A core symptom that is frequently linked with dysregulation of glutamatergic neurotransmission in regard to schizophrenia is impairment or damage of executive functioning as a component of cognitive deficiency. The amino acid D-serine plays the role of an endogenous coagonist at the glutamatergic N-methyl-D-aspartate (NMDA) receptor glycine modulatory site. Considerably reduced serum levels of D-serine were found in patients suffering from schizophrenia compared with healthy control participants. An increase in D-serine led to augmented cognitive functionality in patients suffering from schizophrenia who were undergoing clinical trials and given the treatment of first- and second-generation antipsychotics. The study proposed the hypothesis that the D-serine blood serum levels may be linked with the extent of executive functionality in those suffering from the mental illness in question. For the purpose of examining executive function in such patients, the Rey-Osterrieth Complex Figure, Trail Making, and Wisconsin Card Sorting tests were applied (n = 50). High-performance liquid chromatography was used to gauge the total serine and D-serine levels. The extent of damage was examined through neuropsychological tests and was found to be considerably linked to D-serine serum level and the D-serine/total serine ratio (p < 0.05) in the sample being considered. A lower average serum level of D-serine and lower D-serine/total serine ratio were observed in participants with the worst performance compared with those displaying the best performance-this was true when the patients were split into quartile groups based on their results (p < 0.05). The findings of modified D-serine serum levels and the D-serine/total serine ratio linked to the extent of damage in executive functioning indicate that serine metabolism that is coresponsible for NMDA receptor dysfunction has been changed.
- Publikační typ
- časopisecké články MeSH
- MeSH
- duševní poruchy MeSH
- komunikace MeSH
- krizová intervence metody MeSH
- lidé MeSH
- pokus o sebevraždu * prevence a kontrola MeSH
- rizikové faktory MeSH
- sebevražda * MeSH
- sebevražedné myšlenky MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
Úvod: Zhoršení exekutivních funkcí jako součásti kognitivního deficitu je jedním z často se vyskytujících jádrových příznaků spojených s dysregulací glutamátergní neurotransmise u schizofrenie. Aminokyselina D-serin úèinkuje jako endogenní koagonista na glycinovém mo- dulačním místě N-methyl-D-aspartátového (NMDA) receptoru. U nemocných schizofrenií byla v porovnání se zdravými dobrovolníky zjištěna významně snížená koncentrace D-serinu v krevním séru. D-serin v klinických studiích v augmentaci terapie antipsychotiky 1. a 2. generace také významně zlepšoval postižení kognitivních funkcí. V klinickém sledování jsme u nemocných schizofrenií testovali předpoklad asociace sérové koncentrace D-serinu s intenzitou postižení exekutivních funkcí. Metody: K vyšetření exekutivních funkcí byl u nemocných schizofrenií (n = 50) použit Test cesty (Trail Making Test), Test komplexní figury (Rey-Osterrieth Complex Figure Test) a Wisconsinský test třídění karet (Wisconsin Card Sorting Test). Koncentrace It D-serinu a celkového serinu v krevním séru byly u nemocných stanovovány pomocí HPLC (High Performance Liquid Chromatography). Výsledky: Výkon v testech exekutivních funkcí u nemocných schizofrenií statisticky významně negativně asocioval s hodnotou poměru ne S hodnotou sérové koncentrace D-serinu. U nemocných s horším výnem v testech jsme ve srovnání s nemocnými s lepším výkonem pro¬ 32aii nižší průměrnou sérovou koncentrací D-serinu {p < 0,05). Závěr: Hlavní nálezy naší studie potvrzují předpoklad možnosti vztahu dysregulace glutamátergní neurotransmise a úrovně exekutivních funkcí u nemocných schizofrenií. Hodnoty sérových koncentraCÍ D-serinu a poměru D-serinu k celkovému serinu svědčí pro souvislost změn metabolizmu serinu s dysfunkcí NMDA receptoru u sctschizofrenie. Předpokládáme, že biochemické a klinické hodnocení funkční úrovně glutamátergního systému by mohlo umožňovat klasifikaci specifických podtypů schizofrenie. Identifikace kognitivního deficitu asociovaného s laboratorním průkazem změn v metabolizmu excitačních aminokyselin v CNS pak i cílenou léčbu látkami ovlivňujícími dysfunkční glutamátergní systém.
Introduction : Impairment of executive functions as a part of cogniti- ve deficit is frequently presented as one of the core symptoms associated with dysregulation of glutamatergic neurotransmission in schizophre- nia. Amino acid D-serine acts as an endogenous co-agonist at the glyci- ne modulatory site of the glutamatergic N-methyl-D-aspartate (NMDA) receptor. Significantly decreased D-serine serum levels were reported in patients with schizophrenia in comparison to healthy control subjects. Augmentation with D-serine improved cognitive functions in patients with schizophrenia treated with first and second generation antipsycho- tics in the clinical trials. We hypothesized that the blood serum level of D-serine might be associated with the level of executive functioning in patients with schizophrenia. Methods: Trail Making Test, Rey-Osterrieth Complex Figure Test and Wisconsin Card Sorting Test were used to evaluate executive func- tions in patients with schizophrenia (n=50). D-serine and total serine se- rum levels were measured by High Performance Liquid Chromatography. Results: Performance in the tests evaluating level of executive func- tioning significantly negatively associated with D-serine/total serine ra- tio ( r =-0.29, p< 0.05) but not with D-serine serum level in patients with schizophrenia. Lower average serum level of D-serine was found in pa- tients with the worst performance as compared to the patients with the best performance when divided into the quartile groups according to their results in the tests ( p< 0.05). Conclusion: The main findings of our study confirmed the hypo- thesis that level of executive functioning may be related to dysregulati- on of glutamatergic neurotransmission. Altered serum level of D-seri- ne and D-serine/total serine r atio suggest changes of serine metabo- lism co-responsible for NMDA receptor dysfunction in schizophre- nia. We assume that biochemical and clinical evaluation of glutama- tergic functional level could classify schi zophrenia into specific sub- types. Identification of cognitive dysfunction associated with laboratory evidenced changes in metabolism of excitatory amino acids in the brain may allow better treatment responses to the agents influencing gluta- matergic dysfunctional system.
