Deanna Barch pinpoints the year after college as her pivotal one. With a bachelor's degree in psychology from Northwestern University in hand, Barch decided to get a feel for patient care by taking a job as a case manager working with the chronically mentally ill in central Chicago.

"It was really emotionally demanding," says Barch, now a professor of psychology, psychiatry, and radiology at Washington University in St. Louis. "It was hard for me to go home and not worry about my clients all night long."

Barch had two epiphanies that year. One was prompted by a patient about Barch's age, 21 or 22. He had attended college for a year before experiencing a psychotic break -- often the first serious sign of schizophrenia, which is almost always a lifelong, debilitating disorder. "It was really clear to me he wasn't going to go back to college," Barch says. "Here I was on the verge of my life, the world was my oyster, and here was this poor guy who had had all the same dreams as me, and it was really clear to me -- though less clear to him -- that he was going to have to give up his dreams."

The other epiphany: Realizing that if she chose to become a full-time therapist, she would only be able to treat a limited number of people, but if she engaged in research, she might eventually help many more.

These realizations "really spurred me on," Barch says. "They made clear the necessity of finding causes and early treatments [for schizophrenia]. And they also made clear that I loved doing clinically oriented research and working with patients, [yet] I didn't want a full-time clinical practice career."

Twenty-three years later, Barch has meshed her clinical experience with a thriving career in basic and translational brain science, most of it focused on schizophrenia. She has 120 publications and some $13 million in former and current grants on her curriculum vitae, including seven R01 awards from the National Institutes of Health. Barch is also the co-principal investigator of an ambitious project sponsored by the National Institute of Mental Health (NIMH) to standardize measurements of cognitive deficits in schizophrenia -- sorely needed benchmarks that, Barch hopes, will soon help speed new drugs and other treatments into the clinic.

Thomas Insel, director of NIMH, says that schizophrenia research desperately needs more cognitive neuroscientists, like Barch, who are grounded in the clinical realities of the illness. "NIMH is very interested in creating a cadre of new scientists, like Deanna, who have a deep understanding of brain and behavior from a basic science perspective but who can also apply those insights to solving an immense public health challenge."

Defining interests

About 1% of people around the world have schizophrenia. Yet the mental illness remains, in many ways, an enigma. For the first century of schizophrenia's existence as a defined clinical disorder, Insel says, researchers focused on the delusions and hallucinations that have become synonymous with "schizophrenia." Indeed, many patients suffer debilitating breaks from reality, a primary symptom that generally first appears in adolescence or early adulthood. They often experience flattened emotions, and suicide is tragically common. Symptoms and responses to drug treatments vary widely.

This is part of an article series for CTSciNet, the Clinical and Translational Science Network, an online community. These articles are published on both Science Careers and within CTSciNet.

Yet, as Barch and a few other researchers made clear about a decade ago, other, more subtle symptoms -- such as deficits in memory, planning, decision-making, and abstract thinking -- play a huge role in keeping adults with schizophrenia socially isolated and unable to work.

Barch first became interested in cognitive deficits in schizophrenia while in graduate school at the University of Illinois, Urbana-Champaign, from which she earned a master's degree and a Ph.D. after leaving her Chicago caseworker job. She tried to develop a test that might predict which children and adolescents were at risk for psychosis or schizophrenia. The test -- based on self-reporting -- didn't pan out, but it sealed Barch's interest in the wide range ofcognitive problems that occur in schizophrenia, such as memory deficits, impaired decision-making, and an inability to anticipate pleasure and other rewards.

She then grew curious about the specific brain problems that cause those deficits and decided to ground herself in cognitive neuroscience. So, for a clinical internship and then a postdoc, Barch headed to the Western Psychiatric Institute and Clinic, part of the University of Pittsburgh, joining the laboratory of Jonathan Cohen, a pioneer in using functional magnetic resonance imaging (fMRI) to study mental illnesses.

Those postdoctoral years were "the best of my life," Barch says. She plunged into the exciting, nascent technology of fMRI, which provides information on the brain in action.

Barch also met her future husband, Todd Braver, in Cohen's laboratory. Barch and Braver began collaborating and continue to do so today. Braver's work skews heavily toward basic neuroscience whereas Barch's work is more applied. "It's very synergistic, in that each of us benefits from the unique skills the other brings to the table," Barch says. "A toast at our wedding was about how we wake up and talk about the prefrontal cortex before breakfast, which is kind of true."

While Barch completed her clinical internship in Pittsburgh, she worked as a therapist with mentally ill patients. But, as she had realized earlier, research was her passion. "We were trying all this new imaging stuff, and I didn't have kids, so I could work as late as I needed to," Barch says. "It was just a really exciting time to be involved in this new technology and new methodology and think about applying it to schizophrenia."

Barch and Braver went on the job market together and landed at Washington University in St. Louis in 1998. The following year, they elucidated a new theory of cognitive deficits in schizophrenia. Supported by imaging studies and computer models, the theory suggested that "noise" in the brain's dopamine system contributed to specific cognitive problems. The publication laid out a clear path connecting a measurable brain defect to a suite of behavioral problems.


(Photos: Washington University in St. Louis)
Deanna Barch (right) discusses brain-imaging techniques used to monitor brain activity in people with schizophrenia.

Developing new tools

The theory presaged a wealth of similar measures that Barch and colleagues continue to refine. To that end, in 2007 NIMH launched Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia (CNTRICS), a broad collaboration of neuroscientists aimed at developing standard tools for tracking cognitive deficits in schizophrenia that are sensitive to small changes in a patient's thinking. The field lacks such measures, Insel says, presenting a barrier to developing new drugs. "It's really hard to demonstrate when treatments are working," he says.

By mid-2011, Barch says, CNTRICS will roll out a bundle of tests that will serve as markers for the disease's progression, drawing on extensive research on healthy and mentally ill individuals. They are designed to be easy for clinicians to deploy. "The hope is some of these measures might be good at predicting who is going to respond to" new treatments, she says. Barch is now working with Washington University's technology transfer office to ensure that the tests are made available to anyone for free, including universities, drug companies, and private foundations.

Barch and Braver also help run an interdisciplinary program that's training a new generation of brain scientists. Called the Cognitive, Computational and Systems Neuroscience Pathway, the program -- and Barch -- drew Ph.D. candidate Alan Anticevic to St. Louis 5 years ago. Anticevic wanted a Ph.D. with a clinical bent, but he wasn't interested in a lengthy M.D./Ph.D. program. Barch's lab turned out to be a "great fit," he says. "It's tricky to find labs that have mentors who are both clinicians and stellar researchers. It's even trickier to find principal investigators versed in imaging and clinical work."

Anticevic says that it's not uncommon to get e-mails from Barch -- a self-described workaholic -- with a 4 a.m. time stamp. Early, early mornings are when Barch carves out protected time for heavy thinking and data analysis, she says.

Such long days are a testament to Barch's commitment to understanding, and treating, mental illness. She says she's proud of many of her accomplishments, but then adds, "To be honest, I'd be lying if I said my research has already improved the lives of patients with schizophrenia. That's the goal. But there's so much we need to know to be able to do that."

Brian Vastag is a science journalist in Washington, D.C.

Brian Vastag is a science journalist in Washington, D.C.

10.1126/science.caredit.a1000063