RESEARCH OVERVIEW 2005
Clinical Unit-Based Research
Alcohol and Drug Abuse Treatment Program
Program Professional Personnel: Roger D. Weiss, M.D.
Shelly F. Greenfield, M.D., M.P.H.
Margaret L. Griffin, Ph.D.
Lisa M. Najavits, Ph.D.
Jennifer Sharpe Potter, Ph.D.
Valerie Robbins, M.S.
Monika Kolodziej, Ph.D.
Alisa Busch, M.D., M.S.
Sumita Manwani, M.D.
Scott Provost, M.S.W.
William Jaffee, Ph.D.
Alan Shields, Ph.D.
Hilary Connery, M.D., Ph.D.
The primary goal of the Alcohol and Drug Abuse Treatment Program is to conduct research on the evaluation and treatment of substance dependent patients, with a particular emphasis on patients with substance use disorders and other psychiatric disorders. A major focus of our research group has been the evaluation and development of new treatments for specific subgroups of substance dependent and dually diagnosed patients. Thus, for example, we are currently in the process of testing an integrated group therapy for patients with coexisting bipolar disorder and substance use disorder. Another area of interest has been the treatment of women with substance use disorders. We are currently testing a new group therapy that we developed that specifically meets the needs of women with substance use disorders. We are also participating in a major national collaborative study investigating optimal combinations of pharmacologic and psychosocial treatment for individuals with alcohol dependence.
In addition, our group is directing the Harvard University Northern New England Node of the National Institute on Drug Abuse Clinical Trials Network. The Clinical Trials Network is a major study designed to improve drug abuse treatment in the United States by designing and implementing high-quality scientific research studies in community drug abuse treatment programs. McLean Hospital personnel are collaborating with scientists from several New England universities and clinicians from treatment programs around New England as part of this effort.
Clinical Psychopharmacology Research Program
J. Alexander Bodkin, Ph.D., Director
Investigators in the Clinical Psychopharmacology Research Program recently reported results of a study in which a new transdermal patch, similar to the patch used for years to control nicotine cravings, provides an effective and safe delivery system with few side effects for the class of drugs know as monoamine oxidase (MAO) inhibitors. MAO normally works in both the digestive system and the brain. In the digestive system, it detoxifies tyramine, a potentially harmful by-product of the fermentation of proteins. Taking an MAO inhibitor antidepressant in pill form can block the protective effects of MAO in the digestive system, allowing the tyramine to reach the blood stream. In some instances, this causes blood pressure to rise enough to cause dangerous side effects. The new skin patch drug delivery system completely eliminates this dangerous possibility. This is particularly important since MAO inhibitors are often more effective in individuals who get inadequate relief from other antidepressant medications.
Cognitive Neuroscience Laboratory
Director: Dean Salisbury, PhD, Director
Key Collaborators:
Robert W McCarley, MD. VA Boston Healthcare, Brockton Division
Martha E Shenton, PhD. Brigham & Women’s Hospital, Surgical Planning Laboratory
Deborah Yurgelun-Todd, PhD. McLean Hospital Brian Imaging Center
Researchers in the Cognitive Neuroscience Laboratory focus on clinical research of “first episode” psychosis: Patients who have never before been hospitalized for their illness. In collaboration with the Brain Imaging Center, they have detected evidence of progressive brain reduction around the time of first hospitalization. Using EEG, they have also demonstrated a specific brainwave related to perceiving sounds that appears to be an index of this progressive cortical reduction. These findings suggest that schizophrenia may involve a peri-onset period of active brain degeneration that can be targeted by medications, providing a new avenue of help for patients.
