Structural Abnormalities in the Brains of Human Subjects Who Use Methamphetamine

Abstract

We visualize, for the first time, the profile of structural deficits in the human brain associated with chronic methamphetamine (MA) abuse. Studies of human subjects who have used MA chronically have revealed deficits in dopaminergic and serotonergic systems and cerebral metabolic abnormalities. Using magnetic resonance imaging (MRI) and new computational brain-mapping techniques, we determined the pattern of structural brain alterations associated with chronic MA abuse in human subjects and related these deficits to cognitive impairment. We used high-resolution MRI and surface-based computational image analyses to map regional abnormalities in the cortex, hippocampus, white matter, and ventricles in 22 human subjects who used MA and 21 age-matched, healthy controls. Cortical maps revealed severe gray-matter deficits in the cingulate, limbic, and paralimbic cortices of MA abusers (averaging 11.3% below control; p Ͻ 0.05). On average, MA abusers had 7.8% smaller hippocampal volumes than control subjects ( p Ͻ 0.01; left, p ϭ 0.01; right, p Ͻ 0.05) and significant white-matter hypertrophy (7.0%; p Ͻ 0.01). Hippocampal deficits were mapped and correlated with memory performance on a word-recall test ( p Ͻ 0.05). MRI-based maps suggest that chronic methamphetamine abuse causes a selective pattern of cerebral deterioration that contributes to impaired memory performance. MA may selectively damage the medial temporal lobe and, consistent with metabolic studies, the cingulate-limbic cortex, inducing neuroadaptation, neuropil reduction, or cell death. Prominent white-matter hypertrophy may result from altered myelination and adaptive glial changes, including gliosis secondary to neuronal damage. These brain substrates may help account for the symptoms of MA abuse, providing therapeutic targets for drug-induced brain injury.

Non-treatment-seeking heavy drinkers: Effects of chronic cigarette smoking on brain structure

“…Furthermore, both HD groups demonstrated a similar frequency of previous substance dependence, which primarily involved cocaine, methamphetamine, and cannabis. Chronic misuse of these substances has been reported to adversely affect human brain morphology in active and recently detoxified abusers (e.g., Bartzokis et al, 2000;Matochik et al, 2005;O'Neill et al, 2001;Thompson et al, 2004). The long-term, enduring effects of cocaine, methamphetamine, or cannabis on human brain morphology are largely unknown, especially when dependence is in long-term sustained full remission.…”

Randomized, placebo-controlled trial of bupropion for the treatment of methamphetamine dependence

“…For example, studies have shown extensive reductions in the density and activity of DAT in the striatum in the days following MA use (Chang et al, 2007). Imaging studies have also shown that hypoactivity in the striatum can be correlated with self-reports of depression and anxiety in recovering MA users (Thompson et al, 2004). In addition, cognitive dysfunction and decreased activity of DA receptors caused by prolonged MA use can contribute to poor impulse control and inability to maintain goal-related behavior (Monterosso et al, 2005).…”

Quantitative EEG Abnormalities are Associated With Memory Impairment in Recently Abstinent Methamphetamine-Dependent Individuals

“…1 It is only in the last decade, however, that researchers have examined the effects of methamphetamine on the human brain. For example, the neurobiological abnormalities associated with long-term, high-dose methamphetamine exposure have been described using various neuroimaging 2–5 and electrophysiological 6 techniques. The functional consequences of long-term, high-dose methamphetamine exposure are also reasonably well-established, and include marked deficits on measures of episodic memory.…”

“…2 In another study of 22 subjects, high-resolution MRI revealed that reduced hippocampal volume was associated with poorer performance on a memory test that was constructed specifically for use in that laboratory. 5 …”