Brain imaging technologies are helping scientists learn what goes wrong in the brain to produce mental illness. NIMH researchers are using advanced imaging techniques to examine brain function and structure in people with bipolar disorder.

An important area of imaging research focuses on identifying and characterizing neural circuits - networks of interconnected nerve cells in the brain, interactions among which form the basis for normal and abnormal behaviors. Researchers hypothesize that abnormalities in the structure and/or function of certain brain circuits could underlie bipolar and other mood disorders. Better understanding of the neural circuits involved in regulating mood states will influence the development of new and better treatments, and will ultimately aid in diagnosis.

One of the most consistent findings to date has been the appearance of specific abnormalities, or lesions, in the white matter of the brain in patients with bipolar disorder. White matter consists of groups of nerve cell fibers surrounded by fatty sheaths that appear white in color. These sheaths help the transmission of electrical signals within the brain. While the white matter abnormalities appear in many parts of the brain in individuals with bipolar disorder, they tend to be concentrated in areas that are responsible for emotional processing. These brain changes increase in frequency with age both in people with bipolar disorder and individuals with no mental illness, but they appear more often than expected in young patients with bipolar disorder. This finding suggests that the white matter abnormalities seen with MRI are related to the presence of the disorder. However, some patients with bipolar disorder do not show the white matter changes, and conversely, some entirely healthy individuals have the lesions. Also, it is not yet clear whether these changes contribute to the onset of the disorder, or are in some way a result of becoming ill. While these MRI abnormalities likely indicate one type of malfunction in the brain circuits involved in bipolar disorder, more research is clearly needed to understand their significance and their utility for early diagnosis and treatment.

When neurons become more active, their demand for oxygen, delivered via the blood supply, increases. Using a special measurement technique called functional magnetic resonance imaging (fMRI), scientists can measure these changes in blood oxygen levels in different brain areas in healthy people and those with specific brain disorders, including unipolar and bipolar disorder and schizophrenia. This technique provides a powerful tool for understanding how the brains of individuals with mental disorders process information differently from healthy individuals, and for understanding and even predicting how people with these diseases might respond to different types of drug therapy. For example, NIMH supported researchers have studied how brain regions of healthy people and of people with depression respond differently when emotionally evocative pictures are viewed, and how drug treatment changes the response to these pictures in individuals with depression. Modified versions of both the fMRI and PET techniques, which allow scientists to directly study changes in brain chemistry and the activity of specific signaling molecules (neurotransmitters) in both healthy individuals and people with mood disorders, are enabling researchers to better understand the fundamental characteristics of bipolar disorder.

NIMH is dedicated to improving treatments for bipolar disorder and is investing considerable research effort in pursuit of this goal. Although many people with bipolar disorder can be helped by currently available treatments, significant challenges remain. Rapid cycling is a form of the illness that is difficult to manage. Medication side effects are often troublesome and can lead to reduced treatment adherence. Some regimens work well for years and then gradually lose their effectiveness. NIMH researchers are working at multiple levels - from molecular genetics, to neuroimaging, to behavioral science, to clinical trials - to learn what underlies these and other treatment-related problems and to apply this knowledge toward the development of better treatments and enhanced treatment strategies.