- Publikační typ
- abstrakt z konference MeSH
Dysfunction of the N-methyl-d-aspartate receptor, which is modulated by excitatory amino acids (EAA), is involved in the pathophysiology of schizophrenia. The effects of antipsychotics on EAA metabolism are uncertain. Positive clinical effects of treatment with antipsychotics were not always associated with changes in EAA serum levels in patients with schizophrenia in clinical trials. To examine EAA serum levels in relation to the intensity of psychotic symptoms and the type of medication received we compared these variables among patients with schizophrenia (n = 49) treated with first (FGA) or second (SGA) generation antipsychotics or clozapine. Glutamate, aspartate, glycine, total serine and d-serine serum levels were measured by High Performance Liquid Chromatography. The Positive and Negative Syndrome Scale (PANSS) and the Scale for the Assessment of Negative Symptoms (SANS) were used to assess symptoms of schizophrenia. Lower average levels of glycine and total serine were found in the serum of patients receiving clozapine when compared to the groups of patients treated with FGA or SGA. There were no differences in serum glutamate, aspartate or d-serine levels or in the intensity of schizophrenic symptoms assessed by PANSS or SANS among the groups of patients treated with FGA or SGA or clozapine. Lower glycine and total serine serum levels could be caused by the particular characteristics of the population of patients receiving clozapine rather than as an effect of the clozapine. The results suggest selective deficiency of l-serine synthesis in the patients with resistance to non-clozapine treatment. It might be an unique biochemical and pathophysiological characteristic of the treatment-resistance in schizophrenia.
- MeSH
- antipsychotika terapeutické užití MeSH
- dospělí MeSH
- excitační aminokyseliny krev MeSH
- glycin krev MeSH
- klozapin terapeutické užití MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- neparametrická statistika MeSH
- psychiatrické posuzovací škály MeSH
- schizofrenie krev farmakoterapie MeSH
- senioři MeSH
- serin krev MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Klíčová slova
- nonadherence, injekční antipsychotika s dlouhodobým účinkem,
- MeSH
- adherence k farmakoterapii MeSH
- antipsychotika farmakologie terapeutické užití MeSH
- benzodiazepiny farmakologie MeSH
- hodnocení léčiv statistika a číselné údaje MeSH
- injekce MeSH
- lidé MeSH
- schizofrenie farmakoterapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
- MeSH
- antipsychotika farmakologie terapeutické užití MeSH
- dospělí MeSH
- excitační aminokyseliny * analýza krev MeSH
- glycin analýza krev MeSH
- lidé středního věku MeSH
- lidé MeSH
- schizofrenie * farmakoterapie MeSH
- vysokoúčinná kapalinová chromatografie metody MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
Glycine acts as an endogenous selective co-agonist at the glycine modulatory site of the NMDA (N-methyl-d-aspartate) receptor. Significantly decreased glycine serum levels were reported in patients with schizophrenia in comparison to healthy controls. Administration of glycine improved negative symptoms in patients with schizophrenia treated with antipsychotics in some clinical trials. We hypothesized that glycine serum levels might be associated with intensity of negative symptoms in schizophrenia. Fifty outpatients with the diagnosis of schizophrenia as defined by ICD-10 and fifty age- and gender-matched healthy controls were recruited into the study. Glycine serum levels were measured by high performance liquid chromatography (HPLC). We used the Positive and Negative Syndrome Scale (PANSS) and the Scale for the Assessment of Negative Symptoms (SANS) to assess the symptoms of schizophrenia in the patients. We found mean glycine serum levels to be significantly lower in patients than in controls. This difference was only caused by findings in the male study population. Glycine serum levels were negatively associated with intensity of negative symptoms assessed by the PANSS negative subscale and the SANS total scores in the patients. These data suggest a possible implication of NMDA receptor dysfunction in the pathogenesis of negative symptoms in schizophrenia.
- MeSH
- dospělí MeSH
- glycin krev MeSH
- lidé středního věku MeSH
- lidé MeSH
- mezinárodní klasifikace nemocí MeSH
- mladý dospělý MeSH
- neparametrická statistika MeSH
- neuropsychologické testy MeSH
- psychiatrické posuzovací škály MeSH
- schizofrenie krev patofyziologie MeSH
- sexuální faktory MeSH
- studie případů a kontrol MeSH
- vysokoúčinná kapalinová chromatografie metody MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
