"To pull this all together, we need to look beyond nature versus nurture and pay greater attention to gene-environment interplay. Genetics research really enhances our ability to understand the role of environment," Bulik added.
She went on to discuss a new study she and colleagues are starting that builds upon findings from other studies. Some of the findings came from a Swedish study in which investigators used prospectively collected data about pregnancy and perinatal factors to examine the subsequent development of AN (Cnattingius et al., 1999). This population-based, case-control study was nested in cohorts defined by all live-born girls in Sweden from 1973 to 1984. Data from the Swedish Inpatient Register showed that 781 girls, ages 10 to 21, had been discharged from hospitals in Sweden with a main diagnosis of AN. For each case, five controls were randomly selected, individually matched by year and hospital of birth (n=3905). For girls, cephalhematoma (OR, 2.4; 95% CI, 1.4-4.1) and very preterm birth (lesser than or equal to 32 completed gestational weeks) (OR, 3.2; 95% CI, 1.6-6.2) were both associated with increased risk of AN. In very preterm births, girls who were small for gestational age faced higher risks (OR, 5.7; 95% CI, 1.1-28.7) than girls with higher birth weight for gestational age (OR, 2.7; 95% CI, 1.2-5.8).
Other studies have shown, Bulik said, that women with AN, even those who are recovered, continue to maintain a relatively low body weight, their body mass index (BMI) hovering somewhere about a mean of 19.
"Weight gain during pregnancy for these women is difficult and often inadequate. Pregnancy outcome for these women with anorexia nervosa includes preterm birth, low birth weight, prematurity, stillbirths, low Apgar scores and increased rates of cesarean [Goldman and Koren, 2003]," Bulik said. "The outcomes we are seeing in women with anorexia nervosa and a history of anorexia nervosa are consistent with maternal undernutrition in both animal and human studies, making us wonder if these women are malnourished throughout the course of their pregnancies.
"So what we are hypothesizing is a cycle of risk, wherein a mother with anorexia nervosa fails to maintain adequate nutrition throughout her pregnancy, which increases her risk for labor and delivery complications, prematurity and babies who were small for their gestational age. Those factors, themselves, increase the risk of developing anorexia nervosa later in life, so we have a nasty cycle that can perpetuate itself across generations."
Bulik said she and colleagues are planning to start a study in Norway looking at 100,000 births and the risk of eating disorders. "We have extensive nutritional data on the women. We also have fetal ultrasounds, so we can look at growth in utero, and we have pregnancy outcome variables. The children are going to be followed up throughout adulthood, so we are going to be able to look at them through the ages where they are at risk for developing the disorder. But we can also go back and look at the maternal birth records of the moms, to see how many of the babies were premature, small for their gestational age, or other sorts of problems with labor and delivery. It will enable us to explore the cycle of risk across two generations in 100,000 births," she said. "So we are saying that perinatal events are not exclusively environmental, a genetic tendency toward anorexia may influence inadequate weight gain during pregnancy. It also underscores the importance of prenatal monitoring in pregnant women with current or past eating disorders in order to interrupt the cycle of risk."
The Norwegian study, Bulik added, "might really help us unravel that nexus where genes and environment collide."
(The National Institute of Mental Health is sponsoring a multicenter, international study seeking to determine whether a gene or genes might predispose individuals to develop AN. They need families with at least two members who have or had AN and who would be willing to participate. The study involves the completion of interviews, questionnaires and a blood draw. Participants do not need to travel and will be paid upon completion of the study. For more information call 895-3886, e-mail EdResearch@msx.upmc.edu or visit the Web site at www.angenetics.org--Ed.)