Clinical and Genetic Epidemiology

Myrna M. Weissman, Ph.D., Chief of Psychiatric Research

Phillip B. Adams, Ph.D., Research Scientist IV

David Greenberg, Ph.D., Research Scientist VI

Susan E. Hodge, D.Sc., Research Scientist VII

Laura H. Mufson, Ph.D., Research Scientist V

Mark Olfson, M.D., M.P.H., Psychiatrist II

Daniel Pilowsky, M.D., M.P.H., Psychiatrist II

Virginia Warner, M.P.H., Research Scientist III

Priya J. Wickramaratne, Ph.D., Research Scientist V

The Department of Clinical & Genetic Epidemiology was established in 1987 to gain understanding of the rates and risk factors for mood and anxiety disorders using techniques of epidemiology and genetics and to apply these findings to develop and test empirically-based treatment and prevention interventions.  The research program has projects in four areas.  Highlights of this year’s research will be summarized in the following sections: Genetics, High Risk Longitudinal Studies, Treatment, and Health Services.

Genetic Studies

The Mathematical Genetics Unit   Led by David A. Greenberg, Ph.D. and Susan E. Hodge, D.Sc., the Mathematical Genetics Unit is a collaborative program to enhance capacity to study the genetics of complex human diseases.  The problem of understanding how genes have an impact on human disease will benefit from the knowledge of experts on study design, data collection strategies and data analysis.  Because the field of genetic analysis is relatively new, the group is expected to develop innovative mathematical and statistical techniques to customize analytic approaches to individual studies. 

Genetics of Complex Disorders Training Program    Drs. Hodge and Greenberg (together with Dr. Ruth Ottman in Epidemiology) were funded by NIMH to establish a much-needed training component in statistical genetics.  Details are on our Web site: http://cpmcnet.columbia.edu /dept/sph/epi/gcd/

Genetic Analysis: Psychiatric and Other Complex Diseases     Psychiatric disorders are severe, disabling conditions with enormous public-health impact.  Families represent an important source of information for unraveling the etiology of the psychiatric disorders.  Two of the major tools used by mathematical geneticists and genetic epidemiologists to exploit family studies are linkage analysis and segregation analysis.  Dr. Hodge’s work continues to address specific problems and complications arising in both these methods of analysis.  The overriding theme of her work is to evaluate the robustness of analysis methods, that is, how well do different methods perform when their assumptions are not met?  This is important because psychiatric genetics today is dealing with complex diseases for which the genetics are not known or are poorly understood.  

Genetic Study of Panic Disorder    (M. Weissman, P.I.  in collaboration with A. Fyer, J. Knowles and S. Hodge)  The overall aim is to understand the genetic contribution to panic disorder (PD) using an integrated database of 130 well-characterized multiplex families, family-based triads and advanced molecular genetic approaches. Preliminary analyses indicate a number of surprisingly strong results.  Several loci exhibit maximum lod scores of 3.0 or greater under several analytic models (maximum lod scores 4.0).  We are following up one intriguing finding suggesting a possible new PD syndrome involving interstitial cystitis on Chromosone 13 in collaboration with S. Kaplan, M.D., Chief of Urology at Columbia University.

Genetics of Recurrent Early Onset Major Depression (MDD-RE)    (M. Weissman, P.I.)  MDD-RE is a multi-site study to identify major depression susceptibility genes.  It involves the collection of ~1000 multiple-affected sibling pairs over 6 sites with recurrent, early-onset major depression.  Biological materials and clinical data will be shared with the scientific community.

Epidemiologic Methods in Psychiatric Family Studies    (P. Wickramaratne, P.I.) The major goal of this study is investigating issues of ascertainment bias in epidemiologic family studies. In the past year we have explored how results from family studies of psychiatric disorders are influenced by whether families are identified through adult probands or child probands seeking treatment for a particular disorder. Our findings have helped to reconcile differences in the degree of familial aggregation found in previous studies of familial aggregation of major depressive disorders.                      

 High Risk Longitudinal Studies
  (M. Weissman, P.I.)   The overall aim has been to understand the long-term, temporal sequence and familial patterns of psychiatric and behavioral problems from childhood to adulthood of offspring at high and low risk for depression using clinical and psychophysiologic assessments. This study has had 4 waves of assessments and 3 generations.  A competing renewal in collaboration with Brad Peterson, M.D. and Gerard Bruder, Ph.D. was submitted, whose primary aim is to carry out anatomical and functional MRI studies, integrating the clinical and psychophysiologic data.  This grant received a fundable priority score.

Treatment Studies

Effectiveness of IPT-A in School-based Health Clinics   (L. Mufson, P.I.) The overall aim is to improve the clinical effectiveness of the treatment of adolescent depression in school-based mental health clinics in a poor urban area. Over 500 adolescents were screened for depression and 62 eligible adolescents were enrolled into the randomized clinical trial.  Data analyses are currently underway.  The experience gained from this study is being applied to a New York State Office of Mental Health Program on the effectiveness of empirically-based treatment programs in school-based mental health clinics to improve mental health and school performance in poor urban areas. The first year of the project has been spent finalizing design issues, training the school-based mental health teams on standardized screening and assessment tools, providing didactics on the evidence-based treatments and gaining IRB and Board of Education approvals. Evidence-based treatment delivery and outcome will be compared to treatment as usual both within and between schools. 

