Genes Involved in Mental Disorders

A new study reveals links between brain-derived neurotrophic factor (BDNF) deletion, cognition, and weight gain in humans.

It is difficult to distinguish the role of BDNF that is a nervous system growth factor that plays a critical role in brain development in adult brain. Based on animal study it is suspected that BDNF have many functions in the brain. But no study had shown what happens when BDNF is missing from the human genome. This research provides a step toward better understanding human behaviour and mood by clearly identifying genes that may be involved in mental disorders.

But the McGill researchers have noticed a small region in the genome that plays a role in the devlopment of psychiatric disease and obesity.  

In order to determine the role of BDNF in humans, Prof. Carl Ernst, from McGill's Department of Psychiatry, Faculty of Medicine, screened nearly 35,000 people that were referred to genetic screening at clinics and over 30,000 control subjects in Canada, the U.S., and Europe.

Five individuals were identified with BDNF deletions, all of whom were obese, had a mild-moderate intellectual impairment, and had a mood disorder.

The symptoms they noticed in children were of anxiety disorders, aggressive disorders, or attention deficit-hyperactivity disorder (ADHD), whereas post-pubescent subjects had anxiety and major depressive disorders.  They noticed that the subjects gradually gained weight as they aged.

With this analysis the researchers state that obesity is a long term process when BDNF is being deleted.

"Scientists have been trying to find a region of the genome which plays a role in human psychopathology, searching for answers anywhere in our DNA that may give us a clue to the genetic causes of these types of disorders," says Prof. Ernst, who is also a researcher at the Douglas Mental Health University Institute. "Our study conclusively links a single region of the genome to mood and anxiety."

"Mood and anxiety can be seen like a house of cards. In this case, the walls of the house represent the myriad of biological interactions that maintain the structure," says Ernst, "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.

We now have a molecular pathway we are confident is involved in psychopathology," adds Ernst. "Because thousands of genes are involved in mood, anxiety, or obesity, it allows us to root our studies on a solid foundation. All of the participants in our study had mild-moderate intellectual disability, but most people with these cognitive problems do not have psychiatric problems -- so what is it about deletion of BDNF that affects mood? My hope now is to test the hypothesis that boosting BDNF in people with anxiety or depression might improve brain health."

The details of this finding were published in the Archives of General Psychiatry.