The authors of a new study published online in the Archives of General Psychiatry this week, conclude that a rare deletion of a small region of the genome that codes for BDNF (short for brain-derived neurotrophic factor) plays a role in the development of psychiatric disease and obesity.
In their paper, Carl Ernst, a professor in the Department of Psychiatry at the Faculty of Medicine of McGill University in Montreal, Quebec, Canada, and colleagues, suggest deletion of BDNF, a nervous system growth factor that is important for brain development, leads to major depression, anxiety and obesity.
They are confident they have found a molecular pathway that plays a key role in psychopathology.
Ernst, who is also a researcher at the Douglas Mental Health University Institute (affiliated to McGill), says scientists have been scouring the genome to find regions in our DNA that may tell us something about the genetic origins of psychiatric disorders.
For some time, thanks to animal studies, it has been proposed that BDNF plays several roles in the brain, but no study has yet shown what happens when it is missing from the genome.
In this study, the participants were 35,000 people referred for genetic screening, and over 30,000 controls, in Canada, Europe and the US.
From the genetic screening, five people (including three children) tested positive for BDNF deletions. All five were obese and had mild to moderate intellectual impairment, plus a mood disorder, which in the children comprised anxiety disorder, aggressive disorder, or attention deficit-hyperactivity disorder (ADHD), and in the older subjects comprised anxiety or major depressive disorder.
As they got older, these subject gradually put on weight, which the researchers suggest means obesity happens slowly when it is due to BDNF deletion.
The researchers believe their findings are a step forward in revealing new insights into the genetic underpinnings of human behavior and mood.
“Our study conclusively links a single region of the genome to mood and anxiety,” says Ernst.
He describes the complexity of mood and anxiety as a “house of cards”, where the walls represent all the various biological interactions that maintain the structure of the condition:
“Studying these moving parts can be tricky, so teasing apart even a single event is important. Linking a deletion in BDNF conclusively to mood and anxiety really tells us that it is possible to dissect the biological pathways involved in determining how we feel and act,” he explains.
Ernst says thousands of genes are involved in mood, anxiety and obesity, and this finding allows them to root the study on a “solid foundation”.
However, the study also raises important questions that should trigger further investigations.
“All of the participants in our study had mild-moderate intellectual disability, but most people with these cognitive problems do not have psychiatric problems,” he says, asking, “so what is it about deletion of BDNF that affects mood?”
He and his colleagues now want to test the idea that boosting BDNF in people with anxiety or depression may improve their brain health.
Written by Catharine Paddock PhD