Neurological Disorders

Psychiatric Disorders

            As part of the Pritzker Neuropsychiatric Disorders Research Consortium, we are currently studying schizophrenia, bipolar disorder, and major depression in hopes of gaining insight into the causes of these debilitating mental disorders. Specifically, we are employing a combination of functional genomic assays to measure DNA methylation and gene expression on a global scale to detect molecular changes that associate with one or more psychiatric disorders. Ultimately, we would like to identify genes and/or gene pathways that contribute to psychiatric phenotypes. Our current studies utilize fresh frozen post-mortem brain tissues, and DNA methylation and gene expression are being measured within several brain regions that have been implicated in psychiatric pathology.

Parkinson Disease

            We are also applying functional genomic measurements to try and unravel the molecular complexities that result in Parkinson disease. In this study, we are measuring DNA methylation and gene expression, on a global scale, within a large cohort of Parkinson disease-affected post-mortem tissues. As Parkinson disease is a complex disorder that likely results from the interaction of many different genomic insults with environmental factors, we expect that functional genomics may aid in the elucidation of molecular lesions that associate with the Parkinson disease phenotype. Our Parkinson disease study is being conducted in collaboration with David Standaert at the University of Alabama in Birmingham as well as John Trojanowski at the University of Pennsylvania.

 

Related Publications

Sequeira, A., Morgan, L., Walsh, D. M., Cartagena, P. M., Choudary, P., Li, J., Schatzberg, A. F., Watson, S. J., Akil, H., Myers, R. M., Jones, E. G., Bunney, W. E. and Vawter, M. P.  (2012).  Gene expression changes in the prefrontal cortex, anterior cingulate cortex and nucleus accumbens of mood disorders subjects that committed suicide.  PLoS One. 2012;7(4):e35367. Epub 2012 Apr 30.  PMID: 22558144 [PubMed - in process]. PDF

Sklar, P., Ripke, S., Scott, L. J., Andreassen, O. A., Cichon, S., Craddock, N., Edenberg, H. J., Nurnberger Jr, J. I., Rietschel, M., Blackwood, D., Corvin, A., Flickinger, M., Guan, W., Mattingsdal, M., McQuillin, A., Kwan, P., Wienker, T. F., Daly, M., Dudbridge, F., Holmans, P. A., Lin, D., Burmeister, M., Greenwood, T. A., Hamshere, M. L., Muglia, P., Smith, E. N., Zandi, P. P., Nievergelt, C. M., McKinney, R., Shilling, P. D., Schork, N. J., Bloss, C. S., Foroud, T., Koller, D. L., Gershon, E. S., Liu, C., Badner, J. A., Scheftner, W. A., Lawson, W. B., Nwulia, E. A., Hipolito, M., Coryell, W., Rice, J., Byerley, W., McMahon, F. J., Schulze, T. G., Berrettini, W., Lohoff, F. W., Potash, J. B., Mahon, P. B., McInnis, M. G., Zöllner, S., Zhang, P., Craig, D. W., Szelinger, S., Barrett, T. B., Breuer, R., Meier, S., Strohmaier, J., Witt, S. H., Tozzi, F., Farmer, A., McGuffin, P., Strauss, J., Xu, W., Kennedy, J. L., Vincent, J. B., Matthews, K., Day, R., Ferreira, M. A., O’Dushlaine, C., Perlis, R., Raychaudhuri, S., Ruderfer, D., Hyoun, P. L., Smoller, J. W., Li, J., Absher, D., Thompson, R. C., Meng, F. G., Schatzberg, A. F., Bunney, W. E. , Barchas, J. D., Jones, E. G., Watson, S. J., Myers, R. M., Akil, H., Boehnke, M., Chambert, K., Moran, J., Scolnick, E., Djurovic, S., Melle, I., Morken, G., Gill, M., Morris, D., Quinn, E., Mühleisen, T. W., Degenhardt, F. A., Mattheisen, M., Schumacher, J., Maier, W., Steffens, M., Propping, P., Nöthen, M. M., Anjorin, A., Bass, N., Gurling, H., Kandaswamy, R., Lawrence, J., McGhee, K., McIntosh, A., McLean, A. W., Muir, W., J., Pickard, B. S., Breen, G., St. Clair, D., Caesar, S., Gordon-Smith, K., Jones, L., Fraser, C., Green, E. K., Grozeva, D., Jones, I. R., Kirov, G., Moskvina, V., Nikolov, I., O’Donovan, M. C., Owen, M. J., Collier, D. A., Elkin, A., Williamson, R., Young, A. H., Ferrier, I. N., Stefansson, K., Stefansson, H., Steinberg, S., Gustafsson, O., Bergen, S. E, Nimgaonkar, V., Hultman, C., Landén, M., Lichtenstein, P., Sullivan, P., Schalling, M., Osby, U., Backlund, L., Frisén, L., Langstrom, N., Jamain, S., Leboyer, M., Etain, B., Bellivier, F., Petursson, H., Sigurosson, E., Müller-Mysok, B., Lucae, S., Schwarz, M., Schofield, P. R., Martin, N., Montgomery, G. W., Lathrop, M., Óskarsson, H., Bauer, M., Wright, A., Mitchell, P. B., Hautzinger, M., Reif, A., Kelsoe, J. R. and Purcell, S. M.  (2011).  Large-scale genome-wide association analysis of bipolar disorder identifies a new susceptibility locus near ODZ4.  Nat. Genet. 43: 977-983.  PMID: 21926972.  [PubMed - in process]. PDF

