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      Elevated homocysteine level in first-episode schizophrenia patients—the relevance of family history of schizophrenia and lifetime diagnosis of cannabis abuse

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          Abstract

          Accumulating evidence indicates that elevated homocysteine (Hcy) level occurs in first-episode schizophrenia (FES) patients. We included 56 FES patients and 53 healthy controls (HC). Plasma level of Hcy was significantly higher in FES patients than HC ( p = 0.044). In addition, plasma levels of high-density lipoproteins (HDL) and folate were significantly lower in FES than in HC ( p < 0.001). Positive family history of schizophrenia was associated with lower plasma HDL ( p = 0.041) and vitamin B12 ( p = 0.017), as well as higher level of Hcy ( p = 0.017). Patients with FES, who abused cannabis, had higher levels of Hcy ( p = 0.017), as well as lower levels of vitamin B12 ( p = 0.017) and HDL ( p = 0.041). Plasma Hcy negatively correlated with duration of untreated psychosis ( r = −0.272, p = 0.042). There was a positive correlation between Hcy level and the severity of negative symptoms ( r = 0.363, p = 0.006) and general psychopathology ( r = 0.349, p = 0.008) assessed using Positive and Negative Syndrome Scale (PANSS). Vitamin B12 level was negatively associated with the severity of negative symptoms ( r = −0.406, p = 0.002), while folate level negatively correlated with general psychopathology score ( r = −0.365, p = 0.006) in PANSS. These results indicate that the severity of one-carbon metabolism alterations and HDL deficiency might be associated with family history of schizophrenia and cannabis abuse. Lower vitamin B12 and folate along with elevated Hcy may influence the severity of FES psychopathology.

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          Most cited references70

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          The positive and negative syndrome scale (PANSS) for schizophrenia.

          The variable results of positive-negative research with schizophrenics underscore the importance of well-characterized, standardized measurement techniques. We report on the development and initial standardization of the Positive and Negative Syndrome Scale (PANSS) for typological and dimensional assessment. Based on two established psychiatric rating systems, the 30-item PANSS was conceived as an operationalized, drug-sensitive instrument that provides balanced representation of positive and negative symptoms and gauges their relationship to one another and to global psychopathology. It thus constitutes four scales measuring positive and negative syndromes, their differential, and general severity of illness. Study of 101 schizophrenics found the four scales to be normally distributed and supported their reliability and stability. Positive and negative scores were inversely correlated once their common association with general psychopathology was extracted, suggesting that they represent mutually exclusive constructs. Review of five studies involving the PANSS provided evidence of its criterion-related validity with antecedent, genealogical, and concurrent measures, its predictive validity, its drug sensitivity, and its utility for both typological and dimensional assessment.
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            A polydiagnostic application of operational criteria in studies of psychotic illness. Development and reliability of the OPCRIT system.

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              Neurotoxicity associated with dual actions of homocysteine at the N-methyl-D-aspartate receptor.

              Severely elevated levels of total homocysteine (approximately millimolar) in the blood typify the childhood disease homocystinuria, whereas modest levels (tens of micromolar) are commonly found in adults who are at increased risk for vascular disease and stroke. Activation of the coagulation system and adverse effects of homocysteine on the endothelium and vessel wall are believed to underlie disease pathogenesis. Here we show that homocysteine acts as an agonist at the glutamate binding site of the N-methyl-D-aspartate receptor, but also as a partial antagonist of the glycine coagonist site. With physiological levels of glycine, neurotoxic concentrations of homocysteine are on the order of millimolar. However, under pathological conditions in which glycine levels in the nervous system are elevated, such as stroke and head trauma, homocysteine's neurotoxic (agonist) attributes at 10-100 microM levels outweigh its neuroprotective (antagonist) activity. Under these conditions neuronal damage derives from excessive Ca2+ influx and reactive oxygen generation. Accordingly, homocysteine neurotoxicity through overstimulation of N-methyl-D-aspartate receptors may contribute to the pathogenesis of both homocystinuria and modest hyperhomocysteinemia.
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                Author and article information

                Contributors
                +48-71-7841605 , +48-71-7841602 , mblazej@interia.eu
                Journal
                Metab Brain Dis
                Metab Brain Dis
                Metabolic Brain Disease
                Springer US (Boston )
                0885-7490
                1573-7365
                30 March 2014
                30 March 2014
                2014
                : 29
                : 661-670
                Affiliations
                [ ]Department of Psychiatry, Wroclaw Medical University, 10 Pasteur Street, 50-367 Wroclaw, Poland
                [ ]Department of Genetics, Wroclaw Medical University, 1 Marcinkowski Street, 50-368 Wroclaw, Poland
                Article
                9534
                10.1007/s11011-014-9534-3
                4125810
                24682777
                3c37ca4e-a327-43b7-91e4-ec56e7421dd6
                © The Author(s) 2014

                Open Access This article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.

                History
                : 8 December 2013
                : 18 March 2014
                Categories
                Research Article
                Custom metadata
                © Springer Science+Business Media New York 2014

                Neurosciences
                one-carbon metabolism,homocysteine,vitamin b12,folate,cannabis,first-episode schizophrenia

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