Glutamatergic system – main excitatory brain system is involved in pathophysiology of schizophrenia. Ionotropic glutamatergic NMDA receptor plays an important role in cognitive functioning and participates in mechanisms of control of dopaminergic, noradrenergic and serotoninergic systems. NMDA receptor antagonists as phencyclidyne or ketamine can induce psychosis similar to schizophrenia including also negative and cognitive symptomatology. Glycine is a natural coagonist of NMDA receptor necessary to its proper functioning. Treatment with high doses of glycine (max. 60g orally per day) according to hypothesis of decreased NMDA receptor activity can improve negative symptoms and cognitive functions in schizophrenia .
Purpose of the study: The aim of study was evaluation of changes in cognitive functioning of schizophrenic patients in stable mental state, with predominant negative symptoms (mean 25.7 points in PANSS-Negative symptom subscale), before and after 6-weeks augmentation of antipsychotic treatment with glycine.
Methods: 29 patients with diagnosis of schizophrenia (ICD-10 criterias) in stable clinical state had completed 6 weeks, prospective, open label study (32 patients were enrolled). Patients were treated with antipsychotics (typical and second generation neuroleptics) in stable dosage for at least 3 months. Before and afterwards glycine treatment (0,8 g/kg/day) cognitive functions were assessed with battery of standard neuropsychological tests: Wisconsin Card Sorting Test (WCST, version for PC), Trail Making Test (TMT) and Stroop Task. Clinical changes in negative symptoms were also assessed using PANSS-Negative symptom subscale.
Results: Improvement of working memory, attention and verbal functions after glycine treatment was significant in our group. In week 6 patients used less cards to finish more categories (p<0,001), making significantly fewer perseverative (p<0,001) and nonperseverative (p<0,01) errors. Afterwards glycine intake time needed to finish both parts of TMT was shorter (p<0,01). There was a significant decrease of numbers of errors and period of time necessary to finish second part of Stroop test, what indicates better verbal functioning and attention. Significant improvement in negative symptoms (PANSS-Negative symptom subscale; -16,1%; p<0,001) after use of glycine were observed.
Conclusions: Augmentation of antipsychotic treatment with glycine can improve cognitive functions and negative symptoms in schizophrenic patients. Combined medication was safe and well tolerated. Some patients complained on nausea or gastric discomfort.