Moon, E., Rollins, B., Mesén, A., Sequeira, A., Myers, R. M., Akil, H., Watson, S. J., Barchas, J., Jones, E. G., Schatzberg, A., Bunney, W. E., Delisi, L. E., Byerley, W., and Vawter, M. P.  (2011).  Lack of association to a NRG1 missense polymorphism in schizophrenia or bipolar disorder in a Costa Rican population.  Schizophr. Res.  131: 52-57.  PMID: 21745728.  PMCID: PMC3159824. PDF

McGuire, V., Van Den Eeden, S. K., Tanner, C. M., 
Kamel, F., Umbach, D. M., Marder, K., M.P.H., Mayeux, R., Ritz, B., Ross, G. W., Petrovitch, H., Topol, B., Popat, R. A., Costello, S., Manthripragada, A. D., Southwick, A., Myers, R. M., and Nelson, L. M.  (2011).  Association of DRD2 and DRD3 polymorphisms with Parkinson’s disease in a multiethnic consortium.  J. Neurol. Sci.  307: 22-29.  PMID: 21663922.  PMCID: PMC3155471. PDF

Popat, R. A., Van Den Eeden, S. K., Tanner, C. M., Kamel, F., Umbach, D. M., Marder, K., Mayeux, R., Ritz, B., Webster Ross, G., Petrovitch, H., Topol, B., McGuire, V., Costello, S., Manthripragada, A. D., Southwick, A., Myers, R. M. and Nelson, L. M.  (2011).  Coffee, ADORA2A, and CYP1A2: the caffeine connection in Parkinson’s disease.  Eur. J. Neurol. 18: 756-765.  PMID: 21281405.  [PubMed - in process]. PDF

Bernard, R., Kerman, I. A., Thompson, R. C., Jones, E. G., Bunney, W. E., Barchas, J. D., Schatzberg, A. F., Myers, R. M., Akil, H. and Watson. S. J.  (2010).  Altered expression of glutamate signaling, growth factor, and glia genes in the locus coeruleus of patients with major depression.  Mol. Psychiatry.  16: 634-646.  PMID: 20386568.  PMCID: PMC2927798. PDF

