| 1 | Int J Psychophysiol 2000 Oct 38: 71-9 |
|---|---|
| PMID | 11027795 |
| Title | Left temporal deficit of P300 in patients with schizophrenia: effects of task. |
| Abstract | P300 is often, but not always, observed to be more reduced over left than right temporal lobes in patients with schizophrenia. The possibility that task differences contribute to the inconsistency in the literature was explored in this study. ERPs were collected from 17 right-handed men with schizophrenia (DSM-IIIR) and 11 right-handed healthy male community controls, performing three auditory oddball tasks - respond to a target tone by: (1) counting; (2) pressing a response button with the right index finger; or (3) pressing a response button with the left index finger. Although patients with schizophrenia had smaller and later P300 amplitudes than controls, they did not have smaller P300s over the left temporal scalp (T3) than over the right (T4). P300 recorded over the left (C3) and right (C4) motor cortices indicated sensitivity to responding hand, with greater negativity being associated with contralateral button pressing. Failure to find P300 asymmetry is not related to the presence or absence of a button pressing task, or the hand used for button pressing. Rather, P300 asymmetry may be related to structural neuroanatomical asymmetries. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 2 | Acta Psychiatr Scand 2000 Apr 101: 307-11 |
| PMID | 10782551 |
| Title | Quantitative EEG in 'positive' and 'negative' schizophrenia. |
| Abstract | Quantitative EEG has yielded different results in schizophrenia. The method of quantitative EEG has been relatively poorly used in the studies of the dichotomy into positive and negative schizophrenia. Amplitude values of any particular frequency band (after fast Fourier transformation, FFT) were observed in 47 schizophrenic patients (25 patients with positive and 22 patients with negative schizophrenia) and in 50 normal subjects. The frontal, temporal, parietal and occipital regions (F3, F4, C3, C4, T3, T4, P3, P4, O1 and O2) were observed. Positive and negative schizophrenia were found to differ only in the delta and theta bands over frontal regions. Positive and negative schizophrenic patients were found to differ from normal subjects in delta, theta, alpha and beta 2 bands. Delta and theta activity may play a role as a marker in differentiating between positive and negative schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 3 | Acta Psychiatr Scand 2000 Apr 101: 307-11 |
| PMID | 10782551 |
| Title | Quantitative EEG in 'positive' and 'negative' schizophrenia. |
| Abstract | Quantitative EEG has yielded different results in schizophrenia. The method of quantitative EEG has been relatively poorly used in the studies of the dichotomy into positive and negative schizophrenia. Amplitude values of any particular frequency band (after fast Fourier transformation, FFT) were observed in 47 schizophrenic patients (25 patients with positive and 22 patients with negative schizophrenia) and in 50 normal subjects. The frontal, temporal, parietal and occipital regions (F3, F4, C3, C4, T3, T4, P3, P4, O1 and O2) were observed. Positive and negative schizophrenia were found to differ only in the delta and theta bands over frontal regions. Positive and negative schizophrenic patients were found to differ from normal subjects in delta, theta, alpha and beta 2 bands. Delta and theta activity may play a role as a marker in differentiating between positive and negative schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 4 | Neuropsychobiology 2000 -1 41: 166-70 |
| PMID | 10754432 |
| Title | Quantitative EEG in schizophrenic patients before and during pharmacotherapy. |
| Abstract | The aim of the study was to determine the possible differences in quantitative EEG parameters of schizophrenic patients before and during therapy with neuroleptics. First EEG recordings were obtained from schizophrenic patients (n = 50) who had not been taking any medicaments during the preceding 2 months. Second EEG recordings were obtained during the administration of neuroleptic therapy. Amplitude values of particular spectral segment, i.e. delta, theta, alpha 1, alpha 2, beta 1 and beta 2 (after fast Fourier transformation) were analyzed. The F3, F4, C3, C4, T3, T4, P3, P4, O1 and O2 regions were observed. The effect of pharmacotherapy manifested as a decrease in delta and beta 2 activities. The alterations of the delta spectrum were recorded in each patient subgroup (regardless of the neuroleptic used). The changes in beta 2 activity were registered in patients on haloperidol and fluphenazine. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 5 | Biol. Pharm. Bull. 2002 Mar 25: 291-301 |
| PMID | 11913521 |
| Title | Molecular pharmacology of the Na+-dependent transport of acidic amino acids in the mammalian central nervous system. |
| Abstract | The Na+-dependent transport of L-glutamate (GluT) has been identified in brain tissue more than thirty years ago. Neurochemical studies, performed in various experimental models during 1970's, defined the basic rules for the selection or synthesis of GluT-specific substrates and inhibitors. The protein molecules (transporters) that mediate the translocation of the substrates across the plasma membrane have been cloned and studied during the last ten years. The sites on the transporters that bind the substrates favour glutamate-like or aspartate-like molecules with one positively charged and two negatively charged ionised groups. Substituents at C3 and C4 are often tolerated but substitutions at C2 or alterations of the ionisable groups usually impede the binding. The substrate binding sites display an "anomalous" selectivity towards stereoisomers. These structural requirements are shared by all Na+-dependent glutamate transporters thus making the design of transporter-selective ligands a challenging task. Moreover, the molecular mechanisms of the transport have not yet been adequately elucidated. Data from a wide variety of experimental studies strongly indicate that Na+-dependent GluT regulates the functioning of the glutamatergic excitatory synapses-the most important rapid inter-neuronal signalling system in the mammalian brain. Altered structural and/or functional properties of the Na+-dependent glutamate transporters have been implicated in the damage to the brain tissue following cerebral ischaemia and in the progressive loss of neurons in conditions such as Alzheimer dementia and amyotrophic lateral sclerosis. Furthermore, it seems that fine-tuning of glutamatergic neurotransmission by regulating the Na+-dependent GluT could be useful in the therapy of schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 6 | Clin Neurophysiol 2002 Dec 113: 1954-60 |
| PMID | 12464333 |
| Title | EEG in schizophrenic patients: mutual information analysis. |
| Abstract | The aim of the present study is to assess information transmission between different cortical areas in schizophrenics by estimating the average cross mutual information (A-CMI) and to characterize the dynamical property of the cortical areas of schizophrenic patients from multi-channel EEG by establishing the auto mutual information (AMI). We recorded the EEG from 16 electrodes in 10 schizophrenic patients and 10 age-matched normal controls. We estimated the slope of the AMI to evaluate the complexity of the EEG signal from one electrode and the A-CMI values of all 16x16 pairs of electrodes were calculated to investigate the information transmission of different cortical areas in schizophrenic patients. In T5 and C3 electrodes, the schizophrenic patients had lower complexity than normal controls. The schizophrenic patients had significantly higher interhemispheric and intrahemispheric A-CMI values than the normal controls. These results are consistent with previous findings that suggest left hemispheric hypotemporality and inter- and/or intra-hemispheric overconnectivity in schizophrenics. Our results of the left hemispheric hypotemporality and the increased interhemispheric information transmission in temporal lobe may support the hypothesis that the abnormal laterlization in temporal lobe are due to left temporal lobe deficit in schizophrenic patients. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 7 | Clin Neurophysiol 2002 Dec 113: 1954-60 |
| PMID | 12464333 |
| Title | EEG in schizophrenic patients: mutual information analysis. |
| Abstract | The aim of the present study is to assess information transmission between different cortical areas in schizophrenics by estimating the average cross mutual information (A-CMI) and to characterize the dynamical property of the cortical areas of schizophrenic patients from multi-channel EEG by establishing the auto mutual information (AMI). We recorded the EEG from 16 electrodes in 10 schizophrenic patients and 10 age-matched normal controls. We estimated the slope of the AMI to evaluate the complexity of the EEG signal from one electrode and the A-CMI values of all 16x16 pairs of electrodes were calculated to investigate the information transmission of different cortical areas in schizophrenic patients. In T5 and C3 electrodes, the schizophrenic patients had lower complexity than normal controls. The schizophrenic patients had significantly higher interhemispheric and intrahemispheric A-CMI values than the normal controls. These results are consistent with previous findings that suggest left hemispheric hypotemporality and inter- and/or intra-hemispheric overconnectivity in schizophrenics. Our results of the left hemispheric hypotemporality and the increased interhemispheric information transmission in temporal lobe may support the hypothesis that the abnormal laterlization in temporal lobe are due to left temporal lobe deficit in schizophrenic patients. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 8 | Eur Neuropsychopharmacol 2004 May 14: 227-36 |
