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Lithium, the main drug for treating bipolar disorder, was approved half a century ago, but it doesn't help all patients and has significant side effects
A genetic study involving thousands of people with bipolar disorder has revealed new insights into the molecular basis of the condition
The research was published in the journal Nature Genetics
Big research, big effect
Bipolar disorder is a severe, heritable mood disorder that affects about 1% of the population and usually begins in early adulthood
Scientists at the Stanley Center, in collaboration with colleagues at the Bipolar Exome Consortium around the world, have identified rare differences in DNA sequences that alter proteins, with the hope of discovering differences that have a large impact on disease risk.
The researchers first compared exons, the protein-coding parts of the genome, from about 14,000 people with bipolar disorder and 14,000 healthy controls
The team next integrated results from a large-scale study conducted by the Schizophrenia Exome Sequencing Meta-Analysis (SCHEMA) Consortium
"AKAP11 variants don't contribute much to risk in the entire population, but the real value is that they reveal the source of the disease, and that's why we really focus on them
The protein product of AKAP11 interacts with another protein called GSK3B, a molecular target of lithium, a potential mechanism of efficacy
new variant, new model
To explore the molecular and behavioral effects of the AKAP11 gene variant identified in the study, researchers at the Stanley Center are creating cell and animal models that carry the gene variant
The researchers are also exploring whether AKAP-11 or its molecular partners could serve as biomarkers for the disease to aid in diagnosis or to help ensure that future clinical trials include patients most likely to benefit from a certain treatment
The researchers and colleagues aim to continue recruiting more people with bipolar disorder for large-scale studies to uncover more genetic risk factors
The research was generously supported by the Stanley Family Foundation, Kent and Elizabeth Dawten, and the Dalio Foundation, in addition to funding from the National Institutes of Health
