Fog Fighting
An entry about these past few days and weeks on psychiatry, which when I first began composing it began in frustration, and eventually ended up in hope...
It gets asked so many times. If we biomedical scientists are so smart, why can't we just take the brains of depressed folks, compare them to the brains of not-depressed folks, and do something about depression? You know, collect a bunch of brains, take 'em apart, and figure out the difference is between the few lucky folks who manage to avoid depression, and everyone else?
Well, as it turns out, a group of scientists is doing exactly that...
The completion of the Human Genome Project -- the mapping of the complete human genome -- provided the foundation upon which to revisit old questions in a new light. The functions of a cell are regulated by it's genes; differing patterns of genes turning on and genes turning off lead to different behaviors by a cell; and with the completion of the genome project and it's associated efforts, we have a rough idea what kind of genes we all have. Using modern analytical technologies allow scientists to watch thousands of genes at once to see which ones turn on and which ones turn off in different diseases. For example, depression.
A national alliance of biomedical scientists -- the Pritzker Consortium -- set out to use these methods to attack the problem of depression. Hundreds of people volunteered to, after death, donate their brains to the effort to better understand depression. The Pritkzer Consortium scientists carefully harvested samples from key regions from each of the donated brains, then mapped the patterns of genes that were active and inactive from each region of each brain. The Big Idea (tm) was to compare the patterns of genes active in people without any history of major depression to the patterns of genes active in people *with* major depression, and look for differences. The hope was that by identifying those differences, one might be able to get new ideas about where depression came from -- and how to fight it.
And they found something.
To handwave insanely, in Evans et al., the Consortium's scientists noted that groups of genes were in fact regulated differently in brains from people with major depression vs. people without major depression. In the paper, they highlight differences in the activation and inhibition of genes in the fibroblast growth factor (FGF) family, showing that certain members of that gene family show changes in depressed individuals, changes which get reversed in depressed patients treated successfully with anti-depressants. The fibroblast growth factors are hormones which provide key signals driving the growth and change of tissues, including brain tissue. And more recent follow-up preliminary work, presented at a psychiatry symposium here on campus a few weeks ago, suggest that tinkering with the FGF system in living animals with appropriate treatments can maybe make the mice more or less anxious and depressed.
There is a *giant* distance between these most preliminary experiments and actual treatments for people. And the science itself is only in it's most preliminary stages, with plenty of room for arguments and the need for vast amounts of further work. But this work by local Michigan folks is one of many tiny first steps forward into one of the most vexing of problems facing medicine: attacking the inscrutable fog that are the diseases of psychiatry.
These last few weeks on psychiatry I have found far more frustrating and far more depressing than any of my previous work on wards yet.
In days on the inpatient services, in on-call nights after nights in the Psychiatric ER, I personally found myself far more frustrated, far more depressed, than I ever was on any other service. Outsiders would think that a place like Transplant or Heme/Onc, with all the patients we are too often unable to save, would be more depressing than Psych. But, for me, there is a tremendous difference between the fights we waged to help kids on the Pediatric cancer service, and our efforts in the Psych ER and the Pediatric Psych locked wards. At least on Heme/Onc I knew what the hell enemy I was fighting.
On Heme/Onc, you knew what the problem was. You could map the tumor with imaging systems and dissect the tumor with biopsies. You could map the identifying surface features of the cancer cells with antibodies and characterize the breaks and bumps on the mutant chromosomes inside. You could measure progress by measuring the growth or shrinkage of tumor masses and the numbers of cancerous blast cells in the blood. You actually could tell whether you were winning or you were losing, with numbers and percentages. You at least could figure out what you were actually battling, and tell if your treatments were working or not working. And even those fights you lost you could at least avenge, by taking the tumors back to the lab, taking them apart with molecular biological techniques, learning their secrets, so that next time, the next battle, you could come at it with new drugs targeted against what you'd learned. If nothing else, you could at least give the families of the lost that comfort: that we could learn from what their child had gone through, and use that knowledge to someday help others.
But against depression? Against the quicksand that sucked people down into black holes that many could never escape? Against the enemy that brought to our ER young women with slashed wrists, young men crippled by guns fired by their own hands, patient after patient, young and old, of every race, of every background, into our ER with a whole litany of personal disasters behind them? These last few weeks -- these last few days on call in the Psych ER -- were filled with patients destroyed by drug addiction, domestic violence, attempts at suicide. Patients from broken homes, failed jobs, ruined educations, you name it, all arising from depression's horrible grip. And as a profession, we don't understand damn-all about it.
There's no lab test that can quantify or identify depression. No imaging protocol, no scan of the brain, which can pinpoint it. Our drugs for depression are incredibly inadequate and we really don't have any understanding at all which ones actually work and which ones don't, because we can't even really tell how well the medications we give our patients are actually working. Sometimes they do. Often they don't. We don't really know why. There is no test, no study I can order that can tell me definitively that the drugs I've given them have made their depression 10 or 20 or 50% better -- or even better at all. Not in the same way I can track progress with an exact volume on an attacked tumor or an exact blast count for a in-treatment leukemia. Even the very reports patients give us on how they're feeling are filtered through the same fog that covers their mood and senses. And so for patient after patient who came to us with lives wrecked by depression's power, it just seemed that all we could do was tinker with their drugs, give them an ear to listen and a shoulder to cry on, and when they were sent onwards pray that this time, perhaps, it might actually do some good.
There are a lot of fights we can't win yet in cancer; but at least we know what the hell we're fighting. At least we know where the enemy is, at least have something to study. Fighting cancer -- fighting most disease -- is like taking on a dragon, and looking for the missing scale to target the Black Arrow at. Fighting depression... is like fighting a monster made of smoke. Like swinging a sword into a fog that just makes your patients disappear. That takes your friends away. It's like trying to fight a mist with a blade. And just as frustrating. With depression, there's so far nothing you can target. Nothing you can attack. Against the fog of depression all you can really do for your friends is to try to hug them close in your cloak and hope the fog lifts in time.
Which is why studies like the ones advanced by groups like the Prizker Consortium, by professors here at Michigan, are so important. Like studies like the one I was lucky enough to be a part of last summer. Thousands of scientists worldwide are trying, from dozens of angles, to find a way of defining, measuring, and attacking depression and other psychiatric disorders the way we can attack cancer or diabetes or kidney disease. Searching for a way of finding the elusive heart of the monster made of mist, so that we can finally drive a stake through it. For all the awesome successes achieved by modern medical science, our current ineffectiveness in the face of something as widespread and as crippling as depression is incredibly frustrating, our relative inability to help our patients on psychiatry incredibly depressing. The road ahead for psychiatric disease is far less clear than it is for diseases like cancer. But there is surely a road to be found, and I hope it is not too many more years before we find a way to fight the fog -- and win.