Altered Peripheral Immune Profiles in First-Episode, Drug-Free Patients With Schizophrenia: Response to Antipsychotic Medications.
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ABSTRACT:
SUBMITTER: Chen L
PROVIDER: S-EPMC8652082 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Analyzing the schizophrenia connectome can identify illness-related alterations in connectivity across the brain. An important question that remains unanswered is whether connectivity alterations are already evident at the onset of illness, before treatment with antipsychotic medication and possible influences of neuroprogressive or secondary alterations related to chronic illness duration. In the present study, diffusion tensor imaging and deterministic fiber tractography were performed with 137 antipsychotic-naive first-episode schizophrenia patients and 113 matched healthy controls. Using graph theoretic analysis, groups were compared in global and regional measurements and modularity of white matter connectivity. Compared with controls, the patients showed significantly decreased total connection strength. Furthermore, patients demonstrated significantly decreased connections within and between brain modules. Several local brain regions within association cortex exhibited reduced nodal centralities and abnormal participant coefficient or intra-module degree, some of which were correlated with illness duration and overall functional disability. In never-treated schizophrenia patients, networks showed a less effective organizational pattern of white matter pathways. White matter disconnectivity occurred not only within but also between multiple modules, shedding light on the deficits of anatomical network organization early in the course of schizophrenia.
| S-EPMC5814807 | biostudies-other
Project description:ObjectiveTo investigate the gender differences in the efficacy and side effects of three frequently used antipsychotic medicines (risperidone, olanzapine, aripiprazole) for patients with first-episode schizophrenia during the first year of treatment.MethodsA total of 569 patients with first-episode schizophrenia were randomly assigned to risperidone, olanzapine, and aripiprazole groups. All patients were treated according to their actual clinical needs. Clinical efficacies were assessed by the Positive and Negative Symptom Scale (PANSS) and side effects were assessed by the Udvalg for Kliniske Undersogelser Side-Effect scale (UKU). All assessments were completed at baseline and at 1, 2, 3, 6, 9, and 12 months.ResultsMales had higher baseline PANSS total scores and PANSS negative and general pathological scores. No significant interactions were found between treatment time and gender in psychopathology improvements in all three groups. In the end of the first year, female patients receiving risperidone reported more dermatological symptoms (rashes) than males, female patients receiving olanzapine reported more autonomic side effects and dermatological symptoms than males, and female patients receiving aripiprazole reported more psychotic side effects than males.ConclusionGender differences exhibited in response to antipsychotic treatments for Chinese patients with first-episode schizophrenia. After the first year of antipsychotic treatment, drug-related side effects were more likely presented in female patients than male patients.
| S-EPMC7751687 | biostudies-literature
Project description:Background:The investigation of large-scale intrinsic connectivity networks in antipsychotic-naïve first-episode schizophrenia increases our understanding of system-level cerebral dysfunction in schizophrenia while enabling control of confounding effects of medication and disease progression. Reports on functional connectivity in antipsychotic-naïve patients have been mixed and the relation between network alterations, psychopathology and cognition is unclear. Methods:A total number of 47 patients with first-episode schizophrenia who had never received antipsychotic medication and 47 healthy controls were scanned with functional magnetic resonance imaging under resting conditions. Main outcome measures were differences in functional connectivity between groups and the relationship between network alterations, psychopathology and cognition. Results:Altered connectivity was found between right central executive network (CEN) and right ventral attention network (VAN) (patients > controls, P = .001), left CEN and left VAN (P = .002), and between posterior default mode network and auditory network (P = .006). Association between network connectivity and clinical characteristics was found as interactions between the effects of group and sustained attention (P = .005) and between group and processing speed (P = .007) on the connectivity between right CEN and right VAN. Conclusions:Our findings suggest that the early phase of schizophrenia is characterized by increased connectivity between fronto-parietal networks suggested to be involved in the control of cognitive and sensory functions. Moreover, the present study suggests that the problem of not disengaging the VAN leads to difficulties with attention and possibly subjective awareness.