Group IPT for Depressed Adolescents    L. Mufson received a NARSAD award to adapt and pilot test group IPT for depressed adolescents.

Treatment of Depressed Mothers:  A STAR*D Ancillary Study    (M. Weissman, P.I., D. Pilowsky, M.D co-.P.I.)
The overall aim is to study the impact of a reduction of maternal depressive symptoms on children’s psychiatric symptoms and social functioning, as an ancillary study to the multi-site Sequenced Treatment Alternatives to Relieve Depression study (STAR-D).  Focusing on the common clinical question of what to do next when patients fail to respond to a standard trial of treatment, STAR*D aims at defining which subsequent treatment strategies are acceptable and provide the best clinical results.  This proposed ancillary study (STAR*D-Child) takes advantage of a unique opportunity to follow a large, culturally diverse sample of depressed mothers who will be treated, assessed and followed prospectively to determine the impact on their children ages 7 – 17 years.  Previous studies have demonstrated that children of depressed mothers have over three- to five-fold increased risk of serious and enduring problems.  Little is known about the impact of remission of maternal depression on their offspring. If it is shown that successfully treating maternal depression is associated with diminished risk in offspring, the finding would have wide ranging public health implications. 

IPT for Prepubertal Depression   D. Pilowsky, P.I., was awarded a grant from Klingenstein Foundation to develop the first adaptation of IPT for prepubertal children with depressive symptoms.

Treatment of Depression in Uganda   M. Weissman, L. Verdeli were invited to modify IPT in a group format for depressed patients in Uganda, to train group leaders in preparation for a controlled clinical trial, conducted by John Hopkins University.

Health Services

This study seeks to determine the prevalence, severity, and clinical consequences of sexual side-effects associated with four antipsychotic medications that are commonly prescribed for the treatment of schizophrenia.

Pathways to Specialty Mental Health Care   (M. Olfson, P.I.)  This study examines patterns and predictors of mental health service utilization in a community sample of individuals with affective, anxiety, or substance use disorders.  Findings confirm that there are often long periods of delay between the first onset and the first treatment contact.  The period of delay is particularly long for persons with childhood and adolescent onsets of mental disorders and for individuals with alcohol and drug disorders.  Similar health seeking patterns occur in the United States and Canada, suggesting that the timing of mental health seeking may be more closely related to clinical condition than to the financial and organizational characteristics of the health care system.

Medication Noncompliance in Schizophrenia  (M. Olfson, P.I., C.Boyer Co-PI)  This study involves a novel psychological approach to the treatment of medication noncompliance in schizophrenia.  Outpatients who are receiving short-term inpatient care and have a recent history of medication non-compliance are being randomly assigned to receive compliance therapy or continued usual care.  Compliance therapy draws on the principles of motivational interviewing to increase the patients' awareness of discrepancies between their current behavior and long-term goals.                                                       

Schizophrenia Treatment Guideline Implementation Project   (M. Olfson, P.I.)  There is accumulating evidence that substantial numbers of patients with schizophrenia are prescribed antipsychotic medication regimens that are inconsistent with evidence-based treatment guidelines.  We are conducting a treatment guideline implementation project to determine whether medication algorithms, clinical support, and academic outreach increase the quality of medication management for schizophrenia and improve patient outcomes.  120 patients with schizophrenia or schizoaffective disorder, and 4 public outpatient mental health clinics in Brooklyn, NY are participating.

Psychiatric Disorder and Treatment in an Urban Primary Care Practice    (M. Weissman, P.I., M. Olfson Co-PI)   This is a study of the frequency and treatment of bipolar disorder in 1000 adult patients at the Associates in Internal Medicine (AIMS) of the Columbia Presbyterian Medical Center serving urban, poor, adult, primary care patients.

Achievements and Awards

Achievements of the Department of Clinical and Genetic Epidemiology for the Year 2001 through March 31, 2002 include new funding awards and research findings.  Other researchers in the Department include Yoko Nomura, Ph.D., Lisa Miller, Ph.D., Adriana Feder, M.D., Kristen Pollack Dorta, Ph.D., Helena Verdeli, Ph.D.  Fellows include Amar Das, M.D and Raz Gross, M.D.

 New Grants

Awards and Honors

Myrna Weissman received the American Psychiatric Association (APA) Award for Achievement in Research and was made a Fellow of the New York Academy of Science.

Susan Hodge and David Greenberg established a Mathematical Genetics unit to enhance capacity to study the genetics of complex human diseases.

Mark Olfson’s report on the national increase in treatment of depression received widespread public attention (Olfson M, Marcus SC, Druss BG, Tanelian T, Elinson L, Pincus HA: National trends in the outpatient treatment of depression. JAMA 287: 203-209, 2002.

Laura Mufson was appointed Chief of Clinical Psychology at New York State Psychiatric Institute (NYSPI).

Gary Heiman and Marc Gameroff each received his Ph.D. Marlene Carlson received her M.P.H.

Raz Gross was selected by the APA to attend the Research Colloquium for Junior Investigators.