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Glutamate paths surface in schizophrenia – problems with neurotransmitter may cause schizophrenia

Glutamate paths surface in schizophrenia – problems with neurotransmitter may cause schizophrenia – Brief Article

B. Bower

Much evidence implicates the chemical messenger known as glutamate in brain development. Now, a trio of new studies adds to growing suspicions that disturbed dispersal of this neurotransmitter in two closely related brain areas underlies schizophrenia, a severe mental disorder that afflicts an estimated 1 in 100 adults worldwide.

The investigations link schizophrenia to altered glutamate transmission between the thalamus and the frontal cortex. The thalamus serves as a relay station for messages between the cortex and the rest of the brain. The frontal cortex facilitates social reasoning and analytical thinking. In people, these structures develop anatomical links before birth (SN: 9/1/01, p. 132).

The new data suggest that “in two interrelated brain regions, elements of [glutamate] transmission are altered in schizophrenia,” says psychiatrist Carol A. Tamminga of the University of Maryland in Baltimore. The three reports appear in the September AMERICAN JOURNAL OF PSYCHIATRY.

Glutamate boosts cell activity throughout the brain. It acts on a complex mix of receptors on cell surfaces and gets a lift from certain proteins.

Evidence of altered glutamate transmission in schizophrenia has emerged in the past decade. Researchers have found that drugs that block N-methyl-D-aspartic acid (NMDA) receptors, one of the sites of glutamate activity, induce brief psychotic symptoms in healthy volunteers and make them worse in people with schizophrenia.

However, it’s not clear whether these medications work by dampening glutamate’s effects on brain cells or ultimately strengthening a variety of transmission routes and thus creating a glutamate glut.

One of the new studies supports the latter possibility. Neuroscientist Vahram Haroutunian of the Bronx Veteran Affairs Medical Center in New York and his coworkers focused on three of five known chemical components of NMDA receptors, each of which is regulated by different genes.

Using cloned products of these genes as probes, the researchers found elevated activity of two NMDA-receptor components in frontal-cortex tissue from the brains of 26 deceased people who had been hospitalized for schizophrenia. In the same tissue, Haroutunian’s group also uncovered intensified activity of a protein implicated in glutamate uptake.

When tested in the same way, frontal tissue from 13 deceased adults who had no psychiatric disorders exhibited modest NMDA receptor and protein responses. The brains of a third group, 10 deceased adults who had been diagnosed with Alzheimer’s disease, displayed particularly low responses on these tests.

A second study, led by psychiatrist Robert E. Smith of the University of Michigan Medical School in Ann Arbor, measured activity of two amino acids that act as glutamate transporters, carrying the neurotransmitter from one cell to the next. In thalamic tissue taken from 12 deceased people who had been hospitalized for schizophrenia, this activity was greater than in tissue from other people.

The same amino acids showed substantially lower activity in thalamic tissue taken from eight deceased adults who had no psychiatric ailments.

The third study, led by psychiatrist David A. Lewis of the University of Pittsburgh, used a protein marker that identifies certain cells in a frontal-cortex area that maintains close contacts with the thalamus. Brains from 20 deceased people who had been treated for schizophrenia showed fewer of those cells than did brains from both mentally healthy and depressed people, Lewis’ group says.

In these three studies, results didn’t seem influenced by whether the people with schizophrenia were male or female and had or hadn’t used antipsychotic drugs.

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