Studies of language and verbal memory in the Cognitive Neuroscience Laboratory have revealed problems in schizophrenia in semantic memory concept storage, likely related to neural over-activation, and in verbal memory context maintenance and use, likely related to frontal lobe dysfunctions. Patients seem to have specific problems in recalling and understanding infrequently used meanings of words (e.g., a board meaning a committee), and in using information from preceding sentences (context) to understand new information, and in devising strategies to predict what will occur (expecting the unexpected). These basic cognitive abnormalities may serve as a basis for many of the problems in thinking displayed in schizophrenic thought disorder.
Developmental Biopsychiatry Research Program
Martin Teicher, M.D., Ph.D., Director
Researchers in the Developmental Biopsychiatry Research Program and colleagues in the Brain Imaging Center have continued their exploration of the effects of early childhood traumatic stress on brain development. The research, which uses many techniques for gathering data on the brain including EEG, morphometric MRI, functional MRI, spectroscopy, and diffusion tensor imaging, has identified brain regions that are diminished in size and functional capacity in young adults with trauma histories. The aim of this work is to delineate how certain forms of early experience predispose individuals to develop depression, PTSD, borderline personality disorder, or substance abuse later in life.
The DBRP researchers have also begun a collaborative project with the Massachusetts Department of Youth Services (DYS). They are currently conducting a detailed evaluation of the scope and range of psychiatric difficulties experienced by youths entering DYS. This preliminary study will pave the way for more detailed investigations on the effects of psychiatric treatments provided by DYS as it relates to measures of brain structure and function.
Developmental Psychology and Psychopathology Program
Gil Noam, Ed.D., Director
Researchers in the Developmental Psychology and Psychopathology Program place a special focus on depression and suicide in children and adolescents with the goal of understanding how to prevent youth suicide. They have found that immaturity in thinking and thought processes is significantly related to aggression, conduct problems, and delinquency. The study includes over 2,500 children, and represents one of the largest child psychiatric inpatient samples in the country. At present, research into the relationship between development, psychopathology and brain functioning is underway in collaboration with researchers in the Brain Imaging Center. The work is unique in that it combines a large subject population with many years of follow-up studies.
Work also continues on the group's RALLY prevention program, which arose from their research on depression, violence and suicide among middle school children. Already established in several Boston Public Schools, the RALLY Program is an early intervention program that focuses on detection and prevention, and brings clinicians and teachers together to work toward the combined goals of mental health and academic achievement for at-risk children. The U.S. Department of Education recently awarded a two-year grant to evaluate the effectiveness of the RALLY program for elementary school children in an after-school setting.
More information about Dr. Noam's work and research can be found on the Program in Afterschool, Education and Resiliency (PEAR) web site.
Eating Disorders Education and Prevention Program
Director: Dr. Catherine Steiner-Adair
Project Director: Lisa Sjostrom, Ed.M., Project Director
Investigators in the Eating Disorders Prevention and Education Program in the Child and Adolescent Psychiatry Research Program have developed a curriculum called "Full of Ourselves" (FOO), an innovative primary prevention program that sustains girls in their mental, physical and relational health and decreases their vulnerability to the development of eating disorders. Piloted with more than 800 girls in five states, FOO has been proven to reduce risk for disordered eating by improving eating-related behaviors, increasing self- and body-esteem, promoting body acceptance, providing leadership opportunities, teaching a range of coping strategies, and changing knowledge about health, nutrition and puberty. FOO will be published and nationally distributed by Teachers College Press in fall 2005. Regional leader training institutes will follow to ensure quality implementation.
Laboratory for the Study of Adult Development
Mary Zanarini, Director
For some time now, evidence has been mounting that omega-3 fatty acids (commonly and naturally found in seafood) may be effective in countering some of the more debilitating effects of depression as well as bipolar disorder. Now the nutrient appears effective in combating the effects of borderline personality disorder (BPD) as well. In a carefully controlled study, researchers in the Laboratory for the Study of Adult Development have found a significant decline in both depression and aggression among BPD study subjects who received omega-3 fatty acids. This effect may possibly be due to an increase in cell membrane stabilization in the brain, which is made up of at least 60% lipids. This new treatment may prove to be a safe and effective form of therapy for women suffering from moderately severe BPD.
