This application is a request for competitive renewal or our research on the diagnosis and phenomenology of schizophrenia. The work aims to understand the phenomenology of schizophrenia in terms of its underlying mechanisms, refine our definition of its phenotype, and describe the lifelong trajectory of the illness and its long-term outcome. Since the disorder is characterized by a prolonged lifetime course, longitudinal study of informative cohorts is one of the most powerful strategies for understanding its mechanisms and defining its phenotype. This project seeks to refine the definition of the phenotype of schizophrenia by examining the predictive validity of two different competing models in a large sample of first episode and recent onset patients who are followed longitudinally at multiple time points. One approach, a tridimensional model that defines the phenotype using three symptom clusters (psychoticism, disorganization, and negative symptoms) is currently widely accepted and studied. The second approach proposes a new unitary model of schizophrenia as defined at the systems level by a fundamental cognitive deficit (""""""""cognitive dysmetria"""""""") and at the neural level by an abnormality in cortical-cerebellar-thalamic-cerebellar circuitry (CCTCC). The predictive validity of these two models will be compared using four validators derived from the evaluation of long-term course: clinical outcome psychosocial outcome, cognition, and brain morphology.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Research Project (R01)
Project #
Application #
Study Section
Clinical Psychopathology Review Committee (CPP)
Program Officer
Heinssen, Robert K
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Iowa
Schools of Medicine
Iowa City
United States
Zip Code
Rudd, Danielle S; Axelsen, Michael; Epping, Eric A et al. (2014) A genome-wide CNV analysis of schizophrenia reveals a potential role for a multiple-hit model. Am J Med Genet B Neuropsychiatr Genet 165B:619-26
Onwuameze, O E; Nam, K W; Epping, E A et al. (2013) MAPK14 and CNR1 gene variant interactions: effects on brain volume deficits in schizophrenia patients with marijuana misuse. Psychol Med 43:619-31
Andreasen, Nancy C; Liu, Dawei; Ziebell, Steven et al. (2013) Relapse duration, treatment intensity, and brain tissue loss in schizophrenia: a prospective longitudinal MRI study. Am J Psychiatry 170:609-15
Fusar-Poli, P; Smieskova, R; Kempton, M J et al. (2013) Progressive brain changes in schizophrenia related to antipsychotic treatment? A meta-analysis of longitudinal MRI studies. Neurosci Biobehav Rev 37:1680-91
Andreasen, N C; Wilcox, M A; Ho, B-C et al. (2012) Statistical epistasis and progressive brain change in schizophrenia: an approach for examining the relationships between multiple genes. Mol Psychiatry 17:1093-102
Salinas, Joel; Mills, Elizabeth D; Conrad, Amy L et al. (2012) Sex differences in parietal lobe structure and development. Gend Med 9:44-55
Wassink, Thomas H; Epping, Eric A; Rudd, Danielle et al. (2012) Influence of ZNF804a on brain structure volumes and symptom severity in individuals with schizophrenia. Arch Gen Psychiatry 69:885-92
Ho, Beng-Choon; Andreasen, Nancy C; Ziebell, Steven et al. (2011) Long-term antipsychotic treatment and brain volumes: a longitudinal study of first-episode schizophrenia. Arch Gen Psychiatry 68:128-37
Crespo-Facorro, B; Roiz-Santiáñez, R; Pérez-Iglesias, R et al. (2011) Global and regional cortical thinning in first-episode psychosis patients: relationships with clinical and cognitive features. Psychol Med 41:1449-60
Andreasen, Nancy C; Nopoulos, Peg; Magnotta, Vincent et al. (2011) Progressive brain change in schizophrenia: a prospective longitudinal study of first-episode schizophrenia. Biol Psychiatry 70:672-9

Showing the most recent 10 out of 216 publications