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I was doing a little research and this was all I could find. This is from 2006 and I'm not sure if anyone knows an update on this. Or any theories people have on treating these symptoms.
Here was the interesting tidbits: Psychiatric Genetics
.Subsequently, the whole area of psychiatric genetics has been moving forward very rapidly, especially over the last 5 years. It is clear that schizophrenia is highly inheritable, but it is not due to Mendelian-type genetics. The genetics are complex; multiple genes of modest effects interact to produce the disorder. In the last 5 years, about 10-15 potential-risk genes for schizophrenia have been identified, and about a third of those are 1° of separation from the NMDA receptor. Genetic studies have given some validity to this hypothesis that arose out of chronologic-challenge studies and postmortem studies that the NMDA receptor hypofunction may contribute to the core features of the disorder..
.Ten years ago, my colleague Don Goff, MD, Associate Professor, Department of Psychiatry, Massachusetts General Hospital Schizophrenia Research Program, Boston, Massachusetts, and I decided to test this hypothesis in patients by giving an agent that enhances NMDA receptor function. It is a drug that has been used for 40 years to treat tuberculosis, namely, D-cycloserine. In the initial-dose findings, a study showed that patients with chronic schizophrenia who were treated with D-cycloserine at the optimal dose had a significant reduction in negative symptoms and a significant enhancement in cognitive function..
.Since then, there have been a number of different placebo-controlled, blinded studies with several agents that enhance NMDA receptor function that have shown a reduction in negative symptoms and, to a variable degree, an enhancement in cognition in patients with schizophrenia who are receiving psychotic medications. In some cases with D-serine, which is one of the endogenous modulators of the NMDA receptor, and with glycine, another endogenous modulator of the NMDA receptor, they also showed a significant reduction of positive symptoms in patients who are receiving concurrent antipsychotic medications..
.Now, there is a good deal of interest in the potential of enhancing NMDA receptor function and dealing with those components of schizophrenia -- again, the negative symptoms and cognitive impairment -- that respond poorly, if at all, to the current antipsychotic medications, except for, possibly, clozapine..
.Medscape: Could you speak a bit more about what you are working on right now?.
.Dr. Coyle:.. My collaborators and I have the good fortune of being supported by a major grant from the National Institute of Mental Health (NIMH), and we have a number of different investigators involved. We are trying to go from molecular mechanisms in experimental animals to clinical testing of this hypothesis in humans..
.On the molecular side, we are making mice that are genetically modified so that they have impairments in the NMDA receptor similar to what we believe is happening in humans, and we are looking at how this affects mouse behavior and how we might correct those behavioral abnormalities with novel treatments..
.On the clinical level, my colleagues, Don Goff and Daniel Javitt, MD, PhD, Director of the Program in Cognitive Neuroscience and Schizophrenia, Associate Professor of Psychiatry, New York University School of Medicine, New York, NY, are looking at how the administration of D-serine affects symptoms in schizophrenia, because there is some suggestion that psychosis is sort of a downstream consequence of malfunction in the NMDA receptor. They want to know whether this can forestall the development of psychosis and schizophrenia in individuals who are at high risk..
.We are hoping to discover, in the next 5 years, hard evidence that the strategy is effective, if it is. if it is effective, we want to know how it might be optimally effective and provide a whole new way of treating schizophrenia..
Here was the interesting tidbits: Psychiatric Genetics
.Subsequently, the whole area of psychiatric genetics has been moving forward very rapidly, especially over the last 5 years. It is clear that schizophrenia is highly inheritable, but it is not due to Mendelian-type genetics. The genetics are complex; multiple genes of modest effects interact to produce the disorder. In the last 5 years, about 10-15 potential-risk genes for schizophrenia have been identified, and about a third of those are 1° of separation from the NMDA receptor. Genetic studies have given some validity to this hypothesis that arose out of chronologic-challenge studies and postmortem studies that the NMDA receptor hypofunction may contribute to the core features of the disorder..
.Ten years ago, my colleague Don Goff, MD, Associate Professor, Department of Psychiatry, Massachusetts General Hospital Schizophrenia Research Program, Boston, Massachusetts, and I decided to test this hypothesis in patients by giving an agent that enhances NMDA receptor function. It is a drug that has been used for 40 years to treat tuberculosis, namely, D-cycloserine. In the initial-dose findings, a study showed that patients with chronic schizophrenia who were treated with D-cycloserine at the optimal dose had a significant reduction in negative symptoms and a significant enhancement in cognitive function..
.Since then, there have been a number of different placebo-controlled, blinded studies with several agents that enhance NMDA receptor function that have shown a reduction in negative symptoms and, to a variable degree, an enhancement in cognition in patients with schizophrenia who are receiving psychotic medications. In some cases with D-serine, which is one of the endogenous modulators of the NMDA receptor, and with glycine, another endogenous modulator of the NMDA receptor, they also showed a significant reduction of positive symptoms in patients who are receiving concurrent antipsychotic medications..
.Now, there is a good deal of interest in the potential of enhancing NMDA receptor function and dealing with those components of schizophrenia -- again, the negative symptoms and cognitive impairment -- that respond poorly, if at all, to the current antipsychotic medications, except for, possibly, clozapine..
.Medscape: Could you speak a bit more about what you are working on right now?.
.Dr. Coyle:.. My collaborators and I have the good fortune of being supported by a major grant from the National Institute of Mental Health (NIMH), and we have a number of different investigators involved. We are trying to go from molecular mechanisms in experimental animals to clinical testing of this hypothesis in humans..
.On the molecular side, we are making mice that are genetically modified so that they have impairments in the NMDA receptor similar to what we believe is happening in humans, and we are looking at how this affects mouse behavior and how we might correct those behavioral abnormalities with novel treatments..
.On the clinical level, my colleagues, Don Goff and Daniel Javitt, MD, PhD, Director of the Program in Cognitive Neuroscience and Schizophrenia, Associate Professor of Psychiatry, New York University School of Medicine, New York, NY, are looking at how the administration of D-serine affects symptoms in schizophrenia, because there is some suggestion that psychosis is sort of a downstream consequence of malfunction in the NMDA receptor. They want to know whether this can forestall the development of psychosis and schizophrenia in individuals who are at high risk..
.We are hoping to discover, in the next 5 years, hard evidence that the strategy is effective, if it is. if it is effective, we want to know how it might be optimally effective and provide a whole new way of treating schizophrenia..
Thanks for this heads up. Looks like they have some new info on this. Will share anything interesting I find.
