Gene x Disease Interaction on Orbitofrontal Gray Matter in Cocaine Addiction
Long-term cocaine use has been associated with structural deficits in brain regions having dopamine-receptive neurons. However, the concomitant use of other drugs and common genetic variability in monoamine regulation present additional structural variability. The objective is to examine variations in gray matter volume (GMV) as a function of lifetime drug use and the genotype of the monoamine oxidase A gene, MAOA, in men with cocaine use disorders (CUD) and healthy male controls. Forty individuals with CUD and 42 controls who underwent magnetic resonance imaging to assess GMV and were genotyped for the MAOA polymorphism (categorized as high- and low-repeat alleles). The impact of cocaine addiction on GMV, tested by (1) comparing the CUD group with controls, (2) testing diagnosis x MAOA interactions, and (3) correlating GMV with lifetime cocaine, alcohol, and cigarette smoking, and testing their unique contribution to GMV beyond other factors. The results are: (1) Individuals with CUD had reductions in GMV in the orbitofrontal, dorsolateral prefrontal, and temporal cortex and the hippocampus compared with controls; (2) The orbitofrontal cortex reductions were uniquely driven by CUD with low- MAOA genotype and by lifetime cocaine use; and (3) The GMV in the dorsolateral prefrontal cortex and hippocampus was driven by lifetime alcohol use beyond the genotype and other pertinent variables. Long-term cocaine users with the low-repeat MAOA allele have enhanced sensitivity to gray matter loss, specifically in the orbitofrontal cortex, indicating that this genotype may exacerbate the deleterious effects of cocaine in the brain. In addition, long-term alcohol use is a major contributor to gray matter loss in the dorsolateral prefrontal cortex and hippocampus, and is likely to further impair executive function and learning in cocaine addiction.
- Research Organization:
- Brookhaven National Lab. (BNL), Upton, NY (United States)
- Sponsoring Organization:
- DOE - OFFICE OF SCIENCE
- DOE Contract Number:
- DE-AC02-98CH10886
- OSTI ID:
- 1014359
- Report Number(s):
- BNL-95033-2011-JA; ARGPAQ; R&D Project: MO-085; KP1602010; TRN: US1102740
- Journal Information:
- Archives of General Psychiatry, Vol. 68, Issue 3; ISSN 0003-990X
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
38 RADIATION CHEMISTRY, RADIOCHEMISTRY, AND NUCLEAR CHEMISTRY
ALCOHOLS
BRAIN
COCAINE
DIAGNOSIS
DISEASES
GENES
GENETIC VARIABILITY
GENOTYPE
HIPPOCAMPUS
LEARNING
LIFETIME
MAGNETIC RESONANCE
MALES
NERVE CELLS
OXIDASES
SENSITIVITY
TESTING
cocaine
gene x disease
orbitofrontal gray matter
addiction
MAOA (monoamine oxidase A) gene
CUD (cocaine use disorders)