Researchers Find Way to Increase Neuroplasticity and Treat “Negative” Symptoms of Schizophrenia

Printer-friendly versionPrinter-friendly version
Joseph T. Coyle, M.D. - Brain & behavior research expert on schizophrenia
Joseph T. Coyle, M.D.

Recent research at McLean Hospital and Harvard University Medical School shows a very promising possibility for the future treatment of the “negative” symptoms of schizophrenia by improving neuroplasticity––the ability of the nerve cell networks in the brain to physically adapt to changing conditions. Negative symptoms in schizophrenia include decrease in motivation, lack of attention, emotional flatness, memory loss and social withdrawal.  

The research team was led by Joseph T. Coyle, M.D., a NARSAD Distinguished Investigator Grantee and Foundation Scientific Council Member. Dr. Coyle’s team at Harvard Medical School included Vadim Y. Bolshakov, Ph.D., a two-time NARSAD Grantee and Professor of Psychiatry. The researchers worked with mice to determine if they could find a cluster of abnormalities known to affect the brain’s hippocampus in people with schizophrenia. The mice were genetically engineered to have very low N-methyl-D-aspartate (NMDA) receptor activity in the brain, a condition suspected to be linked to impaired synaptic plasticity, memory formation and the negative symptoms of schizophrenia. The researchers investigated associated abnormalities including overall shrinkage of the hippocampus; decreased density of tiny nodules called dendritic spines, which serve as spots where synapses, or communications junctions, can form between neighboring neurons; and altered signaling pathways that help regulate neuroplasticity.

In a paper published in the May 31st issue of Proceedings of the National Academy of Sciences, Drs. Coyle, Bolshakov and colleagues reported that the mice with low NMDA receptor activity “displayed impaired hippocampal plasticity, as well as the morphological [shape], neurochemical and cognitive abnormalities consistent with what is observed in schizophrenia.” This was an exciting finding, but then they went further. The mice used in the experiments had only about 10 percent of normal NMDA receptor activity because they had been engineered to lack D-serine, one of two molecules needed to activate the receptors. When the researchers treated the mice with D-serine, NMDA receptor function in the hippocampus was restored. Over time, all of the observed hippocampal symptoms proved reversible.  

This new work lends important support to the theory that low activity (“hypoactivity”) in NMDA receptors in the brain can cause pathologies seen in people with schizophrenia and importantly, that the condition may be treatable and the symptoms reversed. While not the sole cause of schizophrenia, the ability to reverse this hypoactive condition in mice suggests it may be possible to develop D-serine-based treatments for use in people―what could prove to be a breakthrough in the treatment of schizophrenia.

Article comments

Interesting. Yers ago there was research regardng "chronic fatigue" disorders and phosphatidyl serine. I remember trying it as a supplement but not having much effect as far as crushing fatigue or "brain fog" which rolled over every afternoon. Mine may have had more to do with the avenue of introduction, as my organs were not metabolizing anything correctly. If I could have worn it in a patch I could have better assessed the outcome for me.

Thank you for your earnest effort and research. Much needed research. Let's keep forging forward and find a breakthrough in the treatment of schizophrenia.

Is the structure/configuration of the NMDA receptor impaired in Schizophrenia so that it could not accept a natutal form of the Amino Acid, D-Serine ? What is the other molecule needed to activate the NMDA receptor ?

Please help my daughter with paranoid schizophrenia! I will do anything for her to get better.

Add new comment

comments

Plain text

  • No HTML tags allowed.
  • Web page addresses and e-mail addresses turn into links automatically.
  • Lines and paragraphs break automatically.

Please note that researchers cannot give specific recommendations or advice about treatment; diagnosis and treatment are complex and highly individualized processes that require comprehensive face-to- face assessment. Please visit our "Ask an Expert" section to see a list of Q & A with NARSAD Grantees.
By submitting this form, you accept the Mollom privacy policy.