| PMID | 15056482 |
| Title | P300 alterations in schizophrenic patients experiencing auditory hallucinations. |
| Abstract | Attentional deficits have been implicated in the pathophysiology of auditory hallucinations in schizophrenia. Since the latency of the P300 component of event-related potentials (ERPs) is considered to be a sensitive measure of stimulus classification speed, while its amplitude-a measure of attentional resource allocation when memory updating is engaged, the present study focuses on the comparison of P300 between healthy subjects and schizophrenic patients experiencing auditory hallucinations and treated with clozapine and olanzapine. The auditory P300 was assessed during the anticipatory period of a short memory test, in 16 male hallucinated schizophrenic patients and 13 male normal subjects matched for age and educational level. The patients were reexamined under identical conditions when their hallucinations had resolved following treatment with clozapine (8 patients) and olanzapine (8 patients). The patients with hallucinations exhibited significantly reduced P300 amplitude at leads Fp1, F3, (C3-T5)/2, F4, Cz and Fz, when compared to the normal controls and at leads Fp1, F3, F4, (C4-T6)/2, C4, P4, Cz and Fz when compared to themselves during the remission phase. However logistic regression models revealed that the most important leads, differentiating the patient group before treatment either with the healthy controls, or with itself after treatment, were that at the left temporoparietal and at the left prefrontal area. Memory performance of the patient group, even after treatment and in spite of its significant improvement, remained significantly less than that of healthy controls. both antipsychotic agents had similar effects on the p300 amplitude and memory performance. These findings indicate that auditory hallucinations in schizophrenia manifest abnormal aspects of attention, mediated by a distributed network involving or affecting the left temporoparietal and left prefrontal area. Additionally, the present study points to an improvement of attentional function in schizophrenic patients experiencing auditory hallucinations, both in the clozapine group but also in the olanzapine group. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 9 | Eur Neuropsychopharmacol 2004 May 14: 227-36 |
| PMID | 15056482 |
| Title | P300 alterations in schizophrenic patients experiencing auditory hallucinations. |
| Abstract | Attentional deficits have been implicated in the pathophysiology of auditory hallucinations in schizophrenia. Since the latency of the P300 component of event-related potentials (ERPs) is considered to be a sensitive measure of stimulus classification speed, while its amplitude-a measure of attentional resource allocation when memory updating is engaged, the present study focuses on the comparison of P300 between healthy subjects and schizophrenic patients experiencing auditory hallucinations and treated with clozapine and olanzapine. The auditory P300 was assessed during the anticipatory period of a short memory test, in 16 male hallucinated schizophrenic patients and 13 male normal subjects matched for age and educational level. The patients were reexamined under identical conditions when their hallucinations had resolved following treatment with clozapine (8 patients) and olanzapine (8 patients). The patients with hallucinations exhibited significantly reduced P300 amplitude at leads Fp1, F3, (C3-T5)/2, F4, Cz and Fz, when compared to the normal controls and at leads Fp1, F3, F4, (C4-T6)/2, C4, P4, Cz and Fz when compared to themselves during the remission phase. However logistic regression models revealed that the most important leads, differentiating the patient group before treatment either with the healthy controls, or with itself after treatment, were that at the left temporoparietal and at the left prefrontal area. Memory performance of the patient group, even after treatment and in spite of its significant improvement, remained significantly less than that of healthy controls. both antipsychotic agents had similar effects on the p300 amplitude and memory performance. These findings indicate that auditory hallucinations in schizophrenia manifest abnormal aspects of attention, mediated by a distributed network involving or affecting the left temporoparietal and left prefrontal area. Additionally, the present study points to an improvement of attentional function in schizophrenic patients experiencing auditory hallucinations, both in the clozapine group but also in the olanzapine group. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 10 | Neurosci. Lett. 2005 Feb 374: 35-7 |
| PMID | 15631892 |
| Title | Classical pathway complement activity in schizophrenia. |
| Abstract | There is considerable evidence to suggest a role for complement in the pathogenesis of schizophrenia, but the data related to the classical pathway complement activity in patients with schizophrenia are conflicting. In the present study, the total hemolytic activity of the complement and the activities of individual complement components, C1, C2, C3 and C4, were determined in the blood serum of schizophrenic patients with positive family history of the disease and healthy subjects. In comparison to the healthy subjects, the mean values of the hemolytic activities of the C1, C3 and C4 complement components in the serum of the schizophrenic patients were significantly higher, and the mean value of the hemolytic activity of the C2 complement component was significantly lower. However, no significant difference was found between the mean values of the total hemolytic activity of complement in schizophrenic patients and healthy subjects. The C3 hemolytic activity was 2.17 times higher in medicated patients than in drug-free patients. Within each group examined no significant difference was found between smokers and non-smokers or between males and females. The results of this study suggest that the pathogenesis of schizophrenia is associated with alterations in activities of complement classical pathway components. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 11 | Neurosci. Lett. 2005 Feb 374: 35-7 |
| PMID | 15631892 |
| Title | Classical pathway complement activity in schizophrenia. |
| Abstract | There is considerable evidence to suggest a role for complement in the pathogenesis of schizophrenia, but the data related to the classical pathway complement activity in patients with schizophrenia are conflicting. In the present study, the total hemolytic activity of the complement and the activities of individual complement components, C1, C2, C3 and C4, were determined in the blood serum of schizophrenic patients with positive family history of the disease and healthy subjects. In comparison to the healthy subjects, the mean values of the hemolytic activities of the C1, C3 and C4 complement components in the serum of the schizophrenic patients were significantly higher, and the mean value of the hemolytic activity of the C2 complement component was significantly lower. However, no significant difference was found between the mean values of the total hemolytic activity of complement in schizophrenic patients and healthy subjects. The C3 hemolytic activity was 2.17 times higher in medicated patients than in drug-free patients. Within each group examined no significant difference was found between smokers and non-smokers or between males and females. The results of this study suggest that the pathogenesis of schizophrenia is associated with alterations in activities of complement classical pathway components. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 12 | PLoS Biol. 2007 Nov 5: e297 |
| PMID | 18001149 |
| Title | Fabp7 maps to a quantitative trait locus for a schizophrenia endophenotype. |
| Abstract | Deficits in prepulse inhibition (PPI) are a biological marker for schizophrenia. To unravel the mechanisms that control PPI, we performed quantitative trait loci (QTL) analysis on 1,010 F2 mice derived by crossing C57BL/6 (B6) animals that show high PPI with C3H/He (C3) animals that show low PPI. We detected six major loci for PPI, six for the acoustic startle response, and four for latency to response peak, some of which were sex-dependent. A promising candidate on the Chromosome 10-QTL was Fabp7 (fatty acid binding protein 7, brain), a gene with functional links to the N-methyl-D-aspartic acid (NMDA) receptor and expression in astrocytes. Fabp7-deficient mice showed decreased PPI and a shortened startle response latency, typical of the QTL's proposed effects. A quantitative complementation test supported Fabp7 as a potential PPI-QTL gene, particularly in male mice. Disruption of Fabp7 attenuated neurogenesis in vivo. Human FABP7 showed altered expression in schizophrenic brains and genetic association with schizophrenia, which were both evident in males when samples were divided by sex. These results suggest that FABP7 plays a novel and crucial role, linking the NMDA, neurodevelopmental, and glial theories of schizophrenia pathology and the PPI endophenotype, with larger or overt effects in males. We also discuss the results from the perspective of fetal programming. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 13 | PLoS Biol. 2007 Nov 5: e297 |
| PMID | 18001149 |
| Title | Fabp7 maps to a quantitative trait locus for a schizophrenia endophenotype. |
