| 1 | Proc. Natl. Acad. Sci. U.S.A. 2000 Aug 97: 9276-80 |
|---|---|
| PMID | 10908653 |
| Title | Subnucleus-specific loss of neurons in medial thalamus of schizophrenics. |
| Abstract | The hypoactivity of dorsolateral prefrontal cortex in schizophrenics is well known. One cause of this hypoactivity may be defective corticocortical or thalamocortical connections. Recent imaging studies of the thalamus suggest reductions in volume of the whole thalamus and reduced activity in the medial group of thalamic nuclei, which may indicate loss of functional input to the cortex. Using stereological techniques in six pairs of individually matched brains from schizophrenics and controls, we measured the volumes and obtained estimates of the number of neurons in the three subnuclei (parvocellular, PC; densocellular, dc; magnocellular, mc) of the mediodorsal nucleus (MD) and from the ventral posterior medial nucleus. There was a significant reduction in total neuron number in MD as a whole but this neuron loss was largely restricted to MDPC and MDdc [-30.9 and -24.5%, respectively (P PC and MDdc has implications for the functional defects observed in schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 2 | Proc. Natl. Acad. Sci. U.S.A. 2000 Aug 97: 9276-80 |
| PMID | 10908653 |
| Title | Subnucleus-specific loss of neurons in medial thalamus of schizophrenics. |
| Abstract | The hypoactivity of dorsolateral prefrontal cortex in schizophrenics is well known. One cause of this hypoactivity may be defective corticocortical or thalamocortical connections. Recent imaging studies of the thalamus suggest reductions in volume of the whole thalamus and reduced activity in the medial group of thalamic nuclei, which may indicate loss of functional input to the cortex. Using stereological techniques in six pairs of individually matched brains from schizophrenics and controls, we measured the volumes and obtained estimates of the number of neurons in the three subnuclei (parvocellular, PC; densocellular, dc; magnocellular, mc) of the mediodorsal nucleus (MD) and from the ventral posterior medial nucleus. There was a significant reduction in total neuron number in MD as a whole but this neuron loss was largely restricted to MDPC and MDdc [-30.9 and -24.5%, respectively (P PC and MDdc has implications for the functional defects observed in schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 3 | Cereb. Cortex 2000 Jan 10: 40-9 |
| PMID | 10639394 |
| Title | Mapping morphology of the corpus callosum in schizophrenia. |
| Abstract | The nature and extent of callosal morphological alterations in schizophrenia remain unresolved. A parametric surface modeling approach using magnetic resonance (MR) images was employed. This provided spatially accurate representations of midsagittal callosal surfaces in schizophrenic patients (n = 25; 15 males) and normal controls (n = 28; 15 males). Areas of functionally relevant callosal channels and measures reflecting callosal shape were visualized and compared across groups. To register neuroanatomical landmarks surrounding the corpus callosum, each three-dimensional MR volume was scaled according to Talairach AC-PC distance, and raw distances included as covariates in multivariate analyses. Results revealed: (i) a marked vertical displacement of the corpus callosum in patients (P < 0.01); (ii) increases in curvature of superior and inferior callosal surfaces (P < 0.001); and (iii) significant increases in maximum widths in anterior and posterior regions in male patients compared to male controls; as well as (iv) increased patterns of callosal variability in female patients but no effects of diagnosis between female groups. These findings demonstrate a clear index of structural neuropathology in male schizophrenic patients. Displacement and curvature increases were highly correlated with structural differences in surrounding neuroanatomical regions, including increased volume of the lateral ventricles (P < 0.01). |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 4 | Prog. Neuropsychopharmacol. Biol. Psychiatry 2000 Aug 24: 925-38 |
| PMID | 11041535 |
| Title | Differential effects of MK-801 on cerebrocortical neuronal injury in C57BL/6J, NSA, and ICR mice. |
| Abstract | 1. Antagonists of the N-methyl-D-aspartate (NMDA) glutamate (Glu) receptor, including [(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate], dizocilpine maleate (MK-801), injure pyramidal neurons in the posterior cingulate/retrosplenial (PC/RS) cortex when administered systemically to adult rats and mice. 2. These results have, to our knowledge, only been reported previously in Harlan Sprague Dawley albino rats and International Cancer Research (ICR) mice, an outbred albino strain. 3. Male Non-Swiss Albino (NSA) mice, an albino outbred strain, and male C57BL/6J (B6) mice, a pigmented inbred strain, were injected systemically with 1 mg/kg of MK-801 in the first experiment. This dose of MK-801 reliably produces cytoplasmic vacuoles in neurons in layers III and IV of the PC/RS cortex in 100% of ICR mice treated 4. There was a significant difference in the number of vacuolated neurons in B6 and NSA mice, as assessed by ANOVA. The NSA were not significantly different than previously examined ICR mice, but the B6 had fewer vacuolated neurons than either of the two outbred strains. 5. In the second experiment, male NSA, ICR, and B6 mice were injected systemically with a high dose, 10 mg/kg, of MK-801. This dose has been demonstrated to result in necrosis in the same population of neurons injured by lower doses of MK-801. 6. An ANOVA indicated that there was a significant difference among the three strains of mice, and a Fisher's protected t revealed that the B6 mice were significantly different from both the NSA and ICR, but that, with our test, those two strains were indistinguishable. 7. Male ICR, NSA, and B6 mice were tested in the holeboard food search task 5 hours after 1 mg/kg of MK-801. There were significant differences between the strains in performance both pre and posttreatment. The effect of the drug was not statistically significant. 8. These results suggest that there may be a genetically mediated difference in the reaction to NMDA receptor antagonists, a finding which may be important given the NMDA receptor hypofunction hypothesis for the etiology of schizophrenic symptoms. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 5 | Cereb. Cortex 2000 Jan 10: 40-9 |
| PMID | 10639394 |
| Title | Mapping morphology of the corpus callosum in schizophrenia. |
| Abstract | The nature and extent of callosal morphological alterations in schizophrenia remain unresolved. A parametric surface modeling approach using magnetic resonance (MR) images was employed. This provided spatially accurate representations of midsagittal callosal surfaces in schizophrenic patients (n = 25; 15 males) and normal controls (n = 28; 15 males). Areas of functionally relevant callosal channels and measures reflecting callosal shape were visualized and compared across groups. To register neuroanatomical landmarks surrounding the corpus callosum, each three-dimensional MR volume was scaled according to Talairach AC-PC distance, and raw distances included as covariates in multivariate analyses. Results revealed: (i) a marked vertical displacement of the corpus callosum in patients (P < 0.01); (ii) increases in curvature of superior and inferior callosal surfaces (P < 0.001); and (iii) significant increases in maximum widths in anterior and posterior regions in male patients compared to male controls; as well as (iv) increased patterns of callosal variability in female patients but no effects of diagnosis between female groups. These findings demonstrate a clear index of structural neuropathology in male schizophrenic patients. Displacement and curvature increases were highly correlated with structural differences in surrounding neuroanatomical regions, including increased volume of the lateral ventricles (P < 0.01). |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 6 | Zh Nevrol Psikhiatr Im S S Korsakova 2001 -1 101: 16-9 |
| PMID | 11586697 |
| Title | [Integral psychopathological model for impulse-control disorders in children, adolescents and young adults with schizophrenia]. |
| Abstract | Integral model for impulse-control disorders in schizophrenia is based on the data of examination of 200 patients who developed schizophrenia in childhood (14%) and adolescence (86%). The model comprises 4 components corresponding to the disorders variety. Phenomenological component (FC) reflects various pathological phenomena (sexual, eating, etc); typical psychopathological component (TPC) concerns mechanisms of their realization (impulsive, compulsive, obsessive, overvalued and transitional); processive component (PC) is represented by typical psychopathological traits comorbid with other psychopathological symptoms; evolutive component (EC) characterizes drive deviations, i.e. such manifestations that do not reach pathological level. FC stability allows considering it as a core in conventional space of the model, being surrounded by the other three components--TPC, PC, EC, thought to be marginal ones. Thus, impulse-control disorder dynamics in schizophrenia occurs due to change of its marginal components. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 7 | J Neural Transm (Vienna) 2001 -1 108: 1081-91 |
| PMID | 11716143 |
| Title | Effects of antipsychotic treatment on membrane phospholipid metabolism in schizophrenia. |
| Abstract | Several studies have shown an increased membrane phospholipid turnover in brain and blood cells of schizophrenic patients. However the specificity of these findings for schizophrenia and the effects of longterm antipsychotic treatment had yet to be demonstrated. In the present study we measured the concentrations of phospholipids in platelet membranes from 67 neuroleptic-free schizophrenic patients compared to both healthy and psychiatric controls, followed by repeated measurements during a 6 months antipsychotic treatment period. At baseline, levels of the main phospholipid components phosphatidylcholine (PC) and phosphatidylethanolamine (PE) were decreased and lysophosphatidylcholine (LPC), a major breakdown product of phospholipid metabolism, was increased in schizophrenic patients compared to healthy and to psychiatric controls, suggesting a specificity of the findings for schizophrenia. During the first 3-weeks on antipsychotic drug treatment LPC levels decreased to control values, but increased again during the following 6 months, reaching significantly higher levels than controls at the end of this period. Thus, at least in peripheral cells an increased breakdown of phospholipids in schizophrenia appears to be present during the acute episode, being influenced only by initial antipsychotic treatment, but without evidence of a long lasting treatment effect on membrane metabolism. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 8 | Psychiatry Res 2001 May 106: 171-80 |
| PMID | 11382539 |
| Title | Phospholipid abnormalities in postmortem schizophrenic brains detected by 31P nuclear magnetic resonance spectroscopy: a preliminary study. |
| Abstract | It has been hypothesized that schizophrenia arises from cell membrane abnormalities due to changes in phospholipid (PL) composition and metabolism. We have used high resolution, in vitro 31P nuclear magnetic resonance (NMR) to characterize the PLs in left frontal cortex (gray matter) of postmortem brain from four schizophrenics and five controls. High resolution 31P NMR spectra were obtained in an organic-solvent system to resolve PL classes (headgroups) and in a sodium-cholate, aqueous dispersion system to resolve phosphatidylcholine (PC) molecular species. Multivariate analysis which included the major PC molecular species and phosphatidylinositol (PI) showed a significant difference between schizophrenics and controls. Analysis of specific interactions showed that the PI was significantly higher in the schizophrenic group than in the control group. There were no differences between the two groups for other individual PL classes, or for individual PL subclasses determined by the linkage type at the sn-1 position on glycerol. There was a trend for total PL content to be higher in schizophrenics than in controls. There was no evidence for elevated lysophosphatidylcholine or lysophosphatidylethanolamine in schizophrenia. The intensity of the PC peak representing molecular species with one saturated and one unsaturated (one or two double bonds) acyl chain was higher for the schizophrenic group than for the control group. Although these results are not in complete agreement with previous studies, they support the idea that PL abnormalities occur in the brain in schizophrenia and that fatty acid metabolism may be abnormal. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 9 | J Neural Transm (Vienna) 2001 -1 108: 1081-91 |
| PMID | 11716143 |
| Title | Effects of antipsychotic treatment on membrane phospholipid metabolism in schizophrenia. |
| Abstract | Several studies have shown an increased membrane phospholipid turnover in brain and blood cells of schizophrenic patients. However the specificity of these findings for schizophrenia and the effects of longterm antipsychotic treatment had yet to be demonstrated. In the present study we measured the concentrations of phospholipids in platelet membranes from 67 neuroleptic-free schizophrenic patients compared to both healthy and psychiatric controls, followed by repeated measurements during a 6 months antipsychotic treatment period. At baseline, levels of the main phospholipid components phosphatidylcholine (PC) and phosphatidylethanolamine (PE) were decreased and lysophosphatidylcholine (LPC), a major breakdown product of phospholipid metabolism, was increased in schizophrenic patients compared to healthy and to psychiatric controls, suggesting a specificity of the findings for schizophrenia. During the first 3-weeks on antipsychotic drug treatment LPC levels decreased to control values, but increased again during the following 6 months, reaching significantly higher levels than controls at the end of this period. Thus, at least in peripheral cells an increased breakdown of phospholipids in schizophrenia appears to be present during the acute episode, being influenced only by initial antipsychotic treatment, but without evidence of a long lasting treatment effect on membrane metabolism. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 10 | Psychiatry Res 2001 May 106: 171-80 |
| PMID | 11382539 |
| Title | Phospholipid abnormalities in postmortem schizophrenic brains detected by 31P nuclear magnetic resonance spectroscopy: a preliminary study. |
| Abstract | It has been hypothesized that schizophrenia arises from cell membrane abnormalities due to changes in phospholipid (PL) composition and metabolism. We have used high resolution, in vitro 31P nuclear magnetic resonance (NMR) to characterize the PLs in left frontal cortex (gray matter) of postmortem brain from four schizophrenics and five controls. High resolution 31P NMR spectra were obtained in an organic-solvent system to resolve PL classes (headgroups) and in a sodium-cholate, aqueous dispersion system to resolve phosphatidylcholine (PC) molecular species. Multivariate analysis which included the major PC molecular species and phosphatidylinositol (PI) showed a significant difference between schizophrenics and controls. Analysis of specific interactions showed that the PI was significantly higher in the schizophrenic group than in the control group. There were no differences between the two groups for other individual PL classes, or for individual PL subclasses determined by the linkage type at the sn-1 position on glycerol. There was a trend for total PL content to be higher in schizophrenics than in controls. There was no evidence for elevated lysophosphatidylcholine or lysophosphatidylethanolamine in schizophrenia. The intensity of the PC peak representing molecular species with one saturated and one unsaturated (one or two double bonds) acyl chain was higher for the schizophrenic group than for the control group. Although these results are not in complete agreement with previous studies, they support the idea that PL abnormalities occur in the brain in schizophrenia and that fatty acid metabolism may be abnormal. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 11 | Psychiatry Res 2001 May 106: 171-80 |
| PMID | 11382539 |
| Title | Phospholipid abnormalities in postmortem schizophrenic brains detected by 31P nuclear magnetic resonance spectroscopy: a preliminary study. |
| Abstract | It has been hypothesized that schizophrenia arises from cell membrane abnormalities due to changes in phospholipid (PL) composition and metabolism. We have used high resolution, in vitro 31P nuclear magnetic resonance (NMR) to characterize the PLs in left frontal cortex (gray matter) of postmortem brain from four schizophrenics and five controls. High resolution 31P NMR spectra were obtained in an organic-solvent system to resolve PL classes (headgroups) and in a sodium-cholate, aqueous dispersion system to resolve phosphatidylcholine (PC) molecular species. Multivariate analysis which included the major PC molecular species and phosphatidylinositol (PI) showed a significant difference between schizophrenics and controls. Analysis of specific interactions showed that the PI was significantly higher in the schizophrenic group than in the control group. There were no differences between the two groups for other individual PL classes, or for individual PL subclasses determined by the linkage type at the sn-1 position on glycerol. There was a trend for total PL content to be higher in schizophrenics than in controls. There was no evidence for elevated lysophosphatidylcholine or lysophosphatidylethanolamine in schizophrenia. The intensity of the PC peak representing molecular species with one saturated and one unsaturated (one or two double bonds) acyl chain was higher for the schizophrenic group than for the control group. Although these results are not in complete agreement with previous studies, they support the idea that PL abnormalities occur in the brain in schizophrenia and that fatty acid metabolism may be abnormal. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 12 | J Abnorm Psychol 2002 Feb 111: 22-41 |
| PMID | 11866176 |
| Title | Response-monitoring dysfunction in schizophrenia: an event-related brain potential study. |
| Abstract | Error-monitoring abnormalities may underlie positive symptoms of schizophrenia. Response-synchronized event-related potentials during picture-word matching yielded error- and correct-response-related negativity (ERN, CRN) and positivity (Pe, PC) and preresponse lateralized readiness potentials (LRP) from 18 schizophrenic patients and 18 controls. Both groups responded faster to matches than nonmatches, although patients were generally slower and made more errors to nonmatches. Compared with controls, patients, particularly with paranoid subtype, had smaller ERNs and larger CRNs, which were indistinguishable. LRPs showed evidence of more response conflict before errors than before correct responses in controls but not patients. Despite ERN/CRN abnormalities, post-error slowing and Pe were normal in patients, suggesting a dissociation of ERN and error awareness. Anterior cingulate and dorsolateral prefrontal cortical dysfunction in schizophrenia are implicated. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 13 | J Abnorm Psychol 2002 Feb 111: 22-41 |
| PMID | 11866176 |
| Title | Response-monitoring dysfunction in schizophrenia: an event-related brain potential study. |
| Abstract | Error-monitoring abnormalities may underlie positive symptoms of schizophrenia. Response-synchronized event-related potentials during picture-word matching yielded error- and correct-response-related negativity (ERN, CRN) and positivity (Pe, PC) and preresponse lateralized readiness potentials (LRP) from 18 schizophrenic patients and 18 controls. Both groups responded faster to matches than nonmatches, although patients were generally slower and made more errors to nonmatches. Compared with controls, patients, particularly with paranoid subtype, had smaller ERNs and larger CRNs, which were indistinguishable. LRPs showed evidence of more response conflict before errors than before correct responses in controls but not patients. Despite ERN/CRN abnormalities, post-error slowing and Pe were normal in patients, suggesting a dissociation of ERN and error awareness. Anterior cingulate and dorsolateral prefrontal cortical dysfunction in schizophrenia are implicated. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 14 | Physiol. Behav. 2003 Nov 80: 359-66 |
