Impairment of Executive Functions Associated With Lower D-Serine Serum Levels in Patients With Schizophrenia.

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.

Glycine serum level in schizophrenia: relation to negative symptoms.

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.

D-serine serum levels in patients with schizophrenia: relation to psychopathology and comparison to healthy subjects.

OBJECTIVES: The main objective was to test the hypothesis of the association between D-serine serum levels and negative symptoms in patients with schizophrenia. Secondary objective was to examine the assumption of D-serine serum levels difference between a population of mostly chronic patients with schizophrenia and healthy controls. METHODS: We recruited outpatients with schizophrenia and age and gender matched healthy controls for the study. D-serine and total serine serum levels were measured by high-performance liquid chromatography (HPLC). The Positive and Negative Syndrome Scale (PANSS) and The Scale for the Assessment of Negative Symptoms (SANS) were used to assess schizophrenic symptoms. Non-parametric statistics was used to test the differences in D-serine and total serine serum levels and rank correlation was used to detect the associations with psychopathology. RESULTS: We did not find any differences between patients (n=50) and controls (n=50) in D-serine serum levels. Patients had significantly lower total serine serum levels and higher D-serine/total serine ratio. D-serine serum levels were not associated with the PANSS or the SANS total and subscales scores. Total se-rine serum levels inversely correlated with the SANS total and the PANSS negative symptom subscale scores. CONCLUSION: Decreased, not increased, serum levels of total serine negatively associated with intensity of negative symptoms were detected in patients with schizophrenia. We did not find any relationship between D-serine serum levels and negative symptoms among the patients. These findings do not agree with the previous reports of decreased D-serine and increased total serine serum levels in schizophrenia.