Warriors versus worriers: The role of COMT gene variants

Behavioral phenotypes are generally complex, reflecting the action of multiple different genes. Nevertheless, there is growing evidence that key gene variants can alter activity within specific neuronal circuits and, therefore, influence particular cognitive-affective phenomena. One example is the catechol-O-methyltransferase (COMT) gene, which has a common variant at codon 158. Those with valine (Val¹⁵⁸) alleles have increased greater COMT activity and lower prefrontal extracellular dopamine compared with those with the methionine (Met¹⁵⁸) substitution. Val¹⁵⁸ alleles may be associated with an advantage in the processing of aversive stimuli (warrior strategy), while Met¹⁵⁸ alleles may be associated with an advantage in memory and attention tasks (worrier strategy). Under conditions of increased dopamine release (eg, stress), individuals with Val¹⁵⁸ alleles may have improved dopaminergic transmission and better performance, while individuals with Met¹⁵⁸ alleles may have less efficient neurotransmission and worse performance. Some evidence suggests that Val ¹⁵⁸ alleles are associated with schizophrenia, while Met ¹⁵⁸ alleles are associated with anxiety.