| PMID | 14637236 |
| Title | Postnatal weight gain inhibition does not account for neurobehavioral consequences of neonatal Borna disease virus infection. |
| Abstract | Neonatal Borna disease virus (BDV) infection of the rat's brain produces neurodevelopmental damage similar to some pathological and clinical features of human developmental disorders, e.g., autism and schizophrenia. Since BDV-infected rats exhibited an inhibition of postnatal weight gain, the present study sought to evaluate a contribution of nutritional status to virus-induced neurodevelopmental injury. We compared neuroanatomical, neurochemical, and behavioral alterations following neonatal BDV infection and rearing in the oversized litters in Fischer344 rats on postnatal day (PND) 26. Despite a comparable weight gain inhibition, different patterns of brain pathology, alterations in brain monoamine systems, and behavioral deficits were observed in the BDV-infected rats compared to the malnourished rats. While no appreciable cell injury was noted in the brains of the malnourished rats, a significant loss of Purkinje cells (PC) and early signs of degeneration of the hippocampal dentate gyrus were found in the BDV-infected rats. Both neonatal BDV infection and postnatal malnourishment increased tissue concentrations of serotonin [5-hydroxytryptamine (5-HT)] in the hippocampus. In contrast, increased turnover of 5-HT in the cortex and hippocampus and elevated turnover of dopamine (DA) in the striatum were found in the malnourished rats only, suggesting that different pathogenic mechanisms might underlie monoamine disturbances in virus-infected and malnourished rats. The observed dissimilar neuroanatomical and neurochemical abnormalities might explain the different responses to novelty in the BDV-infected and malnourished rats. Compared to the control rats, the BDV-infected rats exhibited novelty-induced hyperactivity, while no differences in locomotion were noted between the control and malnourished rats. Taken together, the present data indicate that virus-associated inhibition of postnatal weight gain is unlikely to account for the major BDV-associated neurodevelopmental alterations that seem to be due to specific effects of neonatal BDV infection. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 15 | Clin. Chem. Lab. Med. 2003 Jul 41: 908-14 |
| PMID | 12940517 |
| Title | Fluorometric assays of phospholipase A2 activity with three different substrates in biological samples of patients with schizophrenia. |
| Abstract | The rationale of this study was to understand the complexity of kinetics of fluorogenic phospholipid substrates as well as contradictory findings of clinical papers measuring phospholipase A2 (PLA2) activity using different methodologies. The aim was to recommend to clinicians and researchers what substrate in conjunction with what assay should be used. Two methods, (i) continuous fluorometric assay and (ii) high performance thin layer chromatography (HPTLC) on microplates combined with quantitative image scanning, were studied with three different substrates (bis-BODIPY FL C11-PC, NBDC6-HPC, PED6). The study demonstrates that NBD-PC is not a suitable substrate to measure PLA2 activity using a spectrofluorometer. On the other hand, NBD-PC gives the highest and most reproducible integrated light intensities (ILls) in HPTLC studies. Slow time-dependent increases in fluorescence intensities recorded with biological samples in fluorometers, but not caused by substrate splitting, had to be classified as "perturbation kinetics". PLA2 activities in blood samples of 26 unmedicated schizophrenia patients and 26 age-matched healthy controls were measured by the spectrofluorometric method and then compared with the activity data obtained with the HPTLC method. A significant group difference was found only with the HPTLC. In order to get more reliable results, we recommend that clinicians and researchers use NBD-phosphatidylcholines as PLA2 substrates in biological samples and start with an analytical separation of reaction products followed by image analysis of the fluorescent spots. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 16 | Telemed J E Health 2003 -1 9: 49-55 |
| PMID | 12699607 |
| Title | Treating childhood depression over videoconferencing. |
| Abstract | Effective cognitive-behavioral treatments for childhood depression have developed over the last decade, but many families face barriers to such care. Telemedicine increases access to psychological interventions by linking the child and the clinician using videoconferencing (VC). The current study evaluated an 8-week, cognitive-behavioral therapy (CBT) intervention for childhood depression either face-to-face (F2F) or over VC. The telemedicine setup included two PC-based PictureTel systems at 128 kilibits per second (kbps). Success was defined by (1) decreasing depressive symptoms at similar rates in both the VC group and the F2F group and (2) demonstrating the feasibility of a randomized controlled trial in telemental health. Children were assessed for childhood depression using the mood section of the Schedule for Affective Disorders and schizophrenia for School Age Children-Present Episode (K-SADS-P). Twenty-eight children were randomized to either F2F or VC treatment. The participants completed the K-SADS-P and the Children's Depression Inventory (CDI) at pre- and post-treatment. The CBT treatment across the two conditions was effective. The overall response rate based on post-evaluation with the K-SADS-P was 82%. For the CDI total score, both the Time and the Group by Time effects were significant (p < 0.05). The interaction effect reflected a faster rate of decline in the CDI total score for the VC group. The study serves as a model for building on past research to implement a randomized controlled trial. This information provides persuasive research data concerning treatment effectiveness for clinicians, families, and funders. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 17 | J Int Neuropsychol Soc 2003 Jan 9: 56-63 |
| PMID | 12570358 |
| Title | A consideration of neuropsychologically normal schizophrenia. |
| Abstract | Neuropsychological deficits are considered by many to be core features of schizophrenia. However, about 20% of patients with schizophrenia appear to have normal neuropsychological function. This study investigates this subgroup by comparing a "neuropsychologically normal" schizophrenia group to a non-schizophrenic, non-brain damaged patient comparison (PC) sample, and to patients with definitive brain damage who performed normally on neuropsychological testing. All patients completed the Halstead-Reitan Neuropsychological Test Battery and were classified as neuropsychologically normal or impaired using the Average Impairment Rating (AIR). In a sample of 113 patients with schizophrenia, 19.5% were classified as neuropsychologically normal. The brain damaged neuropsychologically normal group (BD-NN) consisted of 14.3% of 124 subjects. These groups were compared with a patient non-schizophrenic, non-brain damaged group who were selected on the basis of having an Average Impairment Rating in the neuropsychologically normal range. The neuropsychologically normal schizophrenic group performed less well than the non-brain damaged, non-schizophrenic patient comparison group on a number of tests, indicating that patients in this group may not be completely neuropsychologically normal, and would be better characterized as "high-functioning" or near normal. The results are discussed in regard to possible neurobiological differences between neuropsychologically impaired and intact schizophrenic patients, and implications for course and outcome. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 18 | J Int Neuropsychol Soc 2003 Jan 9: 56-63 |
| PMID | 12570358 |
| Title | A consideration of neuropsychologically normal schizophrenia. |
| Abstract | Neuropsychological deficits are considered by many to be core features of schizophrenia. However, about 20% of patients with schizophrenia appear to have normal neuropsychological function. This study investigates this subgroup by comparing a "neuropsychologically normal" schizophrenia group to a non-schizophrenic, non-brain damaged patient comparison (PC) sample, and to patients with definitive brain damage who performed normally on neuropsychological testing. All patients completed the Halstead-Reitan Neuropsychological Test Battery and were classified as neuropsychologically normal or impaired using the Average Impairment Rating (AIR). In a sample of 113 patients with schizophrenia, 19.5% were classified as neuropsychologically normal. The brain damaged neuropsychologically normal group (BD-NN) consisted of 14.3% of 124 subjects. These groups were compared with a patient non-schizophrenic, non-brain damaged group who were selected on the basis of having an Average Impairment Rating in the neuropsychologically normal range. The neuropsychologically normal schizophrenic group performed less well than the non-brain damaged, non-schizophrenic patient comparison group on a number of tests, indicating that patients in this group may not be completely neuropsychologically normal, and would be better characterized as "high-functioning" or near normal. The results are discussed in regard to possible neurobiological differences between neuropsychologically impaired and intact schizophrenic patients, and implications for course and outcome. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 19 | Psychol Med 2004 Nov 34: 1561-9 |
| PMID | 15724886 |
| Title | Self-monitoring in patients with schizophrenia. |
| Abstract | The present study investigated whether a failure of self-monitoring contributes to core syndromes of schizophrenia. Three groups of patients with a DSM-IV diagnosis of schizophrenia (n = 27), with either prominent paranoid hallucinatory or disorganization syndrome, or without these symptoms, and a matched healthy control group (n = 23) drew circles on a writing pad connected to a PC monitor. Subjects were instructed to continuously monitor the relationship between their hand movements and their visual consequences. They were asked to detect gain changes in the mapping. Self-monitoring ability and the ability to automatically correct movements were assessed. Patients with either paranoid-hallucinatory syndrome or formal thought disorder were selectively impaired in their ability to detect a mismatch between a self-generated movement and its consequences, but not impaired in their ability to automatically compensate for the gain change. These results support the claim that a failure of self-monitoring may underlie the core symptoms of schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 20 | Prog. Neuropsychopharmacol. Biol. Psychiatry 2004 Nov 28: 1185-7 |
| PMID | 15610932 |
| Title | Predicting denial function of schizophrenic patients by the picture completion subtest of WAIS-R. |
| Abstract | In the previous study, picture completion (PC) test scores of Wechsler Adult Intelligence Scale Revised (WAIS-R) were negatively associated with recognition of mental illness measured by Schedule for the Assessment of Insight (SAI). Therefore, it can be hypothesized that function measured by the PC test is positively associated with denial function. To investigate this hypothesis, we investigated the relationship between two picture tests (picture completion and picture arrangement) of the WAIS-R and denial function tests (lie scale, frequency scale and correction scale) of the Minnesota Multiphasic Personality Inventory (MMPI) in 26 schizophrenic patients. As a result, the lie scale score and the correction scale score were positively and significantly associated with picture completion whereas no scale score was significantly associated with picture arrangement. The present findings suggest that the positive association between function measured by the PC test and denial function measured by lie and correction scale scores. Further studies are warranted to investigate the usefulness of the PC test for the measurement of denial function in schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 21 | Biol. Psychiatry 2004 Jun 55: 1138-45 |
| PMID | 15184032 |
| Title | Reduced frontal white matter integrity in early-onset schizophrenia: a preliminary study. |
| Abstract | Research suggests that brain frontal white matter (WM) might be qualitatively altered in adolescents with early onset schizophrenia (EOS). Diffusion tensor imaging provides a relatively new approach for quantifying possible connectivity of WM in vivo. Diffusion tensor imaging was used to examine the WM integrity of frontal regions at seven levels from 25 mm above to 5 mm below the anterior commissure-posterior commissure (AC-PC) plane. Three other regions were examined: the occipital region at the AC-PC plane and the genu and splenium of the corpus callosum. Fractional anisotropy was compared between 12 adolescents (nine male, 3 female) with EOS (onset of psychotic symptoms by age 18 years) and nine age-similar healthy comparison subjects (six male, 3 female). Adolescents with EOS had significantly reduced fractional anisotropy in the frontal WM at the AC-PC plane in both hemispheres and in the occipital WM at the AC-PC plane in the right hemisphere. These preliminary data support a hypothesis that alterations in brain WM integrity occur in adolescents with EOS. Abnormalities found in this study were similar to those reported in adults with chronic schizophrenia. Additional studies are needed to assess whether there is progression of WM abnormalities in schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 22 | Prog. Neuropsychopharmacol. Biol. Psychiatry 2004 Nov 28: 1185-7 |
| PMID | 15610932 |
| Title | Predicting denial function of schizophrenic patients by the picture completion subtest of WAIS-R. |
| Abstract | In the previous study, picture completion (PC) test scores of Wechsler Adult Intelligence Scale Revised (WAIS-R) were negatively associated with recognition of mental illness measured by Schedule for the Assessment of Insight (SAI). Therefore, it can be hypothesized that function measured by the PC test is positively associated with denial function. To investigate this hypothesis, we investigated the relationship between two picture tests (picture completion and picture arrangement) of the WAIS-R and denial function tests (lie scale, frequency scale and correction scale) of the Minnesota Multiphasic Personality Inventory (MMPI) in 26 schizophrenic patients. As a result, the lie scale score and the correction scale score were positively and significantly associated with picture completion whereas no scale score was significantly associated with picture arrangement. The present findings suggest that the positive association between function measured by the PC test and denial function measured by lie and correction scale scores. Further studies are warranted to investigate the usefulness of the PC test for the measurement of denial function in schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 23 | Aten Primaria 2004 Nov 34: 493-8 |
| PMID | 15563788 |
| Title | [Schizophrenia in primary health care centers: the SASPE study (alert signs and prodromic symptoms of schizophrenia in primary health care)]. |
| Abstract | To contribute to the knowledge of the alert signs and precursors of the schizophrenia, just as they can appear in the childhood, and of the prodromic signs other ages. Five descriptive studies: three retrospective, one transversal and one longitudinal study, based in the revision of clinical histories of an Community Mental Health Unit closely linked with the APS, additional revisions of the clinical histories of Family Doctors and Peadiatrics of Primary Care, and structured interviews with patients, patient's offspring, and PHC professionals. Two prospective studies: one, with schizophrenic's children; other, of children with alert signs detected in the first childhood. LOCATION OF THE PROJECT: USM-MHU of Sant Martí-La Mina, 5 Sanitary Basic Areas of Barcelona and Sant Adriá (Barcelona), besides the Functional Unit of Attention to the First Childhood of Sant Martí (Barcelona). schizophrenic patients and relatives detected by the USM-MHU. schizophrenic patients and relatives not detected by the USM. MHU-USM assistance staff and assistance staff of 5 ABS and of the Functional Unit of Attention to the First Childhood (UFAPI). Children with alert signs detected in the UFAPI and children with alert signs or risk factors detected in the EAP and in the Pediatric Teams of PC. METHODOLOGY AND INSTRUMENTS: Diagnoses DSM-IV. Structured interviews SCAN and IRAOS. Scales of positive and negative symptoms. Scales or screenings for the first childhood: ARBB, CBCL, and LISMEP. Structured interviews to determine precursory and prodromic signs: FETZ (Colony), ERIE-IRAOS (Hamburg-Barcelona), ERIE-red (reduced version of the IRAOS, adapted by the investigating team). |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 24 | J. Nerv. Ment. Dis. 2004 Nov 192: 734-44 |
| PMID | 15505517 |
| Title | Schizophrenia and the cultural epidemiology of stigma in Bangalore, India. |
| Abstract | Illness-related stigma is a complex and important issue, and its social impact contributes to a hidden burden of many health problems. Mitigating effects of stigma are a priority for mental health policy, especially for schizophrenia. Although numerous studies document its impact on patients and their families, health studies of stigma typically regard it in global terms without adequate attention to the conceptual and practical importance of sociocultural contexts and the particular features of illness that evoke stigma. Research at a psychiatric referral center in Bangalore, India, studied the cultural epidemiology of schizophrenia and stigma in interviews with family caretakers of 60 patients, using a locally adapted EMIC interview and the Positive and Negative Symptom Scale. An index of 13 stigma queries based on Goffman's formulation covered relevant aspects and proved to be internally consistent (Cronbach alpha = 0.81). Multivariate statistical regression and qualitative analysis of narratives were used to analyze this stigma index and identify explanatory variables based on cultural patterns of distress (PD), perceived causes (PC), and previous help seeking (HS). Significant variables included suspiciousness and inappropriate sexual behavior (PD), heredity and bad deeds (PC), and informal help seeking (HS). Previous allopathic help seeking was negatively associated with stigma. Analysis of coded text segments from respondent narratives showed how these variables were related to family-perceived stigma, with reference to marriage practices, moral meanings of schizophrenia, and ways in which effective allopathic care minimized stigma. Findings identify features of schizophrenia-related stigma in India, contribute to comparative culture studies, and inform practical approaches to mitigate stigma through community awareness and improved mental health services. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 25 | Neuroscience 2004 -1 129: 381-91 |
| PMID | 15501595 |
| Title | An animal model of chronic placental insufficiency: relevance to neurodevelopmental disorders including schizophrenia. |
| Abstract | Evidence now suggests that compromised prenatal brain development may increase the risk for the manifestation of neurological disorders such as schizophrenia. We present a guinea-pig model which mimics a condition of human pregnancy, namely, chronic placental insufficiency. Previously we reported that at term there are changes in the brains of these offspring which are relevant to changes in patients with schizophrenia. The aim of this study was to examine whether deficits in brain structure persist to adolescence and young adulthood (8-12 weeks) and have implications for behavioral function. Reduced uteroplacental blood flow was induced via unilateral ligation of the uterine artery at mid-gestation. The brain was examined in control and prenatally compromised (PC) animals 8 weeks after birth using morphometric and immunohistochemical markers. In a separate cohort of animals, prepulse inhibition (PPI) of the acoustic startle response was assessed at 4, 8 and 12 weeks of age. Brain neurochemistry was examined by determining the concentrations of dopamine and its metabolite, dihydroxyphenylacetic acid (DOPAC), at 12 weeks using high performance liquid chromatography. In PC animals compared with controls there was a reduction in brain weight, persistent enlargement of the lateral ventricles, a reduction in the volume of the basal ganglia and septal region and no evidence of gliosis. No differences were observed in concentration of catecholamines in any brain region examined. At 12, but not 4 or 8, weeks of age, PPI was reduced in PC animals compared with controls. The findings of reduced brain weight, ventriculomegaly, reduced basal ganglia volume and absence of astrogliosis in the PC guinea-pig brain at adolescence parallel some of the changes observed in patients with schizophrenia. The impairment of PPI is comparable to sensorimotor gating deficits observed in patients with schizophrenia. These results indicate that adverse prenatal conditions lead to long-term alterations in brain structure and function which resemble alterations seen in patients with schizophrenia and therefore support the early neurodevelopmental hypothesis of schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 26 | Eur. J. Neurosci. 2004 Aug 20: 749-56 |
