P300 development during adolescence: effects of DRD2 genotype.
OBJECTIVE
Young boys at high risk for alcoholism by having a family history of alcoholism (FH+) have lower amplitude of the visual P300 event-related scalp potential. They have also been reported to have a slowing in the rate of P300 amplitude change during adolescence. The present study examined whether the change in P300 amplitude during adolescence in sons of alcoholics and nonalcoholics is affected by D2 dopamine receptor (DRD2) polymorphism.


METHODS
P300 was elicited with a visual discrimination task from 71 adolescent sons of alcoholics and social drinkers (Time 1, T1). The task was readministered 2 years later (Time 2, T2). Comparisons were made between boys who had the DRD2 A1 allele (A1+) and boys who did not (A1-), and between boys with one or both parents being alcoholic (FH+) and boys having no alcoholic parents (FH-).


RESULTS
Discrimination task accuracy was lowest in the highest risk group (A1+, FH+) at T1, and highest in the lowest risk group (A1-, FH-) at T2, producing a significant interaction of allelic group x family history group x session. Reaction time was faster at T2 than T1, and this effect was larger in FH-boys (125 ms) than FH+boys (40 ms). Overall, the behavioral results suggest mild performance deficits on the discrimination task are associated with higher risk for alcoholism. In both testing sessions, P300 attained larger amplitudes in sons of nonalcoholics than sons of alcoholics. At T2 compared to T1, both the latency and amplitude of the P300 were decreased. However, while the developmental P300 latency effect was equivalent in both the A1+ and A1- allelic groups, the P300 amplitude reduction during adolescence, measured both in response to targets and in target minus non-target subtraction waveforms, was only found in boys with the A1- allele.


CONCLUSIONS
Differences in the developmental course of P300 amplitude over the course of adolescence are dependent on DRD2 polymorphism.


CONCLUSIONS
These results suggest the importance of genetic determinants of the dopaminergic system in understanding the P300 as a risk marker for substance abuse using an integrative developmental perspective.
Berman
Steven M
SM
Department of Psychiatry and Biobehavioral Sciences, Alcohol Research Center, University of California, Los Angeles, CA 90024, USA.
Noble
Ernest P
EP
Antolin
Tim
T
Sheen
Courtney
C
Conner
Bradley T
BT
Ritchie
Terry
T
D000293:Adolescent; D000437:Alcoholism / Q000235:genetics* / Q000503:physiopathology; D000483:Alleles; D002648:Child; D004569:Electroencephalography / Q000379:methods; D018913:Event-Related Potentials, P300 / Q000235:genetics* / Q000502:physiology; D005192:Family Health; D005500:Follow-Up Studies; D005838:Genotype; D006801:Humans; D008297:Male; D010775:Photic Stimulation / Q000379:methods; D011597:Psychomotor Performance / Q000502:physiology; D011930:Reaction Time / Q000235:genetics; D017448:Receptors, Dopamine D2 / Q000235:genetics*; D012307:Risk Factors
D017448:Receptors, Dopamine D2