Facilitation of NMDA Receptor Function in Patients With Schizophrenia and Co-morbid Alcoholism

This placebo-controlled study is designed to evaluate the efficacy of glycine, an agonist of the glycine-B co-agonist site of the NMDA receptor, on alcohol consumption and craving as well as negative symptoms in schizophrenia.

Glycine will decrease the rewarding action of ethanol and reduce ethanol consumption. Also, glycine will improve negative symptoms and cognitive deficits in schizophrenia.

OBJECTIVE: Schizophrenia affects about 1% of the general population and is a highly disabling disease. Additionally, the rate of alcohol dependency for patients with schizophrenia is very high. There are no established treatments for alcohol dependency and negative symptoms in schizophrenia. This study will examine whether the addition of glycine to neuroleptic medications will help patients with schizophrenia and alcoholism decrease their drinking as well as improve negative symptoms.

RESEARCH PLAN: An abnormality of the glutamate neurotransmitter system has been hypothesized for both alcoholism and schizophrenia. Studies suggest that the amino acid glycine may improve alcohol dependency and symptoms of schizophrenia by acting on the N methyl D aspartate (NMDA) glutamate receptor. Glycine causes reversal of the effects of ethanol in animal studies and improves mood, social withdrawal and other so called "negative symptoms" of schizophrenia. Consequently, the use of glycine by patients with schizophrenia and alcohol dependency may potentially decrease alcohol craving and alcohol consumption and also improve certain symptoms of schizophrenia. The potential of glycine to improve both alcohol dependency and negative symptoms could represent an important step in the improvement of the quality of life for patients with schizophrenia.

METHODOLOGY/FINDINGS/RESULTS: In order to test this hypothesis, we will use a double blind, placebo controlled study and measure the number of drinks, the degree of craving for alcohol and symptoms of schizophrenia among other parameters. Our principal approach to analyses of medication effectiveness will be the application of the linear mixed effect model. The linear mixed effect model permits a flexible approach for studying change in individuals through time as a random effect, and does not require all patients to have data at all measured points. Our principal model of analysis includes treatment (placebo or glycine), as between subject factor, and time, as within subject factor. Compliance will be also included as a time varying independent variable. This project continues to recruit subjects.

Eligibility Criteria:
Inclusion Criteria:

* DSM-IV diagnosis of schizophrenia or schizoaffective disorder
* DSM-IV diagnosis of alcohol dependence
* Stable treatment with typical or atypical antipsychotics

Exclusion Criteria:

* Axis I diagnosis other than alcohol dependence, schizophrenia, schizoaffective disorder, OCD, and PTSD.
* current drug dependence
* evidence of significant hepatocellular injury evidence by abnormal SGOT or SGPT levels
* history of seizures
* diabetes and medical conditions that would alter glycine metabolism
* positive pregnancy test
* treatment with clozapine, naltrexone or disulfiram