Mental Health Services Research Program
Cathaleene Macias, Ph.D. Director
Fulfilling its mission, Waverley Place, having successfully established its clinical programs, has begun a research program on its innovative methods of community care for the chronically psychiatrically ill. Cathaleene Macias, Ph.D., and Dr. Paul Barreira have submitted an NIMH grant to investigate the affect model for developing the peer counselor role in psychiatric rehabilitation programs. A paper describing Waverley Place has been accepted by the Psychiatric Rehabilitation Journal.
Nursing Research Program
Carol Glod, R.N., Ph.D., Director
Investigators in the Nursing Research Program have observed that certain antidepressants, effective for adults, may also be effective for juvenile depression. In collaboration with researchers in the Brain Imaging Center they have found that specific areas of the brain, the frontal and temporal lobes, are affected by treatment with these antidepressants. They have also found that compared to adolescents without psychiatric disorders, depressed teens show disrupted frontal networks. A better understanding of these mechanisms by which these treatments work may lead to identifying the underlying causes for depression in children and adolescents, and how medications work to reverse depression.
Personality and Psychosocial Research Program
John Gunderson, Director
The Collaborative Longitudinal Study of Personality Disorders (CLPS) focuses on the long term course of Borderline Personality Disorder (BPD) and other personality disorders. Researchers in the Personality and Psychosocial Research Program have shown for the first time that a patient diagnosed with BPD can, in fact, undergo "remission" (e.g., the patients no longer meet the criteria for the illness). About 40% of patients undergo a reduction of symptoms within two years of treatment, and 10% undergo remission within six months. Although most retain many of the social dysfunctions that are costly to society (i.e., in employment, relationships, and recreation), the findings of a lessening of the symptoms within the diagnostic criteria is important to clinicians treating these patients, and offers hope to sufferers of this widespread but understudied disease.
Psychopharmacology Research Laboratory
Andrew Stoll, M.D., Director
Clinician-investigators in the Psychopharmacology Research Laboratory have been conducting research on integrating conventional psychopharmacology with "complementary" treatments such as omega-3 Fatty Acids (a constituent of fish oil), Taurine, and SAMe, to determine how effective they are for treating psychiatric disorders. Preliminary findings indicate that omega-3 fatty acids may be effective as a mood stabilizer and as an antidepressant. Since these naturally occurring products are already available to the public, and in many cases are being self prescribed, it is important to learn how safe and effective they may be for treating psychiatric disorders.
Schizophrenia and Bipolar Disorder Program
Dost Ongur, M.D., Ph.D., Director
Researchers in the Schizophrenia and Bipolar Disorder Program use neuroimaging techniques to measure brain activity as patients with these illnesses carry out a variety of cognitive tasks. Cognitive difficulties are common in schizophrenia and bipolar disorder and these may form the basis of future treatment targets. One recent study from our group found that patients with schizophrenia are impaired in making judgments about pairs of cards which are presented together, and that this impairment is related to abnormal brain activity in a part of the brain called the hippocampus, which is responsible for forming associations between stimuli. It is hoped that work like this will focus our efforts on using treatments to enhance activity in specific brain regions in this illness, thus leading to clinical improvement.
Schizophrenia & Bipolar Disorder Clinic
Franca Centorrino, M.D., Director
Over the past decade, new medications have been developed for the treatment of schizophrenia and bipolar disorder. Although these new drugs have dramatically increased treatment options for these disorders, little is known about the effectiveness and safety of these drugs when used with other medications. Franca Centorrino, M.D. and collaborating researchers have examined the use of these medications from 1989 through the present among inpatients and outpatients at McLean Hospital. By studying and comparing specific combinations of antipsychotics and mood stabilizers, these researchers have uncovered differences in side effects and clinical changes which may lead to improved patient care.