According to the National Institute of Mental Health, more than 50 million people worldwide are suffering from schizophrenia, a chronic and severe mental disorder. It affects how a person thinks, feels and acts. While antipsychotic medications and psychosocial treatments help with symptoms, they often do not heal patients. The cause of schizophrenia has not yet been identified; however, Auburn University College of Engineering postdoctoral fellow Meredith Reid believes the answers lie within the brain, and she’s using new imaging techniques at Auburn University’s MRI Research Center to help advance the understanding and treatment for this psychiatric disorder.

Reid earned an undergraduate degree in biomedical engineering and Spanish, as well as a master’s degree in biomedical engineering and a doctorate degree in biomedical engineering, all from the University of Alabama at Birmingham. For her graduate studies, she trained in the laboratory of Adrienne Lahti, Patrick H. Linton professor in the Department of Psychiatry and Behavioral Neurobiology at UAB and internationally known expert of using MRIs to study schizophrenia.

“It was perfect timing. I was looking for a project in neuroimaging at the same time Dr. Lahti joined UAB and was looking for students to join her lab,” Reid said.

While at UAB, Reid developed a way to look at how abnormal brain activity is related to abnormal neurochemistry, the complex system that allows neurotransmitters to move information around in the brain. After completing her doctoral work, Reid joined the staff at the Auburn University MRI Research Center. She works under the direction of Thomas Denney, director of the center and professor of electrical and computer engineering, and Jeffrey Katz, professor of psychology in the College of Liberal Arts.

The center houses two of the most powerful research and clinical MRI scanners in the world, in particular a 7 Tesla scanner. Not available on the UAB campus, Auburn’s 7T scanner has exceptional field strength and allows Reid to explore real-time brain function and brain structures in schizophrenia patients at nearly microscopic scales.

“Applying MRI and MRS — magnetic resonance spectroscopy — techniques to brain disorders, such as schizophrenia, is a relatively unexplored and extremely promising research area,” Denney said. “Dr. Reid is pushing the envelope with her work, and we are fortunate to have her as part of the Auburn University MRI Research Center team.”

The symptoms of schizophrenia fall into three broad categories, and most individuals with the disease exhibit all three: positive, negative and cognitive. Positive symptoms, such as hallucinations, are treated with antipsychotic medicines; negative symptoms, which are characterized by a lack of facial expressions and loss of motivation, are not often treated. Cognitive impairments, such as reduced mental function and forgetfulness, are the focus of Reid’s current research.

“Many people with schizophrenia have difficulty holding a job. Medication can help with hearing voices, but not with understanding what your boss asks you to do,” Reid said. “There’s been a bit of a shift to characterize these cognitive deficits; in particular we are seeking novel targets for medication that can help treat those cognitive symptoms.”

Some researchers, according to Reid, have looked at post-mortem brain tissue and have found abnormalities in the neurons of the brain’s cortex. This is in the same prefrontal region that is critical for working memory, or the ability to use information immediately after learning it.

“There’s evidence that there is a structural and functional issue in that brain region,” Reid said. “We know patients with schizophrenia have less activity in their dorsolateral prefrontal cortex during working memory, but we don’t quite understand the neurochemical changes that underlie that loss of function.”
Reid received a three-year F32 grant in late 2015 from the National Institutes of Health to study the root causes of memory problems in patients with schizophrenia. Her research combines functional MRI with MRS.

In the brain, explained Reid, neurons constantly signal as a person engages in activities, from controlling their fingers to typing on a keyboard to cognitive tasks such as remembering a person’s phone number. MRI is a technique for measuring and mapping brain signaling activity and MRS is a test for measuring biochemical changes in the brain that underlie this signaling.

“Neurochemistry is hard to measure because we want to do it non-invasively. This is where functional MRS comes in,” Reid said. “It allows us to look at the chemistry while schizophrenia patients are performing a task and we can see how neurotransmitters, and changes in those neurotransmitters, are linked to the abnormal brain signaling deficits in working memory.”

Two of the main neurotransmitters, which are organic compounds involved in or produced by chemical reactions in the human body, are glutamate and GABA. These are critical for brain function, and when a person’s neurons fire, they release these neurotransmitters.

