In this video, Dr. David Rosenthal will talk about the Overview of Genetic Testing.
So, as you all know already, when it comes to treating depression or treatment resistant depression, as the slide says treatment as usual 50% of patients don’t respond to first line therapies, as we all talked about all weekend. Things are fairly abysmal in terms of our ability to really treat treatment resistant depression. The STAR*D trials really point that out, that remission rates, when you start getting into the second, third, fourth antidepressant, remission rates are incredibly low, 13% as they point out by the fourth medication, and intolerance rates go up to a full 34%, which is really quite abysmal.
Genetics 101: Nature and Nurture
A brief review of genetics: genes plus environment determine your phenotype.
Traditionally in psychiatry, we do a pretty good job of evaluating environmental contributors to depression, mood disorders and psychiatric illnesses. But you know, for the first time in the last several years, we’ve had access to these genetic tests that can give us at least one more piece of the puzzle, alleles or alternative forms of genes. Obviously, we get one allele from each parent. So, when somebody has two of the same allele, we say they’re homozygous for a particular genetic trait, or heterozygous, if they have different copies from each parent.
Diet and Nutrition
Patients carrying the S or L (G) allele are at higher risk of side effects and/or lack of response to SSRIs
Okay, the SLC6A4 gene, this is probably one of the most common ones that people are aware of.
So, we use the word coding for that a gene codes for the production of a protein. When I explain it to patients, I say that, you know that your genetic code is like this massive blueprint, just like you’d use a blueprint to build a house. This is the blueprint for the production of a protein, but I think of the serotonin transporter protein as being somewhat like a vacuum cleaner, whose function it is to suck up serotonin molecules in the synaptic cleft and spit them back into the presynaptic neuron after they’ve been used.
Now, the other thing I want to emphasize in terms of mythology about these tests, is that I really want to emphasize that you can’t just choose one gene and say, see, this is what the gene says, and that’s everything. Remember, people are way more complicated than that. You may very well see a notable exception, where you’ve got some patient who’s been on an SSRI for years, and they’re doing great. Don’t take them off the SSRI just because they have two short alleles, you have to always incorporate your clinical judgment.
Brain-derived Neurotrophic Factor and Physical Activity
The utility of this is you can see through the variants, which patients really have trouble, at least genetically speaking, making enough BDNF, so obviously, as has been talked about here, elsewhere, you want as much BDNF as you can get. I know that exercise has been talked about. If you have trouble making BDNF, I call it brain fertilizer, it’s such an important compound for the brain. At least if you don’t make enough there are some things you can do about it. You know, exercise, diet’s been talked about, sleeping well at night, social relationships are really critical for good BDNF. Having toxic people in your life is just a BDNF killer, essentially. So obviously, a lot of people have toxic family. I use it to talk about toxic family members. If you can’t get rid of your family member, it’s critical through psychotherapy to learn how to deal with that family member so that their hostility and putting you down doesn’t affect you in the same way. Good psychotherapy increases BDNF levels quite significantly. It’s a good argument for when people say why can’t I just take the drug? You know, why do I have to go do psychotherapy? Well, psychotherapy is a biological treatment. If you want an argument, here it is.