Bipolar4LifeSupport

From The Quarterly, Spring 2015

When people with bipolar disorder experience depressive episodes, the reward circuits in their brains show impairments similar to those that affect people diagnosed with major depressive disorder (MDD), scientists reported March 13th in the journal Neuropsychopharmacology. When these circuits are weakened, people’s ability to experience pleasure diminishes.

Most clinical studies exploring how depression affects the brain have focused on people with MDD. Because patients with the two disorders may respond differently to antidepressant medications, it’s important to understand the neurobiology of both groups in order to develop effective treatments.

In patients with bipolar disorder and major depressive disorder, connections between different reward processing regions of the brain were weaker than they were in people without depression. This weakening was greater in patients with more severe depression in both groups.

The scientists did find differences between the two groups of depressed patients. Winning money activated a reward center––the ventral striatum––more strongly in patients with bipolar disorder than it did in those with major depressive disorder. And the strength of certain circuit connections was stronger in patients with bipolar disorder than it was in patients with major depressive disorder. These differences might reflect the two groups’ different risks for manic episodes, during which reward responses appear to be heightened rather than dampened, the scientists say.

Why is it so important to distinguish among brain responses to reward? First, symptoms of depression–– which may be more linked to reward-system dysfunction such as loss of pleasure––tend to be less responsive to standard treatments. “Attenuated reward system response may therefore evolve to be a useful biomarker in drug discovery and clinical trials for mood disorders,” Dr. Satterthwaite says. Second, because many people with bipolar disorder first seek clinical help during depressive episodes, identifying differences between bipolar disorder and major depressive disorder could help ensure patients are accurately diagnosed from the start and receive treatment specifically designed to relieve their symptoms.

*Additional Foundation-funded team members: Claudia F. Baldassano, M.D., 2003 Young Investigator (YI) Yvette I. Sheline, M.D., 1998 YI, 2002 and 2005 Independent Investigator; Scientific Council (SC) Member Ruben C. Gur, Ph.D., 2007 Distinguished Investigator (DI) Raquel E. Gur, M.D., 1999 DI Ellen Leibenluft, M.D., SC Member

Researchers have identified several sets of genes linked with abnormal brainwave patterns in people with schizophrenia and psychotic bipolar disorder (PBD). The results reported June 23rd in Translational Psychiatry can help experts learn more about the genetic changes that underlie these disorders and determine whether the same sets of genes are involved in each.

The research was led by Balaji Narayanan, Ph.D., of Olin Neuropsychiatry Research Center, Hartford Hospital, and Yale University, and Godfrey D. Pearlson, M.D., also of Olin Neuropsychiatry Research Center and Yale University. Dr. Pearlson is a Foundation Scientific Council member and a 2000 recipient of a NARSAD Distinguished Investigator grant.

Brainwaves—sometimes called oscillations—are different frequencies of electrical activity in neurons that are related to specific functions in the brain. For instance, theta brainwaves represent learning and memory activity, delta brainwaves are linked to the body’s metabolism, and alpha brainwaves reflect the brain’s “idling” mode. Scientists measure brainwaves with an electroencephalogram or EEG, a technology that records electrical activity using sensors on the scalp.

Earlier studies have shown that people with schizophrenia and PBD have abnormalities in some of these brainwaves, and that these are also found in some of their relatives. To learn more about what causes these abnormalities, Dr. Pearlson and his colleagues compared EEG data and genetic material taken from blood samples of 105 people with schizophrenia, 145 people with PBD, and 56 healthy people. Participants were drawn from the multi-site BSNIP (Bipolar-Schizophrenia Network on Intermediate Phenotypes) study. The team analyzed these data to find out if certain groups of genes were linked to abnormal brainwave patterns.

The researchers uncovered abnormal theta and delta brainwaves in the schizophrenia and PBD patients, although the theta pattern was different in the two disorders. These theta and delta abnormalities were linked with sets of genes that help build new connections between brain cells and control communication pathways between these cells.

The study gives researchers some new leads to follow in understanding the underlying genetics of these disorders. But Dr. Pearlson and colleagues caution that other factors might influence the connection between genes and brainwave patterns, including how severe a patient’s condition might be, and whether he or she is taking antipsychotic medication.

Other team members include Carol A. Tamminga, M.D., a Scientific Council member who received the Distinguished Investigator grant in 1998 and 2010; 1997 Independent Investigator recipients John A. Sweeney, Ph.D. and Matcheri S. Keshavan, M.D.; Brett A. Clementz, Ph.D., a 2000 NARSAD Independent Investigator grant recipient; and Vince D. Calhoun, Ph.D., a 2004 NARSAD Young Investigator recipient.