The Psychiatric Scars of Childhood Trauma

Dolores Malaspina, MD, MSPH

Professor of Psychiatry, Columbia University College of Physicians and Surgeons, Director, Medical Genetics, New York State Psychiatric Institute

This interview was conducted by Norman Sussman on April 26, 2006.

Dr. Malaspina, a distinguished fellow of the American Psychiatric Association with over 150 scientific papers to her name, is at the forefront of research on the neurobiology and heterogeneity of schizophrenia, and is particularly interested in the effects of early stress and trauma on the etiology of psychiatric disease. Her interest in stress sensitivity started, however, before she even went to medical school.

“I was working in the pharmaceutical industry,” she explains. “At that time, we were culturing rat pituitary cells to use for dopamine receptor studies. I had the unpleasant job of picking up and handling the adult rats the day before the study. We thought that this handling would reduce their stress responses on the study day. It probably had little effect, but I became interested in how experiences could lead to later changes in stress sensitivity.”

Dr. Malaspina was able to incorporate her interest into schizophrenia research by probing the common idea that schizophrenia results from an interaction between a genetic diathesis and a “stressor.” “For a number of years, my group has studied the hypothesis that early life events and stress sensitization could trigger the illness in some individuals.”

Prenatal Stress Exposure

“Severe prenatal adversity could cause schizophrenia, even though the disease does not present until late adolescence or early adulthood,” Dr. Malaspina says. “Perhaps the best known evidence for this is the much higher risk for schizophrenia among the Dutch population who were exposed to severe nutritional deprivation in early pregnancy during the Dutch Famine Winter of 1944–1945, compared to those who were not exposed to the famine. This was one of the first direct demonstrations that an environmental stressor occurring during early gestation could increase the risk for schizophrenia.”

Famine is one kind of adversity, but many other fetal exposures are also linked to schizophrenia. These include maternal infections, medical conditions, maternal obesity, and maternal malnutrition. Pregnant women who are obese, starved, or have severe prenatal stress exposure all have an elevation of their glucocorticoids.

“It may be,” Dr. Malaspina says, “that elevated stress hormones are a final common pathway for schizophrenia from an array of different prenatal problems. The stress hormones of the mother in early pregnancy can determine gestation length. If it is an adverse time for a mother to be pregnant, it benefits the fetus and the mother if the birth occurs sooner. In an effort to have the baby develop as quickly as possible, fewer cells may be generated in the fetus, resulting in perhaps fewer neurons.”

The stress can also program fetal gene expression in the hypothalamic pituitary adrenal axis to increase life-long stress sensitivity. Another view of these events is that the developing fetus receives a signal from the mother that the world into which it will be born is likely to be adverse, and it adapts accordingly. For humans, having a high stress response is not particularly beneficial in our world where most stress is psychosocial and persistent. But in other mammals, and perhaps at other times in human evolution, if an offspring was born into a dangerous world, increased stress sensitivity might enhance its ability to survive. For contemporary humans, that stress sensitivity also increases the risk for cardiovascular disease, diabetes, hypertension, and abdominal obesity.

“While we see these as signs of disease risk,” Dr. Malaspina says, “those same physiologic adaptations may have helped early humans survive a time of famine, adversity, predation, or other hardships.”

To better understand the effects stress experienced by pregnant women will later have on their children, Dr. Malaspina and colleagues have been studying the 1967 Six Day War in Israel.

“We are examining data collected on 100,000 pregnancies in Jerusalem between 1966–1974. At that time, Israel was a young nation trying to understand its health needs. Information was collected in early pregnancy and ratings were done of each baby’s health at delivery and during the first few years of life. Many years later, without revealing any individual identifying information, researchers in the Ministry of Health linked the birth cohort to the psychiatric registry.”

An analysis of this data indicates that schizophrenia was significantly overrepresented in the offspring of mothers who were exposed to war stress during their first trimester The risk was up to four times as high for female babies, and was dramatically increased for babies of mothers who lived in the areas that received direct shelling.

Dr. Malaspina would also like to determine the implications of lesser amounts of stress on the health of offspring.

“Schizophrenia may be one extreme end,” she says. “However, prenatal stress may effect those who do not have schizophrenia vulnerability genes quite differently. The prenatal stress exposure increases one’s sensitivity to stress and that may or may not lead to the development of a psychiatric disease, depending upon the environment that someone is exposed to during his or her lifetime.”

Interventions

In Dr. Malaspina’s opinion, there is currently no convincing evidence that using antipsychotic medications in people who are not yet psychotic improves their outcome.

“My colleagues and I are trying to better understand what moves someone from simply being vulnerable to actually having psychosis. Once we do, we might be able to offer some lifestyle changes and other interventions that can benefit individuals at risk for psychosis.”

Conclusion

“For a time,” Dr. Malaspina says, “there was a diminished interest in the role of stress in human psychiatric diseases; stress was considered to be too ubiquitous to explain these conditions. Now, we understand that the programming of the stress response system and exposures to stressors can interact with other disease risk factors. I recall a grant critique not that many years ago that commented to me that looking at a role for stress in explaining some of the deterioration of schizophrenia was old fashioned. We had lost our way for a while by thinking that stress is so common that it could not possibly be linked to human psychiatric disorders.” Dr. Malaspina has helped put the psychiatric community back on track in this regard, and her ongoing research continues to chart the complex and powerful relationship between stress and psychiatric illness.

Disclosure: Dr. Malaspina reports no affiliation with or financial interest in any organization that may pose a conflict of interest.