Clinical & Genetic Epedemiology

Myrna M. Weissman, Ph.D., Chief of Psychiatric Research
Phillip B. Adams, Ph.D., Research Scientist III
Tova Ferro, Ph.D., Research Scientist II
David Greenberg, Ph.D., Research Scientist VI
Steven Greenwald, M.S., Research Scientist III
Susan E. Hodge, D.Sc., Research Scientist VII
Laura H. Mufson, Ph.D., Research Scientist V
Mark Olfson, M.D., Psychiatrist II
Virginia Warner, M.P.H., Research Scientist III
Priya Wickramaratne, Ph.D., Research Scientist V

Other researchers in the department include: Helen Verdeli, Ph.D., Simona Noaghiul, M.D., Daniel Pilowsky, M.D. , Adriana Feder, M.D., Yoko Nomura, Ph.D., Lisa Miller, Ph.D., Kristen Pollack Dorta, Ph.D.; Post Doctoral Fellows Susan L. Slager, Ph.D., Raz Gross, M.D.; and graduate students Steven Greenwald, Marc Gameroff, and Gary Heiman.

New grants awarded to the department included:

Dr. Mufson was one of 10 recipients of the Pfizer Visitng Professor in Psychiatry Award and spent three days as a visiting professor at the University of Miami School of Medicine's Department of Child Psychiatry.

Dr. Weissman was selected as the Heinz Lehman Lecturer at McGill University and was named as one of the area's outstanding women in science by Avenue Magazine.

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 Mathematical Genetics Unit A new unit was established in the CGEU and Genome Center, led by David A. Greenberg and Susan E. Hodge to develop innovative mathematical and statistical techniques; to customize analytic approaches to individual genetic studies; and to expand a much needed training component in statistical genetics.

Genetic Study of Panic Disorder (Principal Investigator, M. Weissman 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 well-characterized multiplex families, family-based triads, and advanced molecular genetic approaches. Collection of 130 multiplex families and 90 family based triads, the largest sample to date, has been completed. A complete genome scan was released to us from the Center for Inherited Diseases (CIDR) on 12/7/00. This project entailed obtaining 392,955 genotypes from 1,005 patient samples using 391 microsatellite markers spaced on average every 9cm over all 22 autosomes and both sex chromosomes. Preliminary analyses indicates 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). In light of the huge amount of undigested data, we are undertaking careful analyses before pursuing additional data collection or a collaborative study. We are following up one intriguing finding suggesting a possible new PD syndrome involving bladder problems in collaboration with S. Kaplan, M.D., Chief of Urology at Columbia.

Genetics of Recurrent Early Onset Major Depression (MDD-RE) (Principal Investigator, M. Weissman). MDD-RE is a multisite study to identify major depression susceptibility genes. It involves the collection of ~1000 multiple-affected sibling pairs with recurrent, early-onset major depression. Biological materials and clinical data will be shared with the scientific community. Data collection is on target.

Genetic Analysis of Complex Psychiatric Disorders (Principal Investigator, S. Hodge) Dr. Hodge's work continues to address specific problems and complications arising in linkage and genetic segregation analysis. The 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. She completed work on the following: identification of a possible "syndrome" within panic disorder; investigation of additional possible "candidate genes" for panic disorder; further localization, and eventual finding of, the gene for primary pulmonary hypertension (PPH), a serious, life-threatening condition; further investigation of complex risk calculations in genetics; extension of previous work on phase ambiguity in single nucleotide polymorphisms (SNPs), extended to the situation of linkage disequilibrium; a discussion of the statistical issues involved in evaluating "model-free" vs. "model-based" methods of linkage analysis; an investigation of the effect of "stoppage" (the phenomenon whereby parents decide, after the birth of a severely affected child, to have fewer children than originally planned) on genetic analyses; and investigation of statistical properties of the "Markov chain Monte Carlo" method of linkage analysis.

Epidemiologic Methods in Psychiatric Family Studies (Principal Investigator, P. Wickramaratne) Dr. Wickramaratne has demonstrated that existing epidemiologic methods for determining familial aggregation may give misleading results in some situations in which they are frequently applied. She has modified a familial aggregation model to allow for risk of disease within a family to vary with some known discrete variate, such as gender of family member. She has shown that if the risk of disorder varies with gender, contrary to current practice, both proband gender as well as relative gender must be controlled for in order to obtain valid tests of familial aggregation. She has developed new statistical methods for evaluating family history screens, specifically, developing statistical methods for formally evaluating the extent of improvement in sensitivity and specificity when using single versus multiple informants in family studies, as well as determining the variation of sensitivity and specificity of a screen with demographic and other characteristics of both relatives and probands. She has also explored how results from family studies are influenced by whether adults or children seeking treatment for a particular disorder are selected as probands. Her findings led to the guidelines for selecting probands for family-genetic studies of early onset recurrent depression.

Family Studies Tracking (FST) data management system (P. Adams) A new data management system (Family Studies Tracking, FST) has been developed to greatly improve security in family/genetic studies and to manage longitudinal investigations with multiple waves of data collection.

