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Highlighting Recent Clinical Developments
Question:
"Can you highlight a few clinical developments that occurred in the past year?"
As Chairman of the U.S. Psychiatric and Mental Health Congress this year and last, one of my small pleasures has been to subversively use my welcome session at Psych Congress as a platform to briefly review what I consider—with no real objectivity at all—to be the most important scientific and clinical developments of the past year. As we prepare for this year’s meeting, I thought I might use this space to highlight a few of the developments that will be featured in my introductory talk.
2012 has not been a banner year for clinical developments. To my knowledge, no new psychopharmacologic agent has been approved this year. We appear to be at least a year away from the arrival of the small cadre of agents that are currently on the approval launching pad. More ominously, I see nothing in this year’s research to suggest that we have made significant progress toward any type of “miracle cure” for the dreadful conditions that mental health clinicians confront.
But this is not to say that the year has been a scientifically dull one. Quite the contrary, science is exploding all around us. In fact, if you are not actively involved in scientific work, or even if you are, but have a horizon limited to your own small area of study, it is hard to really conceive how rapidly things are moving out on the far frontier of knowledge.
The most important example of this phenomenon occurred this past summer. Various top-flight journals published 30 research reports providing the results of a huge, decade-long effort named the “Encyclopedia of DNA Elements (ENCODE)”. The upshot of this stupendous effort is best captured by the title of an editorial about the project in the journal Science: “ENCODE Project Writes Eulogy for Junk DNA”.
If you can remember back to the end of the genome project, the most shocking finding was that among the 3 billion or so DNA bases in our chromosomes only about 21,000 seemed to code for active genes that made proteins. The rest of the material seemed to be accumulated “junk” that did nothing. This immediately led to several questions:
“How could so few genes make something as complicated as a human being?”
“Why has the genome study done so little to advance healthcare discovery?”
The ENCODE project provides incisive answers to both of these questions. First, 21,000 genes cannot make something as stupendous as a human. We now know from this recent work that fully 80 percent of the genome, including most of the “junk DNA”, serves a biochemical purpose. The reason the genome project did not deliver on its expectations is almost certainly because much of what makes us who we are is hidden in the “junk” and not in the official genes.
ENCODE explains that many of the genetic changes (or single-nucleotide polymorphisms, SNPs) that appear to be risk factors for psychiatric disease are buried in these junk regions. Now we know that although these areas of the DNA don’t produce proteins directly they have huge impacts on how we think, feel and behave.
The older I get the more I think life is fundamentally all about relationships, about how one thing affects another and is impacted in turn. This truth is amply reflected in the ENCODE findings. Most “junk DNA” is actually tuning other parts of the genome on and off in response to a huge number of signals. Some of the signals come from the environment, others from various regions of the genome. We know that many psychiatric disturbances are caused, worsened or improved by malfunctioning relationships. I find it fascinating that this same pattern is reflected down into the building block molecules of our bodies. It’s fascinating to learn how areas of DNA operate with each other, how they cooperate, compete and work together. It really seems to be at the core of who we are.
Speaking of relationships let me close by highlighting another of what I consider to be the most important developments of the year: our increasing recognition that our bodies—and our brains—are not fully our own, but are really group property.
I am speaking here of the fact that only one out of ten cells are in our body are mammalian. The other 9 are bacterial. In fact, discoveries over the past year further support seeing humans not as single organisms but rather as mixed-use communities of human and bacterial elements, with most of our bacterial colleagues residing in the gut, lungs and on the skin. Consider the fact that even our mammalian cells reflect the long-ago unions of bacteria. Much of our DNA appears to be of viral origin. Therefore, it is not too far-fetched to see human like this: when the bugs wanted to get a better look around they created us to provide them with consciousness.
The ramifications of this point are huge and stretch from how we raise our children and how we treat infections to how we think about the web of relationships most relevant to optimal emotional functioning. In this regard, it is increasingly apparent that the microbes that share our bodies with us can have powerful effects on brain functioning in adulthood and on how the brain and related neuroendocrine stress systems form during development. Strategies that more effectively mediate our relationships with the microbial world may hold remarkable promise as novel treatments or preventive strategies for mental illness.
Of course, ENCODE doesn’t provide any quick psychiatric fixes, nor is it likely to. But along with our growing appreciation of the power of epigenetics, these findings will certainly open up new avenues for intervention over the next decade.
Here I can only offer teasers for these fascinating ideas. Not to peddle my own wares, but if these ideas are of interest come hear more about them in my session, “Harnessing the Mind Body Connection” at 2012 Psych Congress. And of course, if you can rouse yourself early enough on the first morning of congress, come hear my opening talk and learn more about other key developments that have occurred in the past 12 months.
