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PTSD – a speculation

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“Are you abandoning me? Have you given up on me?”. These were the questions my wife was asking me in my dreams, a week or two, prior to my planned recent travel abroad. No, my wife and I were not engaged in a bitter marital discord or about to break up. Rather, as I have catalogued elsewhere on this blog, my wife endured and fought a very painful battle with cancer before finally succumbing to it. That was almost three years ago. This dream highlights something important about our minds. It draws attention to the fact that although I have never felt it overtly, there is a lingering feeling of guilt that I could and should have done a lot more for her.  Then, of course, there are always undercurrents of hopelessness, and thoughts contemplating the fleeting nature of our existence not to mention inexplicable feelings of sadness, the onset of which could be triggered by a piece of music or a story in the news.  In short, existential angst amplified by looking at life through the lens of a departed individual who is of deep emotional significance to you. Left unchecked, these thoughts and feelings could create a positive feedback loop leading to a full blown depression, and complete withdrawal from society. The checking comes from a grieving process involving intense rationalization or cognitive effort and a constant readjustment of our worldview (could be rational or irrational) to accommodate these life shocks. In fact, most people are able to regain their bearings, given adequate time (note: the recovery period is not the same for everybody).  [ Fortunately for me, this experience has translated into a passion :  to help transform the practice of medicine and delivery of healthcare through innovative use of technology. That is now my singular focus.]

The Wall Street Journal published an article – Last Marine Standing : A Life Tormented by Survival.  It chronicles the life of Marine Lance Cpl. Williams post-Iraq. It is a very poignant article. It has been seven years since 11 members of his team were blown up in a roadside bomb. Cpl.Williams remains tormented by guilt, hopelessness, and other debilitating symptoms that  make it difficult for him to lead a “normal” life. The article offers some clues on how the Army psychiatrists are approaching the treatment of these individuals, as in the following excerpt:

“….The VA’s Dr. Maguen hasn’t met Lance Cpl. Williams. But she says his symptoms are typical of these more-complicated cases “where there are many different elements of moral injury and loss acting together, making it challenging for [the patient] to recover.”

Researchers are just beginning to study the prevalence of these  types of psychological injury among combat veterans and seek treatments to supplement PTSD therapies. In small-scale studies, researchers have found that about 30% of Marines and soldiers seeking treatment reported that moral-injury experiences were the incidents that most haunted them on their return from war.

In a pilot program with the Marines, clinicians used “adaptive disclosure” therapy to treat traumatic loss and moral injury. Patients held mock conversations with dead friends and imagined aloud how their buddies would respond.

The Pentagon has agreed to fund a larger-scale trial among Marines, according to psychologist Brett Litz of the Boston VA, who along with Dr. Maguen is a pioneer in the field. Dr. Maguen, meanwhile, is recruiting candidates for a VA study of treatment for troops troubled by having taken the lives of others…..”

Pioneers they may be, but I don’t think techniques like “adaptive closure” go far enough. Neither do the standard assortment of available drugs in the psychiatrist’s toolkit. As an alternative, I want to propose a cognitive neuroscience framework that may help illuminate the underlying mechanism and motivate approaches to treatments that may prove more effective.

Ever heard of Theory of Mind (ToM). If you have not, don’t worry. From Wikipedia,

Theory of mind is the ability to attribute mental states—beliefs, intents, desires, pretending, knowledge, etc.—to oneself and others and to understand that others have beliefs, desires, and intentions that are different from one’s own…”

We tap into this ability for everything, from buying a gift for our beloved to anticipating the reactions of our bosses when asking for a raise. In short, we have the ability to running simulations of imagined events and predict behaviors of the other actors in the scene. Wearing my scientific hat, I have always wondered whether grief intensely engages the ToM system (because emotional centers are also included)  in our brains. More specifically, I view a large portion of grieving as involving simulations in the brain taking the departed person’s point of view or reliving moments of joint interactions and anticipating how they may have  reacted emotionally (happy, angry, etc.,). “Moving on” is then an disengagement from the simulation behavior (or, at a minimum, significant blunting of the emotional components) specific to the departed individual(s). Disengagement is a function of intense rationalization, which I alluded to earlier.

