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> Cognitive Behavioral Therapy for Psychosis and Schizophrenia Glycine - A possible complementary therapy for schizophrenia (May, 2006 update) INTRODUCTION A novel approach to the treatment of schizophrenia involving glutamatergic neurotransmission and its modulation with simple amino acids is beginning to generate interest among psychiatrists. Not only are more research studies being published in the psychiatric literature but there was an entire workshop on the topic at the most recent meeting of the meeting in Toronto this past May (2006). CONVENTIONAL THEORIES Traditionally, schizophrenia has been thought to be a disease involving the neurotransmitter dopamine. In the early 1950s, it was found that chlorpromazine which was originally developed as an anti-nausea treatment also helped improve psychotic symptoms. It helped relieve the positive symptoms of psychosis by blocking dopamine in the brain. Neurons in the brain are not connected to each other but are separated by gaps called synapses. Chemical messengers are released by one neuron and are received by specialized receptors on the ends of the opposite neuron.

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The messages they convey are then transmitted down the neuron. Dopamine is one such chemical messenger or neurotransmitter. Chlorpromazine acts as an antagonist to dopamine and blocks the dopamine receptors on the ends of neurons. This prevents dopamine from binding to the receptor and sending its message down the neuron. As chlorpromazine helped reduce psychotic symptoms, it was thus believed that schizophrenia was a disease of either too much dopamine or too many dopamine receptors. This theory was further supported by the observations that amphetamines and LSD produce hallucinations similar to schizophrenia. These drugs are dopamine agonists that mean that they mimic the action of dopamine in the brain.

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Their presence has the same effect as increasing the amount of dopamine. Blocking dopamine helped to relieve psychotic symptoms while increasing dopamine produced psychotic like symptoms. These early antipsychotics that only influenced the dopamine system tend to be only effective for the treatment of the positive symptoms of schizophrenia and are not effective for the negative ones. This led to the consideration that other neurotransmitters might also be involved with the disease. The newer atypical antipsychotics that have been developed in recent years, therefore, influence not only the dopaminergic systems but also effect serotonin - another of the neurotransmitters in the brain.

These newer drugs reduce dopamine activity in some parts of the brain and increase serotonin activity in other parts. THE PCP THEORY Over the past few years, attention has been focused on the glutamatergic system involving agents that block N-methyl-d-aspartate or NMDA. Glutamic acid is the major excitatory neurotransmitter in the brain involving 40% of all synapses. Two street drugs, PCP (angel dust) and (the date rape drug) are known to cause behavior that closely resembles that of schizophrenia. These drugs block the N MDA receptors. In fact, the psychosis induced by both PCP and ketamine very closely resemble schizophrenia because they not only produce positive symptoms but also the negative symptoms and cognitive deficits that are so resistant to treatment in schizophrenia. Post mortem evaluations of the brains of people with schizophrenia have shown that they have fewer NMDA receptors than people who do not have the disease.

Both glycine and d-serine (NMDA ) have been found to be decreased in both the blood and cerebrospinal fluid of people with schizophrenia compared to controls. This has all led to the hypothesis that people with schizophrenia have too little NMDA and that is one cause of some of the symptoms of the disease – particularly the negative symptoms and the cognitive deficits. This knowledge has lead to a number of investigations evaluating the effect of various agents that will increase the amount of NMDA in the brains of those with schizophrenia NMDA AGONISTS Glycine is known to act as an agonist for NMDA.

That is it mimics NMDA. Glycine is an amino acid that is found in the protein of all living things. The normal human diet results in an intake of about 2 grams of glycine daily.