| Abstract | Deficits in prepulse inhibition (PPI) are a biological marker for schizophrenia. To unravel the mechanisms that control PPI, we performed quantitative trait loci (QTL) analysis on 1,010 F2 mice derived by crossing C57BL/6 (B6) animals that show high PPI with C3H/He (C3) animals that show low PPI. We detected six major loci for PPI, six for the acoustic startle response, and four for latency to response peak, some of which were sex-dependent. A promising candidate on the Chromosome 10-QTL was Fabp7 (fatty acid binding protein 7, brain), a gene with functional links to the N-methyl-D-aspartic acid (NMDA) receptor and expression in astrocytes. Fabp7-deficient mice showed decreased PPI and a shortened startle response latency, typical of the QTL's proposed effects. A quantitative complementation test supported Fabp7 as a potential PPI-QTL gene, particularly in male mice. Disruption of Fabp7 attenuated neurogenesis in vivo. Human FABP7 showed altered expression in schizophrenic brains and genetic association with schizophrenia, which were both evident in males when samples were divided by sex. These results suggest that FABP7 plays a novel and crucial role, linking the NMDA, neurodevelopmental, and glial theories of schizophrenia pathology and the PPI endophenotype, with larger or overt effects in males. We also discuss the results from the perspective of fetal programming. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 14 | Psychiatry Res 2007 May 151: 11-20 |
| PMID | 17292483 |
| Title | Early and late auditory sensory gating: moderating influences from schizotypal personality, tobacco smoking status, and acute smoking. |
| Abstract | Early (P50) and late (P200) auditory sensory gating were assessed in low and high schizotypal personality groups using Raine's schizotypal Personality Questionnaire. We also assessed the impact of smoking as it relates to low and high schizotypal personalities. Low and high schizoptypal personality groups were divided into subgroups of participants who either smoked or did not smoke tobacco cigarettes. Participants were 39 (18 men) right-handed undergraduates. Using a paired-tone paradigm (40 pairs, 70 dB, 1000 Hz), smokers were tested while abstaining from smoking, and 5 min after smoking. Non-smokers were tested similarly without smoking. Midline and hemispheric sites were evaluated at frontal (F3/Fz/F4), fronto-central (FC3/FCz/FC4), central (C3/Cz/C4), centro-parietal (CP3/CPz/CP4), and parietal (P3/Pz/P4) regions. P50 sensory gating was better at midline sites than left/right hemispheric sites, whereas there was no difference in activation with respect to location for P200 sensory gating. Cz had better P50 sensory gating than other midline regions, whereas Fz, FCz and Cz had better P200 sensory gating than CPz and Pz. Hemispheric comparisons were made. At the central region for non-smokers, high schizotypys showed poorer P50 sensory gating than low schizotypys. Among low schizotypys, smokers showed poorer P50 sensory gating than non-smokers at the fronto-central and central regions smokers showed better P200 sensory gating than non-smokers at the central region. Smoking had no acute impact on either early (P50) or late (P200) sensory gating. Our data support the notion that early sensory gating and late sensory gating represent different sensory gating mechanisms with respect to low and high schizotypy personalities. Individual differences in early and late sensory gating need further investigation. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 15 | Psychiatry Res 2007 May 151: 11-20 |
| PMID | 17292483 |
| Title | Early and late auditory sensory gating: moderating influences from schizotypal personality, tobacco smoking status, and acute smoking. |
| Abstract | Early (P50) and late (P200) auditory sensory gating were assessed in low and high schizotypal personality groups using Raine's schizotypal Personality Questionnaire. We also assessed the impact of smoking as it relates to low and high schizotypal personalities. Low and high schizoptypal personality groups were divided into subgroups of participants who either smoked or did not smoke tobacco cigarettes. Participants were 39 (18 men) right-handed undergraduates. Using a paired-tone paradigm (40 pairs, 70 dB, 1000 Hz), smokers were tested while abstaining from smoking, and 5 min after smoking. Non-smokers were tested similarly without smoking. Midline and hemispheric sites were evaluated at frontal (F3/Fz/F4), fronto-central (FC3/FCz/FC4), central (C3/Cz/C4), centro-parietal (CP3/CPz/CP4), and parietal (P3/Pz/P4) regions. P50 sensory gating was better at midline sites than left/right hemispheric sites, whereas there was no difference in activation with respect to location for P200 sensory gating. Cz had better P50 sensory gating than other midline regions, whereas Fz, FCz and Cz had better P200 sensory gating than CPz and Pz. Hemispheric comparisons were made. At the central region for non-smokers, high schizotypys showed poorer P50 sensory gating than low schizotypys. Among low schizotypys, smokers showed poorer P50 sensory gating than non-smokers at the fronto-central and central regions smokers showed better P200 sensory gating than non-smokers at the central region. Smoking had no acute impact on either early (P50) or late (P200) sensory gating. Our data support the notion that early sensory gating and late sensory gating represent different sensory gating mechanisms with respect to low and high schizotypy personalities. Individual differences in early and late sensory gating need further investigation. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 16 | Drug News Perspect. 2008 May 21: 200-10 |
| PMID | 18560619 |
| Title | The complement system in schizophrenia. |
| Abstract | Several lines of evidence suggest that immunological factors contribute to schizophrenia. Since 1989, the role of complement, a major effector of innate immunity and an adjuvant of adaptive immunity, has been explored in schizophrenia. Increased activity of C1, C3, C4 complement components in schizophrenia has been reported by two or more groups. Two studies on different subject cohorts showed increased MBL-MASP-2 activity in patients versus controls. More then one report indicated a significant high frequency of FB*F allotype and low prevalence of the FS phenotype of complement factor B in schizophrenia. From the data reported, it is likely that the disorder is accompanied by alterations of the complement classical and lectin pathways, which undergo dynamic changes, depending on the illness course and the state of neuro-immune crosstalk. Recent findings, implicating complement in neurogenesis, synapse remodeling and pruning during brain development, suggest a reexamination of the potential role of complement in neurodevelopmental processes contributing to schizophrenia susceptibility. It is plausible that the multicomponent complement system has more than one dimensional association with schizophrenia susceptibility, pathopsychology and illness course, understanding of which will bring a new perspective for possible immunomodulation and immunocorrection of the disease. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 17 | Clin. Biochem. 2008 Apr 41: 355-60 |
| PMID | 18093542 |
| Title | Cryoglobulins as indicators of upregulated immune response in schizophrenia. |
| Abstract | In the present work the concentration of abnormal immune complexes, cryoglobulins (Cgs), in the blood of schizophrenic patients was determined, and immunochemical composition of these complexes was studied. Eighty multiple-episode schizophrenia-affected subjects (55 medicated, 25 drug-free) and 40 healthy controls were involved in the study. Cgs were isolated by exposure of blood serum samples to precipitation at low temperature followed by extensive washings of Cg-enriched pellets. The immunochemical composition of Cgs was analyzed using different electrophoretic and immunoblotting systems. Significantly increased blood serum levels of type III Cgs were detected in all schizophrenia-affected subjects, as compared to controls. We also revealed the presence of C1q and C3 complement proteins and their activation products in Cgs isolated from the blood of schizophrenic patients. The results of the present study suggest that Cgs are involved in schizophrenia-associated upregulated immune response by binding the complement proteins, activating the complement cascade and triggering aberrant apoptosis. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 18 | Clin. Biochem. 2008 Apr 41: 355-60 |
| PMID | 18093542 |
| Title | Cryoglobulins as indicators of upregulated immune response in schizophrenia. |
| Abstract | In the present work the concentration of abnormal immune complexes, cryoglobulins (Cgs), in the blood of schizophrenic patients was determined, and immunochemical composition of these complexes was studied. Eighty multiple-episode schizophrenia-affected subjects (55 medicated, 25 drug-free) and 40 healthy controls were involved in the study. Cgs were isolated by exposure of blood serum samples to precipitation at low temperature followed by extensive washings of Cg-enriched pellets. The immunochemical composition of Cgs was analyzed using different electrophoretic and immunoblotting systems. Significantly increased blood serum levels of type III Cgs were detected in all schizophrenia-affected subjects, as compared to controls. We also revealed the presence of C1q and C3 complement proteins and their activation products in Cgs isolated from the blood of schizophrenic patients. The results of the present study suggest that Cgs are involved in schizophrenia-associated upregulated immune response by binding the complement proteins, activating the complement cascade and triggering aberrant apoptosis. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 19 | Zhonghua Yi Xue Za Zhi 2010 Aug 90: 2026-9 |
