Brain Anomalies Characterize Cocaine-Addicted Patients

Ateam of Harvard researchers has used advanced imaging techniques to uncover a structural difference in the brains of those addicted to cocaine that even the researchers did not expect.

The amygdalas of patients addicted to cocaine were found to be significantly smaller in volume than those of a group of matched, healthy comparison subjects. The team's surprise? The reductions in volume within the amygdalas consistently appeared in a specific pattern.

The research, funded by the National Institute on Drug Abuse, the National Institute of Mental Health, and the Office of National Drug Control Policy, was reported in the November 18 issue of Neuron.

“Work here and at other centers has identified the amygdala's fundamental role in addiction,” explained Hans Breiter, M.D., co-director of the Motivation and Emotion Neuroscience Collaboration at the Harvard-affiliated Massachusetts General Hospital (MGH) departments of radiology and psychiatry.

“[The amygdala] is important for producing drug craving, which has a powerful effect in maintaining drug abuse. 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 subregions of this brain structure.” Breiter is the senior author on the Neuron paper.

Previous work by Breiter and others has linked cocaine use to reduced activity in the amygdala, particularly during times when addicted patients reported feelings of craving. In those previous studies, differences had been identified in surrounding structures, but not in the amygdala itself. The Harvard/MGH team wanted to know whether structural abnormality differences would be found in the amygdala itself—known to be a brain center associated with motivation and reward—that could reflect either vulnerability to cocaine addiction or changes due to drug use.

The researchers analyzed data from 27 patients who were addicted to cocaine and had participated in cocaine infusion studies and 27 healthy control subjects matched for such variables as age and sex.

The amygdalas of all of the patients addicted to cocaine differed from those of the healthy controls in the same specific way, leading the researchers to wonder whether the changes could result from genetic differences tied to an increased vulnerability to 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 amygdalar volume, which makes it hard to argue for alterations due to long-term degeneration,” Breiter explained in a press release.

The authors noted that during adolescence the right side of the amygdala normally becomes larger than the left. In the patients addicted to cocaine, this normal asymmetry was not observed, while the asymmetry was present in the images of the brains of the healthy comparison subjects.

“Asymmetries that appear during the course of development often arise from the actions of specific genes,” noted co-author Gregory Gasic, Ph.D., a researcher at MGH's Martinos Center for Biomedical Imaging. “We cannot, however, rule out rapid changes in amygdalar volumes early in the course of drug use that abolish this asymmetry.”

While the reduction in the volume of the amygdala did not correlate to the duration of cocaine use, those patients whose amygdalas were smallest reported the highest levels of drug craving throughout the day, a finding, Breiter added, that complements earlier associations between drug craving and amygdalar activity.

“Until now, those of us who study addictions have been focusing on the excessive rewards addicts receive from substance abuse,” commented David Gastfriend, M.D., director of addictions research at MGH and a co-author on the Neuron paper.

An abstract of “Decreased Absolute Amygdala Volume in Cocaine Addicts” is posted online at<www.neuron.org/content/article/abstract?uid=PIIS0896627304006907>.▪