A Strong Impulse to Help People Who Live with Mental Illness Propels a Diverse Career in Clinical Brain Research

Deanna Barch, Ph.D., a much honored research scientist who now chairs the department of Psychological and Brain Sciences at Washington University in St. Louis, did not take long in life to discover her passion.

A member of the BBRF Scientific Council and the recipient of four grant awards from BBRF, Dr. Barch knew what career path she wanted to follow in her teen years.

In high school, she trained to serve as a peer-counselor so that she could work with fellow students who were having academic, social, or emotional challenges. She had been sensitized by problems encountered by her brother, who had dyslexia. By the time she went to college, at Northwestern University, she knew that she wanted to become a psychologist.

“I didn’t know anything about research, though, until I took abnormal psychology. My professor had a habit of asking students who did well in the class if they were interested in getting involved in her lab, to do research. She asked me; I said yes, and soon after I was hooked.”

After college, Dr. Barch took a gap year—not to travel the world, as many young people do, but with the idea of becoming a case manager for the chronically mentally ill in inner-city Chicago. Her motivation, once again, was to help people in need, and in a very concrete way—“to help them negotiate their lives with the goal of keeping people out of the hospital,” she remembers.

It was in this job in Chicago that the future Dr. Barch—the following year she would enroll at the University of Illinois, Champaign-Urbana, to pursue her doctorate—had an experience that proved pivotal. What really turned her head was “a young client who was pretty much my age who had recently developed schizophrenia. And it really struck me that here was this young gentleman who had just gotten a diagnosis that was disrupting all of his life plans—and here I was, just starting to act on my life plans.

“This poor person who was not responding well to medications could no longer go to school—this is what really convinced me to go to grad school, to get on a research track, and to work on risk factors and causes of mental illness.”

Today, Dr. Barch’s research seeks to determine the cognitive, emotional and neural bases of risk for the development of schizophrenia and depression, with an eye toward developing preventive measures. In particular she has used various kinds of brain imaging, including functional and structural MRI (magnetic resonance imaging), in search of the neural foundations of disturbances in cognitive control and emotional processing.

INSIGHTS ABOUT MOTIVATION

Some of her most interesting recent research has sought to understand what psychologists and psychiatrists call “motivational impairments.” These affect people with a wide variety of diagnoses, from depression and other mood disorders, to psychosis and schizophrenia.

In depression, patients are often observed to suffer from anhedonia. This means they find it difficult, or in some cases all but impossible, to experience pleasure. It is a characteristic symptom of the illness. People who don’t or can’t experience pleasure or joy are not motivated to seek it. This is a symptom, therefore, that seems to feed the depressed state. Overcoming anhedonia is an important goal of treatment for depression.

One crucial insight that Dr. Barch has recently had is being able to distinguish the problem of motivation, or lack of it, in depression, from something that looks a lot like it in schizophrenia (and indeed, is widely assumed to be the same issue.) Sophisticated research tools, including measurement of brain waves via EEG (electroencephalogram) and functional MRI have led Dr. Barch and her colleagues to hypothesize that in psychosis and schizophrenia, motivational issues “may not really be about a reduction in the ability to have moments of enjoyment or pleasure but perhaps more accurately reflect difficulty in planning or anticipating that various activities might be experienced as pleasurable,” she says.

In other words: while on the surface it may look as if someone with schizophrenia has motivational issues that resemble those of anhedonic depressed patients, in fact Dr. Barch’s research leads her to consider that in schizophrenia, the difficulty in getting motivated may be tied directly to the so-called negative symptoms of the illness—to a spectrum of cognitive impairments. That’s what she means when she points to an inability to anticipate a pleasurable experience. In schizophrenia or psychosis, unlike in depression, there is an ability to experience pleasure. The crux of the problem is in being able to seek it— being able to put oneself in a position to actually have the experience.

DEPRESSION IN PRESCHOOLERS?

Another strong research interest of Dr. Barch’s is related to the anhedonia issue in depression. Her master’s thesis in graduate school sought to develop a measure to assess anhedonia in young people. Over the last decade, often in collaborations with her Washington University colleague and fellow BBRF Scientific Council member Joan Luby, M.D., Dr. Barch has helped to shed important new light on the problem of depression in very young children, as young as the age of 3.

Can children be depressed at age 3? Part of the challenge in studying the subject has been longstanding skepticism about whether it is even possible for a child that young to be clinically depressed. “It’s getting to be less of a problem than it used to be,” Dr. Barch says. But the idea “that kids of this age are not cognitively or emotionally able to feel depressed has been clinical lore for a lot of years and it simply isn’t true. Kids are not always able to articulate what their internal emotional states are, but they certainly display behavioral evidence of feeling depressed—not smiling, a lack of joy, expressing guilt, even, sometimes, expressing suicidal ideation.”

She begins her public talks on the subject by first acknowledging the doubts and then trying to dispel them with facts. “First I tell people about the epidemiological literature, which has documented the occurrence of depression as early as age three. Research shows that about 2 percent of very young children are depressed. This is consistent across the U.S. and other countries. We’ve seen it in Europe as well as in the states, and we’ve seen it in multiple samples. This is not a phenomenon, in other words, that a single research group is studying and no one else sees.”

