How Understanding the Human Genome Can Influence the
Practice of Psychiatry
The Human Genetic Sequencing Project
In April 2003 the human genetic sequencing project was completed. This meant that the 25,000 genes (which are made up of 3 billion chemical bases) in the human DNA were defined and stored in computers. I am far from being a biochemist and am in no way an expert in this area. In fact I didn’t even understand that it would take another three years until we understood the construction of the first human chromosome. However that did not stop me from imagining what the future of psychiatry and all medicine would be like after this great accomplishment.
The Decision Process Before The Genetic Code Was Broken
When a patient comes to me I take a detailed history and do a mental status examination (the psychiatrist equivalent of the physical examination except it is by talking). I inquire about the patient’s family history including medications used by the patient and any medications used by close family members who have the same illness. I make a diagnosis of the patient’s condition and then I may suggest psychotherapy or medication or a combination of both.
Let us say that the patient has a major depression and required an antidepressant medication. I would have many choices from which to choice. I would base my decision on the latest research. I may be influenced in my choice of which medication to use if the patient were highly anxious or had insomnia since some medications are more activating than others and some are more sedating. I would inquire about the patient’s sexual functioning since many of these medications can have sexual side effects. Some medications might help various types of pain or obsessive symptoms which could influence my first choice of a medication. I may have to take into account the patient’s financial status in regard to a choice of a less expensive generic medication or if there were a list of medications, which are less expensive in regard to their insurance coverage. All these factors need to be considered not only with the first choice of medication but very often a medication may be changed or a second one is added and these factors would all be reconsidered.
Very rarely would genetic factors be taken into account in deciding on which medication should be used. (Family history would be helpful in making the diagnosis.) If the patient should be an identical twin with the exact same genetic make up than I would pay exquisite attention in considering a similar diagnosis and choosing the same medication. This occurs only once in every 250 births. If such a person needed a medication I could be pretty sure that their side effects and efficacy probably would be identical or nearly the same as their twin. Of course even identical twins can have different life experiences and therefore their total psychological make up and environmental exposure would not be the same. If a sibling, parent or child had a good or a bad experience with a particular medication that might influence my decision but it would have no where near the significance to me as the situation where the patient would be an identical twin.
How I Imagined the Decision Process Would Be After the Genetic Code was Broken
I had this vision which I told my residents and students how, in the future, patients would come to doctors and would have a card in their wallet with their entire human genetic makeup encoded . The physician would put the card into a device on his or her desk, which would read it and provide information as to any illnesses for which the individual had a clear genetic propensity. It would also tell us the exact medications, which would target and cure these illnesses. In fact it would be possible to construct viruses ( which are DNA particles ), which could alter genetic structure and eliminate the diseases or even the propensity for them. Not only would cancer be cured or prevented but also so would the major mental illnesses I had read about these possibilities in he past and now that the secret of the human genome had been unlocked , I thought that it was just a matter of time before this became a reality.
How Things Now Stand
I am sorry to report that my fantasy has not yet become a reality. The journals and scientific meetings are filled with various pieces of research that might contribute to the puzzle . There are new companies, which offer saliva or blood tests, which will examine DNA. However, there are no genetic research tests, which have substantially changed clinical practice in the past several years.
I would like to give you a sample of some the latest genetic research so you can get a glimpse of where we might be heading with the expansion of our understanding of the genome.
Even before the genome was completely mapped there were many connections to various regions of the chromosomal structure that suggested linkage to schizophrenia.
More recently the International Schizophrenia Consortium pooled genomic data from various data bases and analyzed 8000 schizophrenic patients and 19,000 healthy controls. They found differences in a region on Chromosome 6 between schizophrenics and the controls. This chromosome area is related to the immune system response to infections and autoimmune diseases.
Research by the same group demonstrated that there were genetic similarities in the genome of schizophrenic and bipolar patients that were not shared by nonpsychiatric diseases such as coronary artery disease and rheumatoid arthritis which suggests that these genetic variations are specific to psychiatric disturbances.
Post Partum Symptoms
In still another study, published in the American Journal of Psychiatry November, 2009, showed that genetic variation on specific chromosomes may increase the susceptibility to post partum mood symptoms.
The researchers were able to show some polymorphisms or variations of Chromosome 1, 2, 9 and 14 which could indicate susceptibility to postpartum symptoms . There is a wide range of postpartum symptoms as I outlined in a previous blog. It is essential that evaluation of such symptoms be a part of the pre and post natal care of all women. It may be that the these findings will be helpful in the future for diagnosing and treatment of this condition.
Effectiveness of Antidepressant Medication
There has been some preliminary research to suggest that people with certain alleles related to the serotonin transport system had positive or negative responses to SSRI antidepressant medication . However the latest research which I could find in regard to whether genes and chromosomes will allow us to predict the effectiveness of particular antidepressant therapy was far from conclusive and suggested that there would most probably be multiple interacting genetic factors.
As promising as all this research seems to be, it has not yet changed the way psychiatric diagnosis is made or how treatment is plans are developed. I hope that this will happen in the next few years. Down the road researchers may also be able to design drugs to correct the chromosomal variations that are due to dysfunctional protein arrangements.
Biomarkers May Have to Do if We Don’t Have Complete knowledge of Genetic Makeup
Research has also been moving forward ( perhaps even faster than genetic research) in the area of biomarkers. We have known for a long time that an elevated serum cortisol level, could indicate an emotional state such as anxiety and/or depression . This is not specific enough to be of great help in making a diagnosis which we could make without these tests. However more specific biochemical tests might be helpful in making the diagnosis even though we don’t have the specific genetic markers.
Similarly, if we can use brain imaging to see changes in the brain structure with various psychiatric conditions such as schizophrenia, this may help make the diagnosis.
We may be able to even use various tracing devices to follow the uptake distribution and utilization of various medications in the brain, which should be able to help us in our decision making processes. Even a non evasive procedure such as an EEG may tell us if an antidepressant is working.
The research described above is just a small sample of the explosion of work that is being done .
Ethical Considerations in Utilization of Genetic Research
Even before the sequencing of the human genome , questions have been raised about the ethical considerations that sophisticated knowledge of genetics as well as advanced biomarkers will bring up.
For example with genetic engineering, not only might physical and mental illnesses be avoided but also so might psychological traits where genetic links were discovered. Could this create adverse impact on future generations?
There are also important questions as to how genetic information will be acquired and used. Will individuals be giving full informed consent for this testing and use of their genetic material ? Will there be mandatory genetic testing? Will all newborns have to undergo genetic testing for various conditions?
Also will the knowledge that one has an illness which hasn’t shown it self yet or the propensity to have an illness create problems for people? This may be especially true if there is not an adequate treatment for an illness. For example, not everyone would choose to be tested to determine if they are likely to get Alzheimer’s Disease especially if there were nothing to do to prevent it.
What will happen if the insurance industry gets hold of genetic testing results?
Fortunately the new healthcare legislation is supposed to prevent any discrimination on the basis of preexisting conditions . I assume this will also apply to preexisting genetic variations, which are expected to create various physical and mental conditions.
It looks as if we have a long road to go before physicians will have a genetic code reader on their desk and there may be some important ethical questions along the way.
I welcome your comments of this topic.