Post-Traumatic Stress Disorder: Diagnosis & Therapy

4:00PM Traumatic Brain Injury Clinical Trials from the Past for the Future
Ross Zafonte, DO, Earle P. and Ida S. Charlton Chairman of the Department of Physical Medicine and Rehabilitation, Harvard Medical School; Visiting Professor, Harvard Medical School; Vice President Medical Affairs, Spaulding Rehabilitation Hospital; Chief of Physical Medicine and Rehabilitation, Massachusetts General Hospital, rzafonte@partners.org

Moderator: Steven Schachter, MD, Professor of Neurology, Harvard Medical School; Director of Research, Department of Neurology, Beth Israel Deaconess Medical Center; Associate Director, Clinical Research, Harvard Medical School Osher Institute; Member, Board of the Epilepsy Therapy Development Project; Founder & Editor-in–Chief, Epilepsy & Behavior; Editor-in-Chief of Epilepsy.com; CIMIT Program Leader, Neurotechnology; CIMIT Site Miner, BIDMC, sschacht@bidmc.harvard.edu

As the median age of the world population increases, degenerative diseases will become more common, and regenerative therapy will become increasingly important. Osteoporosis, a disease characterized by thinning of the bones, affects around 300 million people worldwide and may affect one billion people by 2050. In patients with osteoporosis, bone fractures are common and sometimes even lethal. Contrary to what one might think, the bones in one’s body are always changing and are always being renovated. Osteoporosis occurs when osteoclasts, cells that destroy bone, become more active than osteoblasts, cells that create bone. Osteoblasts develop from mesenchymal stem cells, and the number of mesenchymal stem cells in the body decreases with age. Certain researchers have attempted to boost the body’s supply of stem cells by locally injecting stem cells, but this technique leaves much to be desired. It can damage tissue, and it cannot be used to treat diseases in hard-to-reach organs or systemic diseases such as osteoporosis. In almost all cases, it would be safer and more effective to allow stem cells to reach their destinations via a vascular route.

Researchers in the lab of Robert Sackstein of Harvard Medical School are attempting to come up with a way to direct mesenchymal stem cells to the bone marrow. Their system is based on the fact that the bone marrow constitutively expresses e-selectins, a group of adhesion proteins. A potent ligand for e-selectins is HCELL, or hematopoietic cell E-/L-selectin ligand. HCELL can be made from the transmembrane glycoprotein CD44 by adding a few sugar molecules. Like most cells, mesenchymal stem cells express CD44 but do not express HCELL. Dr. Sackstein’s team has developed a method called glucosyltransferase-programmed stereosubstitution (GPS) that uses non-toxic enzymes to convert CD44 into HCELL. Mesenchymal stem cells subjected to GPS become tagged for absorption in the bone marrow. Dr. Sackstein’s group has found that injecting human HCELL-bearing mesenchymal stem cells into mice results in the homing of these cells to the bone marrow and in the subsequent deposition of human bone. The GPS method being developed in the Sackstein lab will hopefully lead to a regenerative therapy for osteoporosis. The technique could also be used, with modifications, to target stem cells to a variety of tissues, and its simplicity may someday enable it to be used in the third world.

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5:00PM Neurological Soft Signs in Post-Traumatic Stress Disorder
Roger Pitman, MD, Professor of Psychiatry, Harvard Medical School and Psychiatrist, Massachusetts General Hospital, rpitman@partners.org

Moderator: Jordan Smoller, MD, ScD, Associate Professor of Psychiatry, Harvard Medical School; Director, Psychiatric Genetics Program in Mood and Anxiety Disorders and Co-Director, Genetics and Genomics Unit, Clinical Research Program, Massachusetts General Hospital, jsmoller@partners.org

Post-traumatic stress disorder (PTSD) is a psychiatric condition resulting from a psychologically traumatic event. We have found evidence of subtle neurological dysfunction, manifest in more neurological soft signs (NSSs), in adult females sexually abused as children and in male Vietnam combat veterans. However, the identical co-twins of combat veterans show comparable NSSs, suggesting that the subtle neurological compromise in not caused by the psychological trauma, but rather serves as a pre-existing, probably genetic, risk factor for developing PTSD upon traumatic exposure.

In contrast to PTSD, traumatic brain injury (TBI) is a neurological condition that results from a physical trauma to the brain. However, mild TBI shares several symptoms with PTSD, e.g., detachment, difficulty concentrating.  Some have suggested that many cases of mild TBI are really somatoform (or “psychosomatic” in layman’s terms) in nature, rather than based upon real brain pathology. Physical aids are needed to make this differential diagnosis.  We hypothesize that if mild cases of TBI in returning veterans are truly of neurological origin, these veterans should have more NSSs than the “baseline” level of NSSs found in PTSD veterans.  Dr. Roger Pitman will help us study this question.

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