The Scientists and Investigators of JBRF

Demitri F. Papolos, M.D.
Director of Research

Dr. Demitri Papolos is an Associate Professor of Psychiatry and Co-Director of the Program in Behavioral Genetics at the Albert Einstein College of Medicine.

A graduate of Harvard College, Dr. Papolos received his M.D. from New York Medical College, and took his psychiatric residency at the New York State Psychiatric Institute of the Columbia University College of Physicians an Surgeons.

After completing his residency, Dr. Papolos joined the faculty of the Albert Einstein College of Medicine as an attending psychiatrist at Jaccobi Hospital. He later moved to the Montefiore Medical Center to become Director of Inpatient Psychiatry and Director of the Treatment Refractory Depression Research Unit. In 1990, with the support of the Ruane Family Foundation, a NARSAD Investigator Award, and an NIMH Physician/Scientist Career Development Award, Dr. Papolos teamed with Dr. Herbert Lachman to establish the Program in Behavioral Genetics at Einstein. The focus of their work was on the novel action of lithium salts on gene expression and the investigation of stress-related animal models of depression.

More recently, Dr. Papolos and his collaborators at Einstein and SUNY-Syracuse have been pursuing a line of inquiry that originated from their study of children and adolescents with an unusual genetic condition known as velo-cardio-facial syndrome (VCFS). They found that a high rate of VCFS patients have bipolar spectrum disorders, and that the behavioral symptoms that arise appear to have a developmental sequence that parallels the pattern of symptom development they have since discovered in patients with childhood-onset bipolar disorder, who were ascertained from the general population.

Because the emergence of the medical and psychiatric symptoms in VCFS is associated with a micro deletion on chromosome 22, their finding may be the first direct link of a psychiatric illness to a discrete molecular target. In an extension of this diagnostic study of VCFS children, a positive allelic association was found between a variant of the COMT gene and ultra-ultra rapid cycling – a pattern of cycling most commonly expressed in childhood-onset bipolar disorder. Prompted by these findings, Dr. Papolos and colleagues examined adult patients with de novo rapid-cycling bipolar disorder from the general population, and again found an association between the low-activity COMT allele and this form of the disorder, a finding that has been confirmed by an independent research team. Following the publication of this work in the American Journal of Psychiatry , the American Journal of Human Genetics, and in Molecular Psychiatry, the COMT gene has become one of the most actively studied genetic variants in psychiatric genetics.

Dr. Papolos edited the monograph Genetic Studies in Affective Disorders, (John Wiley & Sons, 1994), and is the co-author with his wife, Janice, of Overcoming Depression, Third Edition (HarperCollins,1997), the most comprehensive book written for the lay person on depression and manic-depression. The book is now in its 35th printing. Demitri Papolos is also the co-author of the highly acclaimed book, The Bipolar Child, which has been featured on ABC News’s 20/20, the Oprah Winfrey Show and Public Radios’s The Infinite Mind. Dr. Papolos also has a private practice in New York City and in Westport, CT.

Gianni Faedda, M.D.

Dr. Gianni Faedda is a board-certified psychiatrist, clinician and a psychopharmacologist with extensive research experience in the diagnosis and treatment of bipolar affective disorder throughout the life-cycle.

Dr. Faedda trained at the Lucio Bini Center in Cagliari and Rome, followed by a residency at Harvard’s McLean Hospital. After moving to the Albert Einstein College of Medicine in 1992, where he became Director of Research in Child and Adolescent Psychiatry, he received a Stanley Foundation Grant to study the efficacy of lithium salts in the treatment of adolescent-onset bipolar disorder.

In 1995, Dr. Faedda and colleagues published a review of the world literature of over 2000 cases of juvenile-onset bipolar disorder. Entitled “Pediatric-Onset Bipolar Disorder; A Neglected Clinical and Public Health Problem” and published in the Harvard Review of Psychiatry, this work was seminal, and often cited in subsequent research publications in the field.

Currently, he conducts independent research and collaborative projects with centers in the United States and Italy. In 1993, he founded and still directs the Centro Lucio Bini Center of New York. In 1999 he founded Understanding Manic Depression, a non-profit organization promoting public awareness of MDI, and serves as its Executive Director and Chairman of the Scientific Advisory Committee. Since 2000, he has been a member of the Professional Advisory Board for the Child and Adolescent Bipolar Foundation. In addition to being on the Scientific Advisory Council of JBRF, Dr. Faedda is a supervising faculty member of the JBRF Fellowship Program.

Mark G. Frei, Ph.D

Mark G. Frei is a co-founder of Flint Hills Scientific, L.L.C., of Lawrence, Kansas, which he also managed for 16 years. He specializes in real-time quantitative analysis, filtering, identification and control of complex systems and signals and in algorithm development for intelligent medical devices. He is an inventor on over 40 patents, has authored or co-authored over 60 scientific articles and abstracts, and is a world-leader in the field of epileptic seizure detection. Prior to his work with FHS, Dr. Frei was a post-doctoral fellow at the University of Kansas, in the Kansas Institute for Theoretical and Computational Science, the Comprehensive Epilepsy Center, and the Department of Mathematics. He received his Ph.D. in mathematics from K.U., with research specialties in the fields of modeling, prediction, and adaptive control of complex systems. He received his M.S. in applied mathematics/electrical engineering from the University of Southern California and B.A. in mathematics from UCLA. Prior to his doctoral training at the University of Kansas, Dr. Frei was a member of the technical staff of TRW, Inc. in Redondo Beach, CA.

