The depression experienced by people with Huntington disease (HD) may have nothing to do with the emotional stress of knowing you have a devastating, incurable disorder, according to a University of British Columbia study published in the journal Brain.
Using mice models, UBC researchers have discovered that depression in people with HD is caused by a mutant huntingtin protein responsible for HD. The team found that mice with HD show depression symptoms when this protein is compromised. When researchers repaired the protein, the mice showed no symptoms of depression.
“The depression experienced by people with Huntington disease has long been assumed to be a social reaction to knowing you had something incurable, or knowing the disorder runs in your family,” says lead author Mahmoud Pouladi, a PhD candidate in UBC’s Centre for Molecular Medicine and Therapeutics (CMMT). “Our research suggests this depression is a part of the disease’s neurobiology.”
The study also explored the effectiveness of antidepressant drugs on mice with HD. It found that tricyclic and SSRI antidepressants – the two most common antidepressants, both commonly prescribed to treat depression in people with HD – were ineffective at reducing depressive behaviour in mice models.
The study is one of the first to explore the causes of the emotional disturbances related to HD, says Pouladi, a medical genetics student of UBC’s Dr. Michael Hayden, Canada Research Chair in Human Genetics and Molecular Medicine and Director and Senior Scientist at the CMMT at the Child and Family Research Institute. Recent studies suggest as many as 50 per cent of people with HD experience depression, and that the depression can occur long before the manifestation of motor symptoms.
This finding builds on the ground-breaking work of Dr. Hayden, who in 2006 showed that HD could be prevented in mice with the HD mutation. Hayden and colleagues discovered that by preventing the cleavage of the mutant huntingtin protein responsible for Huntington disease in a mouse model, the degenerative physical symptoms underlying the illness do not appear and the mouse displays normal brain function.
Hayden’s team is now trying to test this model of prevention in a mouse using drug inhibitors, and then ultimately in humans.
Huntington disease is a degenerative brain disease that affects one in every 10,000 Canadians. The disease results from degeneration of neurons in certain areas of the brain causing uncontrolled movements, loss of intellectual faculties, and emotional disturbances. Currently, there is no treatment to delay or prevent HD in patients.
To view Pouladi’s study, visit: http://brain.oxfordjournals.org/cgi/content/full/132/4/919
The University of British Columbia (UBC) is one of Canada’s largest public research and teaching institutions and ranks solidly among the top 35 universities in the world. It offers a range of innovative undergraduate, graduate and professional programs in the arts, sciences, medicine, law, commerce and other faculties. UBC ranks in the top 10 universities in North America and number one in Canada for commercializing research, and for its patent activity in the life sciences. For more information, visit: www.ubc.ca.
The Child and Family Research Institute (CFRI) conducts discovery research, clinical investigation, and applied health research to benefit the health of children and families. It is the largest research institute of its kind in Western Canada. CFRI works in close partnership with BC Children’s Hospital and Sunny Hill Health Centre for Children, and BC Women’s Hospital and Health Centre, agencies of the Provincial Health Services Authority; BC Children’s Hospital Foundation; UBC and Simon Fraser University. For more information, visit www.cfri.ca.
The Centre for Molecular Medicine and Therapeutics (CMMT) is a synergistic group of scientists and researchers who share a strong sense of commitment to solve the many genetic questions surrounding human illness and well being. Affiliated with UBC and CFRI, CMMT conducts discovery research and translates that research into effective
clinical and therapeutic strategies to promote health. For more information, visit http://www.cmmt.ubc.ca .
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