Association of the enkephalinase gene with low amplitude P300 waves

Low amplitude of the P300 evoked potential waves has been linked to substan ce abuse. Defects in opioidergic genes regulating reward pathways have been implicated as risk factors in substance abuse. Since the rate of degradati on of enkephalins regulates their CNS level, we focused on the MME gene for metallo-membrane endopeptidase (neutral endopeptidase, enkephalinase). We identified a GT repeat polymorphism 5' to the gene and examined its potenti al association with P300 wave amplitude in 25 male subjects with substance abuse. There was significant association of low mel. wt alleles with low am plitude of the P300 wave at the parietal (p = 0.0087) and coronal (p = 0.00 9) leads. These results support a role of endogenous opioids in the regulat ion of P300 wave amplitude. NeuroReport 10:2283-2285 (C) 1999 Lippincott Wi lliams & Wilkins.