Emory Report

November 30, 1998

 Volume 51, No. 13

Walker, Plotsky among many seeking to unlock stress' link

Stress has been linked to a number of medical conditions from irritable bowel syndrome to heart disease. Currently, a number of Emory researchers from various departments and disciplines are looking at the biological connection between stress and mental illnesses--especially between schizophrenia and depression.

As Psychology Professor Elaine Walker explained, "stress" is usually defined as "any experience that interferes with the individual's normal psychological or behavioral functioning." Exposure to stressful experiences such as excessive noise or interpersonal conflict can lead to biological responses that can be measured in the individual's heart rate and hormone secretion, Walker said.

Her research focuses on schizophrenia, a serious mental illness that usually begins in late adolescence or early adulthood and is characterized by delusions and thought disorder. "One of the longstanding theories about the etiology of schizophrenia is the diathesis-stress model," she said. This model assumes there is a vulnerability to the disorder present at birth that interacts with environmental stressors in creating the mental illness, she said.

The existence of a genetic component to schizophrenia was established many years ago. Studies of identical twins "have been some of the most revealing," Walker said, but these studies have also shown the importance of environmental factors.

Evidence to support the effects of stress on schizophrenia has been found in the life experiences of people with the disorder, who have been shown to experience a higher rate of environmental stressors prior to episodes of illness.

Walker and her colleagues are investigating the way that stress and biological response to stress might influence the development of schizophrenia among adolescents with schizotypal personality disorder. This syndrome, which involves symptoms similar to those of schizophrenia but not as severe, increases the risk of developing schizophrenia later.

In an initial study two years ago, adolescents with schizotypal personality disorder had higher levels of the neurohormone cortisol than a comparison group, "indicating that they may indeed be more biologically sensitive to stress," Walker said.

A recent follow-up study of the same group revealed that the schizotypal adolescents who showed the highest levels of cortisol in the first assessment were more likely to show a worsening of symptoms, while schizotypal adolescents who showed below average levels of cortisol release showed improvement in their symptoms.

"We also found that the adolescents who showed more minor physical abnormalities--such as unusual, abnormal placement of the ears or asymmetry in the limbs or face--were more likely to show a worsening of symptoms over time," Walker said.

Animal studies by other researchers have shown that when the pregnant mother is exposed to stress, her offspring have more minor physical anomalies, Walker noted. And other researchers found that, among humans, the offspring of women who were exposed to severe stressors during their pregnancy were more likely to develop psychiatric disorders, including schizophrenia.

"It is possible that the minor physical anomalies that have been observed in schizophrenia and in adolescents with schizotypal personality disorder are a manifestation of prenatal events-possibly maternal exposure to stress during the prenatal period," she said. "So it may be that exposure to stress is playing a role in vulnerability to schizophrenia beginning as early as the prenatal period."

Stress and Depression

SmithKline Beecham Professor of Psychiatry and Behavioral Sciences Paul Plotsky and his colleagues also have been studying the relationship between stress and depression, and-like Walker-their work looks at the diathesis-stress model.

Similar to schizophrenia, first episodes of depression usually occur in early adulthood. "One of the areas I'm particularly interested in are kids who have experienced abuse, neglect or medical illnesses and have to be hospitalized--such as premature infants--and whether or not we may be setting up a cycle of vulnerability," Plotsky said.

He is using rats and non-human primates to investigate whether early trauma helps create a vulnerability that could be expressed in later life. Since baby rats are very dependent on their mothers for food and warmth during the first few weeks of life, one experiment assessed the effects of moderate maternal separation for the rat pups by placing them in an incubator for 15-minute or three-hour intervals each day. This was done for two weeks, and then the rat pups were allowed to grow up undisturbed.

As adults the rats that were separated from their mothers for three hours a day showed a depression-like syndrome. They over-responded to emotional stressors, froze in new environments and showed a lack of interest in pleasure rewards.

They also chose alcohol over water, although this strain of rat normally doesn't drink alcohol. "So they have many hallmarks that look like the symptoms we see in humans who are depressed," Plotsky said. And when the brains of these rats were examined, Plotsky said researchers found that many critical neurotransmitter systems in the brain were altered and appeared to be hyperactive.

"We think the early adverse experiences, or the early stress, alters the tone of these systems so that they're supersensitive," Plotsky said. This might make an individual organism-whether rat or human-more susceptible to having depression or anxiety-type disorders, he added.

"We would agree that there's probably a genetic component, but we think that basically these things have to act in concert," he said, noting there must be a genetic vulnerability interacting with early trauma. These two factors give a high level of increased vulnerability, he said, so that if someone encounters even moderately stressful situations later in life, their "likelihood of showing an episode of depression is much higher."

--Linda Klein

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