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University of Chicago researchers awarded $3.5 million as part of national consortium to transform diagnosis and treatment of psychotic disorders

October 1, 2015

The National Institute of Mental Health (NIMH) has awarded researchers from the University of Chicago $3.5 million as part of the second phase of the Bipolar-Schizophrenia Network on Intermediate Phenotypes (B-SNIP2) – a multi-university consortium that aims to establish a new system of diagnosis for psychotic diseases based on biomarkers, and guide the development of novel therapies.

B-SNIP2 expands on an initial round of studies in over 2,500 patient and healthy volunteers (B-SNIP1) that shed light on biological and genetic overlaps for the major psychotic disorders schizophrenia, schizoaffective disorder and bipolar disorder. The consortium will now recruit an additional 3,000 study participants over five years to identify biomarkers and establish biologically meaningful definitions and categorizations for these diseases.

Collaborating institutions in B-SNIP2 include teams from Yale University, Harvard University, University of Texas Southwestern Medical Center and University of Georgia.

"Emerging evidence suggests that schizophrenia, schizoaffective disorders and bipolar disorders have similar deficits, with differences in severity but not in pattern," said Elliot Gershon, MD, Foundations Fund Professor of Psychiatry and Human Genetics at the University of Chicago and a principal investigator of B-SNIP2. "Our aim is to reformulate the diagnosis of these psychotic disorders, so that it is based on their underlying biology and not just symptoms."

Although currently classified as different diseases, schizophrenia and bipolar disorder are known to have significant genetic and symptomatic overlaps that suggest these diseases are related and could possibly lie on a spectrum. Psychotic symptoms, depression and suicide can occur in each, and patients can be diagnosed with both disorders at different times of their lives. Recent genetic studies and discoveries of specific changes in brain structure, memory, thinking ability and brain electrical activity are evidence of shared biological roots and support the development of new diagnostic criteria and treatment options.

As part of a major initiative to discover new ways of reclassifying mental illnesses based on neurobiological measures, the NIMH funded the B-SNIP consortium to study intermediate phenotypes – genes and traits which are causal or associated with risk for developing schizophrenia, schizoaffective disorder and bipolar disorder. The project investigated a wide range of biomarkers such as variation in cognitive abilities, brain structure and function, genetics and other factors in around 1,000 patients with psychosis and 1,500 healthy family members.

Significant progress in characterizing intermediate phenotypes was made, and B-SNIP investigators were able to use biomarkers to identify patient clusters that were independent of traditional diagnoses. These "Biotypes" of psychotic disease are thought to be more accurate classifications and better guides for clinical therapy than current diagnostic standards.

To expand and validate these initial findings, B-SNIP2 will recruit an additional 3,000 patients and healthy volunteers over five years. Study participants will undergo a suite of measurements, including traditional behavioral and symptom assessment, tests of cognitive function such as memory and attention, analyses of brain composition, structure and electrical activity, eye movement and auditory tests, and genome-wide genetic analysis.

The combined data will be used to create a Psychosis Biomarker Database. Multivariate statistical analysis, led by Robert Gibbons, PhD, professor of medicine and public health sciences at the University of Chicago, will be used to create quantified and validated Biotypes and subtypes of psychotic disorders, which can potentially serve as the foundation for improved, accurate disease classifications and guide the development of novel therapeutics.

"Previous studies that have looked at the association between individual traits or genes and psychotic disorders have been informative, but not transformative," said Sarah Keedy, PhD, assistant professor of psychiatry and behavioral neurosciences and co-principal-investigator on B-SNIP2. "By measuring these associations in combination, rather than individually, on an unprecedented scale, we hope to establish rational, biologically meaningful categorizations that will allow us to better diagnose, predict onset of, and target treatments for these disorders."

B-SNIP2 is now recruiting patients. For more information and study contacts visit: http://cnpru.bsd.uchicago.edu/BSNIP.html

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