatic improvement. In subgroups with first episode psychosis, S100B levels are higher and BDNF levels are lower. The normalization of both serum levels suggests an effect of antipsychotic treatment on brain neurochemical processes.

Dysfunction of a distributed neural circuitry in schizophrenia patients during a working-memory performance

2005 ◽  
Vol 35 (2) ◽  
pp. 187-196 ◽  
Author(s):  
A. MENDREK ◽  
K. A. KIEHL ◽  
A. M. SMITH ◽  
D. IRWIN ◽  
B. B. FORSTER ◽  
...  
Keyword(s):  
Working Memory ◽  
Memory Performance ◽  
Memory Task ◽  
Anterior Cingulate ◽  
First Episode ◽  
Antipsychotic Treatment ◽  
Compensatory Mechanism ◽  
Control Subjects ◽  
Left Dlpfc ◽  
The Right

Background. In a recent longitudinal study of first-episode schizophrenia patients, we found that while dysfunction of the right dorsolateral prefrontal cortex (DLPFC), right thalamus, left cerebellum and cingulate gyrus normalized with antipsychotic treatment and significant reduction in symptomatology, the left DLPFC, left thalamus, and right cerebellum remained disturbed. In the present study we investigated whether these abnormalities are also present in clinically stable, relatively well-functioning schizophrenia patients in comparison to control subjects during performance of the N-back working-memory task.Method. Twelve schizophrenia and 12 control subjects completed the study. The functional images collected during scanning were analyzed using a random-effects model in a restricted set of six regions of interest (ROIs). In addition, the exploratory search in the entire brain volume was performed.Results. The ROI analyses revealed relative underactivation in the region of the left DLPFC and the right cerebellum, as well as overactivation in the left cerebellum. The exploratory whole-brain search exposed additional overactivation in the medial frontal, anterior cingulate, and left parietal cortices.Conclusions. The present study provides evidence of significant underactivations in stable schizophrenia patients in regions that we have previously observed to be dysfunctional in acutely psychotic and partially remitted patients, together with extensive overactivations in several regions that potentially reflect some compensatory mechanism or increased effort on the working-memory task.

scholarly journals T24. CHANGES IN TELOMERE LENGTH IN YOUNG PEOPLE WITH FIRST EPISODE PSYCHOSIS: A 12-MONTHS FOLLOW-UP STUDY

2020 ◽  
Vol 46 (Supplement_1) ◽  
pp. S240-S240
Author(s):  
Mirian Ayora ◽  
David Fraguas ◽  
Sandra Recio ◽  
Covadonga M Diaz-Caneja ◽  
Maria A Blasco ◽  
...  
Keyword(s):  
Telomere Length ◽  
Young Patients ◽  
Cellular Aging ◽  
First Episode ◽  
Psychotic Episode ◽  
Antipsychotic Treatment ◽  
Published Data ◽  
Healthy Controls ◽  
Significant Difference

Abstract Background Cellular aging is associated with the appearance of several chronic organic diseases, and many neuropsychiatric disorders such as schizophrenia spectrum disorders, which include psychotic disorders. Telomeres are one of the biomarkers of this cellular aging. Researches have shown that shorter telomere length is a biomarker of oxidation and cellular aging. Recent studies have concluded that patients with a first psychotic episode (FEP) have shorter telomere length than healthy controls (HC). However, there is no published data on the change in telomere length in the first years of illness. The purpose of this study is to evaluate the changes in telomere length measured in peripheral blood mononuclear cells (PBMCs) in a sample of patients with early-onset psychosis and healthy subjects. Methods This study included 10 young patients with FEP (50% female, mean age 18.4 years) and 10 young HC (60% female, mean age 16.4 years). PBMCs telomere length was determined using high-throughput quantitative fluorescence in situ hybridization (HT Q-FISH) at baseline and 12-month follow-up. We analysed in our sample of patients if there are significant differences according to the diagnosis and antipsychotic treatment. Results At baseline, we did not find significant differences in telomere length between FEP patients and HC. After one-year follow-up, it was found that telomere length is shorter in patients with FEP than in HC (p=0.007). The diagnostics in the patients’ group were: 60% schizophrenia and 40% other diagnoses (20% psychosis not specified and 20% bipolar disorder). There was no significant difference between changes in telomeres length and diagnosis (p = 0.840). The antipsychotic treatment in the patients’ group after 12 months was: 20% risperidone, 50% aripiprazole, 10% clozapine, 10% paliperidone and 10% quetiapine. We didn′t find a strong association between the shortening of telomeres and the cumulative dose of antipsychotics. Discussion This is one of the first studies where it has been analysed a longitudinal data of telomere length. It is shown that patients with the first episode of psychosis have significantly shorter telomere length than healthy controls. Changes in telomere length during the first years of illness can represent an early marker of accelerated cellular aging. Further studies are needed with a larger sample to know mechanisms responsible for accelerating aging and the role of oxidative stress in the pathogenesis of psychosis.

