Michael Minzenberg, a UC Davis psychiatry researcher, has been awarded a prestigious three-year, $200,000 seed grant from the Dana Foundation to study the brains of patients being treated for schizophrenia to determine how additional treatment to improve cognition interacts with antipsychotic medication.
"Cognition is very important in schizophrenia because it is a strong predictor of outcome. It determines whether a person can be a contributing member of a community, stay out of the hospital and live independently," said Minzenberg, associate professor in the Department of Psychiatry and Behavioral Sciences and a faculty member of the UC Davis Imaging Research Center.
Schizophrenia is chronic mental disorder characterized by decline in thought processes and loss of emotional responsiveness. It affects 3.2 million Americans, the majority of whom are not receiving treatment. It can lead to auditory hallucinations, paranoia and delusions.
Despite the importance of cognition in the rehabilitation of those with schizophrenia, there are no U.S. Food and Drug Administration (FDA)-approved drugs for the improvement of cognition in this patient population.
"Dr. Minzenberg is at the forefront of trying to develop therapies for impaired cognition in schizophrenia, using powerful new non-invasive brain imaging to measure the effects of drugs and other treatments on functional networks in the brain," said Cameron Carter, director of the Center for Neuroscience and the Imaging Research Center at UC Davis.
"His work is suggesting that some of the other medications that patients are taking may interfere with the procognitive effects of some of the newer more promising therapies. If this proves to be true then it will be important to 'fine tune' patients' medications to optimize cognitive outcomes in people with schizophrenia and other brain disorders."
Modafinil is a drug approved by the FDA for the treatment of narcolepsy. It is also known by the brand name Provigil©. Narcolepsy is a chronic neurological disease characterized by sudden urges to sleep, episodes of loss of voluntary muscle tone, vivid dreams while falling asleep or upon awakening, and brief episodes of total paralysis while waking up from sleep. Both genetic and environmental factors appear to contribute to narcolepsy. Although no cure exists, medications can often help restore a patient's quality of life.
Like other stimulants, Modafinil's side effects are relatively mild. It is used off-label to combat the effects of sedatives. Currently, it is not prescribed on a long-term basis to schizophrenia patients.
However, Minzenberg and his colleagues conducted a small, unpublished pilot study that showed Modafinil can improve cognition in patients being treated for schizophrenia.
"What we understand about how Modafinil works in the brain leads us to believe that it might be good for improving cognition deficits of our patients," Minzenberg said.
Because the cause of schizophrenia is unknown, treatment focuses on eliminating symptoms. Antipsychotic drugs are effective at reducing its most serious symptoms: delusions and hallucinations. Any treatment to improve cognition cannot interact with these drugs in a negative way.
"The use of antipsychotic medications is the standard of care in patients with schizophrenia. So, before we can move forward with a large clinical trial involving Modafinil's impact on cognition, we need to know how it interacts with these drugs."
Cognition refers to a range of high-level brain functions, including the abilities to learn, remember information, organize, plan, problem-solve and understand and use language. It is thought to be controlled by an area of the brain called the locus coeruleus, which controls the body's physiological responses to stress and panic, commonly referred to as the "fight or flight" response.
"This area of the brain also serves to coordinate activity in the entire brain as it performs almost any type of task or behavior," Minzenberg said.
Minzenberg and his colleagues will conduct the study at the UC Davis Early Diagnosis and Preventive Treatment of Psychosis (EDAPT) Clinic. Researchers will enroll 60 patients newly diagnosed with schizophrenia. These patients will have a specialized brain scan performed, called functional magnetic resonance imaging or fMRI, and will be randomly assigned to an FDA-approved treatment for schizophrenia.
After eight weeks of treatment, another fMRI scan will be conducted. The patients, who also will have been assigned to either a control or study group, will undergo a third scan while performing a cognitive task.
Functional magnetic resonance imaging allows researchers to see changes in blood flow related to neural activity. Minzenberg and his colleagues will examine whether patients being treated with Modafinil perform better or worse, as measured by the changes in activity in locus coeruleus, depending on which antipsychotic medication they receive.
"We are hoping to find evidence that using Modafinil we can improve brain function in stable schizophrenia patients," Minzenberg said.
The New York-based Dana Foundation is a private philanthropic organization that supports clinical research in neuroscience and neuroimmunology and their interrelationship in human health and disease. For further information, visit www.dana.org.