| PMID | 21029637 |
| Title | [N400 changes elicited by Chinese sentences in first episode schizophrenia]. |
| Abstract | To explore N400 changes elicited by Chinese sentences ending with matching (congruent) or mismatching (incongruent) words in first episode schizophrenia. ERP (event-related potentials) component N400 were recorded by an ERP device in 56 first episode schizophrenia (FES) and 62 normal controls (NC) according to a paradigm of Chinese sentences ending with matching or mismatching words. (1) Latencies: compared with NC, FES showed prolonged N400 latencies in five areas at pre-treatment: in Cz. The latencies were (358 ms ± 32 ms vs 394 ms ± 45 ms, P < 0.01) in congruent and (410 ms ± 29 ms vs 446 ms ± 35 ms, P < 0.01) in incongruent situation. And so did in Fz, Pz, C3 and C4; (2) amplitudes: compared with NC, FES also showed smaller N400 amplitudes in five areas at pre-treatment. The amplitudes were (8.6 µV ± 5.1 µV vs 5.2 µV ± 4.6 µV, P < 0.01) in congruent and (13.4 µV ± 6.7 µV vs 8.5 µV ± 5.9 µV, P < 0.01) in incongruent situation. And so did in Fz, Pz, C3 and C4; (3) the prolonged N400 latencies and decreased amplitudes were negatively correlated with the patients' positive scale and total scale of PANSS. With clear priming effect in first episode schizophrenia, Chinese sentences are suitable stimuli in N400 experiment. They may be used for further study of neural mechanism and early diagnosis of schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 20 | Neurochem. Res. 2010 Jun 35: 894-8 |
| PMID | 20101522 |
| Title | Alternative complement pathway in schizophrenia. |
| Abstract | In the present study, we evaluated functional activity of the alternative pathway of complement in schizophrenia by measuring the alternative pathway hemolytic activity (AH50) of complement as well as hemolytic activity of the complement C3 component (C3H50) in the blood of patients with schizophrenia and healthy subjects. To assess the influence of neuroleptic treatment on measured parameters, both drug-free and medicated patients were examined. In addition, correlation analysis between AH50 and C3H50 has been performed. The results of the present study clearly demonstrate upregulation of the alternative complement cascade in schizophrenia and activator effect of neuroleptics on complement alternative pathway. Based upon the results obtained we hypothesize that hyperactivation of the alternative complement pathway in schizophrenia is stimulated by apoptotic cells. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 21 | Nihon Shinkei Seishin Yakurigaku Zasshi 2010 Nov 30: 197-200 |
| PMID | 21226315 |
| Title | [Analysis of mouse strain-dependent prepulse inhibition points to a role for Shmt1 (SHMT1) in mice and in schizophrenia]. |
| Abstract | Deficits in prepulse inhibition (PPI) are thought to be a biological trait of mental illnesses, including schizophrenia. It is known that the N-methyl-D-aspartate type glutamate (NMDA) receptor function affects PPI integrity and D-serine and glycine are typical endogenous co-agonists for the receptor. In parallel, we re-visited our prior quantitative trait loci (QTL) analysis study that examined C57BL/6 (B6) mice with high PPI and C3H/He (C3) with low PPI, and noticed that the genes encoding enzymes responsible for the productions of D-serine (serine racemase: Srr) and glycine (serine hydroxymethyltransferase 1: Shmt1) map to the chromosome 11 QTL. Therefore, we set out to examine whether brain interstitial fluid (ISF) levels of the two amino acids are different between the two mouse strains, using in vivo microdialysis. Recovery of D-serine and glycine from the dialysate of the frontal cortex was higher in B6 mice, which performed better in PPI, compared to C3 mice. Next, we analyzed the two genes, Srr and Shmt1. We then identified promoter polymorphisms in Shmt1 which elicit lower transcriptional activity in B6 compared to C3 mice. Human studies revealed higher expression levels of SHMT1 in the frontal cortex of postmortem brains from schizophrenics compared to controls, but no changes in SRR levels. In addition, genetic analysis detected a nominal association between SHMT1 and schizophrenia. These results suggest that Shmt1 (SHMT1) is one of the genetic components regulating PPI in mice and is relevant to schizophrenia susceptibility in humans. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 22 | Nihon Shinkei Seishin Yakurigaku Zasshi 2010 Nov 30: 197-200 |
| PMID | 21226315 |
| Title | [Analysis of mouse strain-dependent prepulse inhibition points to a role for Shmt1 (SHMT1) in mice and in schizophrenia]. |
| Abstract | Deficits in prepulse inhibition (PPI) are thought to be a biological trait of mental illnesses, including schizophrenia. It is known that the N-methyl-D-aspartate type glutamate (NMDA) receptor function affects PPI integrity and D-serine and glycine are typical endogenous co-agonists for the receptor. In parallel, we re-visited our prior quantitative trait loci (QTL) analysis study that examined C57BL/6 (B6) mice with high PPI and C3H/He (C3) with low PPI, and noticed that the genes encoding enzymes responsible for the productions of D-serine (serine racemase: Srr) and glycine (serine hydroxymethyltransferase 1: Shmt1) map to the chromosome 11 QTL. Therefore, we set out to examine whether brain interstitial fluid (ISF) levels of the two amino acids are different between the two mouse strains, using in vivo microdialysis. Recovery of D-serine and glycine from the dialysate of the frontal cortex was higher in B6 mice, which performed better in PPI, compared to C3 mice. Next, we analyzed the two genes, Srr and Shmt1. We then identified promoter polymorphisms in Shmt1 which elicit lower transcriptional activity in B6 compared to C3 mice. Human studies revealed higher expression levels of SHMT1 in the frontal cortex of postmortem brains from schizophrenics compared to controls, but no changes in SRR levels. In addition, genetic analysis detected a nominal association between SHMT1 and schizophrenia. These results suggest that Shmt1 (SHMT1) is one of the genetic components regulating PPI in mice and is relevant to schizophrenia susceptibility in humans. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 23 | J. Neurochem. 2010 Dec 115: 1374-85 |
| PMID | 20977478 |
| Title | Analysis of strain-dependent prepulse inhibition points to a role for Shmt1 (SHMT1) in mice and in schizophrenia. |
| Abstract | Deficits in prepulse inhibition (PPI) are known in mental illnesses, including schizophrenia. NMDA receptor function affects PPI integrity and D-serine and glycine are endogenous co-agonists for the receptor. Our previous quantitative trait loci analysis using C57BL/6 (B6) mice with better PPI performance and C3H/He (C3) with lower PPI score, shows that genes for both D-serine synthesizing enzyme and enzyme for reversible conversion between glycine and L-serine (Srr and Shmt1, respectively) are located in the same PPI-quantitative trait loci peak. Therefore, we set out to determine which gene is likely to explain the PPI difference and whether the gene is potentially relevant to schizophrenia. We first examined brain interstitial fluid levels of the two amino acids using microdialysis. Recovery of D-serine and glycine from the dialysate was higher in B6, compared to C3. Next, we analyzed expression levels and genetic polymorphisms of the two genes. There were promoter polymorphisms in Shmt1, which elicit lower transcriptional activity in B6 compared to C3 conforming to the results of brain expression levels, but no functional genetic variants in Srr. Finally, we evaluated expression levels of the two genes in the postmortem brains of schizophrenia and genetic associations with the disease. The SHMT1 levels were higher in schizophrenic brains compared to controls, but no changes in SRR levels. We detected a nominal association between SHMT1 and schizophrenia. These results suggest that Shmt1 (SHMT1), but not Srr, is likely to be one of the genetic components regulating PPI in mice and possibly relevant to schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 24 | J. Neurochem. 2010 Dec 115: 1374-85 |
| PMID | 20977478 |
| Title | Analysis of strain-dependent prepulse inhibition points to a role for Shmt1 (SHMT1) in mice and in schizophrenia. |
| Abstract | Deficits in prepulse inhibition (PPI) are known in mental illnesses, including schizophrenia. NMDA receptor function affects PPI integrity and D-serine and glycine are endogenous co-agonists for the receptor. Our previous quantitative trait loci analysis using C57BL/6 (B6) mice with better PPI performance and C3H/He (C3) with lower PPI score, shows that genes for both D-serine synthesizing enzyme and enzyme for reversible conversion between glycine and L-serine (Srr and Shmt1, respectively) are located in the same PPI-quantitative trait loci peak. Therefore, we set out to determine which gene is likely to explain the PPI difference and whether the gene is potentially relevant to schizophrenia. We first examined brain interstitial fluid levels of the two amino acids using microdialysis. Recovery of D-serine and glycine from the dialysate was higher in B6, compared to C3. Next, we analyzed expression levels and genetic polymorphisms of the two genes. There were promoter polymorphisms in Shmt1, which elicit lower transcriptional activity in B6 compared to C3 conforming to the results of brain expression levels, but no functional genetic variants in Srr. Finally, we evaluated expression levels of the two genes in the postmortem brains of schizophrenia and genetic associations with the disease. The SHMT1 levels were higher in schizophrenic brains compared to controls, but no changes in SRR levels. We detected a nominal association between SHMT1 and schizophrenia. These results suggest that Shmt1 (SHMT1), but not Srr, is likely to be one of the genetic components regulating PPI in mice and possibly relevant to schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 25 | BMC Clin Pathol 2011 -1 11: 10 |