| PMID | 15255985 |
| Title | In vivo 31P NMR spectroscopy shows an increase in glycerophosphorylcholine concentration without alterations in mitochondrial function in the prefrontal cortex of medicated schizophrenic patients at rest. |
| Abstract | The (31)P NMR localised method was used to study the metabolism of phospholipid and high energy phosphate in the prefrontal cortex. The spectra were taken from patients with schizophrenia (11 males) receiving neuroleptic medication, and were compared to normal controls (15 males). Their spectral intensities were analysed using a non-linear least-squares method with a prior knowledge of the fixed chemical shifts and linewidths, leading to further resolution into resonances of glycerophosphorylethanolamine (GPE), glycerophosphorylcholine (GPC), phosphorylethanolamine (PE) and phosphorylcholine (PC). The metabolite concentrations were calculated referring to the spectral intensities of phosphate phantoms with known concentrations. T1 values of phantom and cerebrum were estimated from a series of localised inversion recovery spectra to correct for the signal saturation effects. The schizophrenic patients showed an increased concentration of GPC but not GPE, PE or PC. Furthermore, no difference was observed regarding the concentration of high-energy phosphates such as phosphocreatine, inorganic phosphate and ATP. The patients did not show any differences in mitochondrial function such as phosphorylation potential and the ratio of the rate of ATP synthesis. Thus, an increase in GPC concentration in the prefrontal cortex could be characteristic of the pathophysiology of schizophrenia with mild negative symptoms. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 27 | Aten Primaria 2004 Nov 34: 493-8 |
| PMID | 15563788 |
| Title | [Schizophrenia in primary health care centers: the SASPE study (alert signs and prodromic symptoms of schizophrenia in primary health care)]. |
| Abstract | To contribute to the knowledge of the alert signs and precursors of the schizophrenia, just as they can appear in the childhood, and of the prodromic signs other ages. Five descriptive studies: three retrospective, one transversal and one longitudinal study, based in the revision of clinical histories of an Community Mental Health Unit closely linked with the APS, additional revisions of the clinical histories of Family Doctors and Peadiatrics of Primary Care, and structured interviews with patients, patient's offspring, and PHC professionals. Two prospective studies: one, with schizophrenic's children; other, of children with alert signs detected in the first childhood. LOCATION OF THE PROJECT: USM-MHU of Sant Martí-La Mina, 5 Sanitary Basic Areas of Barcelona and Sant Adriá (Barcelona), besides the Functional Unit of Attention to the First Childhood of Sant Martí (Barcelona). schizophrenic patients and relatives detected by the USM-MHU. schizophrenic patients and relatives not detected by the USM. MHU-USM assistance staff and assistance staff of 5 ABS and of the Functional Unit of Attention to the First Childhood (UFAPI). Children with alert signs detected in the UFAPI and children with alert signs or risk factors detected in the EAP and in the Pediatric Teams of PC. METHODOLOGY AND INSTRUMENTS: Diagnoses DSM-IV. Structured interviews SCAN and IRAOS. Scales of positive and negative symptoms. Scales or screenings for the first childhood: ARBB, CBCL, and LISMEP. Structured interviews to determine precursory and prodromic signs: FETZ (Colony), ERIE-IRAOS (Hamburg-Barcelona), ERIE-red (reduced version of the IRAOS, adapted by the investigating team). |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 28 | Eur. J. Neurosci. 2004 Aug 20: 749-56 |
| PMID | 15255985 |
| Title | In vivo 31P NMR spectroscopy shows an increase in glycerophosphorylcholine concentration without alterations in mitochondrial function in the prefrontal cortex of medicated schizophrenic patients at rest. |
| Abstract | The (31)P NMR localised method was used to study the metabolism of phospholipid and high energy phosphate in the prefrontal cortex. The spectra were taken from patients with schizophrenia (11 males) receiving neuroleptic medication, and were compared to normal controls (15 males). Their spectral intensities were analysed using a non-linear least-squares method with a prior knowledge of the fixed chemical shifts and linewidths, leading to further resolution into resonances of glycerophosphorylethanolamine (GPE), glycerophosphorylcholine (GPC), phosphorylethanolamine (PE) and phosphorylcholine (PC). The metabolite concentrations were calculated referring to the spectral intensities of phosphate phantoms with known concentrations. T1 values of phantom and cerebrum were estimated from a series of localised inversion recovery spectra to correct for the signal saturation effects. The schizophrenic patients showed an increased concentration of GPC but not GPE, PE or PC. Furthermore, no difference was observed regarding the concentration of high-energy phosphates such as phosphocreatine, inorganic phosphate and ATP. The patients did not show any differences in mitochondrial function such as phosphorylation potential and the ratio of the rate of ATP synthesis. Thus, an increase in GPC concentration in the prefrontal cortex could be characteristic of the pathophysiology of schizophrenia with mild negative symptoms. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 29 | Neurochem. Int. 2006 Aug 49: 304-11 |
| PMID | 16567023 |
| Title | Clozapine but not haloperidol suppresses the changes in the levels of neuropeptides in MK-801-treated rat brain regions. |
| Abstract | Noncompetitive NMDA receptor antagonist (+)MK-801 is known to induce neurotoxicity and schizophrenia-like symptomatology where atypical neuroleptic clozapine is effective in contrast to typical neuroleptic, haloperidol. Although neuropeptides are implicated in memory and cognition, their roles in schizophrenia are not well understood. In the present study, we therefore examined the possible roles of neuropeptides, cholecystokinin (CCK) and somatostatin (SS) in the posterior cingulate/retrosplenial cortices (PC/RSC), frontal cortex, and hippocampus of a MK-801-induced schizophrenia-like model rat brain. This study further investigated the pretreated effect of atypical versus typical neuroleptics on the peptidergic system. SS mRNA and peptide levels significantly decreased in the PC/RSC and hippocampus but not in the frontal cortex 3 days after 0.5 mg/kg MK-801 treatment whereas CCK mRNA and peptide levels significantly decreased in all of the brain regions examined. Pretreatment with clozapine but not haloperidol completely recovered the changes in both mRNA and peptide levels of SS and CCK in those brain regions. These data suggest that peptidergic system in the brain presumably plays an important role in the control of negative schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 30 | Psychiatry Clin. Neurosci. 2006 Jun 60: 303-11 |
| PMID | 16732746 |
| Title | Neuropsychological correlates of error negativity and positivity in schizophrenia patients. |
| Abstract | The purpose of the present paper was to determine error-monitoring ability and its relationship with executive function in patients with schizophrenia. In order to evaluate error-monitoring ability, the error negativity (Ne) and error positivity (Pe) were measured using the Stroop task. The correct-related negativity (CRN) and positivity (PC) were also measured. In addition, neuropsychological tests were administered in order to evaluate executive function. The patients with schizophrenia had significantly reduced Ne and augmented CRN amplitudes, but the Pe and PC amplitudes of the patients were comparable to those of the controls. In addition, the Ne amplitude, measured at Fcz was positively correlated with the Trail Making Test (TMT), part B response time, and the categories achieved on the Wisconsin Card Sorting Test (WCST) in patients with schizophrenia. No significant correlations were found between Ne amplitude and performance on the neuropsychological tests in the controls. And no associations were detected between CRN, Pe, PC amplitudes and neuropsychological performance, in either the patients with schizophrenia or the controls. Reduced Ne amplitudes and augmented CRN amplitudes in patients with schizophrenia suggest the dysfunctional behavior-monitoring system in these patients. The functional significances of Ne and Pe are discussed. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 31 | Cyberpsychol Behav 2006 Aug 9: 480-9 |
| PMID | 16901251 |
| Title | Virtual reality exposure therapy: 150-degree screen to desktop PC. |
| Abstract | Virtual reality exposure therapy (VRET) developed using immersive or semi-immersive virtual environments present a usability problem for practitioners. To meet practitioner requirements for lower cost and portability VRET programs must often be ported onto desktop environments such as the personal computer (PC). However, success of VRET has been shown to be linked to presence, and the environment's ability to evoke the same reactions and emotions as a real experience. It is generally accepted that high-end virtual environments (VEs) are more immersive than desktop PCs, but level of immersion does not always predict level of presence. This paper reports on the impact on presence of porting a therapeutic VR application for schizophrenia from the initial research environment of a semi-immersive curved screen to PC. Presence in these two environments is measured both introspectively and across a number of causal factors thought to underlie the experience of presence. Results show that the VR exposure program successfully made users feel they were "present" in both platforms. While the desktop PC achieved higher scores on presence across causal factors participants reported they felt more present in the curved screen environment. While comparison of the two groups was statistically significant for the PQ but not for the IPQ, subjective reports of experiences in the environments should be considered in future research as the success of VRET relies heavily on the emotional response of patients to the therapeutic program. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 32 | Schizophr. Res. 2006 Oct 87: 60-6 |
| PMID | 16875801 |
| Title | Small-world networks and disturbed functional connectivity in schizophrenia. |
| Abstract | Disturbances in "functional connectivity" have been proposed as a major pathophysiological mechanism for schizophrenia, and in particular, for cognitive disorganization. Detection and estimation of these disturbances would be of clinical interest. Here we characterize the spatial pattern of functional connectivity by computing the "synchronization likelihood" (SL) of EEG at rest and during performance of a 2Back working memory task using letters of the alphabet presented on a PC screen in subjects with schizophrenia and healthy controls. The spatial patterns of functional connectivity were then characterized with graph theoretical measures to test whether a disruption of an optimal spatial pattern ("small-world") of the functional connectivity network underlies schizophrenia. Twenty stabilized patients with schizophrenia, who were able to work, and 20 healthy controls participated in the study. During the working memory (WM) task healthy subjects exhibited small-world properties (a combination of local clustering and high overall integration of the functional networks) in the alpha, beta and gamma bands. These properties were not present in the schizophrenia group. These findings are in accordance with a partially inadequate organization of neuronal networks in subjects with schizophrenia. This method could be helpful for diagnosis and evaluation of the severity of the disease, as well as understanding the pathophysiologic mechanisms underlying cognitive dysfunction in schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 33 | Prog. Neuropsychopharmacol. Biol. Psychiatry 2007 May 31: 832-8 |
| PMID | 17374554 |
| Title | Oxidative stress in prefrontal cortex of rat exposed to MK-801 and protective effects of CAPE. |
| Abstract | MK-801 was shown to be one of the most neurotoxic non-competitive NMDA receptor antagonists. It is known that repeated injection of MK-801 was proposed in an animal model in psychosis. The aims of this study are to investigate the contributing effect of oxidative stress in MK-801-induced experimental psychosis model, and to show that prevention of oxidative stress may improve prognosis. Furthermore, there is evidence that oxygen free radicals play an important role in the pathophysiology of schizophrenia. In this study, Wistar Albino rats were divided into three groups: 1st group: Control, 2nd group: MK-801, 3rd group: MK-801+CAPE (Caffeic acid phenethyl ester) group. MK-801 was given intraperitoneally at the dose of 0.5 mg/kg/day for 5 days. CAPE was given to the treatment group while exposed to MK-801. In control group, saline was given intraperitoneally at the same time. After 7 days, rats were killed by decapitation. Prefrontal cortex (PFC) of rats was removed for biochemical and histological analyses. As a result, malondialdehyde (MDA), protein carbonyl (PC), nitric oxide (NO) levels and superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and xanthine oxidase (XO) and adenosine deaminase (AD) enzyme activities were found to be increased significantly in prefrontal cortex (PFC) of MK-801 group (p<0.0001) compared to control group. In CAPE treated rats, prefrontal tissue MDA, PC, NO levels and, GSH-Px, XO, AD enzyme activities were significantly decreased when compared to MK-801 groups (p<0.0001) whereas catalase (CAT) enzyme activity was not changed. Moreover, in the light of microscopic examination of MK-801 groups, a great number of apoptotic cells were observed. CAPE treatment decreased the apoptotic cell count in PFC. The results of this study showed that MK-801-induced neurotoxicity caused oxidative stress in PFC of rats. This experimental study may also provide some evidences for the new treatment strategies with antioxidants in schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 34 | Pharmacol. Biochem. Behav. 2007 Jan 86: 1-7 |
| PMID | 16806445 |
| Title | Effect of MK-801 and ketamine on hydroxyl radical generation in the posterior cingulate and retrosplenial cortex of free-moving mice, as determined by in vivo microdialysis. |
| Abstract | This study investigated the effect of MK-801 and ketamine, N-methyl-D-aspartate (NMDA) receptor antagonists which can induce schizophrenic symptoms and have neurotoxicity in human and animals, on hydroxyl radical (*OH) generation in the posterior cingulate and retrosplenial (PC/RS) cortex of free-moving mice using the salicylic acid trapping technique. MK-801 (0.6 mg/kg) or ketamine (50 mg/kg) acute administration significantly increased *OH levels in mouse PC/RS cortex. The basal *OH levels after MK-801 and ketamine administrations for 7 consecutive days were significantly increased compared with the naive basal levels. MK-801 (0.6 mg/kg) or ketamine (50 mg/kg) challenge after chronic administration further significantly increased dialysate levels of *OH. Our study also found that the release of *OH was secondary to stereotyped behavior, and the intensity of stereotyped behavior induced by MK-801 was more than that induced by ketamine. The results suggested that NMDA receptor antagonists participate in the generation of *OH in the PC/RS cortex of mouse, and oxidative stress, derived from the formation of free radicals, might play an important role in the pathophysiology of these two models of schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 35 | Neurochem. Int. 2007 Jan 50: 196-202 |
| PMID | 16971021 |
| Title | The protective effects of omega-3 fatty acids against MK-801-induced neurotoxicity in prefrontal cortex of rat. |
| Abstract | The aims of this study are to investigate the contribution effect of oxidative stress in MK-801-induced experimental psychosis model, and to show that prevention of oxidative stress may improve prognosis. Because oxidative damage has been suggested in the neuropathophysiology of schizophrenia, the possible protecting agents against lipid peroxidation are potential target for the studies in this field. For this purpose, Wistar Albino rats were divided into three groups: the first group was used as control, MK-801 was given to the rats in the second group and MK-801+omega-3 essential fatty acids (EFA) was given to the third group. MK-801 was given intraperitoneally at the dose of 0.5mg/(kgday) once a day for 5 days in experimental psychosis group. In the second group, 0.8g/(kgday), omega-3 FA (eicosapentaenoic acid, 18%, docosahexaenoic acid, 12%) was given to the rats while exposed MK-801. In control group, saline was given intraperitoneally at the same time. After 7 days, rats were killed by decapitation. Prefrontal brain area was removed for histological and biochemical analyses. As a result, malondialdehyde (MDA), as an indicator of lipid peroxidation, protein carbonyl (PC), as an indicator of protein oxidation, nitric oxide (NO) levels and superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) activities as antioxidant enzymes, and xanthine oxidase (XO) and adenosine deaminase (AD) activities as an indicator of DNA oxidation was found to be increased significantly in prefrontal cortex (PFC) of MK-801 group (P<0.0001) compared to control group. In omega-3 FA treated rats, prefrontal tissue MDA, PC and NO levels as well as SOD, GSH-Px, XO, and AD enzyme activities were significantly decreased when compared to MK-801 groups (P<0.0001) whereas catalase (CAT) enzyme activity was not changed. Moreover, in the light of microscopic examination of MK-801 groups, a great number of apoptotic cells were observed. omega-3 FA supplementation decreased the apoptotic cell count in PFC. The results of this study revealed that oxidative stress and apoptotic changes in PFC may play an important role in the pathogenesis of MK-801-induced neuronal toxicity. This experimental study also provides some evidences for the protective effects of omega-3 FA on MK-801-induced changes in PFC of rats. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 36 | Altern Med Rev 2007 Sep 12: 207-27 |
| PMID | 18072818 |
| Title | Omega-3 DHA and EPA for cognition, behavior, and mood: clinical findings and structural-functional synergies with cell membrane phospholipids. |
| Abstract | The omega-3 fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) are orthomolecular, conditionally essential nutrients that enhance quality of life and lower the risk of premature death. They function exclusively via cell membranes, in which they are anchored by phospholipid molecules. DHA is proven essential to pre- and postnatal brain development, whereas EPA seems more influential on behavior and mood. Both DHA and EPA generate neuroprotective metabolites. In double-blind, randomized, controlled trials, DHA and EPA combinations have been shown to benefit attention deficit/hyperactivity disorder (AD/HD), autism, dyspraxia, dyslexia, and aggression. For the affective disorders, meta-analyses confirm benefits in major depressive disorder (MDD) and bipolar disorder, with promising results in schizophrenia and initial benefit for borderline personality disorder. Accelerated cognitive decline and mild cognitive impairment (MCI) correlate with lowered tissue levels of DHA/EPA, and supplementation has improved cognitive function. Huntington disease has responded to EPA. Omega-3 phospholipid supplements that combine DHA/EPA and phospholipids into the same molecule have shown marked promise in early clinical trials. Phosphatidylserine with DHA/EPA attached (Omega-3 PS) has been shown to alleviate AD/HD symptoms. Krill omega-3 phospholipids, containing mostly phosphatidylcholine (PC) with DHA/EPA attached, markedly outperformed conventional fish oil DHA/EPA triglycerides in double-blind trials for premenstrual syndrome/dysmenorrhea and for normalizing blood lipid profiles. Krill omega-3 phospholipids demonstrated anti-inflammatory activity, lowering C-reactive protein (CRP) levels in a double-blind trial. Utilizing DHA and EPA together with phospholipids and membrane antioxidants to achieve a triple cell membrane synergy may further diversify their currently wide range of clinical applications. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 37 | Neurosci. Res. 2007 Feb 57: 248-58 |
