474
Since 2007, the National Institute of Drug Abuse (NIDA) has sought SNPs for
inclusion in a custom microarray platform to study the genetics and pharmacogenet-
ics of drug abuse, addiction, and related mental disorders. NIDA plans to develop
the so-called Neuroarray and is looking for community input on custom SNPs that
provide in-depth coverage of genes with prior knowledge of association with drug
addiction and related disorders. It intends to make the array available competitively
through standard NIH mechanisms to help researchers study genetic vulnerability to
addiction and related disorders, and to develop genetic patient profi les for targeted
pharmacotherapies.
Genetic Polymorphism and Management of Alcoholism
Several gene variants have been identifi ed as risk or protective factors in alcoholism.
The genes coding for dopamine receptors, serotonin transporters, and dehydroge-
nases represent susceptibility loci for addictive behavior. Polymorphisms of the mu-
opioid receptor (OPRM1) and dopamine D4 receptor (DRD4) genes are associated
with subjective responses to alcohol and urge to drink. A SNP in the OPRM1 gene
has been associated in some studies with the effi cacy of naltrexone in reducing
drinking, but other studies did not fi nd the same effect. The presence of the L versus
the S allele on a serotonin transporter gene has been found to infl uence responses to
ondansetron. Alcoholics with the L-allele have greater alcohol craving than those
with the S-allele, and polymorphisms in another receptor result in differences in
sensitivity to benzodiazepines used to treat early stage alcohol withdrawal systems.
Alcoholism is a complex psychiatric disorder caused by multiple factors, both
genetic and environmental. Furthermore, there are probably different subtypes of
alcoholism each with a distinct genetic background, which require different thera-
peutic approaches. However, gene polymorphisms are not only responsible for a
predisposition to alcoholism, but also for the way an individual responds to treat-
ment. Because of the genetic heterogeneity between alcoholics there is no one drug
that works in all patients, which has made it necessary to provide multiple treatment
options that clinicians can use to fi nd which ones work. A personalized treatment
that matches specifi c interventions to the individual, particularly to an individual’s
genetic profi le, is more effi cient.
Topiramate has been shown to reduce drinking and heavy drinking in individuals
with alcohol dependence whose goal is to stop drinking. A randomized study has
evaluated the effi cacy and tolerability of topiramate in heavy drinkers whose treat-
ment goal is to reduce drinking to safe levels (Kranzler et al. 2014 ). In a European
American subsample of the study, topiramate’s effect on heavy drinking days was
signifi cantly greater than that for placebo only in subjects with SNP rs2832407 in
gene GRIK1, which encodes the kainate GluK1 receptor subunit. The moderator
effect of rs2832407, if validated, would facilitate the identifi cation of heavy drinkers
who are likely to respond well to topiramate treatment and provide an important
13 Personalized Management of Psychiatric Disorders