Research

Bipolar disorder affects millions of individuals across their lifespan and therefore must be studied longitudinally (over the course of decades). Bipolar disorder is known to run in families, but most genes involved have not yet been identified. Additionally, every individual’s response to the illness, life circumstances, and treatment can vary widely. Studying many individuals over time will allow scientists to better understand how to treat and, eventually, prevent bipolar disorder.

Over 20 years of data from our Longitudinal Study are available for research to the scientific community. The Longitudinal Study of Bipolar Disorder, which is the Prechter Program’s flagship project, has enrolled over 1,500 individuals. From these participants, billions of data points have been generated through biological samples (DNA), neuropsychological testing, clinical interviews, bi-monthly follow-ups, and innovative monitoring using mobile devices.

Participants collaborate with the research team in additional studies that have resulted in the acquisition of several big data sets in cell biology, sleep, nutrition, physiology, and genetics.

Learn more about the Longitudinal Study of Bipolar Disorder.

No one genetic change, or chemical imbalance, or life event, lies at the heart of bipolar disorder. Rather, every patient’s experience with the disorder varies from that of others with the condition. But all of their experiences include features that fall into seven classes of phenotypes, or characteristics that can be observed, as the Prechter research team reported in a 2018 paper in the International Journal of Epidemiology.

Our team collected and analyzed tens of thousands of data points about the genetics, emotions, life experiences, medical histories, motivations, diets, temperaments, sleep patterns and thought patterns of our research volunteers. Using those findings, we developed a framework for researchers studying the condition, clinical teams treating it, and patients experiencing it. This framework provides a common structure to use during studies, treatment decisions and more.

Our research finds that bipolar disorder has many causes. Although bipolar disorder tends to run in families, no one gene causes or explains it. Everyone’s experience with bipolar disorder is unique. But all experiences include features that fall into the following seven classes of observable characteristics, or phenotypes:

1. DISEASE: Changes in how certain chemicals function in the brain and affect bipolar disorder.
2. NEUROCOGNITIVE: Changes in thinking, reasoning, and emotion processing.
3. TEMPERAMENT AND PERSONALITY: People with bipolar disorder are frequently more reactive and “temperamental” compared to the average person.
4. MOTIVATED BEHAVIORS: People with bipolar disorder frequently experience substance use disorders and other behavioral patterns.
5. LIFE STORY: Trauma and abuse in childhood, unfortunate life experiences and other challenges contribute to bipolar disorder in complex ways.
6. SLEEP AND CIRCADIAN PATTERNS: Patterns of sleep and circadian rhythms are often different among bipolar patients, causing disruptions in daily patterns and routines.
7. OUTCOMES AND COURSE OF ILLNESS: Measures of how someone’s symptoms change over time and respond to treatment.

Neuropsychology is a specialty field within clinical psychology that aims to understand how behavior, emotion and cognition are influenced by brain functioning. Neuropsychology focuses on the behavioral and cognitive assessment and treatment of patients with brain injury, disease, or severe mental illness, such as bipolar disorder.

In a neuropsychological assessment, brain functioning is evaluated by objectively testing cognitive skills using numerous standardized and validated tests. Test performances are then compared to reference groups of the same age, gender, race, and educational attainment. This normative comparison helps neuropsychologists determine if individuals are performing within expectations, and provides information about cognitive strengths and weaknesses which aid in diagnosis or inform treatment planning. Performances can be compared to others with and without the illness.

In the Prechter Longitudinal Study of Bipolar Disorder, neuropsychology testing provides information about different areas and systems of the brain and how they are impacted by illness, medications, and environmental factors. Test performances can be used to predict functionality, treatment response, and illness recovery. With repeated testing, we can also follow the natural course of cognitive abilities over time in individuals with bipolar disorder.

Several cognitive areas are measured using standardized clinical and experimental neuropsychological tests:

• General intellect
• Motor skills
• Attention and concentration
• Higher-level executive skills (e.g., reasoning, problem solving)
• Learning and memory
• Emotional processing skills

Brain functioning can also be measured through electrophysiology, where we measure the levels of electrical activity across the scalp of research participants using electroencephalograms (EEG), while they perform certain cognitive tasks. The goal is to identify electrophysiological markers that can be used for diagnosing or monitoring disease process or treatments. For example, we have shown that the size of certain brain waves differs in individuals with bipolar disorder who have attempted suicide and those who have not. The difference in amplitude of these waves may represent differences in levels of impulse control.