| PMID | 21867543 |
| Title | Functional characterization of the complement receptor type 1 and its circulating ligands in patients with schizophrenia. |
| Abstract | Whereas the complement system alterations contribute to schizophrenia, complement receptors and regulators are little studied. We investigated complement receptor type 1 (CR1) expression on blood cells, the levels of circulating immune complexes (CIC) containing ligands of CR1, C1q complement protein and fragments of C3 complement protein (C1q-CIC, C3d-CIC), and CR1 C5507G functional polymorphism in schizophrenia patients and controls. We found an increased C1q-CIC level and CR1 expression on blood cells, elevated number of CR1 positive erythrocytes and reduced number of CR1 positive lymphocytes and monocytes in patients compared to controls. No difference in the levels of C3d-CIC between groups was observed. Higher CR1 expression on erythrocytes in CC genotype versus CG+GG for both groups was detected, whereas no difference was observed for other cell populations. Our results indicated that schizophrenia is associated with the increased CR1 expression and C1q-CIC level. Our study for the first time indicated that schizophrenia is associated with the increased CR1 expression and C1q-CIC level. Further studies in other ethnic groups are needed to replicate these findings. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 26 | Neurosci. Res. 2011 Nov 71: 289-93 |
| PMID | 21801761 |
| Title | Altered MHC class I expression in dorsolateral prefrontal cortex of nonsmoker patients with schizophrenia. |
| Abstract | schizophrenia (SZ) is a psychiatric disease with plausible neurodevelopmental etiology. Although genetic studies show significant association of immune molecules loci such as major histocompatibility complex (MHC) class I with SZ, it is not clear whether these immune molecules are involved in the pathology observed in SZ brains. MHC class I and the classical pathway components of complement system (C1q and C3) have been shown to regulate brain neuronal maturation and function. We have examined the expression of MHC class I and complement protein C3 in two frontal cortical regions of postmortem brains of SZ patients. Since cigarette smoking may modulate MHC class I protein expression and a higher rate of smoking is observed in SZ patients, we studied the expression of MHC class I and C3 in relation to the presence of smoking. We found that MHC class I protein expression is reduced in the dorsolateral prefrontal cortex (DLPFC) but not in the orbitofrontal cortex (OFC) of nonsmoker SZ patients. We did not observe SZ-associated changes in C3 mRNA expression. Our exploratory research suggests a potential involvement of MHC class I in SZ and implies that smoking might modulate its expression. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 27 | Bioorg. Med. Chem. Lett. 2011 Mar 21: 1896-9 |
| PMID | 21320776 |
| Title | Synthesis and SAR of sulfoxide substituted carboxyquinolines as NK3 receptor antagonists. |
| Abstract | The neurokinin-3 (NK3) receptor is regarded as a potential novel target for treating patients with schizophrenia. Herein we report the synthesis and SAR of a series of C3-alkylsulfoxide substituted quinolines as potent NK3 receptor antagonists. These compounds have excellent NK3 functional activity, good selectivity and drug-like properties. Several key compounds have good in vitro/in vivo DMPK characteristics, and are active in a gerbil locomotor activity model. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 28 | Proc. Natl. Acad. Sci. U.S.A. 2011 Sep 108: 15444-9 |
| PMID | 21878565 |
| Title | Stereotyped fetal brain disorganization is induced by hypoxia and requires lysophosphatidic acid receptor 1 (LPA1) signaling. |
| Abstract | Fetal hypoxia is a common risk factor that has been associated with a range of CNS disorders including epilepsy, schizophrenia, and autism. Cellular and molecular mechanisms through which hypoxia may damage the developing brain are incompletely understood but are likely to involve disruption of the laminar organization of the cerebral cortex. Lysophosphatidic acid (LPA) is a bioactive lipid capable of cortical influences via one or more of six cognate G protein-coupled receptors, LPA(1-6), several of which are enriched in fetal neural progenitor cells (NPCs). Here we report that fetal hypoxia induces cortical disruption via increased LPA(1) signaling involving stereotyped effects on NPCs: N-cadherin disruption, displacement of mitotic NPCs, and impaired neuronal migration, as assessed both ex vivo and in vivo. Importantly, genetic removal or pharmacological inhibition of LPA(1) prevented the occurrence of these hypoxia-induced phenomena. Hypoxia resulted in overactivation of LPA(1) through selective inhibition of G protein-coupled receptor kinase 2 expression and activation of downstream pathways including G(?i) and Ras-related C3 botulinum toxin substrate 1. These data identify stereotyped and selective hypoxia-induced cerebral cortical disruption requiring LPA(1) signaling, inhibition of which can reduce or prevent disease-associated sequelae, and may take us closer to therapeutic treatment of fetal hypoxia-induced CNS disorders and possibly other forms of hypoxic injury. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 29 | Brain Res. 2011 Mar 1377: 21-31 |
| PMID | 21195697 |
| Title | The effects of catechol-O-methyl-transferase polymorphism Val158Met on functional connectivity in healthy young females: a resting EEG study. |
| Abstract | The catechol-O-methyl-transferase (COMT) gene has been linked to a wide spectrum of human phenotypes, including cognition, affective response, pain sensitivity, anxiety and psychosis. This study examined the modulatory effects of COMT Val158Met on neural interactions, indicated by connectivity strengths. Blood samples and resting state eyes-closed EEG signals were collected in 254 healthy young females. The COMT Val158Met polymorphism was decoded into 3 groups: Val/Val, Val/Met and Met/Met. The values of mutual information of 20 frontal-related channel pairs across delta, theta, alpha and beta frequencies were analyzed based on the time-frequency mutual information method. Our one-way ANOVA analyses revealed that the significant connection-frequency pairs were relatively left lateralized (P<0.01) and included F7-T3 and F7-C3 at delta frequency, and F3-F4, F7-T3, F7-C3, F7-P3, F3-C3, F3-F7 and F4-F8 at theta frequency. The F-test at F7-T3 and F7-C3 theta surpassed the statistical threshold of P<0.003 (after Bonferroni correction). For all the above connection-frequency pairs, there was a dose-dependent trend in the connectivity strengths of the alleles as follows: Val/Val>Val/Met>Met/Met. Our analyses complemented previous literature regarding neural modulation by the COMT Val158Met polymorphism. The implication to the pathogenesis in schizophrenia was also discussed. Further studies are needed to clarify whether there is gender difference on this gene-brain interaction. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 30 | Zhonghua Yi Xue Za Zhi 2011 Nov 91: 3040-3 |
| PMID | 22333055 |
| Title | [Preliminary study on variations and neural generators of error-related negativity in first episode schizophrenics]. |
| Abstract | To explore the variations and their activated brain areas of error-related negativity (ERN) in first episode schizophrenics. ERN was tested by an ERP device and their activated brain areas were compared in 58 first episode schizophrenics (FES) and 62 normal controls (NC) from March 2010 to February 2011. (1) The ERN latencies in the FES group were significantly longer on Cz (58 ± 14 ms), Fz (60 ± 11 ms), C3 (57 ± 17 ms) and C4 (60 ± 13 ms) electrodes compared with those in the NC group (49 ± 13 ms, 47 ± 13 ms, 50 ± 14 ms, 51 ± 12 ms). And the ERN amplitudes were significantly lower than those in the controls in Cz (5.0 ± 2.8 µV; 7.5 ± 3.1 µV, P < 0.01), C3 (5.5 ± 4.0 µV; 8.0 ± 3.7 µV, P < 0.01), Fz (5.0 ± 3.1 µV; 7.7 ± 3.8 µV, P < 0.01) and Pz (4.5 ± 3.3 µV: 7.5 ± 3.0 µV, P < 0.01) electrodes.(2) The variations of ERN latencies and amplitudes showed an insignificant correlation with the positive symptom scores and total scores of PANSS. (3) The activation levels of insula, superior temporal gyrus, middle temporal gyrus and inferior parietal lobule were obviously lower in the FES group than those in the NC group. The anomalies of ERN latencies and amplitudes in first episode schizophrenics may reflect the deficient error-monitoring functions. Further studies are warranted. And such brain areas as insular may contribute pathogenically to the dysfunctions of error-monitoring in schizophrenics. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 31 | Rev Bras Psiquiatr 2012 Mar 34: 119-20 |
| PMID | 22392401 |
| Title | Increased serum levels of C3 and C4 in patients with schizophrenia compared to eutymic patients with bipolar disorder and healthy. |
| Abstract | -1 |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 32 | Niger J Physiol Sci 2012 Jun 27: 19-21 |
| PMID | 23235303 |
| Title | Complement factors in newly diagnosed Nigerian schizoprenic patients and those on antipsychotic therapy. |