Herbert Lachman, M.D.

Dr. Herbert M. Lachman is a psychiatric geneticist and molecular biologist at the Albert Einstein College of Medicine. He is a co-author of 90 scientific papers, book chapters and other publications. Dr. Lachman completed a residency in Internal Medicine and is certified by the Board of Internal Medicine. After completing his residency, Dr. Lachman began his research career as a postdoctoral fellow in the Department of Medicine, Division of Hematology at the Albert Einstein College of Medicine. He then completed a 3 year postdoctoral fellowship in the Department of Cell Biology. During his postdoctoral training and early academic career Dr. Lachman studied the mechanism of leukemia cell transformation and differentiation. He was an early investigator on the role of the c-myc and p53 oncogenes in cellular differentiation and malignant cell growth.

Influenced by the early linkage findings in bipolar disorder and several papers on the molecular basis of lithium action that appeared in the general scientific literature in the late 1980s, Dr. Lachman made an abrupt career change and began his research into the molecular and genetic basis of bipolar disorder and schizophrenia. Dr. Lachman teamed with Dr. Demitri Papolos and to describe a novel action of lithium salts on gene expression. This work prompted a line of investigation that continues to this day in many labs throughout the world.

In the mid 1990’s, Dr. Lachman identified the genetic basis for the variable enzymatic activity found in an enzyme known as COMT. This enzyme is involved in the metabolic degradation of catecholamine transmitters and had long been considered a pathway for the development of mood disorders. This work led to the discovery that the COMT gene may be a modifying factor in both bipolar disorder and schizophrenia. Dr. Lachman, in collaboration with Dr. Demitri Papolos, showed that the variant identified in the original COMT study may increase the risk for the emergence of an ultra-ultra, rapid cycling pattern in patients with bipolar disorder. Dr. Lachman and his collaborators later discovered that the COMT variant is a potential risk factor for violent behavior and suicidality in patients with schizophrenia. Based on these studies, the COMT gene has become one of the most intensively studied genetic variants in psychiatric genetics.

Dr.Lachman was the principal investigator on a NIDA-funded study to identify genes involved in opioid dependence, which resulted in the identification two potential candidate genes. He currently holds two NIMH grants. One grant funds a continuation of his work on molecular and genetic pathways in bipolar disorder and schizophrenia. The other funds a novel approach to explore molecular and cellular phenomena in neuropsychiatric disorders: the development of patient-specific induced pluripotent stem cells (iPSCs). iPSCs are derived from skin cells using a revolutionary process discovered by Japanese investigators 5 years ago. Basically, Dr. Lachman and other researchers in this area are able to turn skin cells into neurons. By creating iPSCs in patients with specific genetic abnormalities (the Lachman lab is focusing on patients with chromosome 22q11 deletions), neurons harboring the defect can be grown in the lab and investigated. The Lachman lab has made fundamental discoveries on genes that are involved in the growth of new neurons and hopes to use the iPSC system to develop assays to rapidly screen for new drugs.

Steven Mattis, Ph.D., A.B.P.P.

Dr. Steven Mattis is Clinical Professor of Neurology (Neuropsychology) at Weill Medical College of Cornell University and Adjunct Professor of Neurology (Clinical Neuropsychology) at New York University. He serves as Director of Neuropsychology Post-Doctoral Training in the Department of Neurology at the Weill Medical College of Cornell University, and is a partner in the Mattis & Luck Center for Neuropsychological Services, LLP.

Dr. Mattis is a Board Certified Clinical Neuropsychologist (American Board of Professional Psychology) and Fellow of the American Psychological Association. He is past-president of the Neuropsychology Division (Division 40) of the American Psychological Association, the International Neuropsychological Society, the American Board of Clinical Neuropsychology, and immediate past-president of the American Board of Professional Psychology.

Steven Mattis has served as Director of Neuropsychology, Department of Neurology, Albert Einstein College of Medicine; Director of Neuropsychology, Department of Psychiatry, Cornell Medical Center; Director of Psychological Services of Hillside Hospital-Long Island Medical Center; and as Grant Reviewer for neuropsychology in the Human Development and Aging Study Section of the National Institutes of Health. He sits on the editorial boards of several journals, and has authored over 50 articles in peer-reviewed journals, book chapters, and is the author of a widely used measure of cognitive impairment in adults.

Dr. Mattis’ research activities in learning disabilities in children and the effects of brain damage on cognition have more recently centered on the neuropsychology of affective disorders. In collaboration with Dr. Demitri Papolos, he is currently investigating the neuropsychological status and variability in status of children with juvenile-onset bipolar disorder.

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