Mood disturbances and regional cerebral metabolic abnormalities in recently abstinent methamphetamine abusers

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.