The Synaptic Bases of Mental Diseases

An innovating treatment of psychosis based on biomarkers

schizophrenia illustration

Two units of the Department of Psychiatry, in partnership with the Harvard Medical School, have tried innovative treatment in patients who have recently developed psychosis. Their results were published in the journal Schizophrenia Bulletin.

The Schizophrenia Research Unit of the Center for Psychiatric Neuroscience (Prof. Kim Do Cuénod) and the Department of General Psychiatry (Prof. Philippe Conus) of CHUV, in partnership with Harvard Medical School, Boston (Prof. Larry Seidman), have conducted a clinical trial with N-acetyl-cysteine (NAC) in patients who have recently developed a psychosis.

The N-acetylcysteine (NAC), an anti-oxidant substance with no side effects used clinically for various indications, is also a precursor of glutathione, one of the most important brain antioxidants, whose metabolism is disrupted in patients. A study, conducted a few years ago by the same group in patients suffering from chronic schizophrenia, had demonstrated that the addition of NAC to the usual neuroleptic treatment had a beneficial effect on certain symptoms of the disease (deficits of communication, expression of emotions and socialization), and improved auditory signal processing and neuronal synchronization, assessed through the electroencephalogram.

With this in mind, this same group began in 2009 the study of the impact of the addition of NAC in patients going through earlier stages of the disease. In this clinical trial, young patients who had recently developed a psychosis, received, in addition to the standard neuroleptic treatment, either NAC or a placebo, for a duration of 6 months. The results, published in the February 2018 issue of the journal Schizophrenia Bulletin, show that:

  • Oral NAC leads to an increase in cerebral glutathione, a molecule that protects brain cells from oxidation;
  • The administration of NAC improves cognitive functions, especially the speed of information processing. This result is particularly promising if we consider that cognitive disorders are common in these patients, that they are one of the main determinants of social integration, and that there is currently no effective drug in this area.
  • And finally, the evaluation in the blood of the cellular oxidation state, makes it possible to identify a subgroup of patients in “high oxidation state” in which the addition of NAC allows a significant improvement of symptoms such as hallucinations, delusions, or the disorganization of thought. Plus, the decrease in symptoms seems to be even more marked when the oxidation state is normalized in the blood.

These results, which need to be confirmed on a larger scale, open the way to an innovative treatment, based on neuroprotection and guided by the measurement of biomarkers of psychosis. It is, indeed, a first step towards personalized treatment, whose indication can be defined on the basis of biological markers, and whose effectiveness can also be measured biologically, which is a first in the field of psychiatry.

Author : Philippe Conus-CHUV – French Version >
Translation : Tania Secalin

Conus P, Seidman LJ, Fournier M, Xin L, Cleusix M, Baumann PS, Ferrari C, Cousins A, Alameda L, Gholam-Rezaee M, Golay P, Jenni R, Woo TW, Keshavan MS, Eap CB, Wojcik J, Cuenod M, Buclin T, Gruetter R, Do KQ;
N-acetylcysteine in a double-blind randomized placebo-controlled trial : Toward biomarker-guided treatment in early psychosis.
Schizophrenia Bullutin 44(2):317-327, Feb 2018. doi:10.1093/schbul/sbx093 >

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