Reduced Levels and Disrupted Biosynthesis Pathways of Plasma Free Fatty Acids in First-Episode Antipsychotic-Naive Schizophrenia Patients.
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ABSTRACT:
SUBMITTER: Zhou X
PROVIDER: S-EPMC7403507 | biostudies-literature |
REPOSITORIES: biostudies-literature
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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:BACKGROUND:Enlarged 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. METHODS:We 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. RESULTS:We 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. LIMITATIONS:This study was not a priori designed to test for differences between schizophrenia patients with or without lifetime substance abuse, and this subgroup was small. CONCLUSION:Reductions 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: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: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: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:The nature of hippocampal changes in schizophrenia before first treatment, and whether hippocampal subfields are affected by antipsychotic treatment are important questions for schizophrenia research. Forty-one first-episode antipsychotic-naïve acutely ill schizophrenia inpatients had MRI scans before and six weeks after antipsychotic treatment. Thirty-nine matched healthy controls were also scanned, twenty-two of which were scanned a second time six weeks later. Volumes of hippocampal subfields were measured via FreeSurfer v6.0 using a longitudinal analysis pipeline. Before treatment, schizophrenia patients had no significant changes in total hippocampal volume but exhibited significantly greater subfield volumes than controls in bilateral molecular layers of the hippocampus (ML), bilateral granular cell layers of the dentate gyrus (GC-DG), and bilateral cornu ammonis area 4 (CA4). After six weeks of antipsychotic treatment, patients showed volume reductions compared with pretreatment scans in total hippocampus bilaterally, with subfield volume reduction noted in previously enlarged subfields (i.e., bilateral ML, GC-DG and CA4) and in bilateral hippocampal tails, left CA1, CA3, and fimbria. Subfields with volume increases before treatment were reduced to the level of healthy controls (bilateral ML and GC-DG) or near to it (bilateral CA4) after treatment. These results indicate subfield-specific hippocampal hypertrophy prior to treatment, and that these abnormalities were reduced after acute antipsychotic therapy in a dose-related manner together with volume reductions in other areas that were not hypertrophic before treatment.
| S-EPMC6072650 | biostudies-literature
Project description:BACKGROUND:Mismatch negativity (MMN) is a measure of pre-attentive auditory information processing related to change detection. Traditional scalp-level EEG methods consistently find attenuated MMN in patients with chronic but not first-episode schizophrenia. In the current paper, we use a source-resolved method to assess MMN and hypothesize that more subtle changes can be identified with this analysis method. METHOD:Fifty-six first-episode antipsychotic-naïve schizophrenia (FEANS) patients (31 males, 25 females, mean age 24.6) and 64 matched controls (37 males, 27 females, mean age 24.8) were assessed for duration-, frequency- and combined-type MMN and P3a as well as 4 clinical, 3 cognitive and 3 psychopathological measures. To evaluate and correlate MMN at source-level, independent component analysis (ICA) was applied to the continuous EEG data to derive equivalent current dipoles which were clustered into 19 clusters based on cortical location. RESULTS:No scalp channel group MMN or P3a amplitude differences were found. Of the localized clusters, several were in or near brain areas previously suggested to be involved in the MMN response, including frontal and anterior cingulate cortices and superior temporal and inferior frontal gyri. For duration deviants, MMN was attenuated at the right superior temporal gyrus in patients compared to healthy controls (p?=?0.01), as was P3a at the superior frontal cortex (p?=?0.01). No individual patient correlations with clinical, cognitive, or psychopathological measures survived correction for multiple comparisons. CONCLUSION:Attenuated source-localized MMN and P3a peak contributions can be identified in FEANS patients using a method based on independent component analysis (ICA). This indicates that deficits in pre-attentive auditory information processing are present at this early stage of schizophrenia and are not the result of disease chronicity or medication. This is to our knowledge the first study on FEANS patients using this more detailed method.
