pathways identified could inform new approaches to treatment
July 21, 2014 (Toronto) – As part of a
multinational, collaborative effort, researchers from Canada’s Centre for
Addiction and Mental Health (CAMH) have helped identify over 100 locations in
the human genome associated with the risk of developing schizophrenia, in what
is the largest genomic study published on any psychiatric disorder to date. The
findings, published online in Nature, point to biological mechanisms and
pathways that may underlie schizophrenia, and could lead to new approaches to
treating the disorder, which has seen little innovation in drug development in
more than 60 years.
Schizophrenia, a debilitating mental illness that affects approximately one out
of every 100 people worldwide, is characterized by hallucinations, delusions,
and disordered thinking, and often emerges in the teens and early 20s. Its
lifetime impact on individuals and society is high, both in terms of direct
health-care and other costs, as well as lost productivity and unemployment,
which costs an estimated $6.85 billion a year in
Medications currently on the
market treat only one of the symptoms of the illness (psychosis), and there are
no effective treatments for the debilitating cognitive symptoms of
schizophrenia. In part, treatment options are limited because the biological
mechanisms underlying schizophrenia have not been understood.
Recent research focusing on
the genetic underpinnings of schizophrenia has revealed the complexity of the
illness. Evidence suggests that it is caused by the combined effects of many
genes, and roughly two dozen genomic regions have been found to be associated
with schizophrenia. The new study confirms those earlier findings, and expands
our understanding of the genetic basis of schizophrenia and its underlying
biology. In the genome-wide association study (GWAS) published in Nature,
the authors looked at 36,989 genetic samples from schizophrenia patients and
113,075 healthy volunteers and found 108 specific locations in the human genome
associated with risk for schizophrenia. Eighty-three of those loci had
not previously been linked to the illness.
“Large collaborative efforts such as this one are needed to
identify genes that influence complex disorders,” said Dr. Jo Knight, Senior
Scientist and Joanne Murphy
Professor in Behavioural Science, who spearheaded CAMH’s
involvement in this project. “The result is a major advance in understanding
the genetic basis of brain functioning in schizophrenia,” said Dr. Knight, who
is also Associate Professor of Psychiatry at the University of Toronto.
The Canadian contribution was conducted
within CAMH’s Campbell Family Mental Health Research Institute, and CAMH
researchers Dr. James Kennedy and Dr. Clement Zai were also on the study team.
The study implicates genes
expressed in brain tissue, particularly those related to the functioning of
brain cells (neurons) and of the channels enabling chemical and electrical
signaling between neurons (synapses). These include genes that are active in
pathways controlling synaptic plasticity – a function essential to learning and
memory – and pathways governing activity in the target cell receiving
researchers found a smaller number of genes associated with schizophrenia that
are active in the immune system. This discovery offers some support for a
previously hypothesized link between schizophrenia and immunological processes.
The study also found an association between the illness and the region of the
genome that holds DRD2 – the gene that produces the dopamine receptor
targeted by all approved medications for schizophrenia – suggesting that other
loci uncovered in the study may point to additional therapeutic targets.
that we were able to detect genetic risk factors on this massive scale shows
that schizophrenia can be tackled by the same approaches that have already
transformed our understanding of other diseases,” said senior author Dr.
Michael O’Donovan, deputy director of the MRC Centre for Neuropsychiatric
Genetics and Genomics at Cardiff University School of Medicine. “The wealth of
new findings has the potential to kick-start the development of new treatments
in schizophrenia, a process which has stalled for the last 60 years.”
The study is the result of
several years of work by the Schizophrenia Working Group of the Psychiatric
Genomics Consortium (PGC), an international, multi-institutional collaboration
founded in 2007 to conduct broad-scale analyses of genetic data for psychiatric
disease. A total of 55 datasets from more than 40 different contributors,
including CAMH, was needed to conduct the analysis.
The samples used in this
study represent all of the genotyped datasets for schizophrenia that the
consortium has amassed to date. The PGC is currently genotyping new samples to
further study schizophrenia and additional psychiatric diseases, including
autism and bipolar disorder.
Core funding for the
Psychiatric Genomics Consortium comes from the U.S. National Institute of
Mental Health (NIMH), along with numerous grants from governmental and
charitable organizations, as well as philanthropic donations. The Canadian contribution was funded in part by the
Canadian Institutes of Health Research grant MOP-115097.
The Centre for Addiction and Mental Health (CAMH)
is Canada's largest
mental health and addiction teaching hospital, as well as one of the world's
leading research centres in its field. CAMH combines clinical care, research,
education, policy development and health promotion to help transform the lives
of people affected by mental health and addiction issues. CAMH is fully
affiliated with the University of Toronto, and is a Pan American Health
Organization/World Health Organization Collaborating Centre. For
more information, please visit www.camh.ca.
Centre for Addiction and Mental Health (CAMH)
416 535 8501 x36015