Volume 1141, Issue 1 p. 195-220

Abuse of Amphetamines and Structural Abnormalities in the Brain

Steven Berman

Steven Berman

Psychiatry and Biobehavioral Sciences

Brain Research Institute, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USA

Greater Los Angeles VA Medical Center, Los Angeles, California, USA

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Joseph O'Neill

Joseph O'Neill

Psychiatry and Biobehavioral Sciences

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Scott Fears

Scott Fears

Psychiatry and Biobehavioral Sciences

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George Bartzokis

George Bartzokis

Neurology

Brain Research Institute, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USA

Greater Los Angeles VA Medical Center, Los Angeles, California, USA

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Edythe D. London

Edythe D. London

Psychiatry and Biobehavioral Sciences

Molecular and Medical Pharmacology

Brain Research Institute, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USA

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First published: 23 October 2008
Citations: 188
Address for correspondence: Edythe D. London, PhD, Professor of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, University of California Los Angeles, 760 Westwood Plaza, Box 175919, Los Angeles, California 90024-1759. Voice: +310-825-0606; fax: +310-825-0812. [email protected]

Abstract

We review evidence that structural brain abnormalities are associated with abuse of amphetamines. A brief history of amphetamine use/abuse and evidence for toxicity is followed by a summary of findings from structural magnetic resonance imaging (MRI) studies of human subjects who had abused amphetamines and children who were exposed to amphetamines in utero. Evidence comes from studies that used a variety of techniques including manual tracing, pattern matching, voxel-based, tensor-based, or cortical thickness mapping, quantification of white matter signal hyperintensities, and diffusion tensor imaging. Ten studies compared controls to individuals who were exposed to methamphetamine. Three studies assessed individuals exposed to 3–4-methylenedioxymethamphetamine (MDMA). Brain structural abnormalities were consistently reported in amphetamine abusers, as compared to control subjects. These included lower cortical gray matter volume and higher striatal volume than control subjects. These differences might reflect brain features that could predispose to substance dependence. High striatal volumes might also reflect compensation for toxicity in the dopamine-rich basal ganglia. Prenatal exposure was associated with striatal volume that was below control values, suggesting that such compensation might not occur in utero. Several forms of white matter abnormality are also common and may involve gliosis. Many of the limitations and inconsistencies in the literature relate to techniques and cross-sectional designs, which cannot infer causality. Potential confounding influences include effects of pre existing risk/protective factors, development, gender, severity of amphetamine abuse, abuse of other drugs, abstinence, and differences in lifestyle. Longitudinal designs in which multimodal datasets are acquired and are subjected to multivariate analyses would enhance our ability to provide general conclusions regarding the associations between amphetamine abuse and brain structure.