Findings provide preliminary support for our hypothesis that levels of estradiol moderate genetic effects on several types of disordered eating attitudes and behaviors. Using a pilot sample of twins, disordered eating exhibited little-to-no genetic influence in twins with low estradiol levels during puberty, but moderate-to-substantial genetic effects in twins with higher estradiol levels. These effects were present even when controlling for age, BMI, and the physical changes of puberty. Taken together, results provide initial support for a role for estradiol in the genetic diathesis of disordered eating attitudes and behaviors during puberty.
The unique effects of estradiol levels above and beyond the influence of the confounding variables deserves note. These findings suggest that estradiol's effects are unlikely to be artifacts of age, increased body weight, or the physical changes during puberty that have been hypothesized to influence disordered eating risk in girls. Results also indicate that age differences in genetic effects observed previously (i.e., increases in heritability between ages 11 and 14; no changes in heritability from age 14 and on) (Klump et al., in press
, Klump et al., 2000
, Klump et al., 2007b
) may be due to increases in estradiol that characterize puberty and typically occur between the ages of 11 and 14 years (Kaltiala-Heino et al., 2003
Moving forward, it will be important to replicate these findings using larger sample sizes and explore mechanisms underlying estradiol's effects. A critical function of estradiol during development is the regulation of gene transcription within the central nervous system (CNS) (Ostlund et al., 2003b
). When activated by hormone, intracellular steroid hormone receptors act as transcription factors to regulate mRNA expression in neurobiological systems. Increased genetic effects on disordered eating during puberty may therefore result from increases in estradiol and its genomic effects on the structure and/or function of the CNS through the production of neurotransmitters, their receptors, or their signal transduction mechanisms. Animal data show that genes and gonadal hormones influence the pattern and timing of changes in brain structure and function during puberty (Ahmed et al., 2008
, Nunez et al., 2002
, Primus and Kellogg, 1991
, Spear, 2000
, Zehr et al., 2006
). Emerging data suggest that these same effects may be present in humans, as levels of estradiol are inversely correlated with changes in neural structures in girls during puberty, and these neural changes appear to be influenced by genetic factors (Lenroot et al., 2009
, Peper et al., 2009a
, Peper et al., 2009b
). Taken together, data across disparate sources suggest that increases in estradiol during puberty may increase genetic influences on disordered eating through differential organization of neural circuitry underlying risk.
Notably, our findings may appear to conflict with those showing that lower
levels of estradiol are associated with increased levels of binge eating over the course of the menstrual cycle in women with BN (Edler et al., 2007
) and women from the community (Klump et al., 2008
). However, the current study focused on a different level of analysis (i.e., within-twin pair similarity versus within-person associations) than previous work. Thus, the current work examines the potential influence of estradiol on heritability
of disordered eating over puberty whereas previous work has examined the potential influence of estradiol on levels
of disordered eating in adult women. The effects of estradiol on disordered eating may differ by developmental stage, such that inverse phenotypic associations are observed in adulthood, whereas no phenotypic (but significant genetic) associations are present during puberty (Klump and Keel, in preparation
). These differential effects fit nicely with the organizational/activational hypothesis of gonadal hormone action which predict: 1) gonadal hormones organize risk for disordered during puberty through changes in gene transcription and resulting changes in brain structure/function; and 2) these changes organize the brain to respond to circulating levels of hormones in adulthood which activate and/or influence the expression of behavior (Sisk and Zehr, 2005
). When hormone organization/activational effects are present, modest phenotypic associations between gonadal hormones and behavior are observed during puberty, whereas significant phenotypic associations are present in adulthood (Sisk and Zehr, 2005
). This pattern of phenotypic associations fits nicely with that observed for disordered eating and could help explain seemingly disparate findings for estradiol during puberty versus adulthood (Klump and Keel, in preparation
Much more research is needed to confirm and replicate our pilot study results and examine speculative hypotheses regarding mechanisms of estradiol's effects. Ideally, future work would address limitations of our pilot study. Our sample sizes were small and limited our ability to conduct biometric model-fitting to quantify the degree of genetic moderation. We examined a community sample of twins whose findings may not generalize to a clinically diagnosed sample. Given the very low prevalence of AN and BN in pre- and early adolescence (Bulik, 2002), it would be difficult if not impossible to examine our hypotheses in a purely clinical sample of twins. Our sample exhibited a wide range of disordered eating attitudes and behaviors, including clinical levels of these characteristics. Thus, our findings likely speak to the range of disordered eating present in the population at large. Nonetheless, additional work in larger twin samples is needed to determine the generalizability of the findings to AN and BN. Studies in larger sample also may track estradiol's role in moderating genetic effects on disordered eating in specific age groups.
Finally, we collected salivary hormone and disordered eating data on a single day. It is preferable to obtain multiple measures on different days to obtain more stable estimates of these phenotypes, particularly estimates of estradiol levels. Future research should obtain multiple measures of hormones, eating disorder phenotypes (i.e., self-report, interview), and covariates in larger samples of twins to confirm and extend this pilot work.