| PMID | 17141345 |
| Title | Suppressive effect of clozapine but not haloperidol on the increases of neuropeptide-degrading enzymes and glial cells in MK-801-treated rat brain regions. |
| Abstract | MK-801, a noncompetitive N-methyl-d-aspartate (NMDA) receptor antagonist, produces neurotoxicity in adult rodent brain, and causes schizophrenia-like psychosis and cognitive dysfunction. Since neuropeptides and neuropeptide-degrading enzymes play important roles in cognitive function, we examined whether or not MK-801-induced schizophrenia-like psychosis is co-related with the changes of these enzymes in rat brain regions. In the present study, we investigated the effect of systemic treatment with MK-801 (0.5mg/kg) on neuropeptide-degrading enzymes, prolyl oligopeptidase (POP) and thimet oligopeptidase (EP 24.15), and glial marker proteins GFAP and CD11b in rat brain regions. The levels of POP and EP 24.15 activities increased significantly three days after treatment with MK-801 in the posterior cingulate/retrosplenial cortices (PC/RSC). Since atypical neuroleptic clozapine but not typical neuroleptic haloperidol prevents the MK-801-induced schizophrenia-like symptoms, we further examined the pretreated effects of the neuroleptics. Clozapine, but not haloperidol, significantly attenuated MK-801-induced changes in the levels of the neuropeptide-degrading enzymes. Immunohistochemical studies on GFAP and CD11b showed the increase in the PC/RSC of MK-801-treated rat brain and the pretreatment with clozapine suppressed these changes. Double immunostain experiments of EP 24.15 and GFAP antibodies demonstrated some co-localization of the neuropeptidase with astrocytes. The present findings suggest that change of neuropeptidases in the brain is in part correlated with changes of glial cells, and may play an important role in the control of schizophrenia-like psychotic disorders. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 38 | Nord J Psychiatry 2007 -1 61: 339-42 |
| PMID | 17990194 |
| Title | Multifractal analysis as an aid in the diagnostics of mental disorders. |
| Abstract | The digitalization of EEGs (electroencephalogram) has showed new possibilities for analyzing electrical activity of brain. This has offered new methods, e.g. multifractal analysis of 1/f(beta) EEG rhythms fluctuations. It is one of highly mathematical methods feasible in routine practice now that modern personal computers (PCs) have reached sufficient computing power. In this study, we applied the multifractal analysis of 1/f(beta) EEG rhythms fluctuations in 33 patients suffering from schizophrenia and schizophrenia-like syndromes, and we had 23 healthy controls. Our results indicated that the patients suffering from schizophrenia have statistically different values compared with the controls. This method is rather easy and quick to perform when using a standard PC. It may have the potential to become an important tool in the diagnostics and analysis of the patients with schizophrenia and schizophreniformic psychoses. It can help to understand the quasi-chaotic processes in neural processing and narrow the gap between the phenomenological psychiatry and bio-psychiatry. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 39 | Schizophr. Res. 2007 Mar 91: 82-6 |
| PMID | 17307337 |
| Title | Task-induced deactivation of midline cortical regions in schizophrenia assessed with fMRI. |
| Abstract | Task-induced deactivations (TIDs) of midline cortical regions are readily observed in fMRI studies and may reflect elements of a 'default-mode' of brain function associated with self-directed mental processes at rest. In this study, we examined this TID phenomenon in schizophrenia and its relevance to patients' symptoms, task performance and level of emotional awareness. Relative to control subjects, patients showed significantly greater TID of the rostral anterior cingulate (rAC)/medial prefrontal cortex (mPFC) and precuneus (PrC)/posterior cingulate cortex (PC). The magnitude of prefrontal TIDs was associated with patients' task performance and emotional awareness for others. The nature of these associations suggests a complex interchange between cognitive and emotional influences on the resting-state activity of these prefrontal 'default mode' regions in schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 40 | Pharmacol. Biochem. Behav. 2007 Jan 86: 1-7 |
| PMID | 16806445 |
| Title | Effect of MK-801 and ketamine on hydroxyl radical generation in the posterior cingulate and retrosplenial cortex of free-moving mice, as determined by in vivo microdialysis. |
| Abstract | This study investigated the effect of MK-801 and ketamine, N-methyl-D-aspartate (NMDA) receptor antagonists which can induce schizophrenic symptoms and have neurotoxicity in human and animals, on hydroxyl radical (*OH) generation in the posterior cingulate and retrosplenial (PC/RS) cortex of free-moving mice using the salicylic acid trapping technique. MK-801 (0.6 mg/kg) or ketamine (50 mg/kg) acute administration significantly increased *OH levels in mouse PC/RS cortex. The basal *OH levels after MK-801 and ketamine administrations for 7 consecutive days were significantly increased compared with the naive basal levels. MK-801 (0.6 mg/kg) or ketamine (50 mg/kg) challenge after chronic administration further significantly increased dialysate levels of *OH. Our study also found that the release of *OH was secondary to stereotyped behavior, and the intensity of stereotyped behavior induced by MK-801 was more than that induced by ketamine. The results suggested that NMDA receptor antagonists participate in the generation of *OH in the PC/RS cortex of mouse, and oxidative stress, derived from the formation of free radicals, might play an important role in the pathophysiology of these two models of schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 41 | Schizophr. Res. 2007 Jul 93: 66-78 |
| PMID | 17433626 |
| Title | Abnormalities of cingulate gyrus neuroanatomy in schizophrenia. |
| Abstract | Abnormalities of the neuroanatomy of the gray matter of the cingulate gyrus, especially its anterior segment, have been suggested to be an important characteristic of schizophrenia. In this study, T1-weighted magnetic resonance scans were collected in 53 individuals with schizophrenia and 68 comparison subjects matched for age, gender, race and parental socioeconomic status. We applied Labeled Cortical Mantle Distance Mapping to assess the volume, surface area and thickness of the cortical mantle within the anterior (AC) and posterior (PC) segments of the cingulate gyrus, excluding the paracingulate gyrus, and related these anatomical measures to measures of psychopathology and illness duration. After covarying for total cerebral volume, individuals with schizophrenia showed smaller AC gray matter volume (p=0.024), thickness (trend, p=0.081), but not surface area (p=0.16), than comparison subjects. Similar group differences were found for PC gray matter volume (p=0.0005) and thickness (trend, p=0.055), but not surface area (p=0.15). Across both groups, there was a significant L>R asymmetry in thickness of the AC, and a significant L>R asymmetry in the surface area of the PC. However, there were no significant group-by-hemisphere interactions. In the individuals with schizophrenia, thinning of the AC, but not the PC, was correlated with a longer duration of illness and a greater severity of psychotic symptoms. Individuals with schizophrenia showed smaller gray matter volumes across the entire cingulate gyrus, mostly due to a reduction in cortical mantle thickness. However, structural measures of the AC were more closely related to clinical features of the illness. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 42 | Int. J. Clin. Pract. 2008 Dec 62: 1943-6 |
| PMID | 18795967 |
| Title | The Information Technology Aided Relapse Prevention Programme in Schizophrenia: an extension of a mirror-design follow-up. |
| Abstract | Decreasing a number of hospital admissions is important for improving outcomes for people with schizophrenia. The Information Technology Aided Relapse Prevention Programme in schizophrenia (ITAREPS) programme enables early pharmacological intervention in psychosis by identification of prodromal symptoms of relapse using home telemonitoring via a phone-to-PC SMS platform. This study was a 1-year extension of a previously published mirror-design follow-up evaluation of programme clinical effectiveness. In total, 73 patients with psychotic illness (45 patients from original sample and 28 newly added subjects) collaborating with 56 family members participated in the clinical evaluation. There was a statistically significant 77% decrease in the number of hospitalisations during the mean 396.8 +/- 249.4 days of participation in ITAREPS, compared with the same time period before participation in ITAREPS (Wilcoxon-signed ranks test, p < 0.00001), as well as significantly reduced number of hospitalisation days when in the ITAREPS (2365 hospitalisation days before and 991 days after ITAREPS enrolment respectively, Wilcoxon-signed ranks test, p < 0.003). The ITAREPS programme represents an effective tool in the long-term treatment of patients with psychotic disorders. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 43 | Schizophr. Res. 2008 Jan 98: 312-7 |
| PMID | 17920245 |
| Title | ITAREPS: information technology aided relapse prevention programme in schizophrenia. |
| Abstract | ITAREPS presents a mobile phone-based telemedicine solution for weekly remote patient monitoring and disease management in schizophrenia and psychotic disorders in general. The programme provides health professionals with home telemonitoring via a PC-to-phone SMS platform that identifies prodromal symptoms of relapse, to enable early intervention and prevent unnecessary hospitalizations. Its web-based interface offers the authorized physician a longitudinal analysis of the dynamics and development of possible prodromes. This work presents preliminary findings from a one-year mirror-design follow-up evaluation of the programme's clinical effectiveness in 45 patients with psychotic illness. There was a statistically significant 60% decrease in the number of hospitalizations during the mean 283.3+/-111.9 days of participation in the ITAREPS, compared to the same time period before the ITAREPS entry (sign test, p<0.004). Variables significantly influencing the number of hospitalizations after the ITAREPS entry (medication compliance along with factors intrinsic to the ITAREPS, i.e. adherence to the programme and involvement of a family member) suggest a critical role of the programme in controlling the number of relapses and subsequent hospitalizations in psychosis. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 44 | Clin Psychol Rev 2008 Mar 28: 521-34 |
| PMID | 17913319 |
| Title | The predictive, convergent, and discriminant validity of perceived criticism: a review. |
| Abstract | People's perceptions of criticism from another individual, known as perceived criticism (PC), have been found to predict symptom course, treatment outcome, and future relapse across a number of disorders, including depression, anxiety disorders, substance abuse, and schizophrenia. Some recent studies, however, have yielded conflicting results, making the overall pattern of findings difficult to interpret. This article reviews the findings on PC and presents a framework for understanding them, focused on predictive, convergent, and discriminant validity. The following questions are addressed: (1) What conclusions can be drawn about the prospective relationship of PC with symptom fluctuation and treatment response across disorders? (2) Does it matter whom respondents rate in terms of PC? (3) Is PC a valid construct for individuals from non-Western cultures? (4) Does the fact that the typical measure of PC consists of only 1 item limit its utility? (5) Is PC best viewed as an accurate reflection of another person's critical behavior, another index of overall satisfaction in an interpersonal relationship, some intraindividual variable (e.g., general sensitivity to criticism), or some combination of these factors? Based on the answers to these and other questions, recommendations for clinical practice and future research related to PC are made. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 45 | Magn Reson Med 2008 Mar 59: 469-74 |
| PMID | 18306399 |
| Title | 31P NMR spectroscopy of phospholipid metabolites in postmortem schizophrenic brain. |
| Abstract | Evidence has been accumulating that schizophrenia involves abnormalities in the composition and metabolism of cell membrane phospholipids (PLs) in the brain. In vivo 31P MRS has been used to measure the metabolic precursors and degradation products of PL metabolism in schizophrenia. Because in vivo line widths are substantially broader than in solution, only the broad phosphomonoester (PME) and phosphodiester bands, or partly resolved resonances of individual metabolites, are typically measured in vivo in the 31P spectrum. In addition to poor resolution, the relatively low signal-to-noise ratio (SNR) makes precise quantitation difficult. An alternative with substantially better resolution and precision for quantitation is high-resolution NMR spectroscopy of extracts of samples from postmortem brain. Here we determine absolute concentrations of the individual PL metabolites phosphocholine (PC), phosphoethanolamine (pe), glycerophosphocholine (gPC), and glycerophosphoethanolamine in aqueous extracts of tissue from frontal, temporal, and occipital cortex of postmortem brain for schizophrenics, controls, and patients with other mental illnesses (psychiatric controls [PC]) using high-resolution 31P NMR spectroscopy. For the complete groups, which included both males and females, there were no statistically significant differences for schizophrenics vs. controls for any of the four PL metabolites in any of the three brain regions. Trends (0.05 < P < 0.10) were noted for increased gPC in schizophrenia in all three regions. PC differed from both controls and schizophrenics in several measures. When only males were considered, gPC was significantly (P < 0.05) elevated in all three brain regions in schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 46 | Magn Reson Med 2008 Mar 59: 469-74 |
| PMID | 18306399 |
| Title | 31P NMR spectroscopy of phospholipid metabolites in postmortem schizophrenic brain. |
| Abstract | Evidence has been accumulating that schizophrenia involves abnormalities in the composition and metabolism of cell membrane phospholipids (PLs) in the brain. In vivo 31P MRS has been used to measure the metabolic precursors and degradation products of PL metabolism in schizophrenia. Because in vivo line widths are substantially broader than in solution, only the broad phosphomonoester (PME) and phosphodiester bands, or partly resolved resonances of individual metabolites, are typically measured in vivo in the 31P spectrum. In addition to poor resolution, the relatively low signal-to-noise ratio (SNR) makes precise quantitation difficult. An alternative with substantially better resolution and precision for quantitation is high-resolution NMR spectroscopy of extracts of samples from postmortem brain. Here we determine absolute concentrations of the individual PL metabolites phosphocholine (PC), phosphoethanolamine (pe), glycerophosphocholine (gPC), and glycerophosphoethanolamine in aqueous extracts of tissue from frontal, temporal, and occipital cortex of postmortem brain for schizophrenics, controls, and patients with other mental illnesses (psychiatric controls [PC]) using high-resolution 31P NMR spectroscopy. For the complete groups, which included both males and females, there were no statistically significant differences for schizophrenics vs. controls for any of the four PL metabolites in any of the three brain regions. Trends (0.05 < P < 0.10) were noted for increased gPC in schizophrenia in all three regions. PC differed from both controls and schizophrenics in several measures. When only males were considered, gPC was significantly (P < 0.05) elevated in all three brain regions in schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 47 | Magn Reson Med 2008 Mar 59: 469-74 |
| PMID | 18306399 |
| Title | 31P NMR spectroscopy of phospholipid metabolites in postmortem schizophrenic brain. |
| Abstract | Evidence has been accumulating that schizophrenia involves abnormalities in the composition and metabolism of cell membrane phospholipids (PLs) in the brain. In vivo 31P MRS has been used to measure the metabolic precursors and degradation products of PL metabolism in schizophrenia. Because in vivo line widths are substantially broader than in solution, only the broad phosphomonoester (PME) and phosphodiester bands, or partly resolved resonances of individual metabolites, are typically measured in vivo in the 31P spectrum. In addition to poor resolution, the relatively low signal-to-noise ratio (SNR) makes precise quantitation difficult. An alternative with substantially better resolution and precision for quantitation is high-resolution NMR spectroscopy of extracts of samples from postmortem brain. Here we determine absolute concentrations of the individual PL metabolites phosphocholine (PC), phosphoethanolamine (pe), glycerophosphocholine (gPC), and glycerophosphoethanolamine in aqueous extracts of tissue from frontal, temporal, and occipital cortex of postmortem brain for schizophrenics, controls, and patients with other mental illnesses (psychiatric controls [PC]) using high-resolution 31P NMR spectroscopy. For the complete groups, which included both males and females, there were no statistically significant differences for schizophrenics vs. controls for any of the four PL metabolites in any of the three brain regions. Trends (0.05 < P < 0.10) were noted for increased gPC in schizophrenia in all three regions. PC differed from both controls and schizophrenics in several measures. When only males were considered, gPC was significantly (P < 0.05) elevated in all three brain regions in schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 48 | Psychoneuroendocrinology 2009 Jul 34: 901-8 |
| PMID | 19195791 |
| Title | Association between arginine vasopressin 1a receptor (AVPR1a) promoter region polymorphisms and prepulse inhibition. |
| Abstract | Arginine vasopressin and the arginine vasopressin 1a (AVPR1a) gene contribute to a range of social behaviors both in lower vertebrates and in humans. Human promoter-region microsatellite repeat regions (RS1 and RS3) in the AVPR1a gene region have been associated with autism spectrum disorders, prosocial behavior and social cognition. Prepulse inhibition (PPI) of the startle response to auditory stimuli is a largely autonomic response that resonates with social cognition in both animal models and humans. Reduced PPI has been observed in disorders including schizophrenia that are distinguished by deficits in social skills. In the current investigation association was examined between PPI and the AVPR1a RS1 and RS repeat regions and PPI in a group of 113 nonclinical subjects. Using a robust family-based strategy, association was observed between AVPR1a promoter-region repeat length, especially RS3) and PPI (30 ms: global p=0.04; 60 ms p=0.006; 120 ms p=0.008). Notably, longer RS3 alleles were associated with greater levels of prepulse inhibition. Using a short/long classification scheme for the repeat regions, significant association was also observed between all three PPI intervals (30, 60 and 120 ms) and both RS1 and RS3 polymorphisms (PBAT: FBAT-PC(2) statistic p=0.047). Tests of within-subject effects (SPSS GLM) showed significant sexxRS3 interactions at 30 ms (p=0.045) and 60 ms (p=0.01). Longer alleles, especially in male subjects, are associated with significantly higher PPI response, consistent with a role for the promoter repeat region in partially molding social behavior in both animals and humans. This is the first report in humans demonstrating a role of the AVPR1a gene in contributing to the PPI response to auditory stimuli. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 49 | Prog. Neuropsychopharmacol. Biol. Psychiatry 2009 Mar 33: 290-5 |