| S-EPMC6444292 | biostudies-literature
Project description:BACKGROUND:Schizophrenia has been conceptualized as a brain network disorder rooted in dysregulated neurodevelopmental processes. Recent neuroimaging studies revealed disrupted brain connectomic organization in adult schizophrenia patients. However, altered developmental trajectories of the functional connectome during the adolescent maturational stage have not been examined. METHODS:The present study combined functional MRI with a graph theoretical approach to examine functional network topology and its age-related development in 39 medication naïve, first-episode patients with adolescent-onset schizophrenia and 31 matched controls (age range: 12-18 years). RESULTS:Patients demonstrated impaired large-scale integration as reflected by reduced global efficiency as well as decreased regional nodal efficiency in highly integrative network hubs, most consistently the hippocampal formation and the precuneus. Furthermore, the left hippocampus showed opposite age-efficiency associations in healthy controls and patients, indicating dysregulated maturational trajectories in adolescent schizophrenia and a particular vulnerability of this region during early pathological attack. CONCLUSIONS:The findings allow an integrative perspective on network and neurodevelopmental perspectives on schizophrenia, suggesting that dysregulated maturation of the functional connectome during adolescence might reflect an early marker for the disorder.
| S-EPMC6483582 | biostudies-literature
Project description:Neurosteroids are both endogenous and exogenous steroids that rapidly alter neuronal excitability through interactions with ligand-gated ion channels and other cell surface receptors. They are originated from cholesterol and have important implications for schizophrenia (SZ) pathophysiology and treatment strategies. Specifically, pregnenolone (PREG), progesterone (PROG) and allopregnanolone (ALLO) exhibit similar psychotropic properties. Using enzyme immunoassay, we compared the neurosteroids in PREG downstream pathways in plasma between healthy controls (HC, n = 43) and first-episode antipsychotic-naïve patients with SZ (FEAN-SZ, n = 53) before antipsychotic drug (APD) treatment. Comparisons were also made particularly along PREG-PROG-ALLO pathway in the same FEAN-SZ patients across multiple time points following initiation of treatment for 12 months (m). Firstly, at baseline, levels of PREG were significantly higher and those of ALLO were lower in FEAN-SZ than in HC, whereas PROG, cortisol, dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEAS) were not different. Consequently, the molar ratios of ALLO/PREG and ALLO/PROG in FEAN-SZ were significantly reduced. Secondly, in response to APD at 1 month, ALLO levels in FEAN-SZ were markedly elevated, whereas PREG and PROG levels decreased. Thirdly, among FEAN-SZ, lower levels of PROG (reflecting higher conversion to ALLO) at baseline may predict better therapeutic outcome after 1 month of APD treatment. These findings point to the perturbations of the PREG-PROG-ALLO pathway early in psychosis, and further study of this pathway may inform alternative and innovative therapeutic targets for SZ.
| S-EPMC5864547 | biostudies-literature
Project description:Accumulating evidence indicates a putative association of telomere length and mitochondrial function with antipsychotics response in schizophrenia (SCZ). However, pharmacological findings were limited and no previous work has assessed this in a prospective longitudinal study. This study assessed telomere length and mitochondrial DNA copy number in first-episode antipsychotic-naïve SCZ patients with 8-week risperidone treatment to evaluate the association between these biomarkers and clinical treatment response. We recruited 137 first-episode antipsychotic-naive SCZ patients (and 144 controls) at baseline and 89 patients completed the 8-week follow-up. Patients, completed follow-up, were divided into Responders (N = 46) and Non-Responders (N = 43) according to the percentage of symptoms improvement. Linear regression analyses show that SCZ patients had significantly lower mtDNA copy number (β = -0.108, p = 0.002), and no alteration of telomere length when compared with healthy controls. In addition, compared with Non-Responders, Responders had significantly lower mtDNA copy number (β = -0.178, p = 0.001), and longer telomere length (β = 0.111, p = 0.071) before the 8-week treatment. After treatment, Responders persisted lower mtDNA copy number comparing with No-Responders (partial η(2) = 0.125, p = 0.001). These findings suggest that telomere length and mtDNA copy number may hold the potential to serve as predictors of antipsychotic response of SCZ patients.
| S-EPMC4683467 | biostudies-other