This study represents a ten year collaboration between the University of Pittsburgh, University of Pennsylvania, and the Texas Biomedical Research Institute. Aim: To better understand underlying genetic causes of mental illness, and study the impact of illness on brain structure and function.

Participants included persons diagnosed with schizophrenia and schizoaffective disorder, their family members, and healthy controls, who completed cognitive and clinical assessments, donated DNA for genetic study, and took part in fMRI scans so we can learn more about brain structure and function.

Findings: data from the study are ongoing. See publication list for prior analyses.

A Family-Based Genome Wide Methylation Scan for Cognition and Schizophrenia

In this study, we are investigating underlying genetic factors that may contribute to schizophrenia risk, and examine effects of schizophrenia and related illnesses on cognition. We are also studying chromosomal abnormalities which may confer risk, particularly abnormalities of the 22q11 chromosome.

Another focus of this study is learning more about the process for generating neurons from induced pluripotent stem cells (iSPCs). Participants have donated small biopsy samples to facilitate this aspect of our work, as well as blood samples for genetic analysis. We have also conducted fMRI scans (brain scans) to better understand how brain structure and function are impacted by illness.

These studies may help us to learn more about genetic factors that are important in how the brain works, how the genetic variations are related to the workings of the brain while the subjects are processing the information, and finally about genes that may cause schizophrenia and related conditions.

Schizophrenia Liability Genes Among African Americans

This large multi site study investigated potential genetic and environmental factors that may create risk for schizophrenia and related disorders in the African American population

Cognitive and clinical data, as well as DNA samples, were drawn from over 1800 participants

This study helped identify chromosomal regions which may harbor susceptibility genes for schizophrenia and suggested that cognitive variables are important targets for gene mapping studies.

STEP GRP and Fast STEP

These large multi site studies collected DNA samples from a large sample of participants with bipolar disorder, their relatives, and healthy controls. They were an outgrowth of a larger treatment study, "Systematic Treatment Enhancement for Bipolar Disorder." Samples were analyzed at existing sites, and also shipped to a central repository run by the National Institutes of Health, so they are available to other scientists studying bipolar disorder.

The studies supported by this grant have provided significant resources, tools and results relevant to efforts to understand the genetic basis of bipolar disorder. These have included

• A large collection of data and DNA samples for future genetic studies to be made available to the scientific community under the auspices of the NIMH Genetics Research Branch;
• Novel statistical methods for linkage and association analyses;
• Evidence implicating novel susceptibility genes for bipolar disorder;
• Genomewide significant evidence implicating two susceptibility genes that suggest a novel pathophysiologic mechanism (ion channelopathy) underlying the disorder. Such discoveries may provide significant new opportunities for understanding the pathogenesis of BD and the development of more specific and effective treatments.