High Risk-Longitudinal Studies Offspring at High and Low Risk for Depression: A 10-Year Follow-Up (Principal Investigator, M. Weissman) We are following up the third generation (grandchildren) of high and low risk grandparents and parents and evaluating psychophysiologic markers and their association with a potentially important phenotype of depression characterized by comorbidity with anxiety and familial loading for MDD. A minority supplement was received to provide Dr. Feder with opportunities to master the research methods of the parent study and to test similar approaches in a sample of poor, urban, minority individuals selected from a primary care internal medicine setting. We are in the second year of data collection and are on target.

Depressed Children Grown-Up (Principal Investigator, M. Weissman) The aim is to determine the continuity between childhood and adult depression by conducting reinterviews with adults who were initially evaluated as children between 1978 and 1984 at the New York State Psychiatric Institute. Key findings have been published this year, the major one being the strong continuity between adolescent onset MDD and MDD in adulthood.

Adult Continuity of Conduct Disorder (Principal Investigator, T. Ferro) As part of the original sample above, 24 subjects were initially diagnosed with conduct disorder (CD) as children and are being followed up. Initial findings indicate the severe persistence of CD into adult behavior problems.

Treatment Studies Effectiveness of Interpersonal Psychotherapy for Adolescents (IPT-A) in School-Based Health Clinics (Principal Investigator, L. Mufson) The overall aim is to improve the clinical effectiveness and cost efficiency of the treatment of adolescent depression in school-based mental health clinics in a poor urban area. This is being accomplished by training school-based mental health professionals in IPT-A and conducting an effectiveness study of IPT-A compared to treatment as usual. Over 200 adolescents have been screened for depression in the school-based clinics and 41 eligible adolescents have been enrolled into the randomized trial. Dr. Mufson provides weekly supervision for the therapist trained in IPT at each of the school sites and K. Pollack Dorta has conducted several in-services on identifying and treating depression in adolescents at the individual schools to educate school staff about the morbidity of untreated adolescent depression.

Interpersonal Psychotherapy by Telephone (IPT-T) (Principal Investigator, L. Miller) The aim of the study is to engage depressed mothers into treatment who do not seek it due to the demands of parenting, work and financial stress. Preliminary findings have shown that IPT delivered over the telephone is both feasible and acceptable to some mothers of young children.

Interpersonal Psychotherapy (IPT) for Depressed Mothers (Principal Investigator, M. Weissman) This study consists of two parts: (1) a screening of mothers bringing depressed children for treatment to determine frequency of depression and other disorders; (2) pilot treatment study to determine whether treatment of the depressed mother using IPT will enhance the effectiveness of treatment given the depressed child. One hundred seventeen mothers bringing their children for treatment have been screened. Findings indicate the high rate of untreated major depression among the mothers. Twelve mothers with major depression were treated with a 12-week course of IPT. Results show that a child's improvement was related to mothers symptom improvement. These pilot results were used to prepare an NIMH grant to fully test out the observation. The grant was awarded in 2001.

Health Services Pathways to Specialty Mental Health Care (Principal Investigator, M. Olfson) 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 (Principal Investigator, M. Olfson, Co-Principal Investigator, C. Boyer) This study involves a novel psychological approach to the treatment of medication noncompliance in schizophrenia. Outpatients who are receiving short-term inpatient care and 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.

Psychiatric Disorder and Treatment in an Urban Primary Care Practice (Principal Investigator, M. Weissman, Co-Principal Investigator, M. Olfson) This is an epidemiologic study of mental disorders, impairment, and mental health treatment of 1007 adult patients at the Associates in Internal Medicine (AIMS) of the Columbia Presbyterian Medical Center serving urban, poor, adult, primary care patients, most of whom are immigrants from the Dominican Republic. Findings indicate the very high rate of psychiatric disorders in this population.

Schizophrenia Treatment Guideline Implementation Project (Principal Investigator, M. Olfson) 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 increases the quality of medication management for schizophrenia and improves patient outcomes. One hundred twenty patients with schizophrenia or schizoaffective disorder and four public outpatient mental health clinics in Brooklyn, NY are participating in the study.

Mental Health Services at New York City Colleges & Universities (Principal Investigator, M. Olfson, Co-Principal Investigator, M. Guardino) Young adulthood is period of high risk for the onset of major mental disorders. Although many American colleges and universities provide mental health services on campus, little is known about these services. A survey is currently being conducted by directors of college counseling and mental health service centers in NYC.

ECT Outcomes in Community Settings: Evaluating Outcomes (Principal Investigator, J. Prudic, Co-Principal Investigator, H. Sackeim, M. Olfson) This NIMH-sponsored project examines associations between variation in ECT technique and clinical outcomes in a large sample of patients with major depression treated in five hospitals within the New York metropolitan area. It is a prospective naturalistic study and the first to follow a group of patients who have received ECT under usual care conditions in the community.