| PMID | 19121361 |
| Title | Effects of acute and chronic administration of MK-801 on c-Fos protein expression in mice brain regions implicated in schizophrenia with or without clozapine. |
| Abstract | This study investigated the effects of acute and chronic administration of the non-competitive NMDA receptor antagonists MK-801 on c-Fos protein expression in different brain regions of mice with or without clozapine. MK-801 (0.6 mg/kg) acute administration produced a significant increase in the expression of c-Fos protein in the layers III-IV of posterior cingulate and retrosplenial (PC/RS) cortex, which was consistent with the previous reports. Moreover, we presented a new finding that MK-801 (0.6 mg/kg) chronic administration for 8 days produced a significant increase of c-Fos protein expression in the PC/RS cortex, prefrontal cortex (PFC) and hypothalamus of mice. Among that, c-Fos protein expression in the PC/RS cortex of mice was most significant. Compared to acute administration, we found that MK-801 chronic administration significantly increased the expression of c-Fos protein in the PC/RS cortex, PFC and hypothalamus. Furthermore, pretreatment of mice with clozapine significantly decreased the expression of c-Fos protein induced by MK-801 acute and chronic administration. These results suggest that c-Fos protein, the marker of neuronal activation, might play an important role in the chronic pathophysiological process of schizophrenic model induced by NMDA receptor antagonist. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 50 | Community Ment Health J 2009 Apr 45: 106-16 |
| PMID | 18841474 |
| Title | The relationships among perceived criticism, family contact, and consumer clinical and psychosocial functioning for African-American consumers with schizophrenia. |
| Abstract | This study examined whether Perceived Criticism (PC) was related to community functioning in a sample of African-American consumers with schizophrenia. The study tested assumptions from the Expressed Emotion literature that were based primarily on samples of white consumers. The study found that PC affected psychiatric symptomatology but not psychosocial functioning. Greater family contact was strongly related to better psychosocial functioning. Findings suggested that the nature and impact of contact between consumer and family for this sample of African-Americans appears different from what has been found in white, middle-class samples. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 51 | Prog. Neuropsychopharmacol. Biol. Psychiatry 2009 Mar 33: 290-5 |
| PMID | 19121361 |
| Title | Effects of acute and chronic administration of MK-801 on c-Fos protein expression in mice brain regions implicated in schizophrenia with or without clozapine. |
| Abstract | This study investigated the effects of acute and chronic administration of the non-competitive NMDA receptor antagonists MK-801 on c-Fos protein expression in different brain regions of mice with or without clozapine. MK-801 (0.6 mg/kg) acute administration produced a significant increase in the expression of c-Fos protein in the layers III-IV of posterior cingulate and retrosplenial (PC/RS) cortex, which was consistent with the previous reports. Moreover, we presented a new finding that MK-801 (0.6 mg/kg) chronic administration for 8 days produced a significant increase of c-Fos protein expression in the PC/RS cortex, prefrontal cortex (PFC) and hypothalamus of mice. Among that, c-Fos protein expression in the PC/RS cortex of mice was most significant. Compared to acute administration, we found that MK-801 chronic administration significantly increased the expression of c-Fos protein in the PC/RS cortex, PFC and hypothalamus. Furthermore, pretreatment of mice with clozapine significantly decreased the expression of c-Fos protein induced by MK-801 acute and chronic administration. These results suggest that c-Fos protein, the marker of neuronal activation, might play an important role in the chronic pathophysiological process of schizophrenic model induced by NMDA receptor antagonist. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 52 | Schizophr. Res. 2009 Nov 115: 88-93 |
| PMID | 19748228 |
| Title | Striatal metabolic alterations in non-psychotic adolescent offspring at risk for schizophrenia: a (1)H spectroscopy study. |
| Abstract | In vivo proton ((1)H) Magnetic Resonance spectroscopy ((1)H MRS) has shown abnormalities in young first-episode patients with schizophrenia. It is unclear whether these abnormalities reflect trait related vs. state related alterations in schizophrenia. We compared young first-degree relatives of schizophrenia patients and healthy controls using (1)H MRS. We hypothesized alterations in the (1)H MRS metabolites N-acetyl aspartate (NAA) and glutamate in corticostriatal and thalamic brain regions. We obtained multi-voxel, short-TE (1)H MRS measurements at 1.5 Tesla in 40 consenting adolescent offspring at risk for schizophrenia (HR), and 48 age matched healthy controls (HC). Absolute levels of NAA, phosphocreatine plus creatine (PCr+Cr), choline-containing compounds (GPC+PC), myo-inositol and glutamate plus glutamine (Glu+Gln) were obtained from the seven different anatomical brain areas (nominal voxel size of 4.5cm(3) each) and corrected for tissue voxel composition. HR subjects showed NAA (p=.0049), PCr+Cr (p=0.028) and GPC+PC (p=0.0086) reductions in the caudate compared with HC subjects. Male HR subjects had significant Glu+Gln reductions compared to male HC subjects (p=.0022). HR subjects had increased NAA in prefrontal white matter. NAA levels in the prefrontal white matter and Glu+Gln levels in the inferior parietal/occipital region were both increased in HR without psychopathology compared with HC subjects. Lower NAA, PCr+Cr and GPC+PC levels may reflect an overall reduction in cellular processes in the caudate of HC subjects, perhaps related to decreases in cell density, or synaptic overpruning. Further studies are needed to examine the pathophysiologic significance of these observations, and their potential predictive value for schizophrenia related psychopathology that may emerge in these at risk relatives during adolescence and early adulthood. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 53 | Eur Arch Psychiatry Clin Neurosci 2010 Feb 260: 51-7 |
| PMID | 19876665 |
| Title | Improving outpatient treatment in schizophrenia: effects of computerized guideline implementation--results of a multicenter-study within the German research network on schizophrenia. |
| Abstract | schizophrenia clinical practice guidelines are developed to provide expert- and evidence-based advice to practicing psychiatrists in order to improve the management of this disorder. However, the application of these guidelines in everyday health care can still be described as nonsatisfying. Within the project "Guideline-supported quality management in outpatient treatment", we investigated whether guideline adherence and quality of outcome can be improved by implementing a computer-based, guideline-oriented decision-support system. Therefore, a disease-specific decision-support system was developed interactively presenting guidelines to support the physicians decision-making process during the treatment of schizophrenia patients. We evaluated the system in a control group design: An experimental group consisting of 15 psychiatrists in private practice used the decision-support system, thus documenting the treatment of schizophrenic patients. Guideline-based algorithms were interactively and case specifically displayed on the PC-screen as soon as predefined triggers were met. A first control group in Munich provided treatment-as-usual, documenting the treatment via paper-pencil. Two further physician groups served as additional comparison groups: one also documented electronically using the decision-support system, however without receiving electronic guideline support, the second group carried out traditional quality circles while also using the paper-pencil approach. As a result of the intervention, we observed a strong initial but time-limited improvement with respect to the core aspects of outpatient treatment in schizophrenia in the experimental group. The findings suggest that decision-support systems, despite their limitations, can be used to enhance treatment outcome in schizophrenia outpatient care. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 54 | Eur Arch Psychiatry Clin Neurosci 2010 Feb 260: 51-7 |
| PMID | 19876665 |
| Title | Improving outpatient treatment in schizophrenia: effects of computerized guideline implementation--results of a multicenter-study within the German research network on schizophrenia. |
| Abstract | schizophrenia clinical practice guidelines are developed to provide expert- and evidence-based advice to practicing psychiatrists in order to improve the management of this disorder. However, the application of these guidelines in everyday health care can still be described as nonsatisfying. Within the project "Guideline-supported quality management in outpatient treatment", we investigated whether guideline adherence and quality of outcome can be improved by implementing a computer-based, guideline-oriented decision-support system. Therefore, a disease-specific decision-support system was developed interactively presenting guidelines to support the physicians decision-making process during the treatment of schizophrenia patients. We evaluated the system in a control group design: An experimental group consisting of 15 psychiatrists in private practice used the decision-support system, thus documenting the treatment of schizophrenic patients. Guideline-based algorithms were interactively and case specifically displayed on the PC-screen as soon as predefined triggers were met. A first control group in Munich provided treatment-as-usual, documenting the treatment via paper-pencil. Two further physician groups served as additional comparison groups: one also documented electronically using the decision-support system, however without receiving electronic guideline support, the second group carried out traditional quality circles while also using the paper-pencil approach. As a result of the intervention, we observed a strong initial but time-limited improvement with respect to the core aspects of outpatient treatment in schizophrenia in the experimental group. The findings suggest that decision-support systems, despite their limitations, can be used to enhance treatment outcome in schizophrenia outpatient care. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 55 | J Psychiatr Res 2010 Aug 44: 688-93 |
| PMID | 20056243 |
| Title | Phospholipid profile in the postmortem hippocampus of patients with schizophrenia and bipolar disorder: no changes in docosahexaenoic acid species. |
| Abstract | Previous studies with postmortem brain tissues showed abnormalities not only in n-3 long-chain polyunsaturated fatty acids (PUFA) but also in phospholipid metabolism in the cortex of individuals with schizophrenia and mood disorder. In this study we investigated whether there is similar abnormality in n-3 long-chain PUFAs and/or in phospholipid profile in the hippocampus of schizophrenia and bipolar disorder patients compared to unaffected controls. Using high-performance liquid chromatography/electrospray ionization-mass spectrometry (LC/MS), the phospholipid contents in the postmortem hippocampus from 35 individuals with schizophrenia, 34 individuals with bipolar disorder and 35 controls were evaluated. Unlike the previous findings form orbitofrontal cortex, we found no significant differences in either n-3 long-chain PUFA or total phosphatidylserine (PS), phosphatidylethanolamine (PE) and phosphatidylcholine (PC). However, docosapentaenoic acid (n-6, 22:5n-6)-PS and 22:5n-6-PC were significantly lower in individuals with schizophrenia or bipolar disorder than the controls. When fatty acid contents were estimated from PS, PE and PC, 22:5n-6 was significantly lower in both patient groups compared to the controls. From these results we concluded that DHA loss associated with these psychiatric disorders may be specific to certain regions of the brain. The selective decrease in 22:5n-6 without affecting DHA contents suggests altered lipid metabolism, particularly n-6 PUFA rather than n-3 PUFA, in the hippocampus of individuals with schizophrenia or bipolar disorder. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 56 | J. Pharmacol. Exp. Ther. 2010 Sep 334: 863-74 |
| PMID | 20504915 |
| Title | In vitro pharmacological characterization of a novel selective alpha7 neuronal nicotinic acetylcholine receptor agonist ABT-107. |
| Abstract | Enhancement of alpha7 nicotinic acetylcholine receptor (nAChR) activity is considered a therapeutic approach for ameliorating cognitive deficits present in Alzheimer's disease and schizophrenia. In this study, we describe the in vitro profile of a novel selective alpha7 nAChR agonist, 5-(6-[(3R)-1-azabicyclo[2,2,2]oct-3-yloxy]pyridazin-3-yl)-1H-indole (ABT-107). ABT-107 displayed high affinity binding to alpha7 nAChRs [rat or human cortex, [(3)H](1S,4S)-2,2-dimethyl-5-(6-phenylpyridazin-3-yl)-5-aza-2-azoniabicyclo[2.2.1]heptane (A-585539), K(i) = 0.2-0.6 nM or [(3)H]methyllycaconitine (MLA), 7 nM] that was at least 100-fold selective versus non-alpha7 nAChRs and other receptors. Functionally, ABT-107 did not evoke detectible currents in Xenopus oocytes expressing human or nonhuman alpha3beta4, chimeric (alpha6/alpha3)beta4, or 5-HT(3A) receptors, and weak or negligible Ca(2+) responses in human neuroblastoma IMR-32 cells (alpha3* function) and human alpha4beta2 and alpha4beta4 nAChRs expressed in human embryonic kidney 293 cells. ABT-107 potently evoked human and rat alpha7 nAChR current responses in oocytes (EC(50), 50-90 nM total charge, approximately 80% normalized to acetylcholine) that were enhanced by the positive allosteric modulator (PAM) 4-[5-(4-chloro-phenyl)-2-methyl-3-propionyl-pyrrol-1-yl]-benzenesulfonamide (A-867744). In rat hippocampus, ABT-107 alone evoked alpha7-like currents, which were inhibited by the alpha7 antagonist MLA. In dentate gyrus granule cells, ABT-107 enhanced spontaneous inhibitory postsynaptic current activity when coapplied with A-867744. In the presence of an alpha7 PAM [A-867744 or N-[(3R)-1-azabicyclo[2.2.2]oct-3-yl]-4-chlorobenzamide hydrochloride (PNU-120596)], the addition of ABT-107 elicited MLA-sensitive alpha7 nAChR-mediated Ca(2+) signals in IMR-32 cells and rat cortical cultures and enhanced extracellular signal-regulated kinase phosphorylation in differentiated PC-12 cells. ABT-107 was also effective in protecting rat cortical cultures against glutamate-induced toxicity. In summary, ABT-107 is a selective high affinity alpha7 nAChR agonist suitable for characterizing the roles of this subtype in pharmacological studies. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 57 | Schizophr Bull 2010 May 36: 455-60 |
| PMID | 19889950 |
| Title | Should the PANSS be rescaled? |
| Abstract | The design of the Positive and Negative Syndrome Scale (PANSS) with item levels ranging from 1 to 7 leads to the trivial result that the 30-item scale's zero level (no symptoms) is 30. This causes serious problems when ratios are calculated which always implicitly depend on a natural zero point (equals 0). Recent publications concerning efficacy of antipsychotics correctly suggest a subtraction of 30 points to every PANSS before calculating percent change (PC). Nevertheless, the traditional approach using uncorrected scores is still in common practice. This analysis aims to clarify which approach is the most appropriate from a statistical perspective.For analysis, data from a naturalistic study on 400 patients with a schizophrenic spectrum disorder and simulated data sets were used. While calculations concerning absolute score values and their differences are not affected, considerable problems arise in calculations of PC and related response criteria. Even significance levels of estimated treatment effects change, depending on the structure of the data (eg, baseline symptom severity). Using a PANSS version with items ranging from 0 to 6 would avoid such often neglected pitfalls. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 58 | Neuroimage 2010 Feb 49: 2783-90 |
| PMID | 19850131 |
| Title | Specific metabolites in the medial prefrontal cortex are associated with the neurocognitive deficits in schizophrenia: a preliminary study. |
| Abstract | We measured brain metabolites in the medial prefrontal cortex of 19 schizophrenic patients and 18 healthy controls by 3 T proton magnetic resonance spectroscopy ((1)H MRS), and examined the relationship between prefrontal cortex-related neurocognitive functions and brain metabolites in the medial prefrontal cortex. The patients with schizophrenia exhibited deficits on the verbal fluency, Wisconsin card sorting test (WCST), trail making test, Stroop test and digit span distraction test (DSDT), but not on the Iowa gambling test. The patients showed statistical significant changes in the ratio of glutamine/glutamate, the ratio of N-acetyl-l-aspartate (NAA)/glycerophosphorylcholine plus phosphorylcholine (GPC+PC) and the levels of taurine in the medial prefrontal cortex compared with normal controls. Furthermore, we found significant correlations of the ratio of glutamine/glutamate with WCST and DSDT scores, the ratio of NAA/(GPC+PC) with verbal fluency and WCST scores, and the levels of taurine with scores on the Stroop test and Trail making test A among the participants. The ratios of NAA/(GPC+PC) and (GPC+PC)/(Cr+PCr) had significant relationships with the duration of untreated psychosis of the schizophrenic patients. The glutamine/glutamate ratio and levels of taurine were significantly related to the duration of illness of the patients. These data suggest that specific metabolites of the medial prefrontal cortex are associated with the neurocognitive deficits in schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 59 | Neuroimage 2010 Feb 49: 2783-90 |
| PMID | 19850131 |
| Title | Specific metabolites in the medial prefrontal cortex are associated with the neurocognitive deficits in schizophrenia: a preliminary study. |
| Abstract | We measured brain metabolites in the medial prefrontal cortex of 19 schizophrenic patients and 18 healthy controls by 3 T proton magnetic resonance spectroscopy ((1)H MRS), and examined the relationship between prefrontal cortex-related neurocognitive functions and brain metabolites in the medial prefrontal cortex. The patients with schizophrenia exhibited deficits on the verbal fluency, Wisconsin card sorting test (WCST), trail making test, Stroop test and digit span distraction test (DSDT), but not on the Iowa gambling test. The patients showed statistical significant changes in the ratio of glutamine/glutamate, the ratio of N-acetyl-l-aspartate (NAA)/glycerophosphorylcholine plus phosphorylcholine (GPC+PC) and the levels of taurine in the medial prefrontal cortex compared with normal controls. Furthermore, we found significant correlations of the ratio of glutamine/glutamate with WCST and DSDT scores, the ratio of NAA/(GPC+PC) with verbal fluency and WCST scores, and the levels of taurine with scores on the Stroop test and Trail making test A among the participants. The ratios of NAA/(GPC+PC) and (GPC+PC)/(Cr+PCr) had significant relationships with the duration of untreated psychosis of the schizophrenic patients. The glutamine/glutamate ratio and levels of taurine were significantly related to the duration of illness of the patients. These data suggest that specific metabolites of the medial prefrontal cortex are associated with the neurocognitive deficits in schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 60 | Biol. Psychiatry 2010 Feb 67: 238-45 |
| PMID | 19765686 |
| Title | Error-related processing dysfunction in children aged 9 to 12 years presenting putative antecedents of schizophrenia. |
