title: Higher serum concentrations of tyrosine and glutamate in schizophrenia patients treated with clozapine, compared to in those treated with conventional antipsychotics.
abstract: BACKGROUND
  The effect of long-term treatment with the atypical antipsychotic clozapine on the serum amino acid profile in schizophrenia patients has not previously been studied.
  
  
  OBJECTIVE
  The aim of this study was to compare serum amino acid patterns in patients on long-term clozapine treatment with long-term conventional antipsychotic treatment, and their relationships to insulin resistance and antipsychotic serum concentrations.
  
  
  METHODS
  Thirty-three patients with schizophrenia or schizoaffective disorder on long-term treatment (mean 8.3 years) with clozapine (n=20) or conventional antipsychotics (n=13) were studied. Amino acids were quantified in fasting serum samples by ion exchange chromatography and markers of insulin resistance and antipsychotic drug concentrations were determined by standard methods.
  
  
  RESULTS
  Several amino acids, most notably tyrosine and glutamic acid, were elevated above the reference range in several patients receiving clozapine. Additionally, significantly higher mean values of tyrosine (1.5-fold, p=0.001), glutamic acid (2-fold, p=0.0005) and six other amino acids were observed in the clozapine group than in the conventional antipsychotic group. Several amino acids were related to insulin resistance in both treatment groups.
  
  
  CONCLUSIONS
  In this study, we show that serum tyrosine and glutamic acid concentrations are markedly elevated in patients on long-term clozapine treatment, compared to patients on long-term conventional antipsychotic treatment. These findings are of importance since these two amino acids have been implicated in the pathophysiology of schizophrenia.
authors.affiliation: Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Kristina
authors.initials: K
authors.lastname: Melkersson
authors.affiliation: School of Health, Nursing and Midwifery, University of the West of Scotland, Scotland, UK.
authors.forename: Moira
authors.initials: M
authors.lastname: Lewitt
authors.affiliation: Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Hall
mesh_terms: D000328:Adult; D000596:Amino Acids / Q000097:blood; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D002852:Chromatography, Ion Exchange; D003006:Clopenthixol / Q000627:therapeutic use; D003024:Clozapine / Q000627:therapeutic use*; D015331:Cohort Studies; D005260:Female; D018698:Glutamic Acid / Q000097:blood*; D006220:Haloperidol / Q000627:therapeutic use; D006801:Humans; D007333:Insulin Resistance; D008297:Male; D008875:Middle Aged; D010546:Perphenazine / Q000627:therapeutic use; D011446:Prospective Studies; D011618:Psychotic Disorders / Q000188:drug therapy*; D012559:Schizophrenia / Q000097:blood / Q000188:drug therapy*; D013881:Thioridazine / Q000627:therapeutic use; D014443:Tyrosine / Q000097:blood*
chemical_list: D000596:Amino Acids; D014150:Antipsychotic Agents; D018698:Glutamic Acid; D014443:Tyrosine; D003006:Clopenthixol; D010546:Perphenazine; D003024:Clozapine; D006220:Haloperidol; D013881:Thioridazine