| S-EPMC6192505 | biostudies-literature
Project description:BackgroundEnlarged ventricles and reduced hippocampal volume are consistently found in patients with first-episode schizophrenia. Studies investigating brain structure in antipsychotic-naive patients have generally focused on the striatum. In this study, we examined whether ventricular enlargement and hippocampal and caudate volume reductions are morphological traits of antipsychotic-naive first-episode schizophrenia.MethodsWe obtained high-resolution 3-dimensional T1-weighted magnetic resonance imaging scans for 38 antipsychotic-naive first-episode schizophrenia patients and 43 matched healthy controls by use of a 3-T scanner. We warped the brain images to each other by use of a high-dimensional intersubject registration algorithm. We performed voxel-wise group comparisons with permutation tests. We performed small volume correction for the hippocampus, caudate and ventricles by use of a false discovery rate correction (p < 0.05) to control for multiple comparisons. We derived and analyzed estimates of brain structure volumes. We grouped patients as those with (n = 9) or without (n = 29) any lifetime substance abuse to examine the possible effects of substance abuse.ResultsWe found that hippocampal and caudate volumes were decreased in patients with first-episode schizophrenia. We found no ventricular enlargement, differences in global volume or significant associations between tissue volume and duration of untreated illness or psychopathology. The hippocampal volume reductions appeared to be influenced by a history of substance abuse. Exploratory analyses indicated reduced volume of the nucleus accumbens in patients with first-episode schizophrenia.LimitationsThis study was not a priori designed to test for differences between schizophrenia patients with or without lifetime substance abuse, and this subgroup was small.ConclusionReductions in hippocampal and caudate volume may constitute morphological traits in antipsychotic-naive first-episode schizophrenia patients. However, the clinical implications of these findings are unclear. Moreover, past substance abuse may accentuate hippocampal volume reduction. Magnetic resonance imaging studies addressing the potential effects of substance abuse in antipsychotic-naive first-episode schizophrenia patients are warranted.
| S-EPMC2834791 | biostudies-literature
Project description:BACKGROUND:Long-term treatment with antipsychotic medications in early episode schizophrenia spectrum disorders is common, but both short and long-term effects on the illness are unclear. There have been numerous suggestions that people with early episodes of schizophrenia appear to respond differently than those with multiple prior episodes. The number of episodes may moderate response to drug treatment. OBJECTIVES:To assess the effects of antipsychotic medication treatment on people with early episode schizophrenia spectrum disorders. SEARCH STRATEGY:We searched the Cochrane Schizophrenia Group register (July 2007) as well as references of included studies. We contacted authors of studies for further data. SELECTION CRITERIA:Studies with a majority of first and second episode schizophrenia spectrum disorders comparing initial antipsychotic medication treatment with placebo, milieu, or psychosocial treatment. DATA COLLECTION AND ANALYSIS:Working independently, we critically appraised records from 681studies, of which five studies met inclusion criteria. John Rathbone from the Schizophrenia Group supported us with the data extraction. We calculated risk ratios (RR) and their 95% confidence intervals (CI) where possible. For continuous data, we calculated mean difference (MD). We calculated numbers needed to treat/harm (NNT/NNH) where appropriate. MAIN RESULTS:Five studies with a combined N = 998 met inclusion criteria. Four studies (N = 724) provided leaving the study early data and results suggested that individuals treated with a typical antipsychotic medication are less likely to leave the study early than those treated with placebo (Chlorpromazine: 3 RCTs N = 353, RR 0.4 CI 0.3 to 0.5, NNT 3.2, Fluphenaxine: 1 RCT N = 240, RR 0.5 CI 0.3 to 0.8, NNT 5; Thioridazine: 1 RCT N = 236, RR 0.44 CI 0.3 to 0.7, NNT 4.3, Trifulperazine: 1 RCT N = 94, RR 0.96 CI 0.3 to 3.6). Two studies (Cole 1964; May 1976) contributed data to assessment of side effects and present a general pattern of more frequent side effects among individuals treated with typical antipsychotic medications compared to placebo. Rappaport 1978 suggested a higher rehospitalisation rate for those receiving chlorpromazine compared to placebo (N = 80, RR 2.29 CI 1.3 to 4.0, NNH 2.9). However, a higher attrition in the placebo group is likely to have introduced a survivor bias into this comparison, as this difference becomes non-significant in a sensitivity analysis on intent-to-treat participants (N = 127, RR 1.69 CI 0.9 to 3.0). One study (May 1976) contributes data to a comparison of trifluoperazine to psychotherapy on long-term health in favour of the trifluoperazine group (N = 92, MD 5.8 CI 1.6 to 0.0); however, data from this study are also likely to contain biases due to selection and attrition. One study (Mosher 1995) contributes data to a comparison of typical antipsychotic medication to psychosocial treatment on six-week outcome measures of global psychopathology (N = 89, MD 0.01 CI -0.6 to 0.6) and global improvement (N = 89, MD -0.03 CI -0.5 to 0.4), indicating no between-group differences. On the whole, there is very little useable data in the few studies meeting inclusion criteria. AUTHORS' CONCLUSIONS:With only a few studies meeting inclusion criteria, and with limited useable data in these studies, it is not possible to arrive at definitive conclusions. The preliminary pattern of evidence suggests that people with early episode schizophrenia treated with typical antipsychotic medications are less likely to leave the study early, but more likely to experience medication-related side effects. Data are too sparse to assess the effects of antipsychotic medication on outcomes in early episode schizophrenia.