A second persuasive line of evidence of depression in young children emerges from longitudinal studies, which follow children over their development, beginning in the earliest years of life. Children who are diagnosed with depression in the preschool years “are at a much increased risk of continuing to have problems with depression and mental health in general as they get older,” Dr. Barch says. This, despite the common response of skeptics that “they’ll grow out of it.” That can certainly happen, but “it doesn’t seem to be true for the majority of kids who have very early depression,” she adds.

A third line of evidence comes from brain activity and structure in affected preschool children. “We see some of the same differences that we see in school-age children, adolescents, and even adults with depression compared with those who are not depressed. This suggests to us that very early depression is on a continuum with depression that might arise later in life.”

Dr. Barch’s research has done much to establish this third line of evidence. The “differences” vis-à-vis children who are not depressed that she alludes to are of three kinds. One difference is that in preschoolers with depression, the brain structure called the hippocampus is reduced in size. The same reductions are seen in older people with depression, and this is important because the hippocampus plays a critical role in our response to stress.

The second difference arises from measurements of brain activity with EEG and looking at how the brain functions with MRI scanning. These show a very important reduction in the brain responses of very young depressed children to rewarding outcomes. In other words, areas that should be responding are less active in these children. This is also seen in older people with depression.

A third research finding concerns activity in the brain’s amygdala, “a brain region that responds to salient, important outcomes, including negative outcomes,” Dr. Barch explains. “We see that the severity of preschool depression corresponds with increased activity in the amygdala,” a phenomenon, again, that has been noted in older depression patients.

“TIPPING” CHILDREN BACK ONTO A HEALTHY PATH

Dr. Luby, with research help from Dr. Barch, has driven the development of a unique therapy for the youngest patients with depression. Called ParentChild Interaction Therapy-Emotion Development (PCIT-ED), they have demonstrated its effectiveness in several studies in recent years. In a study published in 2018, they successfully tested a “module” added to the therapy called “ED,” for “emotion development.” The therapy trains parents to learn to interact successfully with their young children, effectively teaching the parents to teach their children how to experience emotions successfully—“increasing their experiences of positive emotion and decreasing their experiences of negative emotion,” as Dr. Barch puts it. There are no other empirically proven treatments for young children with depression, the team points out.

In a study published last year in Biological Psychiatry, of 118 children aged 4 to 7 years considered to be at risk for earlyonset depression, Drs. Barch, Luby and colleagues focused on children with mothers who suffered from depression— one of the known risk factors for early depression. They were able to measure a reduction in such children of what they call “event-related potential” (ERP), which translates into their ability to respond to pleasant stimuli. The children were divided into two groups, one of which received 18 weeks of PCIT-ED therapy and the other on a waitlist (they later received it).

At the end of the trial, children who received the therapy showed marked improvement in their neural responses to positive stimuli, compared with those who were on the wait list for the therapy. The team concluded that the ERP measure was able to predict in advance which children would respond to the PCIT-ED therapy. If replicated, this could be a very useful intervention.

Drs. Barch, Luby and team wrote that their findings “are particularly novel, given that they are in very young children.” They expressed their “speculative hope that [brain] plasticity is greater” in very young children, “and

thus the impact [of the treatment] may be more enduring.”

Asked about this, Dr. Barch explained: “If you are 25 years old and have spent the last 15, 20 years experiencing depression on and off, that is likely to have an impact on a lot of important developmental experiences that you may either not have had or experienced in a different way. So when you treat someone for the first time at 25, you’re not only treating experiences that they’re having currently, but you have to deal also with the fact that they may have had years of atypical development because they’re experiencing depression or anxiety or something else. It’s very hard to roll that back and to help people relearn things that they couldn’t because they were experiencing depression.

“On the other hand, if you can catch a young person early and perhaps intervene in a way that means it’s less likely they will continue to experience depression, then it seems to me they’re more likely to have normative developmental experiences that themselves may be promoting healthy brain development and behavior. I always think of this as tipping them back on to a healthier developmental trajectory. That’s why we’re hopeful, if this therapy does indeed have a long-lasting effect.”

Looking at trajectories of development over time is another of Dr. Barch’s research commitments. She is one of the founders and leaders of the NIH’s Adolescent Brain and Cognitive Development (ABCD) study, which has now enrolled over 11,000 youths aged 9–11 with the aim of studying them over the next decade, This relates to still other research projects she’s part of, which study how the brain develops during childhood and on how circumstances of adversity, such as poverty, stress, and access to healthcare, influence mental health outcomes.

— Written By Peter Tarr

Click here to read the Brain & Behavior Magazine's March 2020 issue

Deanna Barch, Ph.D.

Chair and Professor of Psychological & Brain Sciences

Professor of Radiology

Gregory B. Couch Professor of Psychiatry

Washington University, St. Louis

BBRF Scientific Council Member

2013 Distinguished Investigator

2006 Independent Investigator

2000, 1995 Young Investigator