Modulation of brain structure by catechol-O-methyltransferase Val(158) Met polymorphism in chronic cannabis users

Addict Biol. 2014 Jul;19(4):722-32. doi: 10.1111/adb.12027. Epub 2013 Jan 14.

Abstract

Neuroimaging studies have shown that chronic consumption of cannabis may result in alterations in brain morphology. Recent work focusing on the relationship between brain structure and the catechol-O-methyltransferase (COMT) gene polymorphism suggests that functional COMT variants may affect brain volume in healthy individuals and in schizophrenia patients. We measured the influence of COMT genotype on the volume of four key regions: the prefrontal cortex, neostriatum (caudate-putamen), anterior cingulate cortex and hippocampus-amygdala complex, in chronic early-onset cannabis users and healthy control subjects. We selected 29 chronic cannabis users who began using cannabis before 16 years of age and matched them to 28 healthy volunteers in terms of age, educational level and IQ. Participants were male, Caucasians aged between 18 and 30 years. All were assessed by a structured psychiatric interview (PRISM) to exclude any lifetime Axis-I disorder according to Diagnostic and Statistical Manual for Mental Disorders-Fourth Edition. COMT genotyping was performed and structural magnetic resonance imaging data was analyzed by voxel-based morphometry. The results showed that the COMT polymorphism influenced the volume of the bilateral ventral caudate nucleus in both groups, but in an opposite direction: more copies of val allele led to lesser volume in chronic cannabis users and more volume in controls. The opposite pattern was found in left amygdala. There were no effects of COMT genotype on volumes of the whole brain or the other selected regions. Our findings support recent reports of neuroanatomical changes associated with cannabis use and, for the first time, reveal that these changes may be influenced by the COMT genotype.

Keywords: COMT; VBM; Val158Met; chronic cannabis users; structural MRI.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Amino Acid Substitution / genetics
  • Brain / drug effects*
  • Brain / physiopathology*
  • Brain Mapping / methods
  • Catechol O-Methyltransferase / genetics*
  • Genetic Predisposition to Disease / genetics
  • Humans
  • Magnetic Resonance Imaging / methods
  • Male
  • Marijuana Abuse / genetics*
  • Methionine
  • Organ Size / drug effects
  • Polymorphism, Single Nucleotide / genetics*
  • Valine
  • Young Adult

Substances

  • Methionine
  • Catechol O-Methyltransferase
  • Valine