| S-EPMC4105695 | biostudies-other
Project description:Membrane phospholipid deficits have been well-documented in schizophrenia (SZ) patients. Free fatty acids (FFAs) partially come from the hydrolysis of membrane phospholipids and serve as the circulating pool of body fatty acids. These FFAs are involved in many important biochemical reactions such as membrane regeneration, oxidation, and prostaglandin production which may have important implications in SZ pathology. Thus, we compared plasma FFA levels and profiles among healthy controls (HCs), affective psychosis (AP) patients, and first-episode antipsychotic-naïve schizophrenia (FEANS) patients. A significant reduction of total FFAs levels was observed in SZ patients. Specifically, significant reductions of 16:0, 18:2n6c, and 20:4n6 levels were detected in FEANS patients but not in APs when compared with levels in HCs. Also, disrupted metabolism of fatty acids especially in saturated and n-6 fatty acid families were observed by comparing correlations between precursor and product fatty acid levels within each fatty acid family. These findings may suggest an increased demand of membrane regeneration, a homeostatic imbalance of fatty acid biosynthesis pathway and a potential indication of increased beta oxidation. Collectively, these findings could help us better understand the lipid metabolism with regard to SZ pathophysiology.
| S-EPMC7403507 | biostudies-literature
Project description:AimThe first-episode psychosis (FEP) represents a critical period to prevent cardiovascular and metabolic morbidity decades later. Antipsychotic (AP)-induced weight gain is one modifiable factor in this period. The purpose of this study is to conduct a meta-analysis of AP-induced weight and body mass index (BMI) change in FEP.MethodsA comprehensive literature search identified 28 articles that reported data on AP-specific weight or BMI change in FEP. We conducted a meta-analysis of short- and long-term mean weight and BMI differences between placebo and AP medications. We also performed subgroup and meta-regression analysis to examine weight, BMI outcomes and their relationship with location (Asian vs. Western), sponsorship and baseline weight and BMIs.ResultsCompared to placebo, AP-caused mean weight gain was 3.22 kg and 1.4 points BMI in the short-term, and 5.30 kg and 1.86 points BMI in the long term. Clinically significant weight gain risk increased about twofold with AP use. Weight gain was associated with duration of AP use. AP medications were associated with more weight gain in Western samples as opposed to Asian samples. Most AP medications were associated with significant body weight gain and BMI increase in FEP patients, except for ziprasidone. Olanzapine and clozapine caused the highest weight gain compared to placebo.ConclusionExcept for ziprasidone, most AP medications were associated with body weight gain and BMI increase in FEP patients. Early and continuing effects of various AP medications on weight gain and BMI increase should be taken into consideration by clinicians.
