Hans Breiter and his colleagues wrote that the finding could not distinguish conclusively whether a smaller amygdala might predispose people to addiction or whether it was a result of the addiction. However, they said that their results indicate that the condition might pre-exist addiction. They suggested that family-based studies and longitudinal studies of cocaine addicts would reveal whether a reduced amygdala volume might underlie a vulnerability to addiction.
In their study, the researchers scanned the brains of 27 cocaine addicts and a matched group of nonaddicts. The scans were done using magnetic resonance imaging, a widely used technique in which harmless magnetic fields and radio signals are used to create three-dimensional images of the brain. The researchers used data from the brain scans to determine the volume of the amygdalas in the subjects.
The researchers found that the amygdalas of the cocaine addicts were significantly smaller than the control subjects--with an average 13% smaller amygdala on the left side of the brain and a 23% smaller structure on the right side. To make sure that the amygdala was uniquely affected, the researchers also compared the size of a neighboring structure, the hippocampus, which plays a role in learning reward and aversion. They found no significant differences between addicts and controls in the volume of that structure.
They found that the volume of the amygdala in the addicts did not correlate with measures of anxiety or depression, cocaine use, or age at which cocaine use began. They also found that the addicts' brains, compared to normal subjects, showed a loss of "laterality," in which the amygdala in the two sides of the brain was normally approximately equal in volume.
Also, the researchers found that the smaller amygdala volumes in the addicts were different than in manic-depressive illness and Alzheimer's disease, in which both the hippocampus and amygdala show a loss in volume.
The researchers cited studies indicating that the amygdala is involved in assessing the rewards or aversive aspects of goals, such as expecting negative outcomes of a course of action.
"These observations are relevant, because cocaine-dependent subjects have significant difficulty identifying the potential negative outcomes of their behavior or acknowledging that these outcomes could transpire," wrote the researchers.
The researchers said that some animal studies suggested that the amygdala changes might represent changes in the brain or damage resulting from drug use. However, they said "An alternative hypothesis is that the observed amygdala abnormalities are a developmental condition that predisposes subjects to cocaine abuse or addiction." They pointed out that the normal relationship in amygdala size between the two sides of the brain was not seen in the cocaine addicts. Also, they said, further evidence of a possible causative relationship of amygdala size was that the amygdala volumes did not correlate with any measure of drug use in the addicts.
"Validation of this hypothesis requires either a longitudinal study of individuals at risk who subsequently may or may not develop the disorder or study of the trait in individuals recruited in a family-based design," wrote Breiter and his colleagues. "Such studies are necessary to determine if the decreased amygdala volume in cocaine addicts represents a brain-based phenotypic marker for illness that could facilitate genetic studies aimed at discovering the genes that modify the risk for addiction," they wrote.
This work was supported by grants from the National Institute of Drug Abuse, from the Office of National Drug Control Policy-Counterdrug for Technology Assessment Center. Further support, in part, was provided by the Massachusetts General Hospital Department of Radiology; the National Center for Research Re- sources; and the Mental Illness and Neuroscience Discovery (MIND) Institute. Clinical studies in the Mallinckrodt General Clinical Research Center (GCRC) were supported by a grant from the National Center for Research Resources (NCRR), National Institutes of Health (NIH). Other support was provided by the National Association of Research on Schizophrenia and Affective Disorders (NARSAD), Theodore and Vada Stanley Foundation Award, and National Institute of Mental Health (NIMH); by the NIMH; by the Amyotrophic Lateral Sclerosis Association and a NARSAD Young Investigator Award; and by the NINDS and the Fairway Trust.
Nikos Makris, Gregory P. Gasic, Larry J. Seidman, Jill M. Goldstein, David R. Gastfriend, Igor Elman, Matthew D. Albaugh, Steven M. Hodge, David A. Ziegler, Fred S. Sheahan, Verne S. Caviness, Jr., Ming T. Tsuang, David N. Kennedy, Steven E. Hyman, Bruce R. Rosen, and Hans C. Breiter: "Decreased Absolute Amygdala Volume in Cocaine Addicts"
Publishing in Neuron, Volume 44, Number 4, November 18, 2004, pages 729–740. http://www.neuron.org.
Journal
Neuron