I believe this can be extended to, at least, certain flavors of PTSD experienced by the veterans returning from war. In these individuals, it is the exaggerated response of the ToM system. In some sense, the systems engaged in “theory of mind” have gone awry. In the link below, is a very interesting conversation with the commander of a bomb diffusion unit.

http://www.npr.org/2012/07/09/156454241/the-life-that-follows-disarming-ieds-in-iraq

He mentions that in crowded places like airports, he is constantly looking at “who he needs to kill” to get to an exit, an example of “theory of mind” misfiring.

My prediction is Transcranial Magnetic Simulation knockout of  selective parts of the ToM system (particularly regions involved in emotions) would help provide relief (at least temporarily) for such individuals or those trapped in the local minima of “overuse of simulations”. The neural correlates of the ToM system are being actively studied by experts in the field and I am pretty sure what I noted above can be mapped onto actual brain sites for targeted therapies.

One of the hallmarks of PTSD is “stress”. Robert Sapolsky wrote a book called “Why Zebras Don’t Have Ulcers?”. The simple answer is, their stress levels are highest only when the predator is in sight. When this happens, they literally run for their life. If they survive, they go back to grazing. No more thinking about who is going to attack me next or what other danger should I worry about now. Out of sight, out of mind. But we on the other hand, have the brilliant twin abilities : running simulations and making predictions. One massive side-effect : grief and its really ugly cousin PTSD, witness Marine Lance Cpl. Williams.

Written by asterix98

February 18, 2013 at 1:49 am

n of 1 medicine

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The history of modern medicine begins around late 18th century with Edward Jenner’s discovery of smallpox vaccine and Humphrey Davy’s discovery of nitrous oxide, whose anesthetic properties proved very useful for making surgeries painless. Since then medicine has made tremendous strides in eradicating major diseases like smallpox, polio, malaria, cholera, and tuberculosis, in most parts of the world. Indeed, the list is long and impressive. Because of these advances, mortality rates have gone down significantly across the globe with a concomitant increase in life expectancy.

Western or allopathic medicine,  as currently practiced, treats the average. This approach has been very effective in treating a wide range of conditions – from the common cold to heart attacks, provided the underlying medical condition or disease has a common physiological basis that is broadly applicable across the entire human population. But, over the years, the field of medicine has discovered there are numerous diseases that have a genetic basis – examples include cancer, diabetes, cardiovascular, and others such as Tay-Sachs disease, sickle cell anemia, which have an even more specific pedigree. These diseases have yet to be corralled and contained.  Recent advances in microbiology have spawned the -omics revolution: microbiomics, proteomics, genomics, metabolomics, to name a few. In an earlier post – the dawn of omics ,  I had tried to captured some of the excitement surrounding these emerging fields of study.

Numerous articles, on these topics, continue to be written in the popular press. Recently, microbes made the cover page of the Economist and the attendant articles can be found here- Microbes maketh the man ; Me,myself, us. The upshot is we have symbiotic partnerships with multiple strains of bacteria that make their home in different nook and crannies of the body.  Here are some specific examples (quoted from the article) on how these microbiomes help us “….The microbiome does many jobs in exchange for the raw materials and shelter its host provides. One is to feed people more than 10% of their daily calories. These are derived from plant carbohydrates that human enzymes are unable to break down. And not just plant carbohydrates. Mother’s milk contains carbohydrates called glycans which human enzymes cannot digest, but bacterial ones can….”

Disturbing this ecosystem results in a myriad of consequences. So,  “…these links are most visible when they go wrong. A disrupted microbiome has been associated with a lengthening list of problems: obesity and its opposite, malnutrition; diabetes (both type-1 and type-2); atherosclerosis and heart disease; multiple sclerosis; asthma and eczema; liver disease; numerous diseases of the intestines, including bowel cancer; and autism….” Probiotic foods then are supposedly targeted at restoring the balance…” If you missed it, yes, autism is on this list !!

