PsychCentral posted a news article about this study.
The above mentioned study is a pharmacogenomic study that performed a genome-wide association study of to detect genetic variants that are associated with antidepressent drug response. Since the previous sentence uses a lot of jargon, I will try to break it down.
Pharmacogenomics is the study of how the genetics of individuals influences their biochemical response to drugs. Namely, we are interested in how well a particular drug treats the disease that it is designed to treat. So, these studies are usually an investigation of the main-effects of a drug, rather than an investigation of the side-effects. (Although the pharmacogenomic approach can also be used to study side-effects, it is hard to get sample sizes that are large enough to find anything with such a study.) The reason we are interested in pharmacogenomic studies is because drug response is partially genetic. For many diseases we know that whether or not a drug works for your parent(s) can well predict whether the drug works for you. So, not only are diseases genetic, but the effective treatments can also be genetic.
To explain how traits can be genetic, first we need to understand what genetic variation is. Humans have two copies of every chromosome, and we have a distinct sequence of nucleotides (the molecular units that make up DNA) on each chromosome. There are sites or positions in the genomic sequence where if we look across many individuals, we find that there are multiple nucleotides that appear at that site. These sites of variation are called single nucleotide polymorphisms (SNPs). If a SNP is responsible for a disease trait then there would be a single mathematical function that relates for each person the nucleotides that they have at the SNP site to disease trait. The simplest examples involve single SNP sites that are Mendelian diseases (either recessive or dominant) and have binary disease traits, or traits that either exist or do not exist. We call diseases complex (or polygenic, meaning that it involves many sites) when the trait is a function of the nucleotides at several SNPs. Now we have described the generative model, i.e. given the genetic data and a mathematical function, decide what the trait value is for each person. The aspect that makes this novel research is that the mathematical function linking the genetics to the trait is unknown. This is why governments and foundations are spending millions of dollars on studies that try to discover these mathematical functions that link genetics to the trait.
The most common type of study that attempts to do this is called the genome-wide association study (GWAS). These studies are used not only for in pharmacogenomics, but also for studying the genetics of heritable disease. A GWAS study that looks for an association between some trait, in this case drug response by depressed individuals when given anti-depressant drugs, and the nucleotides at a particular SNP site. An association (usually meaning a significant correlation) is a specific mathematical function, like the ones that we discussed above, that relates, with few errors, the nucleotides of the individuals at a SNP site to the value of the trait. (The functions we described above were completely general whereas most GWAS methods rely on correlations which are a restricted class of functions.)
The study that was sited at the top of this post, had two main results. The first result is a negative result in terms of being able to use the genome of a patient to identify which drugs will most help them. The second result is a positive result saying that if a patient's close relative responds well to a particular drug then the patient likely will as well.
First, they found many SNPs that are associated with antidepressant drug response. This means that drug response is polygenic and therefore is a complex trait involving multiple SNP sites. Knowing that antidepressant drug response is polygenic helps us know what to look for in the genome. We should be looking for interacting sites that work together to produce the trait. This is a negative result, because it means that there is not just one genetic site that we can use to test for what drug each person will respond to.
Second, the paper gives results about the heritability of drug response. Heritability is the fraction of trait variability that is due to genetics. When we say that the heritability is 42%, we do not mean that there is a 42% chance that a child of a person with the trait will also have the trait. Rather, we mean that heritability is the ratio of the variance of the trait that is due to genetics and the total variance of a trait. Heritability is not about the risk of having a trait but rather it is about whether the trait is genetic or not. A trait having a heritability of 42% means that 42% of the variance of the trait value is due to genetic causes. This main result of the study is best expressed in this sentence
We find that common genetic variants explain 42% (SE = .180, p = .009) of individual differences in antidepressant response.
What can we as potential users of antidepressants take away from all this? First, it will be a while until the science advances to the point that it can predict which drug will work best for us. Second, the best predication about which antidepressants would work well for us is the list of antidepressants that work well for our relatives.
In the wider discussion of which psychotropic drugs may be helpful to a person, it might be quite reasonable to assume that there is heritability of drug response. For example imagine two siblings, one who has anxiety and one who has schizophrenia. (This example is quite plausible because we know that families having bipolar or schizophrenia also have a lot of anxiety and depression.) At any rate, in our imagining, the sibling with the anxiety was diagnosed first and found Zyprexa to be a very useful drug for pro re nata treatment of anxiety. The second sibling, when diagnosed with schizophrenia, recognizes that Zyprexa has worked for their sibling and tries that drug to good effect. As another example, suppose antidepressants cause a family member with bipolar to become manic. Then it might be good for other family members to avoid that class of drugs regardless of which diagnoses they may have.
Although there is not much research yet that elucidates the heritability of psychotropic drug response, the experience of patients indicates that this is a critical aspect of successful treatment. I fervently hope that the research will move in the direction of attempting to elucidate the heritability of drug response, because it would lead to successful treatment.
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