| S-EPMC5589463 | biostudies-literature
Project description:Previous evidence has implicated corticostriatal abnormalities in the pathophysiology of psychosis. Although the striatum is the primary target of all efficacious antipsychotics, the relationship between its functional connectivity and symptomatic reduction remains unknown.To explore the longitudinal effect of treatment with second-generation antipsychotics on functional connectivity of the striatum during the resting state in patients experiencing a first episode of psychosis.This prospective controlled study took place at a clinical research center and included 24 patients with first-episode psychosis and 24 healthy participants matched for age, sex, education, and handedness. Medications were administered in a double-blind randomized manner.Patients were scanned at baseline and after 12 weeks of treatment with either risperidone or aripiprazole. Their symptoms were evaluated with the Brief Psychiatric Rating Scale at baseline and follow-up. Healthy participants were scanned twice within a 12-week interval.Functional connectivity of striatal regions was examined via functional magnetic resonance imaging using a seed-based approach. Changes in functional connectivity of these seeds were compared with reductions in ratings of psychotic symptoms.Patients had a median exposure of 1 day to antipsychotic medication prior to being scanned (mean [SD]?= 4.5 [6.1]). Eleven patients were treated with aripiprazole and 13 patients were treated with risperidone. As psychosis improved, we observed an increase in functional connectivity between striatal seed regions and the anterior cingulate, dorsolateral prefrontal cortex, and limbic regions such as the hippocampus and anterior insula (P <?.05, corrected for multiple comparisons). Conversely, a negative relationship was observed between reduction in psychosis and functional connectivity of striatal regions with structures within the parietal lobe (P <?.05, corrected for multiple comparisons).Our results indicated that corticostriatal functional dysconnectivity in psychosis is a state-dependent phenomenon. Increased functional connectivity of the striatum with prefrontal and limbic regions may be a biomarker for improvement in symptoms associated with antipsychotic treatment.
| S-EPMC4286512 | biostudies-literature
Project description:Schizophrenia has been conceptualized as a disorder arising from structurally pathological alterations to white-matter fibers in the brain. However, few studies have focused on white-matter functional changes in schizophrenia. Considering that converging evidence suggests that white-matter resting state functional MRI (rsfMRI) signals can effectively depict neuronal activity and psychopathological status, this study examined white-matter network-level interactions in antipsychotic-naive first-episode schizophrenia (FES) to facilitate the interpretation of the psychiatric pathological mechanisms in schizophrenia. We recruited 42 FES patients (FESs) and 38 healthy controls (HCs), all of whom underwent rsfMRI. We identified 11 white-matter functional networks, which could be further classified into deep, middle, and superficial layers of networks. We then examined network-level interactions among these 11 white-matter functional networks using coefficient Granger causality analysis. We employed group comparisons on the influences among 11 networks using network-based statistic. Excitatory influences from the middle superior corona radiate network to the superficial orbitofrontal and deep networks were disrupted in FESs compared with HCs. Additionally, an extra failure of suppression within superficial networks (including the frontoparietal network, temporofrontal network, and the orbitofrontal network) was observed in FESs. We additionally recruited an independent cohort (13 FESs and 13 HCs) from another center to examine the replicability of our findings across centers. Similar replication results further verified the white-matter functional network interaction model of schizophrenia. The novel findings of impaired interactions among white-matter functional networks in schizophrenia indicate that the pathophysiology of schizophrenia may also lie in white-matter functional abnormalities.
| S-EPMC7267955 | biostudies-literature
Project description:Many antipsychotic medications carry a substantial liability for weight gain, and one mechanism common to all antipsychotics is binding to the dopamine D2 receptor. We therefore examined the relationship between -141C Ins/Del (rs1799732), a functional promoter region polymorphism in DRD2, and antipsychotic-induced weight gain in 58 first episode schizophrenia patients enrolled in a randomized trial of risperidone versus olanzapine. Carriers of the deletion allele (n=29) were compared with Ins/Ins homozygotes (noncarriers, n=29) in a mixed model encompassing 10 weight measurements over 16 weeks. Deletion allele carriers showed significantly more weight gain after 6 weeks of treatment regardless of assigned medication. Although deletion carriers were prescribed higher doses of olanzapine (but not risperidone), dose did not seem to account for the genotype effects on weight gain. Given earlier evidence that deletion carriers show reduced symptom response to medication, additional study of appropriate treatment options for these patients seems warranted.
| S-EPMC2920359 | biostudies-literature