The other branch of -omics that has gained a lot of currency in the media is genomics. The holy grail for these practitioners – $1000 genome (to sequence, that is). Matthew Herper of Forbes has put together a nice summary article( The Gene Machine) on the most recent developments in gene sequencing. One of the characters he mentions is Jonathan Rothberg, probably the reigning rockstar of this industry, for having invented among other things, the Personal Genome Machine (the article has more specifics). But the point here is gene sequencing has moved from the purview of giant labs to your desktop! Also, the turn around times for having a genome sequenced, for a panel of genes, have come down dramatically. Because of these advances, places like Baylor College of Medicine, MD Anderson and others are undertaking vigorous research efforts to understand and actively treat various cancers.

I was lucky enough to attend a few sessions over two days at the ION World 2012 conference where Rothberg and other luminaries gave keynote speeches. It was really exciting to hear these folks talk of the coming revolution in medicine. This is when I first heard the phrase “n of 1 medicine”.  N of 1 (or personalized medicine)  refers to the practice of medicine based on an individual’s “omic profile” as opposed to the traditional approach of medicine, which is based on the average profile (derived from large populations).

Clearly, we are witnessing medicine’s new frontier. For me, and I am sure for many others, the view from this frontier is breathtaking. Of course, there is a lot of hype surrounding all this. But discounting the hype, there is significant and steady progress being made through multidisciplinary collaborative efforts (cloud computing, bioinformatics, semiconductor technologies, and fundamental science). As of now, next generation sequencing (NGS) efforts are primarily focused on building the tools that allow us to ask the basic questions and get answers in the shortest possible time. Once past this, we will need to focus on translating the science into clinical practice. Because of its very nature, n of 1 medicine may require a throwback to the old fashioned pharmacies where your medication will be mixed in real time based on personalized omit profiling.

Opportunities, to participate in this revolution, abound.

Written by asterix98

September 30, 2012 at 2:49 am

The dawn of “omics”

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I attended a day long workshop at Stanford a couple a weeks ago. The topic  – Emerging Medical Computing: Healthcare Up-Close and Personalized  (14th Annual NFIC Conference June 16th at Stanford University, CA).

The workshop was about “..The intersection of computers with medical data is creating a form of direct and individualized diagnosis and treatment that transform health care to truly being up close and personalized medicine……..

Starting with computer based individual medical modeling based on genetics and biometrics, the conference will move on to cover personalized sensors in monitoring, diagnosis, treatment, and prosthetics….”

I will focus on one of the speakers, Michael Snyder. He spoke on “Adventures in Personal Omics”.  Our health is determined by a combination of our genome and exposure to the environment (epigenetics).  Given this, genome sequencing or genomics, is extremely valuable in understanding and treating human diseases (eg., cancer). Medicine as practiced today treats the average. Personalized genomic sequencing affords us the opportunity to examine human variability in the genetic makeup leading to nuanced understanding of disease risk at the personal level. DNA sequencing seems to be loosely following Moore’s law in that prices have been dropping ~10x in 15 months. Current average cost is about $3.5K, but $1K options are also round the corner. Personalized medicine, allows risk prediction, diagnoses, monitoring and treatment,as well as understanding disease state at an individual level. This is indeed revolutionary. In Snyder’s lab, they are able to produce a personal “omic” profile or POP. In fact, Snyder has been his own subject and has been monitoring his POP over the past 27 months and learned a tremendous deal. He was able to predict his diabetes risk from his POP (eventually he contracted it but was able to manage it). You can read this fascinating story here. Of course, significant challenges remain in translating this to everyday medical practice, because the clinical interpretation component- extracting useful information-  is still very high (~$30K).

There is yet another trend in the realm of personalized health, metaphorically called the “quantified self”.  The economist has a nice overview article – Counting every moment .  These efforts are directed more at the macro indicators of personal health (eg., height,weight, food intake, sleeping etc.,).

