More Than One Way to Change the Brain?

A recent AMA MorningRounds item got my attention. It was from a new items published in the Tennessean in early April 2012 and it was about genetic testing to gauge patient response to antidepressants, mainly looking for genes that are linked to how patients metabolize selective serotonin reuptake inhibitors.  See the story at web link, More doctors look to genetic testing to select best antidepressant for patients | The Tennessean | tennessean.com. It focused on Genomind, a company that makes an assay for several genes involved in depression. You can watch a 40 minute YouTube video about the science behind the assay above. Although it sounds like a very good advertisement for Genomind, I think there’s reason to be skeptical about it.

I think it’s a very interesting story, given that lately we seem to be puzzling over whether antidepressants even work or not (see latest post, Does Psychiatry Work?–With Acknowledgements to Dr. Steve Balt, MD « The Practical Psychosomaticist: James Amos, M.D.).

There’s still a bit of controversy over whether genetic assays like the one Genomind is marketing are ready for prime time. The US Centers for Disease Control and Prevention working group convened to study the issue didn’t seem to think so in 2007. And there is a good deal of caution advised in recent literature, including the paper by Steimer [1]. Steimer says, “To summarize, there are many contradictory study results, the reported effect sizes are small (odd ratio usually less than 2), and it is currently not possible to safely predict therapeutic or adverse effects. The following questions need to be answered: 1) Are the studied genotypes relevant and will genome wide screening discover new markers? 2) Are the phenotypes characterized sufficiently? 3) Do we need gene profiles? Clearly more studies are needed.”

And it’s well to remember what the leading experts in genetics have to say about this issue, which is that this use of technology is probably premature:

http://www.ispg.net/ISPGDownload/GeneticsTestingStatement3.10.pdf.

I think it’s also fair to point out that psychotherapy as well as antidepressants and other psychotropics can change the brain  [2]. I mentioned this in a recent post, Magic Mushrooms or Psychotherapy to Change the Depressed Brain? « The Practical Psychosomaticist: James Amos, M.D. According to Karlsson, about 20 studies have been done in the last two decades demonstrating that talk therapy can induce changes in the brain similar to antidepressant. Different types of psychotherapy such as Cognitive Behavioral Therapy (CBT) and Interpersonal Psychotherapy (IPT) can alter brain function in a variety of psychiatric disorders including but not limited to depression, obsessive compulsive disorder, posttraumatic stress disorder, and panic disorder. Further, dialectic behavior therapy (DBT) led to a decrease in the hemodynamic response to negative stimuli in the right-sided anterior cingulate, the temporal and posterior cingulate cortices, and the left insula [2].”

Karlsson also points out that psychotherapy can lead to changes in gene expression through learning, changes in the strength of synaptic bonds between nerve cells and by causing changes in the shapes of neurons.

And in a post not long ago, we heard from Dr. Karl Deisseroth, MD, PhD, about how we can change behavior by shining a light on it (The University of Iowa Health Sciences Week 2012: The Excitable Brain with Karl Deisseroth, MD, PhD « The Practical Psychosomaticist: James Amos, M.D.).

Would there be anything wrong with shining a light on taking a both/and approach to changing the brain?

1. Steimer, W. (2010). “Pharmacogenetics and psychoactive drug therapy: ready for the patient?” Therapeutic drug monitoring 32(4): 381-386.
Psychiatry is one of the most promising areas for bringing pharmacogenomics to the patient. Psychiatric disorders such as depression and schizophrenia contribute significantly to worldwide morbidity and mortality. Forecasts rank depression second only to ischemic heart disease by 2020. In depression and schizophrenia, 30% to 50% of all patients do not respond sufficiently to the initial treatment regime. Genetic variability has been demonstrated to play an important role in the response to pharmacotherapy. Most data are available with regard to polymorphisms in the genes coding for drug-metabolizing enzymes and recommendations for the choice of personalized dosages based on genotyping results are available. Clinical outcome, in particular adverse effects, has been shown to correlate with the results from genotyping. Incorporating pharmacogenomics into clinical practice has, however, been slow and it is still not clear in which clinical situations genotyping should be performed and what the benefit of such procedures could be beyond therapeutic drug monitoring. Additionally, many studies in psychiatry focus on genetic variation in candidate genes of drug targets. However, despite promising reports, no clear recommendation can be given at present to perform such testing in clinical use.
2. Karlsson, H., MA, MD, PhD (2011). How Psychotherapy Changes the Brain: Understanding the Mechanisms. Psychiatric Times, UBM Medica. 28.

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Comments

  1. That is SO interesting to me–since I never felt that any of the antidepressants did much for me–good or bad. And since I have such a weird serotonin production and management system (the high blood levels because of the carcinoid buggers in my liver), I really wonder what my genes might show.
    mar

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    • I think the science shows that your genes appearance may well depend on the brand–your Levis, your Lee, your Calvin Klein, and so on. No, just kidding; what’s fascinating is that there are so many different paths to the final goal–a happier you.

      Very best wishes,

      Jim Amos, MD

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