(Press-News.org) Scientists know there is a strong genetic component to bipolar disorder, but they have had an
extremely difficult time identifying the genes that cause it. So, in an effort to better
understand the illness's genetic causes, researchers at UCLA tried a new approach.
Instead of only using a standard clinical interview to determine whether individuals met the
criteria for a clinical diagnosis of bipolar disorder, the researchers combined the results from
brain imaging, cognitive testing, and an array of temperament and behavior measures. Using the
new method, UCLA investigators — working with collaborators from UC San Francisco, Colombia's
University of Antioquia and the University of Costa Rica — identified about 50 brain and
behavioral measures that are both under strong genetic control and associated with bipolar
disorder. Their discoveries could be a major step toward identifying the specific genes that
contribute to the illness.
The results are published in the Feb. 12 edition of the
journal JAMA Psychiatry.
A severe mental illness that affects about 1 to 2 percent of
the population, bipolar disorder causes unusual shifts in mood and energy, and it interferes
with the ability to carry out everyday tasks. Those with the disorder can experience tremendous
highs and extreme lows — to the point of not wanting to get out of bed when they're feeling
down. The genetic causes of bipolar disorder are highly complex and likely involve many
different genes, said Carrie Bearden, a senior author of the study and an associate professor of
psychiatry and psychology at the UCLA Semel Institute for Neuroscience and Human Behavior.
"The field of psychiatric genetics has long struggled to find an effective approach to
begin dissecting the genetic basis of bipolar disorder," Bearden said. "This is an innovative
approach to identifying genetically influenced brain and behavioral measures that are more
closely tied to the underlying biology of bipolar disorder than the clinical symptoms alone
are."
The researchers assessed 738 adults, 181 of whom have severe bipolar disorder.
They used high-resolution 3-D images of the brain, questionnaires evaluating temperament and
personality traits of individuals diagnosed with bipolar disorder and their non-bipolar
relatives, and an extensive battery of cognitive tests assessing long-term memory, attention,
inhibitory control and other neurocognitive abilities.
Approximately 50 of these
measures showed strong evidence of being influenced by genetics. Particularly interesting was
the discovery that the thickness of the gray matter in the brain's temporal and prefrontal
regions — the structures that are critical for language and for higher-order cognitive functions
like self-control and problem-solving — were the most promising candidate traits for genetic
mapping, based on both their strong genetic basis and association with the disease.
"These findings are really just the first step in getting us a little closer to the roots of
bipolar disorder," Bearden said. "What was really exciting about this project was that we were
able to collect the most extensive set of traits associated with bipolar disorder ever assessed
within any study sample. These data will be a really valuable resource for the field."
The individuals assessed in this study are members of large families living in Costa Rica's
central valley and Antioquia, Colombia. The families were founded by European and native
Amerindian populations about 400 years ago and have a very high incidence of bipolar disorder.
The groups were chosen because they have remained fairly isolated since their founding and their
genetics are therefore simpler for scientists to study than those of general populations.
The fact that the findings aligned so closely with those of previous, smaller studies in
other populations was surprising even to the scientists, given the subjects' unique genetic
background and living environments.
"This suggests that even if the specific genetic
variants we identify may be unique to this population, the biological pathways they disrupt are
likely to also influence disease risk in other populations," Bearden said.
The
researchers' next step is to use the genomic data they collected from the families — including
full genome sequences and gene expression data— to begin identifying the specific genes that
contribute to risk for bipolar disorder. The researchers also plan to extend their investigation
into the children and teens in these families. They hypothesize that many of the bipolar-related
brain and behavioral differences found in adults with bipolar disorder had their origins in
adolescent neurodevelopment.
INFORMATION:
The study's other authors include Dr. Nelson Freimer, a UCLA
professor of psychiatry and director of the UCLA Center for Neurobehavioral Genetics, and Scott
Fears, assistant professor in the Center for Neurobehavioral Genetics. Please see the paper for
a full list of co-authors. The research was supported by National Institute of Health grants
R01MH075007, R01MH095454, P30NS062691, K23MH074644-01 and K08MH086786, and by Colciencias
(Colombia's Administrative Department of Science, Technology and Innovation) and the Committee
for the Development of Research (CODI) at Colombia's University of Antioquia.
The Semel
Institute for Neuroscience and Human Behavior is an interdisciplinary research and education
institute devoted to the understanding of complex human behavior, including the genetic,
biological, behavioral and sociocultural underpinnings of normal behavior, and the causes and
consequences of neuropsychiatric disorders. In addition to conducting fundamental research, the
institute faculty seeks to develop effective strategies for prevention and treatment of
neurological, psychiatric and behavioral disorder, including improvement in access to mental
health services and the shaping of national health policy.
For more news, visit the
UCLA Newsroom and follow us on Twitter.
Understanding the basic biology of bipolar disorder
Scientists from UCLA, UC San Francisco, Costa Rica and Colombia take steps to identify genetic component to mental illness
2014-02-13
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[Press-News.org] Understanding the basic biology of bipolar disorderScientists from UCLA, UC San Francisco, Costa Rica and Colombia take steps to identify genetic component to mental illness