A few weeks ago I attended the first annual meeting of the One Mind for Research Campaign: Curing Brain Disease. (The group’s new CEO is Ret. General Peter Chiarelli, the commanding officer of the 1st Cavalry Division during the Iraq War, and you could practically taste the battle dust in your mouth at the end of the 3-day offensive to eliminate brain disease and its stigma within 10 years.) The meeting, which included NIMH director Thomas Insel, former NIMH director Steven Hyman, and American Psychiatric Association newly elected president John Oldham, featured sessions on the latest psychiatric neuroscience, stigma, and the aging brain. Here are some highlights:
One non-surprising take-home message is that psychiatric disorders are not only heterogeneous but many (most?) may eventually be best characterized at the level of circuits/systems. Regarding heterogeneity, the consensus among several speakers was that patients classified as having one illness or another should be further “stratified” as much as possible in order to treat with different neurodeficit-specific compounds (which is interestingly contrary to some of the proposed changes to DSM-5, such as lumping Asperger’s and Autism, or eliminating subtypes of schizophrenia). UPDATE (8/24/12) This statement requires clarification. The elimination of subtypes in schizophrenia (paranoid, disorganized, catatonic, undifferentiated, etc.) is due to the belief that the disorder’s clinical heterogeneity may be best understood by using a single diagnosis with distinct symptom “dimensions” of psychopathology – hallucinations, delusions, disorganized speech, abnormal psychomotor behavior, negative symptoms (restricted emotional expression or avolition), impaired cognition, depression, mania – each of which, it is proposed, would be measured on a 4-point severity scale. But it’s important to note that these dimensions, or “domains,” will “cross diagnostic boundaries” introducing a new set of challenges, especially for drug development (Carpenter, 2012).
Here’s an example of why categories can be confounding. Rene Hen gave a fascinating talk on a hippocampus-related process – pattern separation, the way in which our brains are able to reduce “the average overlap between two representations, thus making similar representations more distinct or orthogonalized in order to afford rapid learning without inducing interference and retrieval errors,” which is balanced by pattern completion. Pattern separation is impaired in PTSD as well as schizophrenia.
But I noticed that interest in the intermediate phenotype concept prevalent in psychiatric neuroscience literature during the last decade is now accompanied by an interest in big science, e.g., fresh efforts (reminiscent of Galen’s rete mirabile) to understand structural and functional connections within and across regions of the brain that are, also, exquisitely sensitive to environmental interactions. And this has significant treatment implications. As Emory fear scientist Kerry Ressler remarked, “we have to change how we think about therapy, the brain is not a bag of molecules that can be treated by a drug.”
MIT computational neuroscientist and TED pundit Sebastian Seung (“I am my connectome”) has received a lot of attention in the popular press recently for his work on the connectivity of individual neurons. (According to Seung, the dynamic or functional connectivity of neurons and the white-matter structural “connectome” interact in much the same way water rushing down a mountainside and the terrain over which it flows do.) But one of the most exciting sessions at the conference featured the work of Olaf Sporns and colleagues, who are focusing on structural and functional connectivity at the macro-scale, based on the concept of brain networks. These investigations rely on diffusion imaging (for structural connectivity) and resting state fMRI (for functional connectivity). In his talk, Sporns likened these anatomical connections to complex social or other kinds of networks that exist in the world. (“A common language is emerging,” said Sporns, one that is able to link network interactions within and across multiple levels of organization, which he referred to as “network science.”) Focusing on these interactions seems a little more doable than trying to link objective biomarkers to subjective experience (which Vaughan Bell of Mind Hacks likened to counting commas in a poem).
In the same session, William Seeley gave a fascinating talk on the connectional architecture of neurodegeneration in brain disorders, including Alzheimer’s, each of which has a distinct pattern. His group found, for example, that resting-state connectivity patterns of healthy brains related to episodic memory using fMRI mirrored the atrophy patterns in Alzheimer’s as the disease progressed from the medial temporal lobe to the neocortex. (The more radical idea (that may be reappearing in the science), another speaker said, is that these disorders are connectopathic and initially triggered by rogue proteins.) Here’s a link to the relevant Neuron 2012 paper.
In the session on stigma, Elyn Saks (USC), author of The Center Cannot Hold, discussed the “positive, negative, and cognitive” dimensions of schizophrenia, in regard to the latter dimensions specifically referring to short-term memory, visuo-spatial abilities, etc. She discussed how she was able to balance borderline impairment in some areas of cognition, e.g., short-term memory, by leveraging her strengths and “passed” for many years in academia as “normal.” During the talk I was struck by Dr. Saks’s certainty that psychotherapy is the reason for her lack of negative symptoms, which made me wonder, just how correlated are these symptoms with a person’s level of social disconnection? (The social neuroscience in this area by Naomi Eisenberger – who just published a review in Nature – and others relating social disconnection to some of the same pathways as physical pain is really interesting in this regard.)
Unfortunately, stigma is “alive and well,” according to sociologist Bernice Pescosolido, who spoke eloquently around the depressing fact that despite huge leaps in scientists’ neurobiological understanding of mental illness, despite the disappearance by the rest of us into what Mary-Jo DelVecchio Good calls the “biotechnical embrace” re matters of the mind, there has been virtually no change in Americans’ level of prejudice regarding persons whom NYU anthropologist Emily Martin refers to as living under the description of a mental disorder. We just don’t believe it’s a disease like any other, and if you or your family have the rotten luck to be on the receiving end, this adds astronomically to the confusion, anxiety, and fear about which neuroanthropologist Greg Downey has so eloquently written ( “Slipping into Psychosis”).
Alzheimer’s and the Fountain of Youth
But I don’t want to end this post on such a depressing note. Stanford researcherTony Wyss-Coray discussed the importance of not seeing the brain as an isolated organ. His group is studying the effects of stress, inflammation, and other environmental insults on brain function. In one experiment, the investigators infused the blood of young mice into old mice, and there were many positive effects in terms of neurogenesis, increased synaptic activity, increased spine density, reduced neuroinflammation, and improved spatial memory. (This announcement initiated a small wave of mouse jokes.) A brilliant neuroscientist sittling behind me said in a vaguely accented English (seriously) that it would be a difficult and expensive process to determine which substances within the blood to focus on; in the meantime, why not just transfuse old people with young people’s plasma? This is precisely what John Huston, playing a Joseph Kennedy-esque character, does in the movie Winter Kills (“I get it from the kids up at Amherst”). As the general concluded, “What I’ve learned among other things is that, THIS IS A GOOD TIME TO BE A MOUSE.”