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Elaine Walker: Confronting the Mysteries of Schizophrenia

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Elaine Walker

Some young people wait tables or work retail part time while they are in college.

Elaine Walker chose to work at an adolescent inpatient unit at a psychiatric hospital. Her work at St. Vincent’s Hospital in St. Louis, Missouri deepened her interest in, and dedication to, patients with some of the most challenging brain dysfunctions.

“It’s always been fascinating to me how psychotic disorders that involve significant impairment in the perception of reality can occur in an individual who, in other domains of functioning, including cognitive domains; is coherent and average or above,” Walker said. 

Elaine Walker is the Charles Howard Candler Professor of Psychology and Neuroscience at Emory University in Atlanta, where she has taught since 1986. She is also Director of the Mental Health and Development Program, which is supported by the National Institute of Mental Health.

One goal of Walker’s research is to help determine why some young people with symptoms develop schizophrenia, while others do not. Prevention is the ultimate goal, but before experts can develop and test prevention strategies, they first have to be able to predict, with a higher level of accuracy, which patients are at greatest risk.

“If we are able to identify up to a level of 75 percent, 80 percent, then we are in a range where we could justify a very intensive and perhaps costly intervention,” said Walker.

But right now, they can only identify about 30 percent of those at highest risk. To help improve that number, Walker and other researchers focus on the prodrome, which are symptoms that may occur prior to the clinical onset of schizophrenia. This time period might be characterized by heightened suspiciousness, but not paranoia. During this critical phase, researchers study patients’ brain development; hormonal development; cognitive development; and sensitivity to stress; anything that might be a predictor of risk.

“About 25-30percent of them go on in a few years to develop psychotic disorders. Fortunately, most of them do not,” said Walker.

Whether that progreession occurs or not, dealing with adolescent mental health issues can be frightening and confusing for both patients and their parents.

“The most frequent concern for parents of our patients is that their child has received different diagnoses over the years, and they are frustrated,” said Walker. “A common scenario is for the patient to be diagnosed with ADHD in childhood, show symptoms of depression and anxiety in early adolescence, and then signs of impending psychotic symptoms in mid- adolescence. The reason for this is not necessarily incorrect diagnosis, but rather a reflection of the dramatic changes that are occurring in the brain as children develop,” said Walker.

She says parents are often reassured when they get this bigger picture of what their teenager is experiencing.

“It often restores their confidence in mental healthcare and prepares them for the behavioral changes they are likely to encounter as the child matures. And fortunately, we can tell them that evidence from scientific research indicates that most youth improve as they enter young adulthood, so there is good reason to be patiently optimistic. They appreciate that message,” she said.

 

CONFRONTING HARMFUL MYTHS ABOUT MENTAL ILLNESS

The complexities of the brain and of mental disorders involve centuries of myths and misconceptions. And while some progress has been made, it was only a few decades ago that “blame” for a child with mental illness was cast on bad parenting, especially shaming mothers.

“That grew largely out of the psychoanalysis movement in psychiatry that dominated the field in 1950s and 60s,” said Walker. “The psychoanalytic conception of psychiatric disorders in general was that they were a function of adverse childhood experiences that produced deficits in psychological development.  And the competing perspective is what is now called biological psychiatry and behavioral psychology and neuroscience,” said Walker.

 Gradually, she said, as scientific evidence accumulated, theories that schizophrenogenic mothers and other notions of bad parenting producing schizophrenia fell by the wayside.

Walker works with a broad spectrum of experts; geneticists, psychiatrists, neurologists, endocrinologists, and neuroscientists to understand psychiatric disorders. Earlier in her career, creativity also played a part in one study that used an unusual tool to gain insight about psychotic patients and their histories. Walker and her team studied family home movies to search for possible clues, perhaps precursors to schizophrenia that may have been evident in body movements and facial expressions. Walker and her colleagues studied movies of individuals whose adult psychiatric outcomes were already known, working backward in time.

“That series of studies we conducted in the late ‘80s and early ‘90s was aimed at determining whether early signs of neuromotor abnormalities might be apparent in individuals who later developed schizophrenia or other psychotic disorders. So because psychotic disorders typically have their onset in adulthood; in order to address questions about  precursors in infancy; we have to be able to access what you might call archival data; at that developmental stage. So utilizing home movies provided us with a source of information, like infant development,” she said.

 

GENE STUDIES AND SCHIZOPHRENIA

While gene therapy and genomics are now critical aspects of many disease treatments, it is just one of a many- pronged approach to detection, treatment, and ultimately prevention of brain disorders.

“There aren’t a whole lot of things we can say with a great deal of certainty about schizophrenia or any form of psychosis, except that there is no single gene for it,” said Walker.

“In fact we can’t even account for the occurrence of psychotic disorders on the basis of combinations of hundreds of genes. So what we do know now, as more and more gene studies have accumulated; is that psychotic disorders, frankly, almost all psychiatric disorders; are so complicated in terms of etiology, that we are unlikely to be able to account for them with even a small number of genes,” said Walker.

Researchers are discovering that often the genetic vulnerability for psychotic disorders, and many other developmental disorders, is a function of spontaneous genetic mutations.  They are not inherited from either parent, and they are not present in any other biological family member. Instead, they arise during the course of the development of germ cells in the zygote, and the fetus.

While genetic mutations are common, and are part of how any species evolve; researchers have learned that there are many ways for those mutations to occur, and many disorders associated with them.There are several genetic mutations that dramatically increase risk for schizophrenia and other psychotic disorders. One is 3q29; another is 22q11.

Walker says studies of these spontaneous mutations have shown that individuals who have them are at increased risk of autism, psychotic disorders, anxiety disorders, and intellectual disabilities.  

Along with her research at Emory, Walker works with eight other sites across the U.S. to identify and study individuals who are showing risk signs for psychosis. This collaborative study, known as NAPLS, the North American Prodrome Longitudinal Studies, is reported to the National Institute of Mental Health. For the past 12 years, this study has made it easier to identify enough young people who are showing risk signs, to have combined sample and statistical power.

Walker shares the fast-paced progress made in her research with postdoctoral fellows, graduate students, and undergraduates. Most of the courses she teaches deal with the psychosocial and neurobiological factors associated with mental illnesses. 

“With advances in neuroimaging, genetics, and the neurobiology of stress exposure, the pace of new discoveries in the field has increased dramatically. There are complex interactions among biological and environmental factors that determine vulnerability. The complexity is daunting for researchers, but it is also encouraging because it suggests there may be a variety of approaches to preventive intervention,” she said.

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