What might be the mechanism by which GABRA2 affects risk for externalizing behavior? All of the outcomes that have been associated with GABRA2 (adult alcohol dependence, drug dependence, adult antisocial behavior, childhood conduct problems, adolescent externalizing behavior) are characterized by aspects of impulsivity. Accordingly, it seems plausible that genetic variants in GABRA2 may be involved in a general predisposition toward behavioral disinhibition. The association of GABRA2 with an electrophysiological endophenotype13 may further support this hypothesis, as it has been suggested that the electrophysiological abnormalities evident in individuals at risk for various forms of externalizing psychopathology represent a deficit of central nervous system inhibition and/or an excess of central nervous system excitation.54 This central nervous system hyperexcitability reflects a disequilibrium in the homeostatic mechanisms responsible for maintaining a balance between excitation and inhibition. Variations in GABRA2 may be involved in creating this homeostatic imbalance, which may in turn increase risk for externalizing behavior.