| Abstract | Intervention aimed at preventing schizophrenia may be most effective if targeted at specific, but modifiable, functional impairments that present during childhood. We have developed a novel method of screening community samples aged 9 to 12 years to identify children who present a triad of putative antecedents of schizophrenia (ASz), defined as 1) speech and/or motor development lags/problems; 2) internalizing, externalizing, and/or peer-relationship problems in the clinical range; and 3) psychotic-like experiences. This study examined whether ASz children display brain function abnormalities during error processing that are similar to those exhibited by adults with schizophrenia. Twenty-two ASz children and 26 typically developing (TD) children with no antecedents of schizophrenia completed an error-inducing Go/NoGo task during event-related potential recording. Group differences were examined in the amplitude and latency of four event-related potential components: the initial error-related negativity (ERN) and later error-positivity (Pe) elicited on false-alarm responses to NoGo trials, and the corresponding initial correct response negativity (CRN) and later correct response positivity (PC) elicited during processing of correct responses to Go trials. Relative to TD children, ASz children were characterized by reduced ERN amplitude but unaffected CRN, Pe, and PC amplitudes. No group differences were observed in the latency of any component. Children presenting a triad of putative antecedents of schizophrenia show error-processing dysfunction mimicking that observed in adults with schizophrenia using the same Go/NoGo paradigm. The ASz children displayed specific early error-processing deficits rather than a generalized deficit in self-monitoring. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 61 | J Clin Psychiatry 2010 Jan 71: 14-25 |
| PMID | 19778496 |
| Title | Effectiveness of pharmacotherapy for severe personality disorders: meta-analyses of randomized controlled trials. |
| Abstract | There has been little systematic attempt to validate current pharmacologic treatment algorithms and guidelines for severe personality disorder. We evaluated studies on the effectiveness of psychoactive drugs on specific symptom domains for borderline and/or schizotypal personality disorder. The literature was searched for placebo-controlled randomized clinical trials (PC-RCTs) on the effectiveness of psychopharmacologic drugs in personality disorder patients. The PubMed, PsychINFO, PiCarta, Cochrane, and Web of Science databases were searched using the search terms borderline personality, schizotypal personality, personality disorder, cluster A, cluster B, treatment, drug, pharmacotherapy, antipsychotic, antidepressant, mood stabilizer, effect, outcome, review, and meta-analysis for studies published between 1980 and December 2007, and references were identified from bibliographies from articles and books. Placebo-controlled randomized clinical trials on the efficacy of antipsychotics, antidepressants, and mood stabilizers regarding cognitive-perceptual symptoms, impulsive-behavioral dyscontrol, and affective dysregulation (with subdomains depressed mood, anxiety, anger, and mood lability) were selected in patients with well defined borderline and/or schizotypal personality disorder. Studies whose primary emphasis was on the treatment of Axis I disorders were excluded. Meta-analyses were conducted using 21 retrieved studies. Antipsychotics have a moderate effect on cognitive-perceptual symptoms (5 PC-RCTs; standardized mean difference [SMD]=0.56) and a moderate to large effect on anger (4 PC-RCTs; SMD=0.69). Antidepressants have no significant effect on impulsive-behavioral dyscontrol and depressed mood. They have a small but significant effect on anxiety (5 PC-RCTs; SMD=0.30) and anger (4 PC-RCTs; SMD=0.34). Mood stabilizers have a very large effect on impulsive-behavioral dyscontrol (6 PC-RCTs; SMD=1.51) and anger (7 PC-RCTs; SMD=1.33), a large effect on anxiety (3 PC-RCTs; SMD=0.80), but a moderate effect on depressed mood (5 PC-RCTs; SMD=0.55). Mood lability as an outcome measure was seldomly assessed. Mood stabilizers have a more pronounced effect on global functioning (3 PC-RCTs; SMD=0.79) than have antipsychotics (5 PC-RCTs; SMD=0.37). The effect of antidepressants on global functioning is negligible. Drug therapy tailored to well-defined symptom domains can have a beneficial effect on patients with severe personality disorder. The findings from this study raise questions on current pharmacologic algorithms. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 62 | Psychiatr. Genet. 2011 Dec 21: 307-14 |
| PMID | 21862952 |
| Title | Association between schizophrenia and single nucleotide polymorphisms in lipoprotein lipase gene in a Han Chinese population. |
| Abstract | Many studies have suggested that certain types of lipids such as phospholipids, fatty acids, and cholesterols are involved in the pathology of nervous system diseases. Lipoprotein lipase (LPL), as the key enzyme of triglyceride hydrolysis, is expressed in the brain regions functionally relevant to learning, memory, and other cognitive functions. In addition, both genome-wide linkage and association studies in schizophrenia have implicated the chromosome 8p22 region, in which the LPL gene is located. Therefore, LPL is an attractive candidate gene for schizophrenia and we tested this hypothesis in a case-control sample. In this study, we investigated allele and genotype frequencies distributions of nine single nucleotide polymorphisms (SNPs) within the LPL gene in Han Chinese patients with schizophrenia (n=319) and healthy controls (n=575). Significant differences were detected between case and control groups in the frequencies of rs253 alleles [odds ratio (OR): 1.74; 95% confidence interval (CI): 1.43-2.11; P=3.21×10] and genotypes (OR: 3.08; 95%CI: 2.07-4.56; global P=7.88×10), respectively. Interestingly, this association was observed only in the male (P=5.87×10 for allele; P=1.79×10 for genotype) and not in the female samples (P>0.05). After correcting for multiple testing, the above association remains to be significant (PC<1×10). These results suggest that rs253 C allele and CC genotype confer risk for schizophrenia in men. Our study lends support to the potential role of lipid metabolism in schizophrenia and further investigations are warranted. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 63 | Neural Netw 2011 Aug 24: 568-74 |
| PMID | 21421295 |
| Title | A neural network model of normal and abnormal auditory information processing. |
| Abstract | The ability of the brain to attenuate the response to irrelevant sensory stimulation is referred to as sensory gating. A gating deficiency has been reported in schizophrenia. To study the neural mechanisms underlying sensory gating, a neuroanatomically inspired model of auditory information processing has been developed. The mathematical model consists of lumped parameter modules representing the thalamus (TH), the thalamic reticular nucleus (TRN), auditory cortex (AC), and prefrontal cortex (PC). It was found that the membrane potential of the pyramidal cells in the PC module replicated auditory evoked potentials, recorded from the scalp of healthy individuals, in response to pure tones. Also, the model produced substantial attenuation of the response to the second of a pair of identical stimuli, just as seen in actual human experiments. We also tested the viewpoint that schizophrenia is associated with a deficit in prefrontal dopamine (DA) activity, which would lower the excitatory and inhibitory feedback gains in the AC and PC modules. Lowering these gains by less than 10% resulted in model behavior resembling the brain activity seen in schizophrenia patients, and replicated the reported gating deficits. The model suggests that the TRN plays a critical role in sensory gating, with the smaller response to a second tone arising from a reduction in inhibition of TH by the TRN. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 64 | J Clin Psychopharmacol 2011 Aug 31: 489-96 |
| PMID | 21694626 |
| Title | Differential effectiveness of antipsychotics in borderline personality disorder: meta-analyses of placebo-controlled, randomized clinical trials on symptomatic outcome domains. |
| Abstract | In clinical practice, antipsychotic drugs are widely used in borderline personality disorder (BPD). To evaluate current pharmacological treatment algorithms and guidelines for BPD, the authors reviewed and meta-analyzed studies on the effectiveness of antipsychotics on specific symptom domains in BPD. The literature was searched for placebo-controlled, randomized clinical trials (PC-RCTs) on the effectiveness of antipsychotics regarding cognitive perceptual symptoms, impulsive behavioral dyscontrol, and affective dysregulation (with subdomains depressed mood, anxiety, anger, and mood lability) in BPD. Studies whose primary emphasis was on the treatment of Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition schizotypal personality disorder or Axis I disorders were excluded. Meta-analyses were conducted using 11 retrieved studies including 1152 borderline patients. Antipsychotics have a significant effect on cognitive perceptual symptoms (9 PC-RCTs; standardized mean difference [SMD], 0.23) and mood lability (5 PC-RCTs; SMD, 0.20) as well as on global functioning (8 PC-RCTs; SMD, 0.25), but these effects have to be qualified as small. Antipsychotics have a more pronounced effect on anger (9 PC-RCTs; SMD, 0.39). Antipsychotics did not have a significant effect on impulsive behavioral dyscontrol, depressed mood, and anxiety in BPD. Drug therapy tailored to well-defined symptom domains can have beneficial effects in BPD. At short term, antipsychotics can have significant effects on cognitive-perceptual symptoms, anger, and mood lability, but the wide and long-term use of antipsychotics in these patients remains controversial. The findings from this study raise questions on current pharmacological algorithms and clinical guidelines. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 65 | PLoS ONE 2012 -1 7: e44564 |
| PMID | 22970249 |
| Title | Hypoxic induction of the regulator of G-protein signalling 4 gene is mediated by the hypoxia-inducible factor pathway. |
| Abstract | The transcriptional response to hypoxia is largely dependent on the Hypoxia Inducible Factors (HIF-1 and HIF-2) in mammalian cells. Many target genes have been characterised for these heterodimeric transcription factors, yet there is evidence that the full range of HIF-regulated genes has not yet been described. We constructed a TetON overexpression system in the rat pheochromocytoma PC-12 cell line to search for novel HIF and hypoxia responsive genes. The Rgs4 gene encodes the Regulator of G-Protein Signalling 4 (RGS4) protein, an inhibitor of signalling from G-protein coupled receptors, and dysregulation of Rgs4 is linked to disease states such as schizophrenia and cardiomyopathy. Rgs4 was found to be responsive to HIF-2? overexpression, hypoxic treatment, and hypoxia mimetic drugs in PC-12 cells. Similar responses were observed in human neuroblastoma cell lines SK-N-SH and SK-N-BE(2)C, but not in endothelial cells, where Rgs4 transcript is readily detected but does not respond to hypoxia. Furthermore, this regulation was found to be dependent on transcription, and occurs in a manner consistent with direct HIF transactivation of Rgs4 transcription. However, no HIF binding site was detectable within 32 kb of the human Rgs4 gene locus, leading to the possibility of regulation by long-distance genomic interactions. Further research into Rgs4 regulation by hypoxia and HIF may result in better understanding of disease states such as schizophrenia, and also shed light on the other roles of HIF yet to be discovered. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 66 | Transl Psychiatry 2012 -1 2: e149 |
| PMID | 22892715 |
| Title | Schizophrenia shows a unique metabolomics signature in plasma. |
| Abstract | schizophrenia is a severe complex mental disorder affecting 0.5-1% of the world population. To date, diagnosis of the disease is mainly based on personal and thus subjective interviews. The underlying molecular mechanism of schizophrenia is poorly understood. Using targeted metabolomics we quantified and compared 103 metabolites in plasma samples from 216 healthy controls and 265 schizophrenic patients, including 52 cases that do not take antipsychotic medication. Compared with healthy controls, levels of five metabolites were found significantly altered in schizophrenic patients (P-values ranged from 2.9 × 10(-8) to 2.5 × 10(-4)) and in neuroleptics-free probands (P-values ranging between 0.006 and 0.03), respectively. These metabolites include four amino acids (arginine, glutamine, histidine and ornithine) and one lipid (PC ae C38:6) and are suggested as candidate biomarkers for schizophrenia. To explore the genetic susceptibility on the associated metabolic pathways, we constructed a molecular network connecting these five aberrant metabolites with 13 schizophrenia risk genes. Our result implicated aberrations in biosynthetic pathways linked to glutamine and arginine metabolism and associated signaling pathways as genetic risk factors, which may contribute to patho-mechanisms and memory deficits associated with schizophrenia. This study illustrated that the metabolic deviations detected in plasma may serve as potential biomarkers to aid diagnosis of schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 67 | Transl Psychiatry 2012 -1 2: e149 |
| PMID | 22892715 |
| Title | Schizophrenia shows a unique metabolomics signature in plasma. |
| Abstract | schizophrenia is a severe complex mental disorder affecting 0.5-1% of the world population. To date, diagnosis of the disease is mainly based on personal and thus subjective interviews. The underlying molecular mechanism of schizophrenia is poorly understood. Using targeted metabolomics we quantified and compared 103 metabolites in plasma samples from 216 healthy controls and 265 schizophrenic patients, including 52 cases that do not take antipsychotic medication. Compared with healthy controls, levels of five metabolites were found significantly altered in schizophrenic patients (P-values ranged from 2.9 × 10(-8) to 2.5 × 10(-4)) and in neuroleptics-free probands (P-values ranging between 0.006 and 0.03), respectively. These metabolites include four amino acids (arginine, glutamine, histidine and ornithine) and one lipid (PC ae C38:6) and are suggested as candidate biomarkers for schizophrenia. To explore the genetic susceptibility on the associated metabolic pathways, we constructed a molecular network connecting these five aberrant metabolites with 13 schizophrenia risk genes. Our result implicated aberrations in biosynthetic pathways linked to glutamine and arginine metabolism and associated signaling pathways as genetic risk factors, which may contribute to patho-mechanisms and memory deficits associated with schizophrenia. This study illustrated that the metabolic deviations detected in plasma may serve as potential biomarkers to aid diagnosis of schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 68 | Schizophr. Res. 2012 Aug 139: 73-7 |
| PMID | 22627122 |
| Title | The relationship of trait to state motivation: the role of self-competency beliefs. |
| Abstract | Even when people with schizophrenia describe themselves as generally motivated and eager to engage in activities, they may not actually be motivated in the present moment. In order to better understand the relationship between trait and state motivation, we aimed to assess trait motivation and state intrinsic motivation, and investigate their relations to each other and to criterion-related variables including cognition, negative symptoms, and beliefs about one's own competency-also known as perceived competency (PC). Further, we investigated whether PC mediates the relationships between state intrinsic motivation (IM) and trait motivation dimensions. Forty individuals with schizophrenia or schizoaffective disorders were administered two self-report measures of motivation, the Motivational Trait Questionnaire (Kanfer, R., Ackerman, P., 2000. Individual differences in work motivation: further explorations of a trait framework. Appl. Psychol. 49 (3), 470-482) and the Intrinsic Motivation Inventory for schizophrenia Research (Choi, J., Medalia, A., 2010. Intrinsic motivation and learning in a schizophrenia spectrum sample. Schizophr. Res. 118, 12-19), as well as measures of PC, cognition and symptoms. The results showed that in people with schizophrenia, trait approach motivation, but not trait avoidance motivation, is positively correlated with state intrinsic motivation and PC. There was evidence that PC partially mediates the relationship between trait approach motivation and state intrinsic motivation to do the task. These results support the role of therapies that directly address self-competency beliefs and set the groundwork for future investigations on the impact of such treatments on motivation. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 69 | Psychiatry Res 2013 Dec 214: 365-73 |
| PMID | 24045051 |
| Title | Altered phospholipid metabolism in schizophrenia: a phosphorus 31 nuclear magnetic resonance spectroscopy study. |
| Abstract | Phospholipid (PL) metabolism is investigated by in vivo 31P magnetic resonance spectroscopy (MRS). Inconsistent alterations of phosphocholine (PC), phosphoethanolamine (PE), glycerophosphocholine (GPC) and glycerophosphoethanolamine (GPE) have been described in schizophrenia, which might be overcome by specific editing techniques. The selective refocused insensitive nuclei-enhanced polarization transfer (RINEPT) technique was applied in a cross-sectional study involving 11 schizophrenia spectrum disorder patients (SZP) on stable antipsychotic monotherapy and 15 matched control subjects. Metabolite signals were found to be modulated by cerebrospinal fluid (CSF) content and gray matter/brain matter ratio. Corrected metabolite concentrations of PC, GPC and PE differed between patients and controls in both subcortical and cortical regions, whereas antipsychotic medication exerted only small effects. Significant correlations were found between the severity of clinical symptoms and the assessed signals. In particular, psychotic symptoms correlated with PC levels in the cerebral cortex, depression with PC levels in the cerebellum and executive functioning with GPC in the insular and temporal cortices. In conclusion, after controlling for age and tissue composition, this investigation revealed alterations of metabolite levels in SZP and correlations with clinical properties. RINEPT 31P MRS should also be applied to at-risk-mental-state patients as well as drug-naďve and chronically treated schizophrenic patients in order to enhance the understanding of longitudinal alterations of PL metabolism in schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 70 | Psychiatry Res 2013 Dec 214: 365-73 |
| PMID | 24045051 |
| Title | Altered phospholipid metabolism in schizophrenia: a phosphorus 31 nuclear magnetic resonance spectroscopy study. |
| Abstract | Phospholipid (PL) metabolism is investigated by in vivo 31P magnetic resonance spectroscopy (MRS). Inconsistent alterations of phosphocholine (PC), phosphoethanolamine (PE), glycerophosphocholine (GPC) and glycerophosphoethanolamine (GPE) have been described in schizophrenia, which might be overcome by specific editing techniques. The selective refocused insensitive nuclei-enhanced polarization transfer (RINEPT) technique was applied in a cross-sectional study involving 11 schizophrenia spectrum disorder patients (SZP) on stable antipsychotic monotherapy and 15 matched control subjects. Metabolite signals were found to be modulated by cerebrospinal fluid (CSF) content and gray matter/brain matter ratio. Corrected metabolite concentrations of PC, GPC and PE differed between patients and controls in both subcortical and cortical regions, whereas antipsychotic medication exerted only small effects. Significant correlations were found between the severity of clinical symptoms and the assessed signals. In particular, psychotic symptoms correlated with PC levels in the cerebral cortex, depression with PC levels in the cerebellum and executive functioning with GPC in the insular and temporal cortices. In conclusion, after controlling for age and tissue composition, this investigation revealed alterations of metabolite levels in SZP and correlations with clinical properties. RINEPT 31P MRS should also be applied to at-risk-mental-state patients as well as drug-naďve and chronically treated schizophrenic patients in order to enhance the understanding of longitudinal alterations of PL metabolism in schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 71 | Psychiatr Q 2013 Dec 84: 417-27 |
| PMID | 23456450 |
| Title | Exercise capacity and quality of life in patients with schizophrenia. |
