Dr. Carl Ernst's research featured in the Montreal Gazette

Published: 11 October 2012

Rare genetic mutation linked to psychiatric illnesses, obesity 

B Charlie Fidelman, GAZETTE Health Reporter October 8, 2012 

MONTREAL — Grounding chronic illnesses and mental disorders in human DNA is like trying to tease out a giant riddle that’s complicated by the intricate relationship between biology and behaviour. Hundreds of genes have been associated with psychiatric conditions, some erroneously, and they were not confirmed.

Now a high-level genetic analysis by an international team led by McGill University has made a key discovery linking a genetic mutation and psychiatric disease — plus a surprise connection to obesity.

“We were encouraged by the consistency of what we saw,” said Carl Ernst of McGill University’s department of psychiatry, faculty of medicine, who launched the study as a fellow while at Harvard Medical School in Boston.

“I will make the prediction now — if anyone ever screens a genome from any human being on planet Earth and they see a lesion, the genetic deletion that we found ... the patient they will see will be obese, and will have a psychiatric (illness).”

The mutation lies on chromosome 11 on a short section of the genome that plays a key role in brain plasticity and development. It encodes a nervous system growth factor called brain-derived neurotrophic factor (BDNF).

But before anyone blames a depression, anxiety or weight problem on his or her genes, it should be noted that the mutation is extremely rare.

Published online Monday in a top journal in psychiatry, the Archives of General Psychiatry, the study suggests early interventions in people with the mutation may improve symptoms and reduce public health costs associated with chronic illness.

Researchers compared 38,550 people referred for genetic testing at clinics in Canada, the United States and Europe with a control group of 28,705 people. About 30 researchers pooled their data, making it one of the largest genomic sequencing studies to date.

Results showed that none of the people in the control group had the mutation. Only five individuals in the screened group were found to have one copy of the BDNF gene missing along with a tiny section of genome, Ernst said, and everyone without the gene had the same issues with weight and behaviour.

“The probability of that happening by chance is basically nil,” said Ernst, a researcher at the Douglas Mental Health University Institute.

All five were obese, had intellectual impairments and mood disorders. In children, researchers noted major aggression, anxiety, attention deficit or hyper-activity and their weight gain increased with age.

The findings are supported by similar results in the literature on animal models where the gene was knocked out — rats and mice became obese, anxiety-prone and aggressive.

Scientists have already implicated BDNF in Rett Syndrome, a neurological developmental disorder, Alzheimer’s and Huntington disease as well as for its role in pain, obesity, mood disorders, learning and memory.

“What was unknown is, ‘what happens in humans if it’s not there?’ That’s what this study added,” Ernst said. However, the study, he cautioned, does not prove with 100 per cent certainty that the mutation is responsible for the disorders because a gene on either side of BDNF is also deleted in all the cases.

Despite the small number of patients with BDNF and disorders, the high-quality genetic information used by the McGill group produced results that are quite significant, said Anthony Phillips, scientific director of the Canadian Institutes of Health Research’s Institute of Neurosciences, Mental Health and Addiction.

“It doesn’t tell us how BDNF is producing changes in brain anatomy or chemistry,” said Phillips, who was not involved in the study. “But it clearly indicates that when you see this gene abnormality occurring, that you have to pay attention to it.”

The finding could be used as biomarker for disorders that often appear in adolescence or young adulthood, Phillips said.

“If you could identify someone at an early stage so they might receive care during that vulnerable period, it might lessen the impact of this disease on their entire life.”

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