P02 - 360 Magnetic resonance imaging study of basal ganglia in the first-episode tic disorders onset during child and adolescent

2011 ◽  
Vol 26 (S2) ◽  
pp. 956-956
Author(s):  
J. Sun ◽  
L. Guo ◽  
M. Huang ◽  
X. Huang ◽  
Q. Gong
Keyword(s):  
Basal Ganglia ◽  
Globus Pallidus ◽  
Asymmetry Index ◽  
Tic Disorders ◽  
First Episode ◽  
Intracranial Volume ◽  
Course Of Disease ◽  
Significant Difference ◽  
Tic Severity ◽  
The Right

IntroductionDespite strong evidence that the pathophysiology of tic disorders (TD) involves structural and functional disturbances of the basal ganglia, inconsistent findings from several TD imaging studies have supported contradictory conclusions.ObjectiveTo find brain structural differences between children with of TD and the health children and verify the pathogenesis hypothesis of that basal ganglia play an important role in this disorder.MethodThe right handedness, first-episode TD children were chosen. Yale global tic severity scale (YGTSS) was used to assess the tic severity. MRI scan was performed on TD children and the controls. The volumes of caudate nucleus, putamen, globus pallidus and total intracranial volume were measured on high resolution MR images. We compared the volumes, relative volumes and asymmetry index, AI between groups.ResultsTotally 11 patients finished this study with two excluded for the unclear image caused by tic and 18 subjects (9 TD patients and 9 controls) were finally analyzed. The right globus pallidus is significantly larger in TD patients. The volumes of left caudate increased significantly in both TD patients and controls. There was no significant difference in asymmetry index between two groups, relative volumes did not correlate significantly with the severity of tic and the course of disease.ConclusionThe right globus pallidus may be the primary pathological change of TD. Asymmetry indexes between the two groups are not significantly different. The relative volume of any structure of basal ganglia has no significant correlation with the severity of tic and the course of disease.

Effects of Antipsychotic Treatment on S100B and Oxidative Stress in Patients with Schizophrenia

2019 ◽  
pp. 120-127
Author(s):  
Xuan Wang ◽  
Yun Bian ◽  
Lei Liu ◽  
Yaxue Wu ◽  
Fude Yang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Acute Phase ◽  
Random Effect Model ◽  
First Episode ◽  
Antipsychotic Treatment ◽  
Significant Difference ◽  
Patient Groups ◽  
Drug Naïve ◽  
Drug Free ◽  
And Oxidative Stress

Background: The study aimed to examine the antipsychotic treatment effect on the serum S100B and oxidative stress in patients with schizophrenia. Methods: Subjects consisted of patients with schizophrenia of first-episode drug-naive and drug-free acute phases, and met the DSM-IV diagnostic criteria for schizophrenia. All patients were treated with risperidone for eight weeks. Positive and Negative Syndrome Scale (PANSS) was evaluated, and serum levels of S100B and parameters of oxidative stress including total oxidative status (TOS) and malondialdehyde (MDA) were measured before and after antipsychotic treatment. A general linear random-effect model was used for data analysis. Results: Antipsychotic treatment with risperidone reduced the levels of S100B significantly in the first episode drug-naive patients with schizophrenia (Beta=24.89; p=0.0087) and marginally in the drug-free acute phase (Beta=15.65; p=0.093), no significant difference in the effect on S100B between patient groups (p=0.4785). In contrast, antipsychotic treatment increased the levels of MDA in drug-free acute phase schizophrenia (Beta=-6.55; p<0.0001) but not in the first episode drug-naive patients (beta=-0.57; p=0.6631); the effects on MDA were significantly different between two patient groups (p=0.0020). We found that the levels of S100B were only associated with the PANSS negative score in the drug-free acute phase patients who were treated with antipsychotics. Conclusion: Antipsychotic treatment with risperidone reduced the levels of S100B in first-episode, drug-naive patients with schizophrenia, but may increase the levels of MDA in drug-free acute phase schizophrenia.

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