Recent Gene-Brain-Behavior Studies in Our Laboratory

When the monoamine-oxidase-A (MAOA) gene is deleted it results in aggressive behavior. This relationship was initially found in one human family where the gene had a very rare mutation and it was later validated in mice where this gene was experimentally knocked-out (deleted). Monoamine oxidase A is important for brain chemistry because it is an enzyme that breaks-down the monoamine neurotransmitters: norepinephrine, serotonin, and dopamine. Through this mechanism, MAOA plays an important role in brain development and brain functioning. The ability to map activity of the MAOA enzyme in vivo allowed us to ask whether MAOA brain activity is related to aggression. Brain MAOA activity was measured with positron emission tomography and clorgyline (labeled with carbon 11). We asked the same individuals who were scanned to also complete a personality questionnaire where some of the questions were designed to capture aggressive personality traits. Results pointed to a relationship between aggressive personality and the activity of brain MAOA. People who reported more aggression in the questionnaire also had lower levels of the MAOA enzyme throughout their brain (Alia-Klein et al., 2008).

Genetic risk carriers of the low allele (i.e., low activity) of the MAOA genotype may have increased probability of expressing their anger, potentially through differences in brain functioning during emotional contexts. The emotional context we chose was similar to hearing ‘No!’. Emphatically expressed, the emotional word No! (see study described above, Alia-Klein et al., 2007) can inhibit behavior through early childhood associations of hearing No! with stopping behavior. We assessed brain activity while people heard No! among other words. Results showed that carriers of the low MAOA genotype had reduced frontal cortex brain activation to No! compared with carriers of the high variant. Furthermore, only for carriers of the low-MAOA genotype, the more brain regions such as the amygdala (associated with emotional response) and thalamus (associated with regulating arousal) activated in response to No!, the more these individuals reported that they express their anger in situations of negative evaluation and rejection (Alia-Klein et al., 2009).

Cocaine addiction is also known to be related to brain changes and difficulties with self-control. We therefore asked if there are differences in the MAOA genotype and in gray-matter volume in the brains of cocaine addicted individuals as compared to healthy controls. We found that individuals with cocaine addiction had reductions in gray-matter volume in the frontal cortex and temporal cortex and in the hippocampus as compared to controls. Reductions in the orbitofrontal cortex (a specific region in the frontal cortex involved in evaluation and self-control) were found only in cocaine addicted individuals who carry the low allele of the MAOA genotype. Furthermore, gray-matter reductions were related to the number of years cocaine and alcohol were used: the more years of use, the more reductions were observed in the dorsolateral prefrontal cortex (part of the frontal cortex involved in sustaining attention) and in the hippocampus (a region important for learning and memory) (Alia-Klein et al., 2011).

 


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