| Abstract | The aim of this study was to resolve the relationship between physical capacity (PC) and quality of life (Qol) in schizophrenic patients and healthy controls. 31 patients (PG: 18 male, 13 female) and a control group (CG) of 50 healthy subjects (15 male, 35 female) were involved. PC was assessed as peak oxygen uptake [VO2peak, (ml (min kgKG)(-1))] and power output expressed as watts per kilogram (W kg(-1)). Qol was assessed using the SF-36 questionnaire. Patients with schizophrenia showed reduced VO2peak (male: PG 29 ± 5 vs. CG 44 ± 10; female: PG 21 ± 4 vs. CG 30 ± 8) and power output (male: PG 2.04 ± 0.47 vs. CG 3.43 ± 0.70; female PG 1.40 ± 0.28 vs. CG 2.43 ± 0.52). Scales of the SF-36 questionnaire were lower in the PG. While in the CG correlations were found between PC and several subscales of Qol, this was not the case in the PG. The restricted PC seen in the PG showed no relation to their subjectively assessed worsened Qol, which would indicate that schizophrenic patients evaluate limitations arising from this differently than healthy control subjects. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 72 | Psychiatr Q 2013 Dec 84: 417-27 |
| PMID | 23456450 |
| Title | Exercise capacity and quality of life in patients with schizophrenia. |
| Abstract | The aim of this study was to resolve the relationship between physical capacity (PC) and quality of life (Qol) in schizophrenic patients and healthy controls. 31 patients (PG: 18 male, 13 female) and a control group (CG) of 50 healthy subjects (15 male, 35 female) were involved. PC was assessed as peak oxygen uptake [VO2peak, (ml (min kgKG)(-1))] and power output expressed as watts per kilogram (W kg(-1)). Qol was assessed using the SF-36 questionnaire. Patients with schizophrenia showed reduced VO2peak (male: PG 29 ± 5 vs. CG 44 ± 10; female: PG 21 ± 4 vs. CG 30 ± 8) and power output (male: PG 2.04 ± 0.47 vs. CG 3.43 ± 0.70; female PG 1.40 ± 0.28 vs. CG 2.43 ± 0.52). Scales of the SF-36 questionnaire were lower in the PG. While in the CG correlations were found between PC and several subscales of Qol, this was not the case in the PG. The restricted PC seen in the PG showed no relation to their subjectively assessed worsened Qol, which would indicate that schizophrenic patients evaluate limitations arising from this differently than healthy control subjects. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 73 | Cell. Signal. 2013 Dec 25: 2871-7 |
| PMID | 24055909 |
| Title | Mechanism of dopamine D2 receptor-induced Ca(2+) release in PC-12 cells. |
| Abstract | Intracellular Ca(2+) levels are tightly regulated in the neuronal system. The loss of Ca(2+) homeostasis is associated with many neurological diseases and neuropsychiatric disorders such as Parkinson's, Alzheimer's, and schizophrenia. We investigated the mechanisms involved in intracellular Ca(2+) signaling in PC-12 cells. The stimulation of NGF-differentiated PC-12 cells with 3?M ATP caused an early Ca(2+) release followed by a delayed Ca(2+) release. The delayed Ca(2+) release was dependent on prior ATP priming and on dopamine secretion by PC-12 cells. Delayed Ca(2+) release was abolished in the presence of spiperone, suggesting that it is due to the activation of D2 dopamine receptors (D2R) by dopamine secreted by PC-12 cells. This was shown to be independent of PKA activation but dependent on PLC activity. An endocytosis step was required for inducing the delayed Ca(2+) release. Given the importance of calcyon in clathrin-mediated endocytosis, we verified the role of this protein in the delayed Ca(2+) release phenomenon. siRNA targeting of calcyon blocked the delayed Ca(2+) release, decreased ATP-evoked IP3R-mediated Ca(2+) release, and impaired subsequent Ca(2+) oscillations. Our results suggested that calcyon is involved in an unknown mechanism that causes a delayed IP3R-mediated Ca(2+) release in PC-12 cells. In schizophrenia, Ca(2+) dysregulation may depend on the upregulation of calcyon, which maintains elevated Ca(2+) levels as well as dopamine signaling. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 74 | Schizophr. Res. 2013 Aug 148: 59-66 |
| PMID | 23791389 |
| Title | Brain metabolite alterations in young adults at familial high risk for schizophrenia using proton magnetic resonance spectroscopy. |
| Abstract | Proton magnetic resonance spectroscopy ((1)H MRS) enables in-vivo measurement of several relevant brain metabolites and has provided evidence of a range of neurochemical abnormalities in schizophrenia, especially in glutamate and N-acetyl-aspartate (NAA). While individuals at high familial risk for schizophrenia (HR) exhibit some neurobiological findings observed in the disorder, (1)H MRS findings and their clinical correlates are not well characterized in this population. We compared 23 adolescent and young adult offspring of schizophrenia patients with 24 age- and sex-matched healthy controls using (1)H MRS. We acquired multi-voxel, short TE (1)H MRS measurements at 1.5T and obtained metabolite concentrations of N-acetyl-aspartate (NAA), combined glutamate and glutamine (Glu+Gln) and choline-containing compounds (GPC+PC) for the left and right thalamus, anterior cingulate gyrus, and caudate. We also assessed the relationship between regional metabolite levels, clinical measures and brain volume in a subset of 16 high-risk and 15 control subjects. Compared to healthy controls, high-risk subjects showed reductions in NAA levels in all three regions (thalamus, caudate, and anterior cingulate cortex), increases in Glu+Gln in the thalamus and caudate, and increases in GPC+PC in the anterior cingulate. In HR, thalamic Glu+Gln concentration was positively correlated and thalamic NAA inversely correlated with measures of schizotypy. Anterior cingulate GPC+PC and caudate Glu+Gln were significantly correlated with attenuated psychotic symptom severity. Anterior cingulate NAA was correlated with executive function. Our data suggest the occurrence of metabolic alterations in young relatives of schizophrenia patients similar to those seen in patients with established illness. The observed correlations with cognitive deficits and psychosis-related psychopathology suggest that these metabolic measures may have value as biomarkers of risk for schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 75 | Schizophr Bull 2013 Sep 39: 1027-36 |
| PMID | 22987297 |
| Title | Attentional modulation of source attribution in first-episode psychosis: a functional magnetic resonance imaging study. |
| Abstract | In patients with schizophrenia, the misattribution of self-generated events to an external source is associated with the presence of psychotic symptoms. The aim of this study was to investigate how this misattribution is influenced by dysfunction of attentional processing, which is also impaired in schizophrenia. Participants underwent functional Magnetic Resonance Imaging (fMRI) while listening to prerecorded speech. Their expectancies were manipulated using visual cues that were either congruent (valid) or incongruent (invalid) with the speech. The source (self/other) and the acoustic quality (undistorted/distorted) of the speech were also manipulated. Twenty patients with first-episode psychosis (FEP) and 20 matched healthy controls (HC) were tested. When listening to self-generated speech preceded by an invalid (other speech) cue, relative to HC, FEP patients showed a trend to misidentify their own speech as that of another person. Analysis of fMRI data showed that FEP patients had reduced activation in the right middle temporal gyrus (MTG) and left precuneus (PC) relative to HC. Within the FEP group, the level of activation in the right MTG was negatively correlated with the severity of their positive psychotic symptoms. Impaired attentional modulation in schizophrenia may contribute to the tendency for FEP patients to misattribute the source of self-generated material, and this may be mediated by the right MTG and PC, regions that are involved in both self-referential processing and the integration of sensory information. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 76 | Schizophr. Res. 2013 Aug 148: 59-66 |
| PMID | 23791389 |
| Title | Brain metabolite alterations in young adults at familial high risk for schizophrenia using proton magnetic resonance spectroscopy. |
| Abstract | Proton magnetic resonance spectroscopy ((1)H MRS) enables in-vivo measurement of several relevant brain metabolites and has provided evidence of a range of neurochemical abnormalities in schizophrenia, especially in glutamate and N-acetyl-aspartate (NAA). While individuals at high familial risk for schizophrenia (HR) exhibit some neurobiological findings observed in the disorder, (1)H MRS findings and their clinical correlates are not well characterized in this population. We compared 23 adolescent and young adult offspring of schizophrenia patients with 24 age- and sex-matched healthy controls using (1)H MRS. We acquired multi-voxel, short TE (1)H MRS measurements at 1.5T and obtained metabolite concentrations of N-acetyl-aspartate (NAA), combined glutamate and glutamine (Glu+Gln) and choline-containing compounds (GPC+PC) for the left and right thalamus, anterior cingulate gyrus, and caudate. We also assessed the relationship between regional metabolite levels, clinical measures and brain volume in a subset of 16 high-risk and 15 control subjects. Compared to healthy controls, high-risk subjects showed reductions in NAA levels in all three regions (thalamus, caudate, and anterior cingulate cortex), increases in Glu+Gln in the thalamus and caudate, and increases in GPC+PC in the anterior cingulate. In HR, thalamic Glu+Gln concentration was positively correlated and thalamic NAA inversely correlated with measures of schizotypy. Anterior cingulate GPC+PC and caudate Glu+Gln were significantly correlated with attenuated psychotic symptom severity. Anterior cingulate NAA was correlated with executive function. Our data suggest the occurrence of metabolic alterations in young relatives of schizophrenia patients similar to those seen in patients with established illness. The observed correlations with cognitive deficits and psychosis-related psychopathology suggest that these metabolic measures may have value as biomarkers of risk for schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 77 | Prog. Lipid Res. 2014 Jan 53: 1-17 |
| PMID | 24334113 |
| Title | Long-chain polyunsaturated fatty acids (LCPUFA) from genesis to senescence: the influence of LCPUFA on neural development, aging, and neurodegeneration. |
| Abstract | Many clinical and animal studies demonstrate the importance of long-chain polyunsaturated fatty acids (LCPUFA) in neural development and neurodegeneration. This review will focus on involvement of LCPUFA from genesis to senescence. The LCPUFA docosahexaenoic acid and arachidonic acid are important components of neuronal membranes, while eicosapentaenoic acid, docosahexaenoic acid, and arachidonic acid also affect cardiovascular health and inflammation. In neural development, LCPUFA deficiency can lead to severe disorders like schizophrenia and attention deficit hyperactivity disorder. Perinatal LCPUFA supplementation demonstrated beneficial effects in neural development in humans and rodents resulting in improved cognition and sensorimotor integration. In normal aging, the effect of LCPUFA on prevention of cognitive impairment will be discussed. LCPUFA are important for neuronal membrane integrity and function, and also contribute in prevention of brain hypoperfusion. Cerebral perfusion can be compromised as result of obesity, cerebrovascular disease, hypertension, or diabetes mellitus type 2. Last, we will focus on the role of LCPUFA in most common neurodegenerative diseases like Alzheimer's disease and Parkinson's disease. These disorders are characterized by impaired cognition and connectivity and both clinical and animal supplementation studies have shown the potential of LCPUFA to decrease neurodegeneration and inflammation. This review shows that LCPUFA are essential throughout life. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 78 | Psychiatry Res 2014 Mar 215: 579-85 |
| PMID | 24495574 |
| Title | Environmental factors during adolescence associated with later development of psychotic disorders - a nested case-control study. |
| Abstract | Etiologies of psychotic disorders (schizophrenia and bipolar disorder) are conceptualized as interplay between genetic and environmental factors. The adolescent period is characterized by changes in social roles and expectations that may interact with biological changes or psychosocial stressors. Few studies focus on the adolescents' own reports of perceived risk factors. To assess differences at age 16 between persons who later develop psychotic disorders ("Confirmed Psychosis", CP) and their class-mates ("Population Controls", PC) we collected information on: (1) Social support factors (size of social network and expectancies of social support from friends), (2) Cognitive functioning (concentrating in the classroom, actual grades and expectancies of own academic achievements) and (3) Problems and stressors in families (illness or loss of work for parents), and in relationship with others (exposure to bullying, violence or sexual violation). Self-reported data from students at 15-16 years of age were linked to the case-registers from the "Thematically Organized Psychosis (TOP) Study". The CP group reported more economic problems in their families, smaller social network and lower academic expectation than the PC group. The results support the notion that long-term socioeconomic stressors in adolescence may serve as risk factors for the development of psychotic disorders. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 79 | J. Neurol. Sci. 2014 Mar 338: 12-22 |
| PMID | 24398346 |
| Title | Integrative parietal cortex processes: neurological and psychiatric aspects. |
| Abstract | For many decades the parietal cortex (PC) has been considered the key area in tasks which involve the integration of different stimuli. PC is fundamental to determine spatial sense, information navigation and integration, and is involved in several aspects of the complex motor repertoire and in neurological and psychiatric disorders. In this review, we focus on seven different aspects of PC: (i) neuroanatomy of the parietal cortex; (ii) sensory motor integration processes; iii) hand movement control: reaching, grasping, and pointing; (iv) saccadic eye movements; (v) movement observation; (vi) neurological aspects: ataxia, autism and Parkinson's disease; and (vii) psychiatric aspects: schizophrenia, bipolar disorder and depression. Among these, we related the perspectives which involve the functions of the parietal cortex and mirror neurons and that seem to play a fundamental role in action prediction, planning, observation and execution. Furthermore, we focused on the relationship between posterior parietal cortex (PPC) and hand-guided movements. For this review, we conducted an academic paper search which fulfilled the objective of the study. We conclude that the PC has great participation in different motor functions and neurological/psychiatric disorders. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 80 | Soc Psychiatry Psychiatr Epidemiol 2014 Jul 49: 1083-91 |
| PMID | 24562389 |
| Title | Trend in rates for deaths with mention of schizophrenia on death certificates of US residents, 1999-2010. |
| Abstract | Trends in mortality rates for schizophrenia using multiple causes of death (including contributory causes) coded on death certificates in the US resident population apparently have not been reported. Age-standardized rates for deaths per 100,000 in 1999-2010 at age 15+ years (and for 15-64 and 65+ years) with mention of schizophrenia were examined for the US resident population, including variation by age, gender, race (blacks/African Americans and whites) and region. Deaths at age 15+ years coded with schizophrenia as underlying cause were only 12 % of all deaths with mention of schizophrenia, for which the rate declined from 1.58 in 1999 (3,407 deaths) to 1.32 in 2010 (3,422 deaths) (percentage change or PC = -16 %). Declines were larger in females than males, in whites than blacks, and occurred in the Northeast, Midwest and South but not the West. The rate increased for age 15-64 years (PC = +28 %) (mainly in males), however, while declining for age 65+ years (PC = -35 %). For deaths at age 15-64 years with schizophrenia coded as other than the underlying cause, the largest continuous increase was for endocrine-metabolic diseases (predominantly diabetes mellitus) as underlying cause, with smaller increases in males for cardiovascular diseases, external causes and neoplasms. Trends in the US rate for deaths with mention of schizophrenia varied among the sociodemographic groups examined. The lack of decline for age 15-64 years requires further study especially with regard to mediators (e.g., obesity) of excess mortality in schizophrenia identified from cohort studies. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 81 | Neuron 2015 Mar 85: 1257-72 |
| PMID | 25754824 |
| Title | Pentraxins coordinate excitatory synapse maturation and circuit integration of parvalbumin interneurons. |
| Abstract | Circuit computation requires precision in the timing, extent, and synchrony of principal cell (PC) firing that is largely enforced by parvalbumin-expressing, fast-spiking interneurons (PVFSIs). To reliably coordinate network activity, PVFSIs exhibit specialized synaptic and membrane properties that promote efficient afferent recruitment such as expression of high-conductance, rapidly gating, GluA4-containing AMPA receptors (AMPARs). We found that PVFSIs upregulate GluA4 during the second postnatal week coincident with increases in the AMPAR clustering proteins NPTX2 and NPTXR. Moreover, GluA4 is dramatically reduced in NPTX2(-/-)/NPTXR(-/-) mice with consequent reductions in PVFSI AMPAR function. Early postnatal NPTX2(-/-)/NPTXR(-/-) mice exhibit delayed circuit maturation with a prolonged critical period permissive for giant depolarizing potentials. Juvenile NPTX2(-/-)/NPTXR(-/-) mice display reduced feedforward inhibition yielding a circuit deficient in rhythmogenesis and prone to epileptiform discharges. Our findings demonstrate an essential role for NPTXs in controlling network dynamics highlighting potential therapeutic targets for disorders with inhibition/excitation imbalances such as schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 82 | PLoS ONE 2015 -1 10: e0122861 |
| PMID | 25826220 |
| Title | Deficits in error-monitoring by college students with schizotypal traits: an event-related potential study. |
| Abstract | The present study used event-related potentials (ERPs) to investigate deficits in error-monitoring by college students with schizotypal traits. Scores on the schizotypal Personality Questionnaire (SPQ) were used to categorize the participants into schizotypal-trait (n = 17) and normal control (n = 20) groups. The error-monitoring abilities of the participants were evaluated using the Simon task, which consists of congruent (locations of stimulus and response are the same) and incongruent (locations of stimulus and response are different) conditions. The schizotypal-trait group committed more errors on the Simon task and exhibited smaller error-related negativity (ERN) amplitudes than did the control group. Additionally, ERN amplitude measured at FCz was negatively correlated with the error rate on the Simon task in the schizotypal-trait group but not in the control group. The two groups did not differ in terms of correct-related potentials (CRN), error positivity (Pe) and correct-related positivity (PC) amplitudes. The present results indicate that individuals with schizotypal traits have deficits in error-monitoring and that reduced ERN amplitudes may represent a biological marker of schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 83 | Psychoneuroendocrinology 2015 Feb 52: 43-58 |
| PMID | 25459892 |
| Title | A role for synapsin in FKBP51 modulation of stress responsiveness: Convergent evidence from animal and human studies. |