| Abstract | The role of Complement factors in the pathogenesis of psychiatric disorders is enormous, but the data on levels and functions of complement factors in patients with schizophrenia are scanty and conflicting. To address this issue, levels of Complement regulators (C1 inhibitor and C3 activator) and complement factors (C1q, C3c, C4 and C5) were determined in the serum of newly diagnosed drug free schizophrenic patients, schizophrenic patients on medication and healthy subjects using immune-plates. C1q was significantly reduced in newly diagnosed schizophrenic patients or schizophrenic patients on medication compared with the controls. C3c was significantly reduced in newly diagnosed schizophrenic patients compared with controls or schizophrenic patients on medication. The levels of C3 activators, C1 inhibitors and C4 were similar in the two groups of schizophrenic patients compared with the controls. It may be concluded from this study that C1q is deficient in schizophrenic patients; and that C3c may differentiate newly diagnosed schizophrenia from schizophrenic patients on medication. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 33 | Niger J Physiol Sci 2012 Jun 27: 19-21 |
| PMID | 23235303 |
| Title | Complement factors in newly diagnosed Nigerian schizoprenic patients and those on antipsychotic therapy. |
| Abstract | The role of Complement factors in the pathogenesis of psychiatric disorders is enormous, but the data on levels and functions of complement factors in patients with schizophrenia are scanty and conflicting. To address this issue, levels of Complement regulators (C1 inhibitor and C3 activator) and complement factors (C1q, C3c, C4 and C5) were determined in the serum of newly diagnosed drug free schizophrenic patients, schizophrenic patients on medication and healthy subjects using immune-plates. C1q was significantly reduced in newly diagnosed schizophrenic patients or schizophrenic patients on medication compared with the controls. C3c was significantly reduced in newly diagnosed schizophrenic patients compared with controls or schizophrenic patients on medication. The levels of C3 activators, C1 inhibitors and C4 were similar in the two groups of schizophrenic patients compared with the controls. It may be concluded from this study that C1q is deficient in schizophrenic patients; and that C3c may differentiate newly diagnosed schizophrenia from schizophrenic patients on medication. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 34 | Biol. Psychiatry 2012 May 71: 906-14 |
| PMID | 22458949 |
| Title | Abnormalities of the Duo/Ras-related C3 botulinum toxin substrate 1/p21-activated kinase 1 pathway drive myosin light chain phosphorylation in frontal cortex in schizophrenia. |
| Abstract | Recent studies on GTPases have suggested that reduced Duo and cell division cycle 42 (Cdc42) transcript expression is involved in dendritic spine loss in schizophrenia. In murine models, Duo and Cdc42 phosphorylate p21-activated kinase 1 (PAK1), which modifies the activity of regulatory myosin light chain (MLC) and cofilin by altering their phosphorylation. Therefore, we hypothesized that in schizophrenia abnormal Duo and Cdc42 expression result in changes in MLC and/or cofilin phosphorylation, which might alter actin cytoskeleton dynamics underlying dendritic spine maintenance. We performed Western blot protein expression analysis in postmortem brains from patients diagnosed with schizophrenia and a comparison group. We focused our studies in the anterior cingulate cortex (ACC; n = 33 comparison group; n = 36 schizophrenia) and dorsolateral prefrontal cortex (DLPFC; n = 29 comparison group; n = 35 schizophrenia). In both ACC and DLPFC, we found a reduction of Duo expression and PAK1 phosphorylation in schizophrenia. Cdc42 protein expression was decreased in ACC but not in DLPFC. In ACC, we observed decreased PAK1 phosphorylation and increased MLC phosphorylation (pMLC), whereas in DLPFC pMLC remained unchanged. These data suggest a novel mechanism that might underlie dendritic spine loss in schizophrenia. The increase in pMLC seen in ACC might be associated with dendritic spine shrinkage. The lack of an effect on pMLC in DLPFC suggests that in schizophrenia PAK1 downstream pathways are differentially affected in these cortical areas. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 35 | Eur Arch Psychiatry Clin Neurosci 2012 Oct 262: 565-77 |
| PMID | 22441714 |
| Title | Structural synaptic elements are differentially regulated in superior temporal cortex of schizophrenia patients. |
| Abstract | Inaccurate wiring and synaptic pathology appear to be major hallmarks of schizophrenia. A variety of gene products involved in synaptic neurotransmission and receptor signaling are differentially expressed in brains of schizophrenia patients. However, synaptic pathology may also develop by improper expression of intra- and extra-cellular structural elements weakening synaptic stability. Therefore, we have investigated transcription of these elements in the left superior temporal gyrus of 10 schizophrenia patients and 10 healthy controls by genome-wide microarrays (Illumina). Fourteen up-regulated and 22 downregulated genes encoding structural elements were chosen from the lists of differentially regulated genes for further qRT-PCR analysis. Almost all genes confirmed by this method were downregulated. Their gene products belonged to vesicle-associated proteins, that is, synaptotagmin 6 and syntaxin 12, to cytoskeletal proteins, like myosin 6, pleckstrin, or to proteins of the extracellular matrix, such as collagens, or laminin C3. Our results underline the pivotal roles of structural genes that control formation and stabilization of pre- and post-synaptic elements or influence axon guidance in schizophrenia. The glial origin of collagen or laminin highlights the close interrelationship between neurons and glial cells in establishment and maintenance of synaptic strength and plasticity. It is hypothesized that abnormal expression of these and related genes has a major impact on the pathophysiology of schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 36 | Int J Psychophysiol 2013 Jul 89: 63-71 |
| PMID | 23707337 |
| Title | Interhemispheric EEG coherence is reduced in auditory cortical regions in schizophrenia patients with auditory hallucinations. |
| Abstract | Central auditory processing has been reported to be impaired in schizophrenia patients who experience auditory hallucinations, and interhemispheric transfer in auditory circuits may be compromised. In this study, we used EEG spectral coherence to examine interhemispheric connectivity between cortical areas known to be important in the processing of auditory information. Coherence was compared across three subject groups: schizophrenia patients with a recent history of auditory hallucinations (AH), schizophrenia patients who did not experience auditory hallucinations (nonAH), and healthy controls (HC). Subjects listened to pure tone and word stimuli while EEG was recorded continuously. Upper alpha and upper beta band coherence was calculated from six pairs of electrodes located over homologous auditory areas in the left and right cerebral hemispheres. Significant between-group differences were found on four electrode pairs (C3-C4, C5-C6, Ft7-Ft8 and Cp5-Cp6) in the upper alpha band. Relative to both the HC and nonAH groups, coherence was lower in the AH patients, consistent with the hypothesis that interhemispheric connectivity is reduced in these patients. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 37 | World J. Biol. Psychiatry 2013 Sep 14: 478-89 |
| PMID | 22248022 |
| Title | Metabolic, hormonal and stress-related molecular changes in post-mortem pituitary glands from schizophrenia subjects. |
| Abstract | To identify a molecular profile for schizophrenia using post-mortem pituitaries from schizophrenia and control subjects. Molecular profiling analysis of pituitaries from schizophrenia (n = 14) and control (n = 15) subjects was carried out using a combination of liquid chromatography tandem mass spectrometry (LC-MS(E)), multiplex analyte profiling (MAP), two-dimensional difference gel electrophoresis (2D-DIGE) and Western blot analysis. This led to identification of differentially expressed molecules in schizophrenia patients including hypothalamic-pituitary-adrenal axis-associated constituents such as cortisol, pro-adrenocorticotropic hormone, arginine vasopressin precursor, agouti-related protein, growth hormone, prolactin and secretagogin, as well as molecules associated with lipid transport and metabolism such as apolipoproteins A1, A2, C3 and H. Altered levels of secretagogin in serum from a cohort of living first onset schizophrenia patients were also detected, suggesting disease association and illustrating the potential for translating some components of this molecular profile to serum-based assays. Future studies on the molecules identified here may lead to new insights into schizophrenia pathophysiology and pave the way for translation of novel diagnostics for use in a clinical setting. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 38 | Beilstein J Org Chem 2014 -1 10: 1114-20 |
| PMID | 24991261 |
| Title | Stereocontrolled synthesis of 5-azaspiro[2.3]hexane derivatives as conformationally "frozen" analogues of L-glutamic acid. |
| Abstract | Several strategies aimed to "freeze" natural amino acids into more constrained analogues have been developed with the aim of enhancing in vitro potency/selectivity and, more in general, drugability properties. The case of L-glutamic acid (L-Glu, 1) is of particular importance since it is the primary excitatory neurotransmitter in the mammalian central nervous system (CNS) and plays a critical role in a wide range of disorders like schizophrenia, depression, neurodegenerative diseases such as Parkinson's and Alzheimer's and in the identification of new potent and selective ligands of ionotropic and metabotropic glutamate receptors (GluRs). To this aim, bicycle compound Ib was designed and synthesised from D-serine as novel [2.3]-spiro analogue of L-Glu. This frozen amino acid derivative was designed to further limit the rotation around the C3-C4 bond present in the azetidine derivative Ia by incorporating an appropriate spiro moiety. The cyclopropyl moiety was introduced by a diastereoselective rhodium catalyzed cyclopropanation reaction. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 39 | Clin Psychopharmacol Neurosci 2014 Apr 12: 48-53 |
