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Edythe D. London, PhD; Sara L. Simon, PhD; Steven M. Berman, PhD; Mark A. Mandelkern, MD, PhD; Aaron M. Lichtman, MD; Jennifer Bramen, BS; Ann K. Shinn, MA; Karen Miotto, MD; Jennifer Learn, PhD; Yun Dong, MD, PhD; John A. Matochik, PhD; Varughese Kurian, MS; Thomas Newton, MD; Roger Woods, MD; Richard Rawson, PhD; Walter Ling, MD

Arch Gen Psychiatry. 2004;61:73-84.

Background  Mood disturbances in methamphetamine (MA) abusers likely influence drug use, but the neurobiological bases for these problems are poorly understood.

Objective  To assess regional brain function and its possible relationships with negative affect in newly abstinent MA abusers.

Design  Two groups were compared by measures of mood and cerebral glucose metabolism ([¹⁸F]fluorodeoxyglucose positron emission tomography) during performance of a vigilance task.

Setting  Participants were recruited from the general community to a research center.

Participants  Seventeen abstaining (4-7 days) MA abusers (6 women) were compared with 18 control subjects (8 women).

Main Outcome Measures  Self-reports of depressive symptoms and anxiety were measured, as were global and relative glucose metabolism in the orbitofrontal, cingulate, lateral prefrontal, and insular cortices and the amygdala, striatum, and cerebellum.

Results  Abusers of MA provided higher self-ratings of depression and anxiety than control subjects and differed significantly in relative regional glucose metabolism: lower in the anterior cingulate and insula and higher in the lateral orbitofrontal area, middle and posterior cingulate, amygdala, ventral striatum, and cerebellum. In MA abusers, self-reports of depressive symptoms covaried positively with relative glucose metabolism in limbic regions (eg, perigenual anterior cingulate gyrus and amygdala) and ratings of state and trait anxiety covaried negatively with relative activity in the anterior cingulate cortex and left insula. Trait anxiety also covaried negatively with relative activity in the orbitofrontal cortex and positively with amygdala activity.

Conclusions  Abusers of MA have abnormalities in brain regions implicated in mood disorders. Relationships between relative glucose metabolism in limbic and paralimbic regions and self-reports of depression and anxiety in MA abusers suggest that these regions are involved in affective dysregulation and may be an important target of intervention for MA dependence.

From the Departments of Psychiatry and Biobehavioral Sciences (Drs London, Simon, Berman, Lichtman, Miotto, Learn, Dong, Newton, Rawson, and Ling and Mss Bramen and Shinn), Molecular and Medical Pharmacology (Dr London), and Neurology (Dr Woods), and the Brain Research Institute (Drs London and Berman), the David Geffen School of Medicine at UCLA, University of California, Los Angeles; the Department of Physics, University of California, Irvine (Dr Mandelkern); and the Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, Md (Dr Matochik and Mr Kurian).

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