HOPE
for new understanding of schizophrenia


Partnerships

A middle-of-the-night phone call from the emergency room is not unusual for Nina Kraguljac, M.D., an assistant professor in the Department of Psychiatry and Behavioral Neurobiology.

What she encounters is often a patient at his or her most vulnerable: one who has presented symptoms of schizophrenia, whose family is worried about the diagnosis and confused about what happens next or whether a normal life will ever be possible.

Kraguljac wants to overcome the stigma of mental illness and to help patients, many of them in their late teens or early 20s, figure out how to get back on track.

“We see better outcomes; we see patients who can go back to school, get jobs, get married and have families,” Kraguljac said. “We’re working on the stigma, even at the healthcare professional level. Schizophrenia does not have to be a death sentence.

“Often, you’re the only one who has hope for them.”

Physicians at UAB call Kraguljac because they know she may want to recruit them for a study in Dr. Adrienne Lahti’s Neuroimaging and Translational Research Laboratory at UAB, which researches patients with schizophrenia and scans their brains before and during treatment. Lahti and Kraguljac credit the collaborative nature of UAB’s medical and academic community with the interest in their study.

“The residents all know about our research and know that patients need to be treated right away and need to be scanned right away,” Kraguljac said.

But their patients are not just research subjects — they are the hope for a breakthrough in understanding schizophrenia, and, perhaps, new treatments one day.

In April, Dr. Lahti’s lab embarked on a new five-year study, funded by a $4 million grant from the National Institute of Mental Health and powered in part by the University’s Cheaha supercomputer, the fastest high-performance computing cluster in Alabama.

The lab uses multi-modal brain imaging techniques — different types of scanning methods such as MRI, PET and spectroscopy — to take pictures of patients’ brains at different positions and different times.

It is important, Lahti said, to scan patients before they begin treatment, so the lab can analyze how treatment affects their brains.

“You don’t know if what you see is what you want to see” unless you have a baseline for the study, she said.

Schizophrenia is a disabling mental disorder; it affects how a person thinks, feels and behaves. The illness affects 1 to 2 percent of the population, with onset most likely in the late teens and early 20s for men and the late 20s to early 30s for women.

Symptoms include hallucinations, delusions, poor executive functioning and memory problems. Scientists believe genetic factors as well as environmental factors — such as exposure to viruses, malnutrition before birth and psychosocial factors — contribute to the disease’s development.

Because schizophrenia is a diverse disorder whose causes are unknown, finding the right treatment is difficult.

The Lahti lab’s goal is to find similarities among brain scans to put patients in subtypes, with the hope that patients in those subgroups could have more individualized treatment.

“We are trying to understand the heterogeneity of the disease,” Lahti said. “We use a large number of techniques to divide them into subgroups.”

 

The lab has collected, as Lahti says, a “humongous” amount of data.

But to do analysis on so much data, a computational expert is needed.

Enter Thomas Anthony, a scientist on UAB IT’s research computing team, who was an investigator on Lahti’s grant application to the NIMH.

Anthony’s experience and the supercomputer’s speed help analyze the brain scans quickly. “What I could do on my own computer would take six and a half years,” Kraguljac said. “For Thomas, it takes about two days. It really changed the way we look at data. It changed the things we can do."

The power of the Cheaha supercomputer, as well as the imaging and clinical facilities at UAB, helped place Lahti’s grant in the first percentile — basically the highest score a grant can achieve from NIMH.

Lahti hopes that after the current grant is complete, she can apply for more funding to continue her work.

“We want to really follow this population over time,” she said. “If at the end of five years we have begun to crack the heterogeneity of schizophrenia, that would be successful. It’s there; it’s in the data. It really needs to be understood.”

Determining subgroups among schizophrenia patients can help determine if new treatments — or existing treatments for other diseases — can help them.

Currently, antipsychotic medications and psychosocial therapy treatments are used to manage and reduce the symptoms of schizophrenia. But Lahti and Kraguljac said new treatments could be found in existing medications.

For example, some patients’ brain scans show inflammation in certain areas. Common medications that reduce inflammation could be used in conjunction with other treatments to help alleviate symptoms.

“In that subset of patients, the scans help us try to visualize the inflammatory process,” Kraguljac said. “Even simple things like an anti-inflammatory agent could be used as part of treatment.”

While the percentage of patients with such inflammation is small, “if you identify that one out of 10 people, you might see very different outcomes,” Kraguljac said.

So brain imaging — and analyzing it with the supercomputer with Anthony’s help — is the first step to separating the subgroups of patients with schizophrenia.

“At the end of the day, we have learned a lot of things,” Lahti said. “Computational psychiatry will increase the speed at which we learn things.”

The doctors say Anthony meets with them regularly — up to three hours a day, three times a week when the study was getting off the ground.

“Thomas is so enthusiastic,” Kraguljac said. “He can talk about (the computations) in a way that we understand.

“The speed of the supercomputer is not the most important thing for us — it’s the people who run it.”

And it is the people who take part in the study whose lives Lahti and Kraguljac and their team are trying to impact — and the lives that will be affected in the future by the disease.

Patients who opt not to take part in the study, or who don’t qualify, often are treated at UAB’s First Episode Clinic, which Lahti founded eight years ago.

Brain imaging helps show patients, and their families, that their disease is not in their imagination.

“This is a real biological thing,” Kraguljac said. “That alleviates some of their worry. Their brain just processes information in a different way.”

Finding the right treatment for patients — especially with early intervention — can help send them back to their lives.

“Often, we are able to get them back on track, to finish their schooling, to get a job that has health insurance to pay for treatment,” Lahti said.

Understanding the diverse nature of schizophrenia through the Lahti lab’s study can help give patients new options for treatment — and a healthy dose of hope.