Who We Are

The National Institute of Mental Health (NIMH) has joined forces with university medical
schools across the country including Harvard University, Mount Sinai School of Medicine, University of California Los Angeles, University of California San Diego, University of Colorado Health Sciences Center, University of Pennsylvania, and the University of Washington. Through this collaborative research project we hope to learn more about the genetic basis of specific heritable neurocognitive and neurophysiological deficits (called “endophenotypes”) in schizophrenia patients. These deficits in functions like memory can cause many “downstream” problems in activities of daily living.

Understanding the genetic components of these functions in schizophrenia patients is crucial to finding out about the neurobiological basis, risk factors, and heritability of this illness. It may also help to create more effective treatments, and hopefully someday, the development of a cure for this devastating disorder.


Background

Dr. David Braff, the Director of the Consortium on the Genetics of Schizophrenia (COGS), and the other distinguished COGS faculty, have a long history of dedication to the treatment of schizophrenia patients and of successful peer-reviewed schizophrenia research. He and the roster of internationally-renowned schizophrenia researchers of the COGS are particularly interested in the role that the heredity of endophenotypes plays in vulnerability to and the development of the disorder. In order to involve the minimal number of whole families needed to run a scientifically sound study, we wanted to include prominent clinical researchers and their “home universities” from across the country (see Investigators). As such, the COGS Principal Investigators at each University throughout the US have an established history of excellence in schizophrenia research.

It is especially important that we have many testing centers because in order to study familial trends and genetics of endophenotypes in schizophrenia, many whole families are needed. This differs from other research studies because not only is the person with the disorder tested, but all of the available first-degree relatives must also have their endophenotypes ascertained.

In addition to the testing centers, a world class data management group at UCLA and a renowned statistical genetics team (see Investigators) were recruited to ensure the success of the Consortium.

After years of planning and working together, the project was submitted to the NIMH to request federal funding. The project was approved and funded in May 2003 as one of the most important and well-funded endeavors in mental health research. The project is approved for an initial period of 5 years (until May 2008), at which point the scientists plan to expand upon the COGS with exciting follow-up studies.


Purpose and Goals

Schizophrenia runs in families, but despite intense research efforts, the precise genetics of this complex and disabling disorder remain unknown. The first efforts to find a “schizophrenia gene” have been greatly complicated by the likely involvement of multiple genes. Therefore, researchers have developed new methods to tackle the goal of gene identification. Previous studies utilized the clinical diagnosis of schizophrenia as the trait of interest. In contrast to studying the genes that lead to schizophrenia, this study utilizes measures of brain functioning present in schizophrenia patients and their first degree relatives as tools to help to understand the genetics of schizophrenia.

Many previously published scientific studies have shown that not only are people with schizophrenia more likely to show abnormalities in these endophenotypes, but so are their totally normally functioning first degree relatives who do not have schizophrenia but are “gene carriers”. This model is also being successfully used in hypertension and diabetes research. The measures of brain functioning we look at are: memory, concentrations, brain waves, eye blink responses, and eye movements. We hope to “trace” these traits in the families and then trace the corresponding genes related to these traits. Ultimately, once genes related to endophenotypes in schizophrenia are identified, scientists can develop better treatments and potential cures that reverse these abnormalities .


Research Summary

We are now in the the fifth and final year of Phase I of the COGS study and have embarked upon an exciting new phase of data analysis. Most of the first year in this very ambitious project was spent recruiting and hiring staff, purchasing and setting up equipment, setting up the laboratories, conducting extensive quality control on the equipment and laboratory procedures, fine tuning the criteria for including a family, developing family recruitment strategies, and setting up an intricate database to store and distribute thousands of pieces of data. Also in the first year, the testing sites were busy finding families that graciously agreed to participate in this important research. This extensive and rigorous recruitment effort has continued throughout all of the project years. Since the COGS was funded, we have tested hundreds of subjects and collected thousands of pieces of clinically important information. We will be continuing these efforts in the next phase of the project, Phase II, by expanding the research and data analyses, and identifying new genetic findings and answers. The scientists are busy analyzing these data and publishing results to the scientific community. Many new manuscripts and papers are now available to the scientific and public community. Please see our Publications page for a list of all the papers and abstracts produced from COGS.


Current Progress

The COGS project had a start date of April 2003. To ensure optimal testing conditions and results, the first six months was devoted to obtaining equipment and supplies, developing the endophenotype paradigms and training personnel from each of the sites on the six endophenotype measures via in person meetings at UCSD. Therefore the first families were not enrolled until October 2003. Since then, we have rigorously screen over 6,000 patients for the strict enrollment criteria (see Calkins et al. 2007), enrolled and completed testing on over 280 families, and another 63 families are enrolled and in the process of testing. In total, the COGS database includes phenotypic and/or genotypic information from approximately 333 probands, 944 family members, and 531 community comparison subjects for a total of 1,808 participants as of June 2007. If we continue to enroll families at this rate, we will have a total of 350 COGS families by March 2008. We realized early in the COGS project that families with "contrast" and more than 2 total siblings afforded us increased statistical power; over 30% of the families have more than 2 siblings, and thus we will have an estimated 816 sib pairs at the end of the COGS funding period (as opposed to the originally proposed 420) for statistical genetics analyses. The COGS has already become a unique and accessible national resource for current and future studies of the neurobehavioral and genetic architecture of complex diseases such as schizophrenia, bipolar, obsessive compulsive and other disorders. As such, directors of groups studying the schizophrenia prodrome (Ty Cannon, Ph.D.), obsessive compulsive disorder (Carol Matthews, M.D.), bipolar disorder (John Kelsoe, M.D.), and borderline personality disorder (Larry Siever, M.D.) have benefited explicitly from the COGS organizational and Quality Assurance structure on multiple measures. In addition, COGS expertise is being leveraged at each test site to conduct novel brain imaging, neurophysiological, neurocognitive, functional outcome, and model organism studies.

We would like to thank all of the families that have been generous enough to donate their time and energy to the COGS project. We are very appreciative and can’t thank them enough for contributing to not only our project, but also to society’s need to have a better understanding of the genetics of schizophrenia as a prelude to creating better models and treatments of this devastating disorder. Without their help and participation, the COGS project would not be as successful as it is right now. Together we hope researchers, patients, and their families will find the path to effectively preventing and maximally treating schizophrenia.