| PMID | 24851121 |
| Title | Drug Treated Schizophrenia, Schizoaffective and Bipolar Disorder Patients Evaluated by qEEG Absolute Spectral Power and Mean Frequency Analysis. |
| Abstract | Research of electroencephalograph (EEG) power spectrum and mean frequency has shown inconsistent results in patients with schizophrenic, schizoaffective and bipolar disorders during medication when compared to normal subjects thus; the characterization of these parameters is an important task. We applied quantitative EEG (qEEG) to investigate 38 control, 15 schizophrenic, 7 schizoaffective and 11 bipolar disorder subjects which remaine under the administration of psychotropic drugs (except control group). Absolute spectral power (ASP), mean frequency and hemispheric electrical asymmetry were measured by 19 derivation qEEG. Group mean values were compared with non parametrical Mann-Whitney test and spectral EEG maps with z-score method at p < 0.05. Most frequent drug treatments for schizophrenic patients were neuroleptic+antiepileptic (40% of cases) or 2 neuroleptics (33.3%). Schizoaffective patients received neuroleptic+benzodiazepine (71.4%) and for bipolar disorder patients neuroleptic+antiepileptic (81.8%). schizophrenic (at all derivations except for Fp1, Fp2, F8 and T6) and schizoaffective (only at C3) show higher values of ASP (+57.7% and +86.1% respectively) compared to control group. ASP of bipolar disorder patients did not show differences against control group. The mean frequency was higher at Fp1 (+14.2%) and Fp2 (+17.4%) in bipolar disorder patients than control group, but no differences were found in frequencies between schizophrenic or schizoaffective patients against the control group. Majority of spectral differences were found at the left hemisphere in schizophrenic and schizoaffective but not in bipolar disorder subjects. The present report contributes to characterize quantitatively the qEEG in drug treated schizophrenic, schizoaffective or bipolar disorder patients. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 40 | Clin Psychopharmacol Neurosci 2014 Apr 12: 48-53 |
| PMID | 24851121 |
| Title | Drug Treated Schizophrenia, Schizoaffective and Bipolar Disorder Patients Evaluated by qEEG Absolute Spectral Power and Mean Frequency Analysis. |
| Abstract | Research of electroencephalograph (EEG) power spectrum and mean frequency has shown inconsistent results in patients with schizophrenic, schizoaffective and bipolar disorders during medication when compared to normal subjects thus; the characterization of these parameters is an important task. We applied quantitative EEG (qEEG) to investigate 38 control, 15 schizophrenic, 7 schizoaffective and 11 bipolar disorder subjects which remaine under the administration of psychotropic drugs (except control group). Absolute spectral power (ASP), mean frequency and hemispheric electrical asymmetry were measured by 19 derivation qEEG. Group mean values were compared with non parametrical Mann-Whitney test and spectral EEG maps with z-score method at p < 0.05. Most frequent drug treatments for schizophrenic patients were neuroleptic+antiepileptic (40% of cases) or 2 neuroleptics (33.3%). Schizoaffective patients received neuroleptic+benzodiazepine (71.4%) and for bipolar disorder patients neuroleptic+antiepileptic (81.8%). schizophrenic (at all derivations except for Fp1, Fp2, F8 and T6) and schizoaffective (only at C3) show higher values of ASP (+57.7% and +86.1% respectively) compared to control group. ASP of bipolar disorder patients did not show differences against control group. The mean frequency was higher at Fp1 (+14.2%) and Fp2 (+17.4%) in bipolar disorder patients than control group, but no differences were found in frequencies between schizophrenic or schizoaffective patients against the control group. Majority of spectral differences were found at the left hemisphere in schizophrenic and schizoaffective but not in bipolar disorder subjects. The present report contributes to characterize quantitatively the qEEG in drug treated schizophrenic, schizoaffective or bipolar disorder patients. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 41 | Schizophr. Res. 2015 Jul 165: 201-11 |
| PMID | 25956630 |
| Title | Protein expression of targets of the FMRP regulon is altered in brains of subjects with schizophrenia and mood disorders. |
| Abstract | Fragile X mental retardation protein (FMRP) is an RNA binding protein with 842 target mRNAs in mammalian brain. Silencing of the fragile X mental retardation 1 (FMR1) gene leads to loss of expression of FMRP and upregulated metabotropic glutamate receptor 5 (mGluR5) signaling resulting in the multiple physical and cognitive deficits associated with fragile X syndrome (FXS). Reduced FMRP expression has been identified in subjects with autism, schizophrenia, bipolar disorder, and major depression who do not carry the mutation for FMR1. Our laboratory has recently demonstrated altered expression of four downstream targets of FMRP-mGluR5 signaling in brains of subjects with autism: homer 1, amyloid beta A4 precursor protein (APP), ras-related C3 botulinum toxin substrate 1 (RAC1), and striatal-enriched protein tyrosine phosphatase (STEP). In the current study we investigated the expression of the same four proteins in lateral cerebella of subjects with schizophrenia, bipolar disorder, and major depression and in frontal cortex of subjects with schizophrenia and bipolar disorder. In frontal cortex we observed: 1) reduced expression of 120 kDa form of APP in subjects with schizophrenia and bipolar disorder; 2) reduced expression of 61 kDa and 33k Da forms of STEP in subjects with schizophrenia; 3) reduced expression of 88 kDa form of APP in subjects with bipolar disorder; and 3) trends for reduced expression of 88 kDa form of APP and homer 1 in subjects with schizophrenia and bipolar disorder, respectively. In lateral cerebella there was no group difference, however we observed increased expression of RAC1 in subjects with bipolar disorder, and trends for increased RAC1 in subjects with schizophrenia and major depression. Our results provide further evidence that proteins involved in the FMRP-mGluR5 signaling pathway are altered in schizophrenia and mood disorders. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 42 | PLoS ONE 2015 -1 10: e0136372 |
| PMID | 26305563 |
| Title | A Preliminary Genetic Analysis of Complement 3 Gene and Schizophrenia. |
| Abstract | Complement pathway activation was found to occur frequently in schizophrenia, and complement 3 (C3) plays a major role in this process. Previous studies have provided evidence for the possible role of C3 in the development of schizophrenia. In this study, we hypothesized that the gene encoding C3 (C3) may confer susceptibility to schizophrenia in Han Chinese. We analyzed 7 common single nucleotide polymorphisms (SNPs) of C3 in 647 schizophrenia patients and 687 healthy controls. Peripheral C3 mRNA expression level was measured in 23 drug-naïve patients with schizophrenia and 24 controls. Two SNPs (rs1047286 and rs2250656) that deviated from Hardy-Weinberg equilibrium were excluded for further analysis. Among the remaining 5 SNPs, there was no significant difference in allele and genotype frequencies between the patient and control groups. Logistic regression analysis showed no significant SNP-gender interaction in either dominant model or recessive model. There was no significant difference in the level of peripheral C3 expression between the drug-naïve schizophrenia patients and healthy controls. In conclusion, the results of this study do not support C3 as a major genetic susceptibility factor in schizophrenia. Other factors in AP may have critical roles in schizophrenia and be worthy of further investigation. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 43 | Neurochem. Res. 2015 May 40: 906-14 |
| PMID | 25720829 |
| Title | C3 Polymorphism Influences Circulating Levels of C3, ASP and Lipids in Schizophrenic Patients. |
| Abstract | Excessive activation of complement is associated with many diseases including schizophrenia. Investigation of C3 polymorphisms, circulating C3, cleavage product ASP/C3adesArg, and lipid metabolism. Cross-sectional analysis. C3 genotyping (CC vs GG for R102L) was performed on 434 Tunisian people consisting of 272 schizophrenic (SZ) patients and 162 control subjects. In a age- and gender-matched subgroups of the three genotypes (131 SZ and 112 NOR), plasma triglycerides, total cholesterol (C), LDL-C, HDL-C, ASP, and complement C3 were measured. C3 gene polymorphism influences BMI and plasma C3, ASP, triglyceride, total cholesterol, LDL-C and HDL-C among SZ patients (p < 0.05-0.0001), with increasing values demonstrated from CC (common form) to CG (heterozygote form) to GG (rare homozygote) forms. Significant correlations between plasma C3 and BMI, triglyceride, HDL-C and ASP (p < 0.05-0.0001) were observed, while ASP correlated with BMI and LDL-C (p = 0.005, p = 0.001, respectively) in SZ patients. Further, proportional conversion of C3 to ASP (%ASP/C3) also increased (p < 0.0001, GG>CG>CC). C3 polymorphisms and plasma C3, ASP and %ASP/C3 correlated with lipid parameters in this SZ population, suggesting that factors predisposing patients to schizophrenia are permissive for complement pathway activation and dyslipidemic influences. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 44 | Neurochem. Res. 2015 May 40: 906-14 |
