Several lines of research have implicated the brain's glutamate system in the symptoms of schizophrenia, but the ways that abnormalities in glutamate function produce these symptoms are far from clear.
Laboratory studies in healthy individuals may be helpful in providing insights into the neurobiology of symptoms associated with schizophrenia, which are commonly grouped into positive symptoms (hallucinations and delusions), and negative symptoms (including social withdrawal, lack of emotional expression and motivation deficits).
A recent study published in Molecular Psychiatry suggests that one way that disturbances in glutamate function may contribute to symptoms of schizophrenia is by altering the synchrony of various brain regions.
Naomi Driesen, associate research scientist in psychiatry and in neurology, is the study's lead author.
Many years ago, Yale investigators showed that a drug that blocks the NMDA glutamate receptor transiently produces symptoms resembling the positive and negative symptoms of schizophrenia in healthy people.
Typically, brain regions that are generating a particular behavior will fire in a coordinated pattern. This pattern of synchrony is generally also present when the person is resting.
However, in this new study, researchers showed that the extent to which the NMDA receptor blocker produced positive symptoms was correlated with the extent to which it increased the synchrony in activity between several cortical regions and the rest of the brain. Driesen's study also showed that the degree to which the NMDA receptor blocker produced negative symptoms correlated with reductions in the synchrony of portions of the striatum and thalamus with the rest of the brain.
These findings suggest that when there are deficits in glutamate synaptic function, as have been implicated in schizophrenia, brain regions receive abnormal input from many other brain regions. While this pharmacological model cannot mimic the entire neurobiology of schizophrenia, this data may provide important insights into the underlying mechanisms of schizophrenia.
Driesen will present the Molecular Psychiatry study as part of a symposium entitled “NMDA Receptors and Brain Oscillations: A New Light on Positive and Negative Symptoms” that she will chair at the Annual Scientific Convention of the Society of Biological Psychiatry in May 2013.
John H. Krystal, the Robert L. McNeil Jr. Professor of Translational Research and chair of Yale's Department of Psychiatry, is senior author of the study.
Additional Yale authors include Gregory McCarthy, Michael Bloch, Deepak Cyril D'Souza, Ralitza Gueorguieva, George He, Ramachandran Ramani, Alan Anticevic, and Peter Morgan. Other contributing authors include Raymond Suckow (New York State Psychiatric Institute), Zubin Bhagwagar (Bristol-Myers Squibb), and Vince Calhoun (University of New Mexico).
Related link:
Molecular Psychiatry: Relationship of resting brain hyperconnectivity and schizophrenia-like symptoms produced by the NMDA receptor antagonist ketamine in humans.