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Porto, Portugal | September 20-22, 2012
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9
ASSOCIATION STUDY OF THE ESTROGEN RECEPTOR 1
GENE IN EATING DISORDERS
Margarita C.T. Slof-Op ‘t Landt
1,2,3
, Ingrid Meulenbelt
2
, Meike
Bartels
3
, Jouke J. Hottenga
3
, Dorret I. Boomsma
3
, P. Eline
Slagboom
2,4
, Eric F. van Furth
1
1
Center for Eating Disorders Ursula, Leidschendam,
Netherlands,
2
Leiden University Medical Centre, Molecular
Epidemiology Section, Leiden, Netherlands,
3
Dept.
of Biological Psychology, VU University, Amsterdam,
Netherlands,
4
Netherlands Consortium for Healthy Ageing,
Leiden University Medical Center, Leiden, Netherlands
Introduction: The female predominance and pubertal onset of
most eating disorders (ED) are indications that sex hormones
might be involved in the onset of ED. In the current study
we further investigated the reported association between
the estrogen receptor 1 (ESR1) gene and anorexia nervosa
by Versini et al. (2010). Methods: We applied a two-stepped
design. First allele frequencies of 8 ESR1 SNPs of 258
women with an ED from the GenED study (119 AN, 72
BN) and 365 random control women from the Netherlands
Twin Registry (NTR) were compared. Subsequently (trend)
significant associations were tested in a second independent
group for replication. The second group consisted of 262
women with an ED (125 AN) from the GenED study and
1080 random control women from the NTR. Results: The
ESR1 rs3020407 (OR=1.38, 95% CI 1.01-1.87, p=0.04)
and rs726281 (OR=1.34, 95% CI 0.99-1.82, p=0.06) were
associated with anorexia nervosa (AN). We are currently
testing these two SNPs in the second case-control sample.
Conclusions: In the initial study two ESR1 SNPs were
associated with AN, one of these SNPs rs726281 was also
associated with AN in the study by Versini et al. (2010).
We will present the results of the two-stepped case-control
association analyses of the ESR1 gene in ED.
10
White Matter Integrity is Reduced in Bulimia
Nervosa
Guido K.W. Frank
1
, Lisa N. Mettler
1
, Allyson Wood
1
, Megan E.
Shott
1
, Tamara Pryor
2
1
University of Colorado, Anschutz Medical Campus, Aurora,
CO, USA,
2
Eating Disorders Center Denver, Denver, CO, USA
Purpose of the Study:
Altered white matter (WM)
functionality has been reported in anorexia nervosa and this
study was to investigate whether brain WM functionality is
altered in bulimia nervosa (BN).
Method:
Twenty-one control
(CW, mean age 27±7 years) and 19 BN women (mean age
25±5 years) underwent brain diffusion tensor imaging (DTI)
to measure fractional anisotropy (FA; an indication of WM
axon integrity) and the apparent diffusion coefficient (ADC;
reflecting WM cell damage).
Results:
Superior longitudinal
fasciculus, arcuate fasciculus and fornix FA were significantly
reduced in BN. FA values in those regions correlated
negatively with state and trait anxiety in CW. BN ADC values
were increased in fornix, superior fronto-occipital, superior
longitudinal, and inferior fronto-occipital fasciculus, as well
as left cingulum, and were positively related to severity of
BN symptoms and adverse childhood events.
Discussion:
WM integrity is disturbed in BN, including fornix WM axon
abnormalities, as previously reported in anorexia nervosa. BN
behavior and adverse childhood life events seem to be directly
related to WM alterations.
11
HYPERMETHYLATION OF THE GLUCOCORTICOID
RECEPTOR GENE PROMOTER IN BULIMIC WOMEN
WITH AND WITHOUT BORDERLINE PERSONALITY
DISORDER: INDEX OF DYSREGULATION, EXPOSURE TO
CHILDHOOD ABUSE, OR BOTH?
Howard Steiger
1,2,3
, Patricia Groleau
1,2,3
, Benoit Labonte
1,2
,
Gustavo Turecki
1,2
, Ridha Joober
1,2
, Kenneth R Bruce
1,2,3
, Mimi
Israel
1,2,3
1
Douglas Institute, Montreal, QC, Canada,
2
McGill University,
Montreal, QC, Canada,
3
Eating Disorders Program, Douglas
Institute, Montreal, QC, Canada
Introduction.
DNA methylation is thought to serve in the
epigenetic regulation of gene expression, by reducing
DNA accessibility and gene expression. The glucocorticoid
receptor (GR) gene (NR3C1) modulates individual’s
stress responsiveness. Previous studies have associated
methylation of the GR gene with exposure to developmental
stress and such psychopathological manifestations as
Borderline Personality Disorder (BPD).
Method.
We examined
the extent to which GR promoter methylation in women with
Bulimia Nervosa (BN) corresponded to childhood- abuse
exposure or heightened psychopathology—and compared
GR methylation (measured using bisulfite treatment and
EpiTYPER® methods) across 14 women with BN and
BPD, 47 women with BN and no BPD and 30 normal-eater
women.
Results.
We observed a significant site x group
(BN with BPD vs BN no BPD vs normal-eater) interaction
(p <.02) indicating the BN with BPD group to show 1.9%
to 5.5% increases in methylation at specific promoter-
region sites. We also observed a trend towards site x group
interaction for an overall bulimic/nonbulimic distinction (p
<.10), with greater methylation in BN. Parallel effects owing
to childhood abuse were not observed.
Conclusions.
Our
findings suggest that BN, especially when co-occurring
with BPD, coincides with hypermethylation of the GR gene
promoter (implying an epigenetically determined alteration
in GR expression). However, our findings are such as to
imply that hypermethylation corresponds more closely
to psychopathological manifestations in BN than it does
to childhood abuse. We discuss theoretical and clinical
implications of the preceding.
12
Influence of Peers on Disordered Eating
in Women and Men in College and at 10-year
follow-up
Pamela K. Keel
1
, K. Jean Forney
1
, Tiffany A. Brown
1
, Todd F.
Heatherton
2
1
Florida State University, Tallahassee, FL, USA,
2
Dartmouth
College, Hanover, NH, USA
Introduction: Research supports associations between
peer behaviors and disordered eating in late adolescent
and young adult men and women. However, no study has
examined both peer dieting and peer influences on binge
eating as simultaneous predictors of disordered eating nor
has any study examined evidence for their continued effects
over a duration of follow-up in which peer groups change
dramatically. Methods: The current study examined how
college roommates’ dieting and encouragement to binge were
associated with disordered eating levels in 566 women and
232 men when they were in college and at 10-year follow-
up. Data come from a longitudinal epidemiological study with
high retention (79%) of a randomly selected college sample
followed over 10 years. Given that college represents a time
of transition from living with parents to living with peers,
mothers’ and fathers’ frequent dieting also were included in
models. Results: For women, roommate and mom dieting
were significant predictors of both drive for thinness and
bulimia scores in college and at 10-year follow-up. For both
men and women, roommate encouragement to binge was a
significant predictor of drive for thinness and bulimia in college
but not at 10-year follow-up. Conclusions: The enduring
influence of peer dieting over a long duration of follow-up
in women may reflect internalization of the thin ideal and
highlights the potential for peer-led interventions to have long-
term benefits in this group.
PLENARY/ORAL ABSTRACTS