1 Boring Old Man

Half my life ago, I was a research oriented Internist whose career had been sidetracked by a draft notice, and I found myself working in an overseas Air Force hospital seeing patients. It was a lot different from the City Hospital where I trained seeing desperately ill patients. The Air Force has a pretty healthy population of soldiers and dependents so the pace was remarkably different from my previous life – fairly routine stuff. I was astounded at how many people I saw who came for vague physical symptoms, but whose problems were in their lives rather than their bodies. I actually started counting – 75% was the result. I started asking "how’s your life?" a lot, and without much prodding began to hear lots of stories. The lady admitted for muscle weakness suspected to be a dire immune disease turned out to be struggling with an attraction to her husband’s best friend. The treatment? Treating her husband’s alcoholism. I have hundreds of stories like that. Even the people with disease had lives. The lady whose Ulcerative Colitis couldn’t be controlled? Her teen-aged daughter was acting out against an overly strict father who was struggling against his own feelings having this sexy young chick living in his house. The treatment? Mom and daughter went home to West Virginia for the daughter to finish High School. The daughter stopped acting out; Mom’s Ulcerative Colitis abated; and even Dad seemed better. Then there was the old contract teacher who had a smoldering case of hepatitis he contracted in World War II in the Pacific. He suddenly developed liver failure and was dying. He turned out to have secondary syphilis in the liver. The lady? A long time affairee in Germany – a General’s wife. Where did she get it? Shame on you General! He survived this extra assault with Penicillin, but in the end, it was the straw that broke his liver’s back and he died two years later. There was so much in this "how’s your life?" business in everything that came my way that I headed back for training in Psychiatry and Psychoanalysis.

Well, there was a lot more to it than I knew. There were major diseases like Schizophrenia and Manic-Depressive Illness. There were all those things that happen when development gets off track – personality problems, neuroses, tons of stuff to be learned, psychiatric medications to be learned about, etc. But it was all very interesting and I was glad I’d finally figured out what it was I was really interested in doing. I was teaching and practicing, having a grand old time, but then something happened. It seemed like all of a sudden, it was all about drugs. I certainly found that interesting, but it didn’t replace the other stuff. The new antidepressants were a great improvement. For some people, it was all they needed. But for the majority, it took the edge off enough for them to actually began to look at "how’s your life?" When I figured out that the Department I was in was focusing on just the drugs, I moved on to private practice to do what I learned to do. I’m still at it part time.

The findings promise to enable clinicians to match treatments to genetic subtypes. “We hope in the near future to be where infectious disease and oncology are in [terms of] individualized treatment,” Nemeroff said. “We should be able to see patients, study them in terms of their genomics, characterizing them biologically, then match them to a particular treatment regimen. “That’s what we do in oncology, and there is no reason why we can’t do it in psychiatry,” he said. “Ten or 20 years from now, we will be sending our patients to the laboratory to characterize them in terms of genetic polymorphisms and/or to an imaging laboratory. Then based on those findings, and on the clinical presentation of the patient, we will be able to do what we can’t do right now, which is to answer the question—of all the treatments that are effective for depression, what is the best one for this particular patient?”

It’s a study done in Japan [as you can see from most of the author’s names]. 96 depressed people were put on a drug that has both SSRI [Selective Serotonin Reuptake Inhibitor] and Noradrenergic effects [meaning that it combines the properties of both major classes of antidepressants]. Their Depression was followed for six weeks using a rating scale. Then they typed their genotype for four enzymes that effect Serotonin and Norepinephrine. That’s not my point. My point is in these graphs:

Each one is the responses of patients based on one of the enzymes separated by genotype. My point is that they all look really close to the same to me. As it turns out, there is a barely statistical difference in the center graph between the blue line and the red line [p<0.03]. Earth shattering? Not! Then they broke down the patients based on some cut-off number on their depression scale and compared the responders to the non-responders for the genotypes. The only significance is shown in red [click on the table to see all of their data]:

This table says if you’re a TT for one of the genes [NET182C], you’re more likely to respond to the drug. But note that this difference is in a gene [T/C] that was not longitudinally significant [left graph]. Finding significance in non-significant series by plucking out a piece of data that’s then digitized by a cut-off point isn’t exactly kosher. That’s called massaging the data in some circles. Over and above that, assuming that their rating scale defines a true group of people; that their cut-off defines success; and the significance in this small japanese sample represents a real difference; it’s still really kind of hard to look at these numbers and conclude that "Genes Will Someday Help Select Depression Treatment" or as he puts it in another version, "Neurobiological Predictors of Treatment Response in Major Depression: Moving Toward Personalized Medicine in Psychiatry." When you take an aspirin for a headache, you’d like a bit more significance than this. Frankly, I doubt these results would be duplicated in a large study.