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Buffalo Physician
Winter 2009
39
Buffalo Physician
Winter 2009
oreover, the research-
ers have shown
for the
first time that the metabolic
programming occurs in the
fetal hypothalamus, the area of
the brain responsible for maintaining the
body’s energy homeostasis (body weight)
throughout life.
Levels of the hormones insulin and
leptin also were elevated in fetuses of these
obese mother rats, abnormalities that have
been correlated with increased appetite
and insulin resistance (a prelude to diabe-
tes), as well as obesity and hypertension.
“Our earlier studies looked at newborn
rats of the obese mothers in the post-
weaning period, so we didn’t know how
early this programming occurred,” says
Mulchand Patel, PhD, UB Distinguished
Professor of Biochemistry and senior
author on the study. “Now we know it
occurs in utero and specifically in the
hypothalamus.
“While these studies were done with
rats, there is good reason to think the
mechanism would be similar in humans,”
he says. “The fact that more than one-
third of women of child-bearing age in the
United States are expected to be over-
weight or obese during pregnancy, based
on a 2003 study, does not portend well for
good health of their offspring.”
The new findings were published in
the October 2008 issue of the American
Journal of Physiology, Endocrinology and
Metabolism. Malathi Srinivasan, PhD,
research scientist in the UB Department
of Biochemistry, is first author.
ship at Western Psychiatric Institute and
Clinic in Pittsburgh, Pennsylvania, is first
author of the study, which was published
in the October 2008 issue of the Journal of
Consulting and Clinical Psychology.
Additional findings from a subset
of divorced couples with children with
ADHD showed that several characteristics
within the family contribute individu-
ally to the risk of divorce: age of the child
when diagnosed; race and ethnicity of the
parents; severity of coexisting disorders in
children with ADHD, such as opposition-
al-defiant disorder (ODD) and conduct
disorder (CD); education levels of the
parents; and a father’s antisocial behavior
(trouble with the law).
“We believe this is the first study to
find that both parent and child factors
individually predict the rate and time of
divorce,” says Pelham. “Moreover, this is
the only study to demonstrate that the
severity of the child’s disruptive behav-
ior, specifically those with ODD or CD,
increases the risk of divorce.
“Certainly we are not suggesting that
having a child with ADHD is the
only reason these marriages
end in divorce,” he adds.
“Disruptive child behavior
likely interacts over time
with other existing stress
in the family to spark
conflict in a marriage and,
ultimately, divorce.”
Wymbs’ research documents
that when parents interact
with an ADHD child, they
are more distressed, argue
with one another more and
view one another as less sup-
portive as compared to when
they interact with a child
without ADHD.
Data for the study was
gathered from a subset of
oreover, among couples in the
study who were divorced, marriages
involving children with ADHD
ended sooner than marriages with
no ADHD-diagnosed children.
William E. Pelham Jr., PhD, UB Dis-
tinguished Professor of Psychology and
Pediatrics and director of UB’s Center for
Children and Families, is senior author on
the study, which is the first to look at this
issue in depth. Pelham is known inter-
nationally for his ADHD treatment and
research and each year conducts UB’s
Summer Treatment Program, a highly
successful behavior-modification program
that has helped hundreds of children with
ADHD and has been replicated nationwide.
Brian T. Wymbs, PhD, who received
his doctorate in clinical psychology at UB
and is completing a postdoctoral fellow-
participants in a larger investigation
called the Pittsburgh ADHD Longitu-
dinal Study (PALS), which is funded by
grants from the National Institute on
Alcohol Abuse and Alcoholism and the
National Institute on Drug Abuse to Pel-
ham and Brooke Molina, PhD, from the
University of Pittsburgh.
Results showed that 22.7 percent of
parents of children with ADHD had
divorced by the time the child was eight
years old, compared to 12.6 percent of
parents in the control group. Divorce
rates of parents with and without chil-
dren with ADHD were not significantly
different after children passed the eight-
year mark.
“Families that ‘survive’ through that
age, perhaps because they are low on all
of the risk factors, apparently will make it
through the rest of the child’s childhood,”
Pelham notes.
Of the characteristics that may con-
tribute to risk of divorce, a father’s
antisocial behavior proved to be
the largest factor.
BP
Metabolic programming,
sometimes called dietary pattern-
ing, isn’t a new phenomenon, Patel notes.
“Epidemiologic studies of malnourished
mothers showed that their babies often
were underweight and at increased risk
for several chronic diseases as adults.
Animal studies on maternal protein mal-
nourishment or caloric restriction have
shown that pre- and immediate postnatal
nutritional modifications have long-term
consequences on adult-onset diseases.”
Patel and colleagues are pioneers in the
investigation of metabolic programming
effects when the composition of the diet is
manipulated—changing the percentages
of carbohydrates and fat, while keeping
calories constant.
Patel reported evidence of metabolic
programming in 2002, when his labora-
tory showed that in rats, consumption of
a milk formula high in carbohydrates dur-
ing the critical early weeks of postnatal life
caused permanent changes in pancreatic
islets, leading to overproduction of insulin
and development of obesity in adulthood.
“Metabolic signals are reset in response
to a high carbohydrate milk formula
given to newborn rats during the suckling
period, which induces permanent changes
at the molecular level in our rat model,”
Patel explains. “The HC [high carbohy-
drate] phenotype is maintained for life
and is spontaneously transmitted to suc-
ceeding generations.”
Unlike many models investigating the
role of maternal obesity on their off-
spring, the mother rats used in this study
consumed normal laboratory chow during
pregnancy, Patel points out.
“Our findings that malprogramming
effects induced during fetal development
in the altered intrauterine environment in
obese mother rats predispose the offspring
for adult-onset obesity underscore the
importance of women maintaining opti-
mal conditions during their pregnancies,”
concludes Patel.
Additional contributors to the study
from the School of Medicine and Biomed-
ical Sciences were Catherine Dobbs and
Tao Gao, in the Department of Biochemis-
try; Hasam Ghanim and Paresh Dandona,
in the Department of Medicine; and Peter
J. Ross and Richard W. Browne, in the UB
Department of Biotechnical and Clinical
Laboratory Sciences.
Ghanim and Dandona also are affiliated
with Kaleida Health’s Diabetes and Endo-
crinology Center of Western New York.
Patel’s research is supported in part
by grants from the National Institutes
of Health.
BP
A Factor
in Divorce
Parents of a child with
attention deficit hyperac-
tivity disorder (ADHD)
are nearly twice as likely
to divorce by the time the
child is eight years old
than parents of children
without ADHD, accord-
ing to a study conducted
by UB researchers.
Our earlier studies looked at
newborn rats of the obese mothers
in the post-weaning period, so we
didn’t know how early this pro-
gramming occurred. Now we know
it occurs in utero and speci-
fically in the hypothalamus.
—Mulchand Patel, PhD
Obesity from the Outset
Laboratory study shows obesity programmed in utero
Researchers in the School of Medicine and
Biomedical Sciences have found that fetuses of
obese mother rats were programmed in utero to
develop obesity in adulthood.
M
M
By
Lois
Baker
Research News
By
Lois
Baker
To learn more about this study,
its methodology and findings,
visit the UB NewsCenter web-
site at www.buffalo.edu/news
and search “ADHD.”
Additional researchers on the
study were Elizabeth M. Gnagy
from UB, Brooke Molina
and Tracey Wilson from the
University of Pittsburgh, and
Joel Greenhouse from Carnegie
Mellon University.
