Study finds shift in patterns of glutamate and GABA in visuospatial working memory network
Disruptions in certain regions of the visuospatial working memory network may lead to its impairment in schizophrenia, according to a new study published in Biological Psychiatry
Philadelphia, January 18, 2018 - A new study in Biological Psychiatry has characterized the patterns of brain neurotransmitters glutamate and GABA in a network of regions that temporarily maintain and process visual information about the location of objects in space, a cognitive ability referred to as visuospatial working memory. The study, conducted by researchers at the University of Pittsburgh, reports that the patterns are altered in people with schizophrenia, suggesting a potential explanation for the impairments in visuospatial working memory that characterize people with the disorder.
The new findings suggest that the precise balance between the excitatory, or "accelerator", and inhibitory, or "brake", neurotransmitters might be shifted in certain regions in schizophrenia. Optimal function of visuospatial working memory requires a precise balance of the activity between glutamate and GABA, so the alterations may be what's leading to disrupted visuospatial working memory in the disorder.
In the study, first author Gil Hoftman, MD, Ph. D., and colleagues first mapped the normal levels of gene products involved in the production and use of glutamate and GABA in brain tissue from people unaffected by schizophrenia. They examined four regions of the cortex--the outermost layers of the brain where high level thinking takes place--that form the network responsible for visuospatial working memory. Levels of the gene products appeared in distinct patterns across the regions. Compared to the normal brain, the levels of the gene products were altered in the cortical regions in schizophrenia--increased or decreased in some regions, and unchanged in others.
According to David Lewis, MD, who led the study, the results suggest two new insights into the brain mechanics of working memory and how it goes wrong in schizophrenia. "First, in the normal human brain, the relative weighting of markers of excitatory and inhibitory neurotransmission differ markedly across the distributed cortical network that mediates working memory," said Dr. Lewis. "Second, in schizophrenia this weighting is disrupted by region-specific alterations in markers of both excitatory and inhibitory neurotransmission," he added.
The findings suggest that multiple disruptions may occur as information passes through the different regions in the network. "This paper highlights that differences in the cortical abnormalities across brain regions may give rise to the profile of symptoms associated with schizophrenia," said Dr. John Krystal, Editor of Biological Psychiatry.
Notes for editors
The article is "Altered Gradients of Glutamate and GABA Transcripts in the Cortical Visuospatial Working Memory Network in Schizophrenia," by Gil D. Hoftman, Samuel J. Dienel, Holly H. Bazmi, Yun Zhang, Kehui Chen, and David A. Lewis (http://dx. doi. org/ 10. 1016/ j. biopsych. 2017. 11. 029). It appears in Biological Psychiatry, published by Elsevier.
Copies of this paper are available to credentialed journalists upon request; please contact Rhiannon Bugno at Biol.Psych@UTSouthwestern.edu or +1 214 648 0880. Journalists wishing to interview the authors may contact David Lewis, MD, at firstname.lastname@example.org.
The authors' affiliations and disclosures of financial and conflicts of interests are available in the article.
John H. Krystal, MD, is Chairman of the Department of Psychiatry at the Yale University School of Medicine, Chief of Psychiatry at Yale-New Haven Hospital, and a research psychiatrist at the VA Connecticut Healthcare System. His disclosures of financial and conflicts of interests are available here.
About Biological Psychiatry
Biological Psychiatry is the official journal of the Society of Biological Psychiatry, whose purpose is to promote excellence in scientific research and education in fields that investigate the nature, causes, mechanisms and treatments of disorders of thought, emotion, or behavior. In accord with this mission, this peer-reviewed, rapid-publication, international journal publishes both basic and clinical contributions from all disciplines and research areas relevant to the pathophysiology and treatment of major psychiatric disorders.
The journal publishes novel results of original research which represent an important new lead or significant impact on the field, particularly those addressing genetic and environmental risk factors, neural circuitry and neurochemistry, and important new therapeutic approaches. Reviews and commentaries that focus on topics of current research and interest are also encouraged.
Biological Psychiatry is one of the most selective and highly cited journals in the field of psychiatric neuroscience. It is ranked 6th out of 142 Psychiatry titles and 10th out of 258 Neurosciences titles in the Journal Citations Reports® published by Thomson Reuters. The 2016 Impact Factor score for Biological Psychiatry is 11.412.
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