Brain Chemicals Glutamate and Glycine Elevated in First-Episode Psychosis

Young people in their first episode of psychosis show elevations in the brain chemicals glutamate and glycine, according to a new study published in the journal Biological Psychiatry.

Abnormal brain activity in psychotic disorders, such as schizophrenia and bipolar disorder, is thought to stem in part from impaired function of the NMDA (N-methyl-D-aspartate) receptor, a vital mediator of brain signaling involved in learning and memory. Importantly, this receptor is activated by the chemicals glutamate and glycine.

The study, which provides the first ever measurement of glycine levels in patients with psychotic disorders, could potentially serve as a marker in the development of future treatments aimed at restoring the function of NMDA receptors.

Until now, reliable detection of glycine in the human brain has been extremely challenging with the use of conventional techniques, as an overlapping signal interferes with its detection. In the new study, the researchers applied a new method of a brain imaging technique known as MRS (magnetic resonance spectroscopy) to suppress the interfering signal and reveal the hidden glycine signal.

The researchers found that glycine levels were higher in 46 patients who were experiencing first-episode psychosis, compared with 50 healthy participants.

“Our findings suggest that glycine abnormalities may play a role in the earliest phases of psychotic disorders,” said Dr. Dost Öngür of Harvard Medical School and leader of the study.

The researchers also found increased levels of glutamate in psychosis patients, a finding which falls in line with other studies showing elevated glutamate in patients with first-episode psychosis. The elevations in both glutamate and glycine suggest that NMDA receptors receive abnormal stimulation in psychotic disorders.

The increased levels of glycine were actually the opposite of what the researchers expected to find. In fact, researchers have tried raising glycine levels in patients to compensate for the underperforming NMDA receptors, but found no success. The new findings revealing higher levels early on in the disease might help to explain why glycine supplementation hasn’t worked as well as researchers hoped.

“This study supports the notion of different developmental phases in the biology of schizophrenia. These phases might require somewhat different treatments,” said Dr. John Krystal, Editor of Biological Psychiatry.

Three in 100 people will experience psychosis at some point in their lives, according to the National Institute of Mental Health (NIMH). Symptoms may include hallucinations, paranoia, delusions and/or disordered thoughts and speech patterns.

Source: Elsevier