Understanding Cognitive Impairments in Bipolar Disorder and Psychosis

For more than a century, psychiatrists have known that neurocognitive impairments exist in patients with schizophrenia. However, only very recently have researchers learned that these deficits—which affect attention, memory, and executive functioning —are also present in patients with bipolar disorder (BPD) and psychosis.

Katherine Burdick, PhD, Associate Professor of Psychiatry and Neuroscience and Chief of Neuropsychology Research at the Icahn School of Medicine at Mount Sinai, was among the first scientists to begin studying neuropsychological dysfunction in BPD. Her research has shown that impairments in attention, verbal learning, and executive functioning are in fact key features of both BPD and schizophrenia. At Mount Sinai, her laboratory focuses on understanding the genetic mechanisms and environmental factors that contribute to the development of cognitive deficits in BPD and schizophrenia as well as other psychotic disorders. She is also testing novel therapies that may improve such impairments.

“Neurocognitive impairment is a fundamental yet often under-recognized feature of BPD,” says Dr. Burdick. “As a result, many patients become disabled and are unable to work or perform activities of daily living. Our goal is to understand the clinical, genetic, and environmental factors that are related to cognitive impairment, to characterize this impairment, and ultimately to improve neuropsychological functioning in these patients.”

One area that Dr. Burdick is exploring is the frequency of neurocognitive impairment in BPD. Research shows that approximately 90 percent of schizophrenic patients suffer from cognitive deficits compared to only 40 to 60 percent of BPD patients. Understanding why certain patients develop significant cognitive difficulties while others do not is critical in optimizing patients’ quality of life, she says.

Recently, Dr. Burdick was awarded an R01 grant from the National Institute of Mental Health (NIMH) to study the predictors of cognitive impairment in 350 bipolar patients. In addition to testing for the severity of neurocognitive impairment, her team will attempt to determine the clinical and biological predictors of cognitive impairment in BPD by incorporating several novel measures such as sleep quality measures, tasks of affective processing, and markers of inflammation in the blood. The study will also explore the relationship between neurocognitive impairment and functional disability in the areas of independent living, occupational status, and social functioning in the community.

Dr. Burdick’s research also extends, more broadly, to patients suffering from psychosis. As part of a recent VA Merit award to be conducted at the James J. Peters VA Medical Center in the Bronx, her team will study 300 veterans with psychosis to determine what causes cognitive deficits. The study will also try to identify biological moderators of neurocognitive impairment by performing genetic modeling using DNA. Since the veteran population has additional environmental factors at play including trauma and substance use, her team hypothesizes that the etiology of the cognitive dysfunction may be multi-factorial.

“Psychotic illnesses represent a major economic burden to the VA Health System and significantly reduces the quality of life for the individual with exceedingly high rates of functional disability,” explains Dr. Burdick. “Optimizing care for these patients is of critical importance.”

In another study, recently funded as an R34 by the NIMH, Dr. Burdick is attempting to treat the cognitive problems that are found in patients with BPD using the drug modafinil—a psychostimulant that treats daytime sleepiness and promotes alertness. Sleep abnormalities are found in more than 90 percent of patients with BPD, even during periods of relative affective remission. As a result, daytime sleepiness may contribute to deficits in attention, memory, and executive functioning even when patients are stable. Forty-eight patients with BPD that are not experiencing acute symptoms will receive either modafinil or a placebo for a period of eight weeks. Dr. Burdick and her colleagues will evaluate the effects of the drug on measures of sleep quality, daytime wakefulness, and neurocognition. Cognitive functioning will be assessed using the MATRICS Consensus Cognitive Battery supplemented by several domain-specific tasks at the beginning, middle, and end of the study.

“This study represents one of the first controlled trials targeting these deficits in BPD,” says Dr. Burdick. “Our goal is to identify a novel approach for treating persistent symptoms of bipolar disorder that are not adequately addressed with current mood stabilizing agents. We hope this drug may result in a more complete recovery for patients and significantly improve day-to-day cognitive functioning.”