| PMID | 25720829 |
| Title | C3 Polymorphism Influences Circulating Levels of C3, ASP and Lipids in Schizophrenic Patients. |
| Abstract | Excessive activation of complement is associated with many diseases including schizophrenia. Investigation of C3 polymorphisms, circulating C3, cleavage product ASP/C3adesArg, and lipid metabolism. Cross-sectional analysis. C3 genotyping (CC vs GG for R102L) was performed on 434 Tunisian people consisting of 272 schizophrenic (SZ) patients and 162 control subjects. In a age- and gender-matched subgroups of the three genotypes (131 SZ and 112 NOR), plasma triglycerides, total cholesterol (C), LDL-C, HDL-C, ASP, and complement C3 were measured. C3 gene polymorphism influences BMI and plasma C3, ASP, triglyceride, total cholesterol, LDL-C and HDL-C among SZ patients (p < 0.05-0.0001), with increasing values demonstrated from CC (common form) to CG (heterozygote form) to GG (rare homozygote) forms. Significant correlations between plasma C3 and BMI, triglyceride, HDL-C and ASP (p < 0.05-0.0001) were observed, while ASP correlated with BMI and LDL-C (p = 0.005, p = 0.001, respectively) in SZ patients. Further, proportional conversion of C3 to ASP (%ASP/C3) also increased (p < 0.0001, GG>CG>CC). C3 polymorphisms and plasma C3, ASP and %ASP/C3 correlated with lipid parameters in this SZ population, suggesting that factors predisposing patients to schizophrenia are permissive for complement pathway activation and dyslipidemic influences. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 45 | Pharmacogenomics J. 2015 Oct -1: -1 |
| PMID | 26503818 |
| Title | Complement 3 and metabolic syndrome induced by clozapine: a cross-sectional study and retrospective cohort analysis. |
| Abstract | Metabolic syndrome (MetS) is considered to be an adverse effect of long-term treatment with atypical antipsychotics, particularly clozapine. There is strong evidence that the activation of inflammatory pathways interferes with normal metabolism and contributes to the development of MetS. C3, which is an inflammation molecule, has been reported to be associated with MetS. Because C3 is a heritable trait, we accordingly hypothesized that the gene encoding C3 (C3) would be a candidate gene for inter-individual variation in clozapine-induced MetS. We recruited 576 schizophrenia patients taking clozapine and measured the serum levels of fasting metabolic parameters. We then examined C3 mRNA and genotyped seven polymorphisms in C3. The expression quantitative trait locus (eQTL) data available for tissues were extracted by the Genotype-Tissue Expression Portal. A total of 105 patients' medical records were retrospectively reviewed to obtain the metabolic parameters during the initial 2-year clozapine treatment. The relative expression levels of C3 mRNA in patients with MetS were significantly higher than in those without MetS (P=0.02). C3 single-nucleotide polymorphism (SNP) rs2277984 was marginally associated with MetS (allelic P=0.06, odds ratio=1.36, 95% confidence interval (CI): 1.07-1.72). We found a significant association of rs2277984 with fasting triglyceride (TG) levels (P=0.004). Further, eQTL analysis revealed that rs2277984 regulates C3 expression in the liver (P=0.002). Similar results were found in the retrospective cohort analysis. The receiver operating characteristic curve showed a significant effect of the rs2277984 G allele on the percentage change of TG levels, with an area under the curve of 0.71 (95% CI: 0.60-0.81). C3 is likely to enhance TG accumulation and to confer susceptibility to clozapine-induced MetS. The C3 SNP rs2277984 may be a potential biomarker for predicting MetS risk in patients receiving clozapine treatment.The Pharmacogenomics Journal advance online publication, 27 October 2015; doi:10.1038/tpj.2015.68. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 46 | Chin. Med. J. 2015 Aug 128: 2215-9 |
| PMID | 26265616 |
| Title | Follow-up of N400 in the Rehabilitation of First-episode Schizophrenia. |
| Abstract | The N400 component of event-related potentials (ERP) has recently drawn widespread attention at home and abroad. This study was to explore the relationship between N400 changes and risperidone treatment and rehabilitation infirst-episode schizophrenia (FES). ERP component N400 was recorded by Guangzhou Runjie WJ-1 ERP instruments, in 58 FES before and 6 months, 15 months after risperidone treatment, and in 62 normal controls. The patients' syndromes were assessed by Positive and Negative Syndrome Scale (PANSS). And the stimuli are Chinese sentences with matching (congruent) or mismatching (incongruent) ending words. N400 latencies were prolonged, and amplitudes were decreased in Cz, Pz, Fz, C3, C4, in FES compared with in NC, before treatment. The prolonged N400 latencies and decreased amplitudes were negatively correlated with the patients' positive scale and total scale of PANSS. There are significant differences of N400 amplitudes and latencies in 6 months and 15 months follow-up after treatment. Before treatment, 6 months and 15 months after treatment, N400 latencies are 446 ± 35 ms, 440 ± 37 ms, 414 ± 31 ms (F = 9.72, P < 0.01) in incongruent situation; N400 amplitudes are 5.2 ± 4.6 ?V, 5.7 ± 4.8 ?V, 7.3 ± 5.0 ?V (F = 2.06, P > 0.05) in congruent situation, and 8.5 ± 5.9 ?V, 10.1 ± 5.0 ?V, 11.9 ± 7.0 ?V (F = 3.697, P < 0.05) in incongruent situation. N400 could be used to predict the effects of treatment of schizophrenia to some degree. The linguistic and cognitive impairment in schizophrenia can be improved by antipsychotic drugs. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 47 | Psychiatry Res 2015 Aug 228: 431-40 |
| PMID | 26154818 |
| Title | No evidence for mirror system dysfunction in schizophrenia from a multimodal TMS/EEG study. |
| Abstract | Dysfunctional mirror neuron systems have been proposed to contribute to the social cognitive deficits observed in schizophrenia. A few studies have explored mirror systems in schizophrenia using various techniques such as TMS (levels of motor resonance) or EEG (levels of mu suppression), with mixed results. This study aimed to use a novel multimodal approach (i.e. concurrent TMS and EEG) to further investigate mirror systems and social cognition in schizophrenia. Nineteen individuals with schizophrenia or schizoaffective disorder and 19 healthy controls participated. Single-pulse TMS was applied to M1 during the observation of hand movements designed to elicit mirror system activity. Single EEG electrodes (C3, CZ, C4) recorded brain activity. Participants also completed facial affect recognition and theory of mind tasks. The schizophrenia group showed significant deficits in facial affect recognition and higher level theory of mind compared to healthy controls. A significant positive relationship was revealed between mu suppression and motor resonance for the overall sample, indicating concurrent validity of these measures. Levels of mu suppression and motor resonance were not significantly different between groups. These findings indicate that in stable outpatients with schizophrenia, mirror system functioning is intact, and therefore their social cognitive difficulties may be caused by alternative pathophysiology. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 48 | Neurochem. Res. 2016 Apr 41: 944 |
| PMID | 26961885 |
| Title | Erratum to: C3 Polymorphism Influences Circulating Levels of C3, ASP and Lipids in Schizophrenic Patients. |
| Abstract | -1 |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 49 | Schizophr. Res. 2016 May -1: -1 |
| PMID | 27156240 |
| Title | The glial phosphorylase of glycogen isoform is reduced in the dorsolateral prefrontal cortex in chronic schizophrenia. |
| Abstract | Reduced glutamatergic activity and energy metabolism in the dorsolateral prefrontal cortex (DLPFC) have been described in schizophrenia. Glycogenolysis in astrocytes is responsible for providing neurons with lactate as a transient energy supply helping to couple glutamatergic neurotransmission and glucose utilization in the brain. This mechanism could be disrupted in schizophrenia. The aim of this study was to explore whether the protein levels of the astrocyte isoform of glycogen phosphorylase (PYGM), key enzyme of glycogenolysis, and the isoform A of Ras-related C3 botulinum toxin substrate 1 (RAC1), a kinase that regulates PYGM activity, are altered in the postmortem DLPFC of chronic schizophrenia patients (n=23) and matched controls (n=23). We also aimed to test NMDAR blockade effect on these proteins in the mouse cortex and cortical astrocytes and antipsychotic treatments in rats. Here we report a reduction in PYGM and RAC1 protein levels in the DLPFC in schizophrenia. We found that treatment with the NMDAR antagonist dizocilpine in mice as a model of psychosis increased PYGM and reduced RAC1 protein levels. The same result was observed in rat cortical astroglial-enriched cultures. 21-day haloperidol treatment increased PYGM levels in rats. These results show that PYGM and RAC1 are altered in the DLPFC in chronic schizophrenia and are controlled by NMDA signalling in the rodent cortex and cortical astrocytes suggesting an altered NMDA-dependent glycogenolysis in astrocytes in schizophrenia. Together, this study provides evidence of a NMDA-dependent transient local energy deficit in neuron-glia crosstalk in schizophrenia, contributing to energy deficits of the disorder. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |