Identification of Genes Involved in Major Mood Disorders

National Institute Of Mental Health

Investigators

Linked publications & trials

Abstract

NCT00001174 Understanding Bipolar Disorder Through Genetics We started studying the genetics of bipolar disorder back in 2007. Our early research showed that many different genes play small roles in the condition, meaning it's influenced by a mix of genetic factors. More recently, a large international research group we’re part of studied over 50,000 people with bipolar disorder. They found over 260 genetic regions linked to the condition—many of them new discoveries. These common genetic changes explain about one-third of the inherited risk for bipolar disorder. Interestingly, many of the genes are connected to medications like antipsychotics and mood stabilizers. Suicide Risk and Shared Genetics One of our studies looked at why people with bipolar disorder are more likely to attempt suicide. It found that the same genetic factors that increase risk for depression, smoking, risk-taking, and sleep problems also play a role in suicide attempts. This suggests that these issues may share a common biological root. Lithium Treatment and Genetics Some of our other studies are exploring why some people respond well to lithium, a common treatment for bipolar disorder. For example, we have found that genes related to the immune system and other mental health conditions like schizophrenia and ADHD may influence how well lithium works. In future, this research could help doctors predict who will benefit most from lithium. Studying Unique Populations We also study bipolar disorder in large families and special populations. Studying these communities helps us uncover genetic clues that are harder to find in the general population. For example, we collaborated with a large group of researchers who study the Old Order Amish, a population with a unique genetic background. This helped us find rare genetic changes that double the risk for bipolar disorder. Some of these changes were also linked to depression. So far, we’ve collected genetic data from over 1,500 people in Amish and Mennonite communities. These populations are especially useful for studying rare genetic changes. Participants also take tests to measure mood, anxiety, and thinking skills that may reflect genetic risk factors. Blood cells from some participants are turned into stem cells for laboratory research. This provides a rich resource to study how genes affect mental health. Using Genetic Scores to Understand Bipolar Disorder We’re also using genetic data to create scores that estimate a person’s overall genetic risk for bipolar or other mental health disorders. These scores help us understand why the condition looks different in different people. For example, we found that people with bipolar disorder who also have anxiety may carry genetic risks for both conditions. This could lead to better treatments that address both issues. Sharing Genetic Results with Participants A few of our research participants may carry a genetic change that is already known to contribute in a major way to mental illness. We’re working with participants who have these changes to offer genetic counseling and help them understand their results. We’re also studying how learning about their genetics affects their mood, anxiety, and understanding of their condition. New Genetic Mutations and Bipolar Disorder Not all genetic risk factors are inherited. Although they are rare, new genetic mutations that arise by chance when DNA is passed from parents to children can provide powerful clues about which genes are most important. For example, we have found new, apparently harmful, mutations in 42 genes that are present in participants with bipolar disorders or related mental health conditions. These genes are linked to brain development, learning, and the immune system. These findings support the idea that new mutations may play a role in bipolar disorder by disturbing particular biological systems. These systems may be good targets for future studies aimed at developing new treatments. Mood and Thinking in Families We also looked at how mood symptoms and thinking skills run in families. People with bipolar disorder had higher mood symptoms, but these varied among their relatives. About 30% of these symptoms were inherited. While mood symptoms were clearly linked to genetics, thinking problems didn’t show strong genetic connections. This suggests that cognitive issues in bipolar disorder may be caused more by the illness itself or its treatment. What’s Next We now have data from over 1,600 people in more than 500 families across the U.S., Brazil, and Canada. This includes DNA, genetic sequences, mental health diagnoses, and stem cells. This is one of the largest and most detailed collections of its kind. We hope it will help research for years to come. In the coming year, we plan to enroll more participants in our study, do more genetic testing, and offer genetic counseling to more people. We will also continue to work with large consortia aimed at mapping specific genes involved with bipolar disorder and related conditions. We aim to learn even more about how genetics influence bipolar disorder so that this knowledge can be used to improve treatment.