Alteration of Brain Structure With Long-Term Abstinence of Methamphetamine by Voxel-Based Morphometry

Background: A large portion of previous studies that have demonstrated brain gray matter reduction in individuals who use methamphetamine (MA) have focused on short-term abstinence, but few studies have focused on the effects of long-term abstinence of methamphetamine on brain structures.Materials and Methods: Our study includes 40 healthy controls and 44 abstinent methamphetamine-dependent (AMD) subjects who have abstained for at least 14 months. For every AMD subject, the age when they first used MA, the total time of MA use, the frequency of MA use in the last month before abstinence, the duration of abstinence and the craving score were recorded. Here we used magnetic resonance imaging (MRI) to measure the gray matter volume (GMV) of each subject with voxel-based morphometry method. Two-sample t-test (AlphaSim corrected) was performed to obtain brain regions with different gray matter volume (GMV) between groups. In addition, partial correlation coefficients adjusted for age, years of education, smoking, and drinking were calculated in the AMD group to assess associations between the mean GMV values in significant clusters and variables of MA use and abstinence.Results: Compared with the healthy control group, AMD group showed increased gray matter volumes in the bilateral cerebellum and decreased volumes in the right calcarine and right cuneus. Moreover, GMV of left cerebellum are positively correlated with the duration of abstinence in the AMD group (p = 0.040, r = 0.626).Conclusions: The present study showed that the gray matter volume in some brain regions is abnormal in the AMD subjects with long-term abstinence. Changes in gray matter volume of visual and cognitive function regions suggested that these areas play important roles in the progress of MA addiction and abstinence. In addition, positive correlation between GMV of the left cerebellum crus and duration of abstinence suggested that prolonged abstinence is beneficial to cognitive function recovery

Autophagy as a gateway for the effects of methamphetamine: From neurotransmitter release and synaptic plasticity to psychiatric and neurodegenerative disorders.

As a major eukaryotic cell clearing machinery, autophagy grants cell proteostasis, which is key for neurotransmitter release, synaptic plasticity, and neuronal survival. In line with this, besides neuropathological events, autophagy dysfunctions are bound to synaptic alterations that occur in mental disorders, and early on, in neurodegenerative diseases. This is also the case of methamphetamine (METH) abuse, which leads to psychiatric disturbances and neurotoxicity. While consistently altering the autophagy machinery, METH produces behavioral and neurotoxic effects through molecular and biochemical events that can be recapitulated by autophagy blockade. These consist of altered physiological dopamine (DA) release, abnormal stimulation of DA and glutamate receptors, as well as oxidative, excitotoxic, and neuroinflammatory events. Recent molecular insights suggest that METH early impairs the autophagy machinery, though its functional significance remains to be investigated. Here we discuss evidence suggesting that alterations of DA transmission and autophagy are intermingled within a chain of events underlying behavioral alterations and neurodegenerative phenomena produced by METH. Understanding how METH alters the autophagy machinery is expected to provide novel insights into the neurobiology of METH addiction sharing some features with psychiatric disorders and parkinsonism