Prefrontal white matter impairment in substance users depends upon the catechol-o-methyl transferase (COMT) val158met polymorphism

► Significant COMTval158met × Drug Use interaction in prefrontal white matter was found. ► Reduced prefrontal FA was found only in Met allele homozygotes who are also drug users. ► Elevated prefrontal dopamine and drug may interact to alter white matter structure. ► Relevance to known prefrontal cortical deficits in addiction is discussed.