SPECTS

The Stanley Program for Epidemiology, Prevention and Treatment of Schizophrenia is comprised of 8 laboratories that examine the Gene-Environment (G x E) interactions that increase the risk of developing psychiatric disorders. This is achieved by analyzing samples and data from large, extremely well characterized population registries and by collecting data and samples from patients at various stages of their illness to examine G x E interactions. The program is dedicated to developing biomarkers used to predict onset and progression of illness, and to develop treatment strategies. SPECTS has established that exposure to Toxoplasma gondii (TOXO) and HSV contribute to the etiology of schizophrenia and thus includes programs to understand the biological impact of these organisms on the CNS and to develop more effective treatments against them. The program has developed biomarkers for disease diagnosis and to monitor therapy and also provides a coordinated site for testing samples from individuals participating in clinical trials with the goal of identifying individual markers of clinical response.

SPECTS Labs

The Stanley Neurovirology Laboratory, Johns Hopkins University, U.S.A., Robert Yolken

As the core of the SPECTS program the lab facilitates the collection and analysis of samples and develops new strategies for the effective prevention and treatment of psychiatric disorders. The group has pioneered the development of assays to characterize the inflammation associated with psychiatric patients. Through whole genome sequencing they are identifying novel pathogens associated with these disorders and through collaborations with members of the SPECTS program and others they have optimized and are now maximizing the utility of large epidemiological data sets world-wide to understand the gene-environmental interactions underlying these disorders. www.stanleylab.org

Stanley Research Program at NCRR, Aarhus, Denmark, Preben Bo Mortensen

Utilize the extensive Danish population based registers of healthcare data and biobank of samples, including maternal serum and amniotic fluid to understand the infectious, inflammatory and immune etiologies of psychiatric disorders. Dr. Mortensen and colleagues have done groundbreaking work in identifying events in early life which are associated with the later development of schizophrenia and bipolar disorder. They have access to samples and clinical data that can be used both for infectious disease (in collaboration with us) and genetic studies (in collaboration with the Stanley Center at the Broad Institute). We expect that their efforts will become even more valuable as the number of individuals from whom samples and data are available continues to grow.

Stanley Research Program at Stockholm, Sweden, Hakan Karlsson

Utilize the Swedish registry of extensive data on ~15 million people born 1932-2011 to identify populations with psychiatric disorders and their first degree relatives to determine the G x E interactions that increase the risk for psychiatric disorders. Maternal serum from pregnancies and neonatal blood spots as well as blood from adult patients and controls can be accessed. The Swedish population, while smaller than the Danish one, has the advantage that adult individuals with these disorders can be identified, assessed, and retested for infectious disease exposures. This group also provides expertise in the area of retroviruses and their role in the etiology of major mental illnesses.

Stanley Research Program at WRAIR, U.S.A., Natalia Webber

Examination of serum from a large population of healthy US military personnel who later developed schizophrenia or BD has shown that infection and/or immune activation can occur prior to onset of psychiatric symptoms. Additional studies are designed to identify the risk factors that predict psychiatric disorders that occur in this military population.

Stanley Research Program at Cambridge, England, Sabine Bahn

This group has had a major impact on the understanding of psychiatric disorders through their development and application of proteomic technology. They have successfully developed high-throughput technologies to identify biomarkers and diagnostic assays for schizophrenia and BD and have contributed to the development of the first diagnostic test used by psychiatrists in the diagnosis and management of individuals with schizophrenia or bipolar disorder. While this test still needs more work, it has gotten the psychiatric community interested in these types of assays and provided the first data regarding their implementation.

Stanley Research Program at Sheppard Pratt, U.S.A., Faith Dickerson

This is a clinical research group that provides valuable sets of biological samples and clinical data for analysis in collaboration with other members of the SPECTS program. Their ability to enroll and follow patients has allowed for the longitudinal evaluation of individuals with schizophrenia and bipolar disorder and for the performance of clinical trials. This program continues to grow in terms of the number of individuals being evaluated, the clinical trials program, and now includes additional clinical diagnostic groups. In collaboration with the neurovirology lab they will develop the scientific rational to facilitate the diagnosis, prevention, and treatment of schizophrenia and BD.

Stanley Research Program at Pittsburg, U.S.A. Vishwajit L Nimgaonkar

The primary aim is to develop an effective treatment for the cognitive impairment in schizophrenia by focusing on HSV-1 infection as a putative causative factor for the cognitive impairment. This group performed an important study on the use of the currently available medication valacyclovir and are now working to develop new medications which may be more effective for the long term treatment of the latent form of the herpesviruses likely to be in the brains of individuals with schizophrenia and bipolar disorder.

Stanley Research Program at Michigan, U.S.A., Vernon Carruthers

Chronic Toxoplasma gondii infection is a risk factor for schizophrenia. This program provides essential expertise in the biology of T gondii necessary for the development of new medications and other therapeutic strategies. They provided critical input for the development of the anti-Toxoplasma quinolone medications which are currently undergoing pre-clinical evaluation. While their previous studies relied on mouse models for the screening of anti-Toxoplasma compounds, they have now initiated studies directed at developing cell culture assays for the screening of new drugs effective against the tissue cyst form of the parasite. This may lead to a large increase in compounds which we can screen for this activity and then develop as potential drugs. T. gondii also upregulates interferon-γ which increases Indolamine 2,3-dioxygenase (IDO). IDO controls neural infection and also leads to increased kynuric acid which has been implicated in the etiology of schizophrenia. Future studies will lead to new therapeutic strategies for treating schizophrenia. http://www.med.umich.edu/microbio/bio/carruthers.htm

Future projects

SMRI does not have a general grants program; however we would consider inquiries from investigators interested in working on our core areas, particularly in the areas of immunology and infectious diseases in relation to mental illness. The amounts of funding available for these projects are relatively small and all inquiries and pre-screening of proposed projects should be directed to Dr. Bob Yolken at rhyolken@gmail.com before any formal application is made.