Research

Clinical Genetics

Recent studies provide considerable evidence that schizophrenia (SZ) and psychotic bipolar disorder (BP) may share overlapping etiologic determinants. Identifying disease-related genetic effects is a major focus in SZ BP research, with enormous implications for diagnosis and treatment for these two disorders.

Efforts have been multifaceted, with the ultimate goal of describing causal paths from specific genetic variants, to change in neuronal functioning, to altered brain anatomy, to behavioral and functional impairments. Parallel efforts have identified and refined several alternative endophenotypes that are stable, heritable, have (partly) known biological substrates, and are associated with psychosis liability.

Although many such endophenotypes have been individually studied in SZ, and to a lesser extent in BP, no study has comprehensively assessed a panel of these markers in the two disorders with parallel recruitment, and the extent to which they mark independent aspects of psychosis risk, or their overlap in the two disorders. This line of investigation will potentially impact our conceptualization of psychotic disorders, help us make critical strides to identify the pathophysiology of psychosis, and guide development of new specific treatments targeting particular deficits.

The overall goal of the proposed research is to examine a broad panel of putative endophenotypes in affected individuals with schizophrenia and bipolar and their unaffected relatives in order to:

  • Characterize the degree of familial phenotypic overlap between SZ and psychotic BP
  • Identify patterns of endophenotypes unique to the two disorders
  • Contrast the heritability of endophenotypes across the disorders

To achieve these goals, we will recruit 500 SZ and 500 BP I (with psychosis) probands, ~1,700-2,000 first degree relative probands, and 500 unrelated nonpsychiatric controls from five centers. We will obtain measures of neurophysiology (e.g., eye tracking, P50 gating, PPI, and P300), neurocognition (e.g., attention/vigilance, episodic and working memory), and brain structure (e.g., volumes of gray and white matter in specified brain regions). We will collect blood for future genetic studies.

We will assess the degree of familial aggregation endophenotypes in SZ and BP relatives. Establishing similarities and differences in the endophenotypic signatures within SZ and BP families will provide important insights for future genetic studies, and clarify concepts about common and distinct aspects of pathophysiology, potentially meaningful heterogeneity with disorders, and the clinical boundaries of the two commonest psychotic disorders in adult psychiatry. This research will be conducted by five experienced research groups, with a long history of close and productive collaboration.

More information is available via the B-SNIP website.

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Gene-Environment interaction in Schizophrenia

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Tissue Collections: DNA and Fibroblasts

If you would like to participate in one of our research studies, please visit the Volunteer Information page.