It gets even more interesting. Matt Ridley wrote a piece in the WSJ on the microbial ecosystem that is very essential for our functioning. He writes “… the startling statistic that there are at least 10 times as many bacterial cells (belonging to up to 1,000 species) in your gut as there are human cells in your entire body: that “you” are actually an entire microbial zoo as well as a person. You are 90% microbes by cell count, though not by volume—a handy reminder of just how small bacteria are.” These microbes make up between two to five pounds of your body weight!  Just like Snyder, Larry Smarr, an astrophysicist turned computer scientist, is meticulously charting his microbial makeup and has discovered fascinating facts about his body and explanations for his illness, even educating the doctors that were treating him, in the process. You can read all about this in the Atlantic article – Measured Man.

I could’nt help wondering that all of these efforts are bringing on a whole new meaning to the Socratic quote “A life unexamined is not worth living”.

Written by asterix98

July 4, 2012 at 6:32 pm

Trends in the lifesciences

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If you are interested in healthcare or the lifesciences, this is a great time to get involved. Especially if you are a technologist. There are a number of reasons. The trajectory of healthcare costs is soaring and the trends are unsustainable. There are not enough doctors to handle the demand for care. Most affected is the aging population. After decades of stubbornly resisting the  rapid adoption of technological advances, the healthcare industry seems ready to embrace them. Witness the power of a tool like Watson from IBM. Cloud computing, big data, wireless sensors, wireless technology (near and far field), tablet computing combined with trends in bioengineering, molecular genetics, biomedical engineering and other disciplines is now enabling a very exciting interdisciplinary effort that is poised to revolutionize healthcare and lifesciences. (In the 90s, the genesis of cognitive neuroscience,  combined forces from computer science, neuroscience, psychology, physics, and other fields to make significant advances in the understanding of the human brain. I am proud to have been a part of it).

In an earlier blog, I wrote about one such effort at the Smolke lab at Stanford. A couple of days ago, I learned of this great  program at John Hopkins University. You can read more about CBID here. It brings together partners from the industry, biomedical engineering and medicine to deliver, pratical and immediately applicable innovations to healthcare both in the developed and developng world. One brilliant example of a product developed at CBID is a marker like pen filled with the ingredients required for detecting eclampsia (high blood pressure) in pregnant women. What is neat about this device is that it enables women in the underdeveloped world to be diagnosed at the cost of pennies. You simply mark a piece of paper with the device. The women pee on the paper and the litmus test indicates Yes or No. A clever part of this design : the cap of the marker is the same color as a positive result. Neat!

Other examples of innovation (not from CBID) include the Mobisanti portable ultrasound for your mobile phone!! Skin implants for Alzheimer’s patients to keep track of them and even guide them. Subvocal speech recognition (out of NASA) and this one is way out there : the Proteus raisin microchip. This is a biodegradable chip that can be swallowed. It sends out a signal to the doctor that you have taken the pill (something drastic like this is necessary because the medical adherence rate is about 21% !!).

We at iNDx Technologies are bringing together pathologists, physicians, molecular geneticists, and technologists, to deliver some innovative products for enabling integrated diagnostics for improving quality of care at reduced costs. Stay tuned!

Written by asterix98

February 26, 2012 at 1:50 am

Woodpeckers

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 So what is remarkable about woodpecking? Consider this, the woodpecker pecks at the rate of 20 times per second. The impact per contact is about 1200 g’s of force!! And still, the woodpecker flies away with its brain still intact.

Researchers, working in the fascinating area of study called Bioengineering, have unraveled the genius of nature  behind this extraordinary feat. Essentially, a progressive set of bone structures dampen the shock and a final filament like layer absorbs the vibrations. These same researchers have replicated this prinicple synthetically and had outstanding success in protecting sensitive electronic circuits from extreme shock.

Awesome!

Written by asterix98

February 27, 2011 at 7:29 am

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