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Slot
machines
and the cingulate cortex
The neurobiology of pathological
gambling bears striking similarities to that of drug craving.
From the green towers of the
world’s largest casino rising up from the Connecticut farmland to
the smash-hit television program Who Wants to Be a Millionaire,
a culture that promotes and glorifies gambling is all around us.
But until recently, little
has been done to investigate gambling addiction, a significant health
problem that may be as prevalent as some other major psychiatric illnesses
such as schizophrenia, according to Marc N. Potenza, Ph.D. ’93, M.D.
’94, an assistant professor of psychiatry and director of the Problem
Gambling Clinic at Yale.
Research suggests a rise in
the rate of pathological gambling during the explosive growth of legalized
gambling in the United States, which began with state lottery systems
in the 1960s, proliferated with riverboat gambling and casinos on Native
American reservations two decades later, and now continues to expand with
Internet gambling and video poker.
While historically viewed
simply as a sin or vice, pathological gambling has symptoms similar to
those of drug addiction, said Potenza, who is using brain imaging and
drug trials to better understand its causes and to develop more effective
treatments.
“The gambling industry
is huge,” he said. The $51 billion generated from casinos, lotteries
and horse race betting exceeds the revenues of the movie, theme park and
music industries combined. One estimate pegs the societal cost of problem
gambling—including legal fees for divorces and incarceration, as
well as health bills—at $5 billion a year. Potenza believes the price
could run far higher.
While it is estimated that
86 percent of adults have gambled at some point in their lives, fewer
than 10 percent develop a problem and fewer than 3 percent of those become
pathological gamblers, he said. Still, many compulsive gamblers report
devastating troubles—their lives torn apart by bankruptcy, divorce
and criminal activity. About a fifth of pathological gamblers attempt
suicide.
Problem and pathological gamblers,
though, have had few treatment options available. For example, about 85
percent of callers to the Connecticut Council on Problem Gambling’s
hotline reported never having received any prior help for a gambling problem.
Potenza is working to change that.
The Problem Gambling Clinic,
a collaboration between Yale’s Department of Psychiatry and the Connecticut
Mental Heath Center, is one of only four sites in the U.S. to participate
in the first multicenter trial of a drug to treat compulsive gambling.
Initial data from the trial evaluating the effects of paroxetine (Paxil)
are encouraging, said Potenza. He is also using functional magnetic resonance
imaging to monitor the brain activity of both gamblers and healthy subjects
who have viewed videotaped cues intended to spark the urge to gamble.
Only in the pathological gamblers did viewing the cues lead to lower activity
in the anterior cingulate cortex, a brain region which has been repeatedly
implicated in previous studies of drug craving and mood states. While
further study is needed, the neuroimaging study may help identify a possible
intervention point for patients with the addiction.
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Multiple
sclerosis the target of experimental Schwann cell transplant
Physicians and researchers
are hoping that cells from a nerve in a patient’s ankle will stem
the degeneration of the nervous system caused by multiple sclerosis.
In July a Yale team transplanted
Schwann cells from the sural nerve into a patient’s brain in an effort
to reverse the stripping away of myelin, the protective sheath that surrounds
nerve fibers in the spinal cord and brain. It was the first central nervous
system transplantation to repair the myelin-forming cells in a patient
with multiple sclerosis.
“The purpose of this
experiment was to determine whether the procedure is safe and has enough
promise to justify future research,” said Timothy Vollmer, M.D.,
associate professor of neurology and principal investigator on the experiment.
Animal studies have found
that Schwann cells, which make myelin in peripheral nerves, can replace
oligo-dendrocytes, which make myelin in the brain and spinal cord. Vollmer
and his team wanted to determine whether Schwann cells can not only survive
in the human brain, but also wrap myelin around nerve fibers and restore
normal function.
Over two days in July Vollmer’s
team first isolated Schwann cells from the sural nerve in the patient’s
ankle. Then, a neurosurgery team led by Dennis D. Spencer, M.D., HS ’76,
used a magnetic resonance imaging machine to guide a needle through the
patient’s frontal lobe and inject the cells into a previously identified
multiple sclerosis lesion. For the next six months researchers will monitor
the patient with both neuro-imaging and functional assessments. Then surgeons
will perform a biopsy to see whether the cells survived and made myelin.
The team included Jeffrey
D. Kocsis, Ph.D., Stephen G. Waxman, M.D., Ph.D., and others. The research
is funded by The Myelin Project in Washington, D.C.
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Home
monitors deemed inadequate for spotting SIDS
Events that home monitors
routinely detect as warning signs for sudden infant death syndrome (SIDS),
such as a prolonged cessation of breathing or a slow heart rate, may be
common even in healthy infants, according to Yale researchers. “This
study calls into question the utility of home monitoring for SIDS,”
said George Lister, M.D. ’73, HS ’75, professor of pediatrics
and anesthesiology. The findings were published in March in JAMA: The
Journal of the American Medical Association.
