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Imaging study finds a structural difference
in the brains of cocaine addicts
Structure involved with motivation
and reward is smaller, could reflect impaired judgement
BOSTON - November 17, 2004 - A team led by researchers from
Massachusetts General Hospital (MGH) has used advanced imaging techniques
to identify an unexpected structural difference in the brains of
cocaine addicts. The report in the Nov. 18 issue of Neuron
describes how a key structure called the amygdala, which previous
research has linked to the brain's reward-processing system, is
smaller in cocaine addicts than in healthy volunteers. While the
current study cannot determine whether this difference is a cause
of addiction or results from an early event in the course of drug
use, the findings suggest a need to reformulate current strategies
for treating cocaine addiction.
"Work here and at other centers has identified the amygdala's
fundamental role in addiction. It is important for producing drug
craving, which has a powerful effect in maintaining drug abuse,"
says Hans Breiter, MD, co-director of the Motivation and Emotion
Neuroscience Collaboration in the MGH Departments of Radiology and
Psychiatry, and a senior author of the current study. "No one
anticipated such a specific pattern of volume reduction in the amygdalas
of cocaine addicts - pointing to potential problems in a small number
of sub-regions of this brain structure."
Earlier
studies by Breiter's group and others used advanced imaging
techniques to show how cocaine use affects the activity of key structures
deep within the brain. Among those findings was reduced activity
in the amygdala, particularly during times when addicts reported
feelings of craving. In the few previous studies that examined brain
structure in cocaine addicts, abnormalities were found only in regions
connected to the amygdala. Pursuing those observations, the researchers
sought to discover whether structural abnormalities would be found
in the amygdala itself that could reflect either vulnerability to
cocaine addiction or changes caused by drug use.
Researchers at the Center for Morphometric Analysis at the Martinos
Center for Biomedical Imaging used newly developed imaging and
anatomical techniques to produce extremely detailed information
about the structure of the amygdala. Led by co-first author Nikos
Makris, MD, PhD, they reanalyzed data gathered in earlier imaging
studies of 27 cocaine addicts who had participated in cocaine infusion
studies. For purposes of comparison, they did the same analysis
on images gathered from 27 healthy controls, who matched the addicts
in a number of variables. The amygdalas of cocaine addicts were
found to have significantly less volume than those of the healthy
controls, particularly in specific areas on the right side of the
brain.
Several characteristics of the changes observed in this study suggest
that they may result from genetic differences that could underlie
an increased vulnerability to cocaine addiction. "All of the
cocaine addicts studied - those whose drug use extended for decades
and those who had been using for as little as one year - had the
same sort of reduction in amygdala volume, which makes it hard to
argue for alterations due to long-term degeneration," Breiter
says.
Previous studies have shown that, during healthy adolescent development,
the right amygdala becomes larger than the left amygdala, leading
to a normal asymmetry between the right and left sides. In the current
study, co-first author Gregory Gasic, PhD, noted that this asymmetry
was absent in the cocaine-dependent subjects but was present in
the healthy controls. "Asymmetries that appear during the course
of development often arise from the actions of specific genes. We
cannot, however, rule out rapid changes in amygdala volumes early
in the course of drug use that abolish this asymmetry," says
Gasic, who is also with the Martinos Center."
Although there was no correlation of amygdala size with the duration
of cocaine addiction, those addicts whose amygdalas were smallest
reported the highest levels of drug craving experienced throughout
the day, a finding that complements earlier associations of drug
craving with amygdala activity. Perhaps most intriguing is the fact
that early studies by Breiter and other investigators have revealed
a key role for the amygdala in alerting other brain regions to the
possibility of undesirable events or bad outcomes, since drug addicts
commonly have difficulty evaluating the long-term consequences of
their actions.
"Until now, those of us who study addictions have been focusing
on the excessive rewards addicts receive from substance abuse. But
it's more complicated than that," says David Gastfriend, MD,
director of Addictions Research at MGH and a co-author of the Neuron
paper. "In combination with other work, this study suggests
that, when the opportunity for excitement presents itself, some
people cannot make good judgements - just like teenagers who take
excessive risks in pursuit of thrills. It looks like this is a continuing
problem for people with cocaine addiction, and now we know where
in the brain that problem resides."
The authors note that further studies are required to definitively
determine whether the amygdala changes precede cocaine addiction
or result from drug use. These findings represent the first output
of a long-term Phenotype-Genotype Project in Addiction and Depression,
directed by Breiter and Gasic, which will use advanced imaging technology
to investigate the interaction between genetic differences and functional
brain activity in these disorders. Other early results from that
project suggest that the changes observed in this study may be unique
to cocaine addiction.
"No matter if these changes reflect a predisposition to addiction
or very rapid degenerative changes, there are clear public policy
implications," says Breiter. "Further research will help
us better understand the implications of these changes and develop
ways to apply them to preventing or treating cocaine addiction."
The study's other co-authors are Larry Seidman, PhD, Jill Goldstein,
PhD, Matthew Albaugh, Steven Hodge, David Zeigler, Fred Sheahan,
Verne Caviness, MD, PhD, David Kennedy, PhD, and Bruce Rosen, MD,
PhD, of the MGH; Ming Tsuang, DSc, MD, PhD, of the University of
California at San Diego, and Steven Hyman, MD, former director of
the National Institue of Mental Health who is current provost of
Harvard University. The study was supported by grants from the National
Institute of Drug Abuse, the Office of National Drug Control Policy,
the National Institute of Mental Health, and other supporters.
Massachusetts General Hospital, established in 1811, is the original
and largest teaching hospital of Harvard Medical School. The MGH
conducts the largest hospital-based research program in the United
States, with an annual research budget of more than $400 million
and major research centers in AIDS, cardiovascular research, cancer,
cutaneous biology, medical imaging, neurodegenerative disorders,
transplantation biology and photomedicine. In 1994, MGH and Brigham
and Women's Hospital joined to form Partners HealthCare System,
an integrated health care delivery system comprising the two academic
medical centers, specialty and community hospitals, a network of
physician groups, and nonacute and home health services.
Media Contact: Sue
McGreevey, MGH Public Affairs
Physician Referral Service: 1-800-388-4644
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