“The first goal of my project is to test different MRS methods on our scanner to see which one gives us the best measurement of glutamate and GABA, especially glutamate which stimulates the brain and is important for memory formation,” described Reid. “The second step is to use functional MRS to test whether we can see glutamate changes while healthy individuals use their working memory.”
Once the method is in place, the final stage is to test patients by comparing individuals with schizophrenia to a healthy population group.

Reid said she will not only be looking at higher or lower glutamate levels, but also whether glutamate dynamics are different in schizophrenic patients. Ultimately, the goal would be a new target for a new medication that would alleviate the cognitive deficits associated with schizophrenia.

“If we can show this works in schizophrenia, we may be able to extend this research to other disorders such as depression, post-traumatic stress disorder, anxiety and many other applications,” Reid added. “I’m hopeful this work is going to provide researchers with a better understanding of the neurochemistry of these disorders and of the brain in general.”

Sidebar:

Imagine the life of a person who hears voices in their head. They can’t socialize, watch and understand a sporting event or movie, or hold a job. Daily medication allows this person to cook, drive a car, shop for groceries and mow the lawn; however, the chronic illness of schizophrenia won’t allow the individual to lead a normal life, and no cure exists.

Ron Lipham, a 1974 Auburn University electrical engineering alumnus and retired CEO and president of Utility Consultants, and his wife, Lynda, understand the challenges this person faces. Their family member, who they describe as kind, patient and unselfish, struggles daily with this devastating illness.

“Lynda and I want to bring awareness to this disease and are committed to supporting research,” Ron said. “We have an amazing team of engineers at Auburn, and psychiatry experts in schizophrenia at the University of Alabama at Birmingham, who are making significant strides in our underserved region of the country.”

The Tennessee residents have established the Lipham Fund for Excellence in the Samuel Ginn College of Engineering. The five-year fund supports a collaborative research study in schizophrenia with researchers from the Auburn University MRI Research Center and UAB. The study will provide preliminary data of persons who have a high risk of developing schizophrenia.

Schizophrenia is a neurological brain disorder that affects 50 million people worldwide. It affects the way a person thinks, makes decisions and relates to others. Schizophrenia is usually first diagnosed in a person’s late teens or early-to-late 20s. Research has shown one-third of patients identified as “high risk,” because of having a parent with schizophrenia or showing attenuated symptoms of psychosis, will develop a psychotic disorder in the following few months to few years.

“It is important to diagnose and treat schizophrenia as early as possible. The period surrounding the onset of psychosis is believed to be associated with a pathological process affecting brain function with significant loss in social and intellectual abilities,” said Adrienne Lahti, Patrick H. Linton professor in the Department of Psychiatry and Behavioral Neurobiology at UAB and internationally known schizophrenia expert. “The longer the period remains untreated, the worse the subjects’ outcome. Targeted interventions could be developed and early subtle signs of psychosis could be detected and treated to prevent onset or lessen the severity of schizophrenia.”

Lahti’s research has found abnormally high levels of glutamate, a neurotransmitter critical for brain function, in various brain regions of patients with the disease. Researchers at the MRI Research Center are able to use a 7 Tesla scanner, one of only a few scanners in the world with this field strength, to measure glutamate with great precision.

“Once a group of high risk patients has been identified by Dr. Lahti at her clinic, our postdoctoral fellow, Dr. Meredith Reid, will scan these individuals, as well as a healthy control group, and measure glutamate levels and resting state measurements for structural and functional connectivity,” said Tom Denney, professor of electrical and computer engineering and director of the MRI Research Center. “We will scan the same high-risk patients every few months and test whether these measurements can provide markers indexing the probability of patients who may develop schizophrenia.”

The Liphams’ hope their fund will serve as a catalyst for others to help support ongoing schizophrenia research.

“It’s heartbreaking to have a loved one who is so bright and kind, but whose life is greatly diminished by such a debilitating disease,” Lynda said. “Ron and I want to do all we can, particularly if we can help prevent children from developing this disorder.”

Preliminary data from the multi-year pilot study is anticipated to encourage additional sponsorship funding for the recruitment and imaging of additional patients and the continuation of potential targeted interventions.