Bipolar disorder runs in families — it is a complex genetic disorder in which the core feature is disturbance in mood ranging from extreme elation, or mania, to severe depression, usually accompanied by disturbances in thinking and behavior. Bipolar disorder, also known as manic depression, is a chronic and devastating psychiatric illness. Its causes are not yet fully understood, but genetic factors are thought to play a large role.

The Prechter Program’s goals are to discover the fundamental biological changes that cause the illness and develop new interventions to treat and prevent bipolar disorder. Researchers do this through the study of the longitudinal course of the illness in people who are diagnosed with bipolar disorder.

The Heinz C. Prechter Bipolar Research Program has one of the nations’ largest databases for bipolar genetics. Investigators are working with research teams on specific studies to collect phenotypic information, or observable traits, and DNA samples from over 1,500 bipolar individuals and control participants.

In March 2014, a team of researchers led by Sue O’Shea, Ph.D., and Melvin McInnis, M.D., published a report of the first stem cell lines (iPSC) generated from patients with bipolar disorder.

K. Sue O’Shea, Ph.D., the Crosby-Kahn Collegiate Professor of Cell and Developmental Biology and director (retired) of the University of Michigan Center for Pluripotent Stem Cell Research, is a leader in research using induced pluripotent stem cells (iPSCs) to model bipolar disorder at the cellular level. Our community’s generous philanthropy has helped Dr. O’Shea recruit some of the best and brightest in the field for this work. These experts changed how we see bipolar disorder.

The O’Shea lab sampled skin tissue from adults living with bipolar disorder and those without. Then, after turning the skin cells to stem cells (iPSCs) in the lab, the team became the first in the world to grow brain cells from these stem cells. This allowed researchers to examine, for the first time, how brain cells derived from people with and without bipolar disorder look and behave when analyzed under a microscope. With donor support, the team was able to dig even deeper and use this “brain in a dish” model to study inhibitory and excitatory neurons and astrocytes, vital support cells in the brain.

A long held theory is that when neurons malfunction, it can contribute to bipolar disorder. In an effort to examine the differences between control neurons and bipolar neurons, the team identified a difference in the respective content of small particles called exosomes, which appear to influence the development and function of neurons. Dr. O’Shea led experiments that introduced bipolar exosomes into the medium populated with iPSC-derived brain cells from control groups. Researchers in O’Shea’s lab demonstrated that the introduced bipolar exosomes caused a reduction of the electrical activity of neurons, indicating that these particles have the potential to be a site of medical intervention, possibly leading to new treatments and a testable biomarker of bipolar disorder.

Dr. O’Shea’s lab has laid the foundation for critical knowledge of bipolar disorder and trained a new generation of thoughtful medical scientists who are tackling some of the most important questions in bipolar and mood disorder research. Dr. O’Shea retired in 2024, but her research has set the stage for work on the next frontier of bipolar cell biology.

Digital Health is a rapidly evolving field, focused on using mobile and wearable devices to improve the diagnosis, management, and prevention of adverse health conditions. The Prechter Program has been conducting research in digital health for bipolar disorder for over a decade. We are focused on using these technologies to identify early warning signs to facilitate timely interventions.

Our collaborations across the University of Michigan with the Computer Science and Engineering Division, Eisenberg Family Depression Center, the Sleep and Circadian Research Lab, Precision Health, e-Health and Artificial Intelligence (e-HAIL), and the Department of Learning Health Sciences strengthen our digital health research initiatives. These partnerships have enabled researchers to develop groundbreaking technology and lead studies looking at how digital health technologies can help improve outcomes in mental health care and treatment. Our Program's long-term goals of digital health research is to provide innovative tools that people living with bipolar disorder can use to help manage their health and well-being.

Prechter Program Digital Health Initiatives include:

• PRIORI (Predicting Individual Outcomes for Rapid Intervention), a proprietary app and set of algorithms that analyze the sound waves of speech patterns and identify changes in a person's speech to predict mood fluctuations. Our most recent study with the app is PRIORI Ambient.
• LifeGoals, a smartphone application that provides a self-paced and comprehensive evidenced-based psychoeducation program for bipolar disorder.
• A comprehensive program of research that uses smartphone and wearable devices to identify early warning signs related to mood, behavior, and sleep and circadian changes in individuals with bipolar disorder.