In the last lecture, I showed you a list of some of the biological, physiological, and developmental risk factors that have been discovered. Today, we're going to look at genetic predisposition in greater detail. It's clear that genetics do contribute to the risk for drug addiction. Stated simply, this means that if your parents or other family members have abused or, or are abusing drugs then the chances, or the risk that you will also abuse drugs increases. The best data for this comes from, what we call, cross adoption studies. Sons of alcoholics adopted at birth to nonalcoholic families have a four fold greater probability of becoming alcoholic than their stepbrothers. Conversely, sons of nonalcoholic parents adopted and raised by alcoholic families, did not tend to become alcoholics even when their step brothers did. These studies and a large number of many other studies like them indicate that genes are involved in becoming a drug addict. But, it's also been shown that genes do not totally determine your drug related life. They can influence drug taking, but they do not, by themselves, fully determine it. You can not get away with saying, that I take drugs simply because my parents do or did. Let's continue to talk about genetics. We've talked about the fact that genes are found in DNA. Which is found in the chromosomes. A mutation is a change in the DNA sequence. It could be a change in a single nucleotide, a duplication of a sequence, and insertion of a sequence, a deple, a deletion of a sequence or a copy or repair error. Mutations can have an effect on function. This isn't surprising because a mutation in a gene, is likely going to effect the protein made from it. There can be a loss of function, which means that the gene product has no or a lesser function as a result of the mutation. There can be a gain of function where the new product has an improved function. The mutation can also result in a dominant negative which means that the gene product antagonizes the original gene and its product. A lethal mutation leads to the death of the individual and a back mutation is a mutation that results in the original gene. A harmful mutation decreases the health performance of the individual. A bene, a beneficial mutation does the opposite. A neutral mutation has no effect. And the effect of a mutation might be mixed, in that it could be beneficial in some way and perhaps harmful in another way. We will be using the word polymorphism. This refers to the simultaneous existence in a population of different mutations. In other words, your genes may not be the exact same as mine even though we function about the same. These mutations occurred in our ancestors, and are passed down. SNPs or Single Nucleotide Polymorphisms are used in studies of heritability. An example of a SNP is shown in the image. Some of us might carry the GC version of the gene, while others of us might carry, carry the AT version of the gene. Obviously, the SNPs we are considering are not lethal because those, having them would die. But SNPs can affect the function of the protein because they can affect the make up and structure of the protein. One of the versions of the protein might be found more often in addicts for example. In that case, one could say that it might partly cause the addiction. It would at least be associated with addiction. A SNP in the mu opiate receptor protein is found more frequently in a group of heroin addicts. A SNP occurring in a dopamine receptor is more frequent in alcoholics. It's not yet clear how much the different SNPs influence addiction or why they should. This is a current area of research. Also we know that an association does not prove that it's a cause. Nevertheless, associations of SNPs with addiction have been very useful in exploring the molecular basis of the disorder. Let's consider the genetics of nicotine receptors and there role in smoking. In week three, I mentioned that nicotine receptors were composed of subunits, each made by different genes. And I mentioned that nicotine receptors are actually receptors for the neurotransmitter acetylcholine. This image from the National Institute on Drug Abuse, shows bundles of five subunits in a circle. Where there is an open core, which represents a channel for ions.This bundling is just a rough schematic of the receptor. Note that there are different kinds of subunits. One has Alpha 1 and Beta 2, another is Alpha 7 and so forth. Each of these multiple subunits are produced by different genes. It's been shown that the occurrence of a certain SNP in the Alpha 5 subunit is associated with pleasure from a first cigarette and with increased risk of dependence among early smokers. So here's a link between the composition of the receptor for nicotine and the likelihood that someone will become a smoker. It isn't clear yet, how the occurrence of these subunits and SNPs create the vulnerability. But it's a compelling topic for future research. When researchers figure out why, then maybe we can counteract the effect somehow. No single mutation or polymorphism causes addiction. Some studies indicate that dozens of genes are involved in addiction. It's been suggested that many genes have to interact with the environment to produce addiction. Addiction is not like Cystic Fibrosis, where a single gene causes the disease. This is good in the sense that without simple genetic determinism. Our behaviors, environment, and medications can be altered or used somehow to reduce our vulnerability to use drugs. Finally, it's important to mention that while certain genes or polymorphisms can confer a vulnerability, they can also be protective. They can reduce the likelihood that you will use drugs. For example, a mutation in an enzyme that metabolizes alcohol causes an illness in those drinking alcohol and the mutation reduces drinking. It's found in Asian populations. Another example, a SNP in a gene that metabolizes nicotine is more frequent among nonsmokers. So mutations can be both bad and good in terms of associating with drug use or nondrug use. In summary, this has been a very brief and partial view of a very large field of study, showing that some genes and polymorphisms are involved with and associated with drug addiction. 40 to 60% of the variance in the inheritability of alcoholism can be traced to genetics. It's not 100%. No single gene causes drug addiction. Presumably, many genes, plus the environment and perhaps personal factors somehow produce the addict. The involvement of many genes, environment, and perhaps personal factors in producing drug abuse is, in a sense, a good thing. It means that there are at least some variables that we are in control of. We can fight against addiction. Personal responsibility for our behavior is still a big factor in preventing and dealing with drug use.