Schizophrenia is a neurodevelopmental syndrome that affects approximately 1 percent of the U.S. population and is characterized by the presence of hallucinations and delusions. Genetic factors are thought to account for the majority of the vulnerability to illness for this syndrome. These genetic factors are thought to be composed of major, moderate ant mild effect loci. The identification and characterization of genetic factors of even mild effect loci is a critical step in the process of understanding the pathogenesis of this group of disorders. In prior moleular studies, the candidate has identified an exonic polymorphism (HOPA12bP) in a critical portion of a gene for a thyroid receptor co-activator named HOPAthat is associated with a behavioral endophenotype that include schizophrenia and hypothyroidism. In this five year training grant, the candidate proposes to focus on the behavioral syndrome that is associated with the polymorphism and 1) demonstrate segregation of the polymorphism with illness. 2 refine the phenotype associated with the polymorphism, and 3) identify other mutations that may be related to illness. Scientific Aims of this grant are 1). Peform case control analyses on schizophrenic probands with the HOPA12bp polymorphism. Schizophrenic HOPA probands will be identified and compared to matched case controls for cognitive/behavioral, endocrinological and medical differences. 2. Conduct a focused linkage study of the families of HOPA12bp probands. Structured interviews will be used to assess the presence of cognitive/behavioral and medical co-morbidity in the first-degree relatives of control and HOPA12bP probands. These results will be correlated with genetic status. 3). Conduct SSCP analysis across the HOPA Gene to detect other potentially pathogenic mutations. Mutation analysis will be performed using DNA from other schizophrenic patients to detect other mutations in theHOPA gene that can result in result in this syndrome or related phenotypes. Training Aims of this grant are to 1) develop clinical skills in the diagnosis and standardized measurement of complex behavior and endocrinological disorders, and 2) learn medical and psychiatric epidemiology, ethics, and biostatistical approaches to complex disorders. The net effect will be to produce an independent investigator capable of functional and translational research.
| Philibert, Robert A; Ryu, Gi-Yung; Yoon, Jae-Geun et al. (2007) Transcriptional profiling of subjects from the Iowa adoption studies. Am J Med Genet B Neuropsychiatr Genet 144B:683-90 |
| Philibert, Robert A; Crowe, Raymond; Ryu, Gi-Yung et al. (2007) Transcriptional profiling of lymphoblast lines from subjects with panic disorder. Am J Med Genet B Neuropsychiatr Genet 144B:674-82 |
| Philibert, Robert; Madan, Anup; Andersen, Allan et al. (2007) Serotonin transporter mRNA levels are associated with the methylation of an upstream CpG island. Am J Med Genet B Neuropsychiatr Genet 144B:101-5 |
| Philibert, Robert A; Gunter, Tracy; Black, Donald W et al. (2006) Association of elevated free T4 levels with depressive symptoms in patients with psychotic disorders. Schizophr Res 87:334-5 |
| Philibert, Robert; Gunter, Tracy; Hollenbeck, Nancy et al. (2006) No association of the C677T methylenetetrahydrofolate reductase polymorphism with schizophrenia. Psychiatr Genet 16:221-3 |
| Forman-Hoffman, V; Philibert, R A (2006) Lower TSH and higher T4 levels are associated with current depressive syndrome in young adults. Acta Psychiatr Scand 114:132-9 |
| Philibert, Robert (2006) Merging genetic and environmental effects in the Iowa Adoption Studies: focus on depression. Ann Clin Psychiatry 18:219-22 |
| Philibert, Robert A (2006) A meta-analysis of the association of the HOPA12bp polymorphism and schizophrenia. Psychiatr Genet 16:73-6 |
| Bradley, Sarah L; Dodelzon, Katerina; Sandhu, Harinder K et al. (2005) Relationship of serotonin transporter gene polymorphisms and haplotypes to mRNA transcription. Am J Med Genet B Neuropsychiatr Genet 136B:58-61 |
| Sandhu, Harinder K; Hollenbeck, Nancy; Wassink, Thomas H et al. (2004) An association study of PCQAP polymorphisms and schizophrenia. Psychiatr Genet 14:169-72 |
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