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February 08, 2005
Brain chemistry and Prevention
Targeting synapses and myelin in the prevention of schizophrenia.
There are many research efforts that are trying to understand how the brain works and how it develops in order to try to prevent the start of psychotic symptoms in those who might be prone to schizophrenia. There a part of the brain known as the prefrontal cortex (PFC) this is above the forehead, which has been implicated in schizophrenia. This part of the brain is involved in what is known as “executive functioning” which allows us to pay attention and use our working memory (which allows us to hold several facts or thoughts in memory temporarily while solving a problem or performing a task). This article focused on summarizing some of the processes that go on at the brain level and potential ways that they could be manipulated in order to prevent the onset of schizophrenia.
Synapses are gaps between nerve cells in the brain which allow important connections within the brain. Research is suggesting that synaptic connections within the PFC may be disturbed in schizophrenia. Many of the functions of the PFC take a while to develop – usually until late teenage or early adulthood years – times which are considered to be of vulnerability and opportunity. The authors propose that in schizophrenia, during these critical teenage/early adulthood years there may be disruptions in normal developmental processes in the brain known as “synaptic pruning” in the PFC and “axonal myelination” linking various frontal brain parts with memory parts (temporal lobe structures). The authors suggest that such disturbances in normal brain development may then either directly trigger or indirectly contribute to the onset of schizophrenia symptoms. They speculate that it could also be that there maybe functional unmasking of preexisting synaptic deficits by an otherwise normal synaptic pruning process.
One preventive strategy might be to try and change the course of these developmental events in those who are at high risk such as those in the prodromal stages of the illness (prodromal means before the actual onset of psychotic symptoms). The authors go into details on brain chemistry and circuits (especially involving a brain chemicals known as GABA and 5-HT2c) that might be involved and suggest two medication based methods for how synaptic pruning and axonal myelination could potentially be manipulated. They suggest that medications that increase the transmission of GABA such as tiagabine (Gabitril) maybe the key for helping with the synaptic pruning problem. They suggest that m-chlorophenylpiperazine (m-CPP) and Trazodone (a commonly used antidepressant) could help with the axon mylenation problem.
However, so far these are just theories proposed by the authors and much more research and testing in needed to see whether these drugs are able to help in preventive efforts. Regardless, this article highlights the idea that we need to have a much better understanding of what is going on at the smallest of levels in the brain - cellular and molecular – in order to generate hypotheses of new preventive and therapeutic strategies that can perhaps help in prevention efforts.
Acknowledgements: Grant support provided by the Stanley Medical Research Institute and the National Institute of Mental Health.Posted by Farzin at February 8, 2005 12:14 AM