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A General Method for Evaluating Deep Brain Stimulation Effects on Intravenous Methamphetamine Self-Administration
Published on: January 22, 2016
Independent and combined effects of methamphetamine use disorders and APOEε4 allele on cognitive performance and
Hannah A Wang1, Hua-Jun Liang1, Thomas M Ernst1,2
1Department of Diagnostic Radiology and Nuclear Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA.
Aims:
Prior studies showed that methamphetamine (METH) users had greater than normal age-related brain atrophy; whether having the apolipoprotein E (APOE)-ε4 allele may be a contributory factor has not been evaluated. We aimed to determine the independent and combined effects of chronic heavy METH use and having at least one copy of the APOE-ε4 allele (APOE-ε4+) on brain morphometry and cognition, especially in relation to aging.
Methods:
We compared brain morphometry and cognitive performance in 77 individuals with chronic heavy METH use (26 APOE-ε4+, 51 APOE-ε4-) and 226 Non-METH users (66 APOE-ε4+, 160 APOE-ε4-), using a 2 × 2 design (two-way analysis of co-variance). Vertex-wise cortical volumes, thickness and seven subcortical volumes, were automatically measured using FreeSurfer. Linear regression between regional brain measures, and cognitive scores that showed group differences were evaluated. Group differences in age-related decline in brain and cognitive measures were also explored.
Results:
Regardless of APOE-ε4 genotype, METH users had lower Motor Z-scores (P = 0.005), thinner right lateral-orbitofrontal cortices (P < 0.001), smaller left pars-triangularis gyrus volumes (P = 0.004), but larger pallida, hippocampi and amygdalae (P = 0.004-0.006) than nonusers. Across groups, APOE-ε4+ METH users had the smallest volumes of superior frontal cortical gyri bilaterally, and of the smallest volume in left rostral-middle frontal gyri (all P-values <0.001). Smaller right superior-frontal gyrus predicted poorer motor function only in APOE-ε4+ participants (interaction-P < 0.001). Cortical volumes and thickness declined with age similarly across all participants; however, APOE-ε4-carriers showed thinner right inferior parietal cortices than noncarriers at younger age (interaction-P < 0.001).
Conclusions:
Chronic heavy use and having at least one copy of the APOE-ε4 allele may have synergistic effects on brain atrophy, particularly in frontal cortices, which may contribute to their poorer cognitive function. However, the enlarged subcortical volumes in METH users replicated prior studies, and are likely due to METH-mediated neuroinflammation.
Insights
Methamphetamine (METH) use and the APOE-ε4 gene may synergistically accelerate brain atrophy, especially in frontal regions. This combination may worsen cognitive function and motor skills in METH users.
Area of Science:
- Neuroscience
- Genetics
- Psychiatry
Background:
- Prior research indicates methamphetamine (METH) users experience accelerated age-related brain atrophy.
- The role of the apolipoprotein E (APOE)-ε4 allele in this process remains unclear.
Purpose of the Study:
- To investigate the independent and combined effects of chronic heavy METH use and the APOE-ε4 allele on brain structure and cognitive function.
- To examine how these factors interact with aging.
Main Methods:
- A 2x2 design compared METH users (n=77) and non-users (n=226), stratified by APOE-ε4 carrier status.
- Brain morphometry (cortical volumes, thickness, subcortical volumes) was assessed using FreeSurfer.
- Cognitive performance, including motor skills, was evaluated.
Main Results:
- METH users exhibited reduced motor skills, thinner lateral-orbitofrontal cortices, smaller left pars-triangularis volumes, and larger pallida, hippocampi, and amygdalae, irrespective of APOE-ε4 status.
- APOE-ε4+ METH users showed the most significant reductions in superior frontal cortical gyri volumes.
- Smaller frontal volumes predicted poorer motor function specifically in APOE-ε4+ METH users.
- While overall age-related decline was similar, APOE-ε4 carriers displayed thinner inferior parietal cortices at younger ages.
Conclusions:
- Chronic METH use and the APOE-ε4 allele may interact synergistically, leading to enhanced brain atrophy, particularly in frontal regions, and potentially contributing to cognitive deficits.
- Enlarged subcortical volumes in METH users are likely linked to METH-induced neuroinflammation.
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