Genes for susceptibility to violence lurk in the brain

Each year >1.6 million people are killed through violence (1). Preventing violence is one of the most important global concerns. The political, social, or economic causes of violence are well studied, but more recently the awareness has grown that biological causes, which may explain individual differences in predisposition to violence, also need to be investigated. Here it is crucial to distinguish between impulsive reactive violence and predatory violence because the biological bases of these two types of aggression are likely to be different (2). Predatory violence particularly characterizes a smaller group of true psychopaths, whereas reactive violence is common across antisocial groups (3). An important theoretical advance in our knowledge about the brain basis of reactive violence has been made by Meyer-Lindenberg et al.(4) in this issue of PNAS. A wealth of twin and adoption studies confirms that individual differences in violent/antisocial behavior are heritable (5). It is unlikely that genes directly code for violence; rather, allelic variation is responsible for individual differences in neurocognitive functioning that, in turn, may determine differential predisposition to violent behavior. Genes regulating serotonergic neurotransmission, in particular monoamine oxidase A (MAOA), have been highlighted in the search for a genetic predisposition to violence (6). The MAOA gene is a well characterized functional polymorphism consisting of a variable number of tandem repeats in the promoter region, with high-activity (MAOA-H) and low-activity (MAOA-L) variants. The MAOA-H variant is associated with a lower concentration of intracellular serotonin, whereas the MAOA-L variant is associated with a higher concentration of intracellular serotonin. It is unclear at present whether MAOA-H or MAOA-L should be considered the risk variant for impulsive violence. Given that existing studies have used very different populations and measures and have not always controlled for concurrent environmental risk or other genetic influences, contradictory findings are perhaps to …