JUL 03, 2019 10:49 AM PDT

Treating Psychosis by Targeting a Genetic Mutation

WRITTEN BY: Carmen Leitch

It may one day be possible to treat psychiatric disorders with therapies that target genetic mutations. New research has shown that in some psychosis patients, tailoring a treatment to a gene dysfunction can relieve symptoms of their disease. The work also demonstrated how some gene defects are linked to the etiology of psychosis. The findings have been reported in Biological Psychiatry.

Image credit: Pixabay

There are not many known genetic mutations that have a major influence on the risk of psychiatric disorders, but some have been found. Researchers led by Deborah L. Levy, Ph.D. of McLean Hospital, which is an affiliate of Harvard Medical School, recently found a copy-number variant (CNV) mutation in two of four patients. The two individuals each carried two extra copies of the glycine decarboxylase gene (GLDC), which catabolizes glycine.

The researchers thought that the CNV mutation could cause a drop in glycine levels in the brain. In schizophrenia, glutamatergic functioning is disrupted, which may be influenced by this mutation.

The scientists assessed molecules that could restore glycine or glutamate function, and found that they helped relieve symptoms of psychosis in the patients carrying the mutation. They experienced a reduction in mood symptoms, less social withdrawal, and enhanced emotional engagement. While a cohort of only two patients is tiny, it shows that there is room for improvement in the treatment of psychiatric diseases.

"The compelling aspect is that this CNV can be linked to pathophysiology, and, as the new study shows, to treatment," noted Dr. Levy. "This approach contrasts with the standard clinical practice of treating individuals on the basis of clinical symptoms or diagnosis independent of specific genetic variants."

"It is important to note that the two subjects studied here bore little clinical resemblance, with distinctly different symptom burdens, and highly dissimilar courses of illness," explained the study first author J. Alexander Bodkin, MD of McLean Hospital. The treatment may, therefore, have been effectively improving an impaired biological mechanism, which was not dependent on a very specific clinical diagnosis.

"Most studies of rare structural variants will have very small sample sizes, complicating the usual approach to statistical analysis. Nevertheless, because the effects of a targeted treatment can be large, it is important to prioritize opportunities to study even small groups of patients who may benefit," added author Charity J. Morgan of the University of Alabama.

"The substances that they administered, glycine and D-cycloserine, do not produce noticeable behavioral effects in healthy people or in patients with psychotic disorders. However, because these substances replaced a deficient cofactor involved in neural communication in these particular individuals, their administration alleviated mood and psychosis symptoms," said John Krystal, MD, the Editor of Biological Psychiatry. As in these cases, we expect psychiatry to develop more instances where specific treatments can be developed to meet the needs of particular groups of patients."

Learn more about copy number variation from the video.


Sources: AAAS/Eurekalert! via Elsevier, Biological Psychiatry

About the Author
  • Experienced research scientist and technical expert with authorships on 28 peer-reviewed publications, traveler to over 60 countries, published photographer and internationally-exhibited painter, volunteer trained in disaster-response, CPR and DV counseling.
You May Also Like
DEC 12, 2019
Genetics & Genomics
DEC 12, 2019
How Liquid Biopsies Can Teach Us About Cancer Drug Resistance
Cancer patients often endure challenging treatment courses to shrink their tumors, but the tumors can make a powerful comeback....
DEC 12, 2019
Genetics & Genomics
DEC 12, 2019
Gates Foundation and NIH Pledge $200 Million for Gene Therapies in Africa
Over the next four years, the National Institutes of Health and the Bill and Melinda Gates Foundation plan to each invest $100 million towards the developm...
DEC 12, 2019
Drug Discovery & Development
DEC 12, 2019
Gene Variant Could Be a Therapeutic Target For Alzheimer Disease
A variation in genetics for an individual at high-risk for Alzheimer development has defied the odds for being dementia-free way beyond anticipated. The in...
DEC 12, 2019
Genetics & Genomics
DEC 12, 2019
Linking Genes and Behavior in an Assessment of Personality in Animals
Anyone that's owned dogs knows that they have a personality, and the same is true of mice....
DEC 12, 2019
Genetics & Genomics
DEC 12, 2019
Plants Moved to Land by Stealing Genes from Soil Bacteria
Algae were the first pants on earth, and they lived underwater. How they managed to move onto land was largely a mystery, until now. By studying the genome...
DEC 12, 2019
Genetics & Genomics
DEC 12, 2019
22 Genes Discovered that Predict Skin Cancer from Sun Exposure
Australia has the highest rate of skin cancer in the world, with around 49 cases per 100,000 people. Now, researchers at the QIMR Berghofer Medical Researc...
Loading Comments...