| Abstract | Both the molecular co-chaperone FKBP51 and the presynaptic vesicle protein synapsin (alternatively spliced from SYN1-3) are intensively discussed players in the still insufficiently explored pathobiology of psychiatric disorders such as major depression, schizophrenia and posttraumatic stress disorder (PTSD). To address their still unknown interaction, we compared the expression levels of synapsin and five other neurostructural and HPA axis related marker proteins in the prefrontal cortex (PFC) and the hippocampus of restrained-stressed and unstressed Fkbp5 knockout mice and corresponding wild-type littermates. In addition, we compared and correlated the gene expression levels of SYN1, SYN2 and FKBP5 in three different online datasets comprising expression data of human healthy subjects as well as of predominantly medicated patients with different psychiatric disorders. In summary, we found that Fkbp5 deletion, which we previously demonstrated to improve stress-coping behavior in mice, prevents the stress-induced decline in prefrontal cortical (PC), but not in hippocampal synapsin expression. Accordingly, PC, but not hippocampal, synapsin protein levels correlated positively with a more active mouse stress coping behavior. Searching for an underlying mechanism, we found evidence that deletion of Fkbp5 might prevent stress-induced PC synapsin loss, at least in part, through improvement of PC Akt kinase activity. These results, together with our finding that FKBP5 and SYN1 mRNA levels were regulated in opposite directions in the PFC of schizophrenic patients, who are known for exhibiting an altered stress-coping behavior, provide the first evidence of a role for PC synapsin in FKBP51 modulation of stress responsiveness. This role might extend to other tissues, as we found FKBP5 and SYN1 levels to correlate inversely not only in human PFC samples but also in other expression sites. The main limitation of this study is the small number of individuals included in the correlation analyses. Future studies will have to verify the here-postulated role of the FKBP51-Akt kinase-synapsin pathway in stress responsiveness. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 84 | Psychoneuroendocrinology 2015 Feb 52: 43-58 |
| PMID | 25459892 |
| Title | A role for synapsin in FKBP51 modulation of stress responsiveness: Convergent evidence from animal and human studies. |
| Abstract | Both the molecular co-chaperone FKBP51 and the presynaptic vesicle protein synapsin (alternatively spliced from SYN1-3) are intensively discussed players in the still insufficiently explored pathobiology of psychiatric disorders such as major depression, schizophrenia and posttraumatic stress disorder (PTSD). To address their still unknown interaction, we compared the expression levels of synapsin and five other neurostructural and HPA axis related marker proteins in the prefrontal cortex (PFC) and the hippocampus of restrained-stressed and unstressed Fkbp5 knockout mice and corresponding wild-type littermates. In addition, we compared and correlated the gene expression levels of SYN1, SYN2 and FKBP5 in three different online datasets comprising expression data of human healthy subjects as well as of predominantly medicated patients with different psychiatric disorders. In summary, we found that Fkbp5 deletion, which we previously demonstrated to improve stress-coping behavior in mice, prevents the stress-induced decline in prefrontal cortical (PC), but not in hippocampal synapsin expression. Accordingly, PC, but not hippocampal, synapsin protein levels correlated positively with a more active mouse stress coping behavior. Searching for an underlying mechanism, we found evidence that deletion of Fkbp5 might prevent stress-induced PC synapsin loss, at least in part, through improvement of PC Akt kinase activity. These results, together with our finding that FKBP5 and SYN1 mRNA levels were regulated in opposite directions in the PFC of schizophrenic patients, who are known for exhibiting an altered stress-coping behavior, provide the first evidence of a role for PC synapsin in FKBP51 modulation of stress responsiveness. This role might extend to other tissues, as we found FKBP5 and SYN1 levels to correlate inversely not only in human PFC samples but also in other expression sites. The main limitation of this study is the small number of individuals included in the correlation analyses. Future studies will have to verify the here-postulated role of the FKBP51-Akt kinase-synapsin pathway in stress responsiveness. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 85 | Rapid Commun. Mass Spectrom. 2015 Aug 29: 1491-500 |
| PMID | 26212164 |
| Title | Lipidomic analysis of p-chlorophenylalanine-treated mice using continuous-flow two-dimensional liquid chromatography/quadrupole time-of-flight mass spectrometry. |
| Abstract | Although serotonin deficiency is involved with various physiological disorders such as Alzheimer's disease, Parkinson's disease, schizophrenia and depression, the serotonin-dependent pathomechanisms remain poorly understood, particularly from a lipidomics perspective. This study therefore aimed to identify novel lipid biomarkers associated with serotonin deficiency by lipid profiling of p-chlorophenylalanine (PCPA)-treated, serotonin-deficient mice using continuous-flow normal-phase/reversed-phase two-dimensional liquid chromatography/quadrupole time-of-flight mass spectrometry (NP/RP 2D LC/QTOFMS). Principal component analysis (PCA) was performed to distinguish significantly altered lipids between the PCPA-treated mice and control mice. Eighteen lipid biomarkers were associated with PCPA-induced serotonin deficiency. Specifically, lipid species of lysophosphatidylethanolamine (LPE), phosphatidylethanolamine (PE), sphingomyelin (SM), galactosylceramide (GalCer), glucotosylceramide (GluCer), lactosylceramide (LacCer) and triacylglycerol (TG) were down-regulated whereas glycerophosphocholine (PC) and phosphatidylinositol (PI) were up-regulated in the PCPA-treated mice compared with control mice. This work demonstrates the significant effects of serotonin deficiency on lipid metabolisms and will facilitate improved understanding of pathomechanisms in serotonin deficiency, particularly from a lipidomics perspective. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 86 | Psychopathology 2015 -1 48: 310-6 |
| PMID | 26346129 |
| Title | Self-Disorders, Neurocognition and Rationality in Schizophrenia: A Preliminary Study. |
| Abstract | Although the very idea that the generative disorder in schizophrenia is a disturbance of the self is as old as the schizophrenia concept itself, empirical studies have only recently emerged, documenting that anomalous self-experiences (i.e. self-disorders, SDs) aggregate in schizophrenia spectrum disorders but not in other mental disorders. The aim of this study is to explore potential associations between SDs, neurocognitive performance, rationality and IQ in patients with schizophrenia. The sample comprises 31 patients diagnosed with schizophrenia (DSM-IV). All patients underwent comprehensive evaluation. SDs were assessed with the Examination of Anomalous Self-Experience scale. Neurocognitive performance was measured with 4 PC-implemented subtests from the Cambridge Neuropsychological Test Automated Battery. Rationality was measured using syllogism tests. The IQ was indexed by a summary score of 4 IST-2000-R computerized subtests. No correlation was found between SDs and neurocognitive performance or between SDs and IQ. SDs were found to correlate with rationality. Neurocognitive performance correlated with rationality, and both correlated with IQ, respectively. The lack of correlation between SDs and neurocognitive performance is consistent with the results from the only previous study exploring this issue, suggesting that SDs depict something essential to schizophrenia, whereas neurocognitive impairment does not. The correlation between SDs and rationality indicates that the syllogism tests reflect something central for schizophrenia, but the result needs further corroboration from larger, empirical studies. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 87 | Am. J. Med. Genet. A 2015 Mar 167A: 529-36 |
| PMID | 25691406 |
| Title | Craniofacial dysmorphology in 22q11.2 deletion syndrome by 3D laser surface imaging and geometric morphometrics: illuminating the developmental relationship to risk for psychosis. |
| Abstract | Persons with 22q11.2 deletion syndrome (22q11.2DS) are characterized inter alia by facial dysmorphology and greatly increased risk for psychotic illness. Recent studies indicate facial dysmorphology in adults with schizophrenia. This study evaluates the extent to which the facial dysmorphology of 22q11.2DS is similar to or different from that evident in schizophrenia. Twenty-one 22q11.2DS-sibling control pairs were assessed using 3D laser surface imaging. Geometric morphometrics was applied to 30 anatomical landmarks, 480 geometrically homologous semi-landmarks on curves and 1720 semi-landmarks interpolated on each 3D facial surface. Principal component (PC) analysis of overall shape space indicated PC2 to strongly distinguish 22q11.2DS from controls. Visualization of PC2 indicated 22q11.2DS and schizophrenia to be similar in terms of overall widening of the upper face, lateral displacement of the eyes/orbits, prominence of the cheeks, narrowing of the lower face, narrowing of nasal prominences and posterior displacement of the chin; they differed in terms of facial length (increased in 22q11.2DS, decreased in schizophrenia), mid-face and nasal prominences (displaced upwards and outwards in 22q11.2DS, less prominent in schizophrenia); lips (more prominent in 22q11.2DS; less prominent in schizophrenia) and mouth (open mouth posture in 22q11.2DS; closed mouth posture in schizophrenia). These findings directly implicate dysmorphogenesis in a cerebral-craniofacial domain that is common to 22q11.2DS and schizophrenia and which may repay further clinical and genetic interrogation in relation to the developmental origins of psychotic illness. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 88 | Schizophr Bull 2015 Jan 41: 144-53 |
| PMID | 24939881 |
| Title | Dysconnectivity within the default mode in first-episode schizophrenia: a stochastic dynamic causal modeling study with functional magnetic resonance imaging. |
| Abstract | We report the first stochastic dynamic causal modeling (sDCM) study of effective connectivity within the default mode network (DMN) in schizophrenia. Thirty-three patients (9 women, mean age = 25.0 years, SD = 5) with a first episode of psychosis and diagnosis of schizophrenia--according to the Diagnostic and Statistic Manual of Mental Disorders, 4th edition, revised criteria--were studied. Fifteen healthy control subjects (4 women, mean age = 24.6 years, SD = 4) were included for comparison. All subjects underwent resting state functional magnetic resonance imaging (fMRI) interspersed with 2 periods of continuous picture viewing. The anterior frontal (AF), posterior cingulate (PC), and the left and right parietal nodes of the DMN were localized in an unbiased fashion using data from 16 independent healthy volunteers (using an identical fMRI protocol). We used sDCM to estimate directed connections between and within nodes of the DMN, which were subsequently compared with t tests at the between subject level. The excitatory effect of the PC node on the AF node and the inhibitory self-connection of the AF node were significantly weaker in patients (mean values = 0.013 and -0.048 Hz, SD = 0.09 and 0.05, respectively) relative to healthy subjects (mean values = 0.084 and -0.088 Hz, SD = 0.15 and 0.77, respectively; P < .05). In summary, sDCM revealed reduced effective connectivity to the AF node of the DMN--reflecting a reduced postsynaptic efficacy of prefrontal afferents--in patients with first-episode schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 89 | PLoS ONE 2015 -1 10: e0122861 |
| PMID | 25826220 |
| Title | Deficits in error-monitoring by college students with schizotypal traits: an event-related potential study. |
| Abstract | The present study used event-related potentials (ERPs) to investigate deficits in error-monitoring by college students with schizotypal traits. Scores on the schizotypal Personality Questionnaire (SPQ) were used to categorize the participants into schizotypal-trait (n = 17) and normal control (n = 20) groups. The error-monitoring abilities of the participants were evaluated using the Simon task, which consists of congruent (locations of stimulus and response are the same) and incongruent (locations of stimulus and response are different) conditions. The schizotypal-trait group committed more errors on the Simon task and exhibited smaller error-related negativity (ERN) amplitudes than did the control group. Additionally, ERN amplitude measured at FCz was negatively correlated with the error rate on the Simon task in the schizotypal-trait group but not in the control group. The two groups did not differ in terms of correct-related potentials (CRN), error positivity (Pe) and correct-related positivity (PC) amplitudes. The present results indicate that individuals with schizotypal traits have deficits in error-monitoring and that reduced ERN amplitudes may represent a biological marker of schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 90 | Clin Neurophysiol 2015 Sep 126: 1717-26 |
| PMID | 25515589 |
| Title | An event-related potential investigation of error monitoring in adults with a history of psychosis. |
| Abstract | Previous research suggests that deficits in error monitoring contribute to psychosis and poor functioning. Consistent with the NIMH Research Domain Criteria initiative, this study examined electrophysiological brain activity, appraisal of self-performance, and personality traits related to psychosis during error monitoring in individuals with and without a history of psychosis across disorders. Error-related negativity (ERN), correct response negativity (CRN), error positivity (Pe), and correct response positivity (PC) were recorded in 14 individuals with a history of psychosis (PSY) and 12 individuals with no history of psychosis (CTR) during a flanker task. Participants continuously rated their performance and completed the schizotypal Personality Questionnaire-Brief Revised (SPQ-BR). Compared with CTR, PSY exhibited reduced ERN and Pe amplitudes and was also less accurate at evaluating their performance. Group differences were specific to error trials. Across all participants, smaller Pe amplitudes were associated with greater scores on the SPQ-BR Cognitive-Perceptual factor and less accuracy in subjective identification of errors. Individuals with a history of psychosis, regardless of diagnosis, demonstrated abnormal neural activity and imprecise confidence in response during error monitoring. Results suggest that disruptions in neural circuitry may underlie specific clinical symptoms across diagnostic categories. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 91 | Eur Child Adolesc Psychiatry 2016 Feb -1: -1 |
| PMID | 26921232 |
| Title | Attenuated psychotic and basic symptom characteristics in adolescents with ultra-high risk criteria for psychosis, other non-psychotic psychiatric disorders and early-onset psychosis. |
| Abstract | While attenuated psychotic symptoms (APS) and basic symptoms (BS) are the main current predictors of psychosis in adults, studies in adolescents are scarce. Thus, we (1) described the prevalence and severity of positive, negative, disorganization, general, and basic symptoms in adolescent patients at ultra-high risk for psychosis (UHR), with other non-psychotic psychiatric disorders (PC) and with early-onset psychosis (EOP); and (2) investigated BS criteria in relation to UHR criteria. Sixty-nine 12-18-year-old adolescents (15.3 ± 1.7 years, female = 58.0 %, UHR = 22, PC = 27, EOP = 20) were assessed with the structured interview for prodromal syndromes (SIPS) and the schizophrenia proneness instrument-child and youth version (SPI-CY). Despite similar current and past 12-month global functioning, both UHR and EOP had significantly higher SIPS total and subscale scores compared to PC, with moderate-large effect sizes. Expectedly, UHR had significantly lower SIPS positive symptom scores than EOP, but similar SIPS negative, disorganized, and general symptom scores. Compared to PC, both EOP and UHR had more severe basic thought and perception disturbances, and significantly more often met cognitive disturbances criteria (EOP = 50.0 %, UHR = 40.9 %, PC = 14.8 %). Compared to UHR, both EOP and PC significantly less often met cognitive-perceptive BS criteria (EOP = 35.0 %, UHR = 68.2 %, PC = 25.9 %). BS were significantly more prevalent in both EOP and UHR than PC, and UHR were similar to EOP in symptom domains. Given the uncertain outcome of adolescents at clinical high-risk of psychosis, future research is needed to determine whether the combined assessment of early subjective disturbances with observable APS can improve the accuracy of psychosis prediction. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 92 | Neuropsychopharmacology 2016 Apr 41: 1319-28 |
| PMID | 26354045 |
| Title | Alterations in High-Frequency Neuronal Oscillations in a Cynomolgus Macaque Test of Sustained Attention Following NMDA Receptor Antagonism. |
| Abstract | A growing body of evidence indicates that neuronal oscillations in the gamma frequency range (30-80?Hz) are disturbed in schizophrenic patients during cognitive processes and may represent an endophenotype of the disease. N-methyl-D-aspartate (NMDA) receptor antagonists have been used experimentally to induce schizophrenia-like symptoms including cognitive deficits in animals and humans. Here we characterized neuronal oscillations and event-related potentials (ERPs) in Cynomolgus macaques fully trained to perform a continuous performance test (CPT) in the presence and absence of the NMDA antagonist phencyclidine (PCP). Macaques (n=8) were trained to touch 'target' stimuli and ignore 'distractor' stimuli presented randomly on a touchscreen. Subsequently, all subjects were implanted with epidural EEG electrodes over frontal (FC) and parietal cortices (PC) and later tested under vehicle (saline, i.m.) or acute PCP (0.1-0.3?mg/kg, i.m.) conditions. Compared with vehicle treatment, PCP produced a significant dose-dependent decrease in CPT performance accuracy and increased reaction times. Furthermore, PCP elevated the amplitudes of 'low' (30-50?Hz) and 'high' (51-80?Hz) gamma oscillations in FC and PC around target presentations for all correct responses. The CPT accuracy was inversely correlated with the gamma band amplitude in the presence of PCP. Additionally, PCP delayed the N100 peak latency in FC, and prolonged and suppressed the cognitively relevant P300 component of mean ERPs in FC and PC, respectively. The NMDA receptor antagonist-induced alteration in neuronal oscillations and ERPs may contribute to the observed cognitive deficits in macaques, and enhance our understanding of EEG recordings as a translatable biomarker. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |
| 93 | Neuropsychopharmacology 2016 Apr 41: 1319-28 |
| PMID | 26354045 |
| Title | Alterations in High-Frequency Neuronal Oscillations in a Cynomolgus Macaque Test of Sustained Attention Following NMDA Receptor Antagonism. |
| Abstract | A growing body of evidence indicates that neuronal oscillations in the gamma frequency range (30-80?Hz) are disturbed in schizophrenic patients during cognitive processes and may represent an endophenotype of the disease. N-methyl-D-aspartate (NMDA) receptor antagonists have been used experimentally to induce schizophrenia-like symptoms including cognitive deficits in animals and humans. Here we characterized neuronal oscillations and event-related potentials (ERPs) in Cynomolgus macaques fully trained to perform a continuous performance test (CPT) in the presence and absence of the NMDA antagonist phencyclidine (PCP). Macaques (n=8) were trained to touch 'target' stimuli and ignore 'distractor' stimuli presented randomly on a touchscreen. Subsequently, all subjects were implanted with epidural EEG electrodes over frontal (FC) and parietal cortices (PC) and later tested under vehicle (saline, i.m.) or acute PCP (0.1-0.3?mg/kg, i.m.) conditions. Compared with vehicle treatment, PCP produced a significant dose-dependent decrease in CPT performance accuracy and increased reaction times. Furthermore, PCP elevated the amplitudes of 'low' (30-50?Hz) and 'high' (51-80?Hz) gamma oscillations in FC and PC around target presentations for all correct responses. The CPT accuracy was inversely correlated with the gamma band amplitude in the presence of PCP. Additionally, PCP delayed the N100 peak latency in FC, and prolonged and suppressed the cognitively relevant P300 component of mean ERPs in FC and PC, respectively. The NMDA receptor antagonist-induced alteration in neuronal oscillations and ERPs may contribute to the observed cognitive deficits in macaques, and enhance our understanding of EEG recordings as a translatable biomarker. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizotypal |