Proof of Concept

Psychogenomics is a blog that is designed to help with a proof of concept project based in the Behavioral Health Section of St. Agnes Hospital, Fond du Lac, WI.
The idea is to see if readily available genomic information from 23andMe or similar companies can be transformed into information that is useful for both the patient and their provider in regard to treatment and diagnostic decisions.
In the past ten years or so there has been an exponentially growing body of knowledge regarding genes and disease.  The field of psychiatry has been part of this epiphany especially in regard to how medications affect both the disease processes seen in patients and how patients respond to medication.  In addition there has been work linking these genes, especially the Single Nucleotide Polymorphisms (SNPs) that act as markers, to diagnosis.  The latter research may have global influence on how we view diagnosis in the near future.
Mental health providers rely on the Diagnostic and Statistical Manual 5 (DSM-5) as the common nomenclature of psychiatric disease.  This work is not based on strong scientific bases, rather it is reliant on describing and categorizing phenomena according to both historical and clinical observations.  The book takes clusters of symptoms and signs and assigns diagnoses based on these often overlapping conglomerations and then assigns a name.  In turn theses diagnoses are classified into larger units based on mood, thought processes, cognitive abilities and a host of smaller categories.
The DSM-5 is not close to perfect, but it is all we have and it serves as a rough guideline for treatment.  Ironically, many of the treatments are capable of crossing the diagnostic lines and help patients with varying diagnoses.  Thus a patient with schizophrenia may end up taking the same medication that a patient with a depression does and both patients improve.
I say improve because, for the most part, psychiatric illnesses are chronic and incurable.  The major psychiatric illnesses - Major Depression, Mood Disorders such as Manic Depressive Disease, Schizophrenia, Schizo-affective Disorder, Anxiety Disorders, etc. - all seem to be inherited although there is hardly a one to one correlation to family history and the presence of illness.  Patients who have demonstrated severe illness probably have a genetic component that will not go away with the treatments we have now.
These days most providers realize this and have a host of tools (medication, therapies, somatic treatments) that will help but because of the fuzzy nature of diagnosis, the vast array of medications and treatments, and the significant side effects that can occur, especially with medication, it is often a crap shoot as to what will help and what will not.
There have been a number of large open studies such as STAR*D for depression that looked at tens of thousands of patients and developed algorithms for treatment.  Instead of just tossing one of sixty or so antidepressants at a patient to see it it works, the STAR*D study came up with a flow chart that allowed you to treat in a "logical" manner according to the statistical analyses of the study.
While these algorithms are very helpful (they exist for mood disorder and psychoses too) they are still not as precise as they could be.  Some of the reasons for this imprecision lies in the fact that individuals have specific responses to medications based on their enzyme efficiency (i.e. how they metabolize the various medications) and their susceptibility to illness.  There are other factors, of course, but these days we have the technology to determine what enzyme variants a patient might have and, if the studies are correct, even be able to tell if a specific medication will be more appropriate for a patient.  In addition there is some proof that we can tell what the disease processes is (remember, a lot of them look alike) through a study of the patient's genetic structure.
Thus this project. 
23andMe makes available to consumers a snapshot of their genes from a part called the exome.  The exome is responsible for the production of  a significant number of enzymes and the readout from 23andMe contains about 1,000,000 of the SNPs mentioned above.  (For contrast there are probably over a billion SNPs in the body.)  Of these million SNPs there are a finite number that are involved in the production of important enzymes and medical science has identified a large number of them.  SNPs are segments of the genes involved and they can have variation in the amino acids that make them up.  When these SNPs change - and the changes are limited to only four amino acids - they effect the ability of the enzymes to work or have some other not so obvious change in the whole system.  Each of us carries a pair of these alleles so it is possible to have at least four variants and as many as seventeen in one case depending on whether or not the SNPs are duplicated, repeated, or even there (there are some people who have certain SNPs missing.)   It can be very confusing especially if SNPs influence the effects of other SNPs but on a practical basis most of the science is moot as we tend to look at the results and not the biochemistry.  (Just like the rest of medicine, it is an applied science, after all.)
So if this information is available, and chances are that many of the million SNPs are available for the $99 that 23andMe charges, we should find a way to utilize it.  It appears that we are able to access these SNPs and the way is rather inexpensive because a provider can use open sources while retaining the confidentiality demanded by ethical practices and the law.
Thus I am setting up this blog.
It will serve as a test bed for ideas and can also be used to generate ideas through crowd sourcing.  Several friends of mine have anonymously donated their  23andMe raw data for this project and St. Agnes has generously donated money and expertise for the computer part. My main source of inspiration is the book "Psychiatric Pharmacogenomics" by the late David Mrazek, MD who, until his untimely death, was chairman of the behavioral health section of the Mayo Clinic.
I guess we will see.

Disclaimers:
1) This blog is not intended to diagnose or treat any medical illness.  It is merely a meeting place for ideas that will help the professionals become more precise and accurate.  (There is a difference, look it up.)

2) I am not endorsing any product mentioned here and St. Agnes Hospital certainly isn't endorsing any product.  They are just providing me with some  support because they think I may have a good idea.  Vendors such as 23andMe will be coming out of the woodwork once the FDA business is over because they provide an accurate service that defines SNPS.  The books mentioned are considered to be important in the field but are rife with controversy according to some.  If you have a better source, please let me know.

Michael J Keyes, MD
Fond du Lac, WI