A study group made up of physicians
at institutions around the country monitored 1,079 infants, some healthy
and others considered at high risk for SIDS, for periods ranging from
16 to 66 weeks. Infants who were born prematurely, had a sibling who died
of SIDS or had experienced a life-threatening event that required intervention
were classified as high risk. “The threshold for an ‘event’
conventionally used for home monitoring picked up so many infants that
it would be hard to separate those who are normal and not normal,”
said Lister, who chaired the study group. Researchers then used special
monitors to record breathing and heart rate patterns around the time of
an “event.”
The most extreme events, those
that lasted a very long time by usual medical standards, were common only
in infants born prematurely, but occurred before the age when SIDS was
prevalent. The study group concluded, therefore, that extreme events are
not immediate precursors to SIDS. “These early events might be markers
of vulnerability to SIDS,” said Lister, “but are unlikely to
be events that directly evolve into SIDS.”
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Instead
of a needle, simple measurements rule out Down syndrome
Yale researchers have developed
an algorithm that allows physicians to gauge the risk of Down syndrome
in fetuses without resorting to amniocentesis, an invasive procedure that
could cause a miscarriage. Instead, physicians rely on what is called
an ultrasonic biometry algorithm, which measures risk based on a number
of factors, including information gathered by ultrasound—measurements
of the fetus’s upper arm and skin at the back of the neck.
In a study published in the
May issue of the American Journal of Obstetrics and Gynecology,
Ray O. Bahado-Singh, M.D., associate professor of obstetrics and gynecology,
reported that the algorithm proved accurate in almost 80 percent of cases.
Having this assessment allows parents to determine whether to proceed
with amniocentesis.
Down syndrome is a congenital
disorder caused by an extra chromosome 21. Children affected have mild
to moderate mental retardation, shorter stature and flattened facial features.
Women over 35 have a higher risk of giving birth to a child with Down
syndrome, but using age alone physicians detect only about one in five
cases, said co-author Joshua A. Copel, M.D., professor of obstetrics and
gynecology and pediatrics. “Using blood tests and ultrasound we apply
adjustments to the mother’s age-related risk,” Copel said. “This
would mean fewer amniocenteses and a higher percentage of abnormal babies
identified.”
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Pathologists
set new criteria for cancer precursor
Pathologists tracking the
progression of disease from acid reflux to esophageal inflammation to
Barrett’s esophagus, a precursor of cancer, can’t always agree
on how to evaluate biopsies. Now, a national group of gastrointestinal
pathologists founded by a Yale professor has developed new criteria for
grading premalignant changes in cells, also referred to as dysplasia.
Criteria for grading dysplasia
were established in 1988, but still led to inconsistent results among
pathologists. “That grading decision,” said Marie E. Robert,
M.D., associate professor of pathology, “is made by looking through
a microscope at a slide of a biopsy. It is very subjective.”
Using their new criteria,
Robert and 11 other gastrointestinal pathologists found that they agreed
more often on categorizing dysplasia. Among the revisions they suggested
was more attention to the location of atypical cells. Atypical epithelial
cells on the surface of the mucosa are more predictive of future cancer
than cells in the deep mucosa. The new criteria also sought to clarify
the difference between low-grade dysplasia, which requires routine follow-up,
and high-grade dysplasia, which usually prompts surgical resection, Robert
said.
A follow-up study of patients
found a correlation between diagnoses with the new criteria and cancer
risk. “When we modified and discussed the criteria, the risk of developing
cancer went up in a linear fashion, after earlier biopsy diagnoses of
negative, low-grade and high-grade dsyplasia,” Robert said. “That
would argue that our new criteria are valid and can guide clinicians and
patients on how they ought to be followed once these diagnoses are made.”
The Gastrointestinal Pathology
Study Group, which included pathologists from Johns Hopkins University,
the University of Michigan, Vanderbilt University and others, published
their findings in April in Human Pathology.
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Jobs
and brain cancer may be linked
Farm workers, waitresses and
people who work with rubber or cleaning chemicals are at a higher risk
for brain cancer, according to a study by Yale scientists published this
spring in the journal Occupational and Environmental Medicine.
Tongzhang Zheng, Sc.D., associate professor of epidemiology and environmental
health, found that an increased risk of brain cancer was associated with
a variety of jobs involving gasoline, solvents, agriculture, rubber and
plastic production, textiles, electric services, electronic equipment,
plumbing and sheet metal. The higher risk, Zheng said, could be due to
exposure to pesticides, solvents, dyes, metal fumes and other carcinogens.
“More studies are needed, however,” he said, “because it
could also be due to chance.”
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