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 and 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 changes 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 broad 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: 1) characterize the degree of familial phenotypic overlap between SZ and psychotic BP; 2) identify patterns of endophenotypes unique to the two disorders, and 3) contrast the heritability of endophenotypes across the disorders. To achieve these goals, we will recruit 500 SZ and 500 BP I (with psychosis) probands, ~1700-2000 1st degree relatives of these probands, and 500 unrelated non-psychiatric 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 of 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 within disorders, and the clinical boundaries of the two commonest psychotic disorders in adult psychiatry. This research will be conducted by 5 experienced research groups, with a long history of close and productive collaboration. ? ? Public Health Relevance: This multisite project will identify endophenotypes (or liability markers) that are shared and different in schizophrenia and bipolar disorder. Findings from these studies will provide important insights for future genetic studies, and clarify concepts about common and distinct aspects of pathophysiology, potentially meaningful heterogeneity within disorders, and the clinical boundaries of the two commonest psychotic disorders in adult psychiatry. ? ? ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
1R01MH077852-01A2
Application #
7387205
Study Section
Special Emphasis Panel (ZRG1-HOP-V (60))
Program Officer
Heinssen, Robert K
Project Start
2007-09-28
Project End
2011-05-31
Budget Start
2007-09-28
Budget End
2008-05-31
Support Year
1
Fiscal Year
2007
Total Cost
$853,313
Indirect Cost
Name
University of Maryland Baltimore
Department
Psychiatry
Type
Schools of Medicine
DUNS #
188435911
City
Baltimore
State
MD
Country
United States
Zip Code
21201
Abush, Hila; Ghose, Subroto; Van Enkevort, Erin A et al. (2018) Associations between adolescent cannabis use and brain structure in psychosis. Psychiatry Res Neuroimaging 276:53-64
Rodrigue, Amanda L; McDowell, Jennifer E; Tandon, Neeraj et al. (2018) Multivariate Relationships Between Cognition and Brain Anatomy Across the Psychosis Spectrum. Biol Psychiatry Cogn Neurosci Neuroimaging 3:992-1002
Rubin, Leah H; Li, Siyi; Yao, Li et al. (2018) Peripheral oxytocin and vasopressin modulates regional brain activity differently in men and women with schizophrenia. Schizophr Res 202:173-179
Hochberger, W C; Combs, T; Reilly, J L et al. (2018) Deviation from expected cognitive ability across psychotic disorders. Schizophr Res 192:300-307
Reilly, James L; Hill, S Kristian; Gold, James M et al. (2017) Impaired Context Processing is Attributable to Global Neuropsychological Impairment in Schizophrenia and Psychotic Bipolar Disorder. Schizophr Bull 43:397-406
Eum, Seenae; Hill, S Kristian; Rubin, Leah H et al. (2017) Cognitive burden of anticholinergic medications in psychotic disorders. Schizophr Res 190:129-135
Tandon, Neeraj; Nanda, Pranav; Padmanabhan, Jaya L et al. (2017) Novel gene-brain structure relationships in psychotic disorder revealed using parallel independent component analyses. Schizophr Res 182:74-83
Lencer, R; Mills, L J; Alliey-Rodriguez, N et al. (2017) Genome-wide association studies of smooth pursuit and antisaccade eye movements in psychotic disorders: findings from the B-SNIP study. Transl Psychiatry 7:e1249
Hager, Brandon; Yang, Albert C; Brady, Roscoe et al. (2017) Neural complexity as a potential translational biomarker for psychosis. J Affect Disord 216:89-99
Rubin, Leah H; Yao, Li; Keedy, Sarah K et al. (2017) Sex differences in associations of arginine vasopressin and oxytocin with resting-state functional brain connectivity. J Neurosci Res 95:576-586

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