Scott, L.J., Muglia, P., Kong, X.Q., Guan, W., Flickinger, M., Upmanyu, R., Tozzi, F., Li, J.Z., Burmeister, M., Absher, D., Thompson, R.C., Francks, C., Meng, F., Antoniades, A., Southwick, A.M., Schatzberg, A.F., Bunney, W.E., Barchas, J.D., Jones, E.G., Day, R., Matthews, K., McGuffin, P., Strauss, J.S., Kennedy, J.L., Middleton, L., Roses, A.D., Watson, S.J., Vincent, J.B., Myers, R.M., Farmer, A.E., Akil, H., Burns, D.K., and Boehnke, M.  (2009). Genome-wide association and meta-analysis of bipolar disorder in individuals of European ancestry.  Proc. Natl. Acad. Sci. U.S.A.  106: 7501-7506.  PMID: 19416921.  PMCID: PMC2678639. PDF

Rollins, B., Martin, M. V., Sequeira, P. A., Moon, E. A., Morgan, L. Z., Watson, S. J., Schatzberg, A., Akil, H., Myers, R. M., Jones, E. G., Wallace, D. C., Bunney, W. E. and Vawter, M. P.  (2009).  Mitochondrial variants in schizophrenia, bipolar disorder, and major depressive disorder.  PLoS ONE.  4: e4913.  [Epub 2009 Mar 17].  PMID: 19290059.  PMCID: PMC2654519. PDF

Shao, L., Martin, M. V., Watson, S. J., Schatzberg, A., Akil, H., Myers, R. M., Jones, E. G., Bunney W. E. and Vawter, M. P.  (2008).  Mitochondrial involvement in psychiatric disorders.  Ann. Med.  40: 281-295.  PMID: 18428021.  PMCID: PMC3098560. PDF

Akil, H., Evans, S. J., Turner, C. A., Perez, J., Myers, R. M., Bunney, W. E., Jones, E. G., Watson, S. J. and the Pritzker Consortium.  (2008).  The fibroblast growth factor family and mood disorders.  Novartis Found. Symp.  289: 94-96; discussion 97-100, 193-195.  PMID: 18497097.

Atz, M., Walsh, D., Cartagena. P., Li, J., Evans, S., Choudary, P., Overman, K., Stein, R., Tomita, H., Potkin, S., Myers, R., Watson, S. J., Jones, E. G., Akil, H., Bunney, W. E. Jr., Vawter, M. P. and Members of National Institute of Mental Health Conte Center and Pritzker Neuropsychiatric Disorders Research Consortium.  (2007).  Methodological considerations for gene expression profiling of human brain.  J. Neurosci. Methods.  163: 295-309.  PMID: 1751205.  [PubMed - indexed for MEDLINE]. PDF

Li, J. Z., Meng, F., Tsavaler, L., Evans, S. J., Choudary, P. V., Tomita, H., Vawter, M. P., Walsh, D., Shokoohi, V., Chung, T., Bunney, W. E., Jones, E. G., Akil, H., Watson, S. J. and Myers, R. M.  (2007).  Sample matching by inferred agonal stress in gene expression analyses of the brain.  BMC Genomics.  8: 336.  PMID: 17892578.   PMCID: PMC2213675. PDF

Elbaz, A., Nelson, L. M., Payami, H., Ioannidis, J. P. A., Fiske, B. K., Annesi, G., Carmine, A., Factor, S. A., Ferrarese, C., Hadjigeorgiou, G. M., Higgins, D., Kawakami, H., Krueger, R., Marder, K., Mayeux, R., Mellick, G., Nutt, J., Ritz, B., Samii, A., Tanner,C. M., Van Broeckhoven, C., Van Den Eeden, S. K., Wirdefeldt, K., Zabetian, C. P., Dehem, M., Montimurro, J.S., Southwick, A., Myers, R. M., and Trikalinos, T. A.  (2006).  Lack of replication of thirteen single-nucleotide polymorphisms implicated in Parkinson’s disease: a large-scale international study.  Lancet Neurol. 5: 917-923.  PMID: 17052658.  [PubMed - indexed for MEDLINE].

Vawter, M. P., Tomita, H., Meng, F., Bolstad, B., Li, J., Evans, S., Choudary, P., Atz, M., Shao, L., Neal, C., Walsh, D., Burmeister, M., Speed, T., Myers, R., Jones, E. G., Watson, S. J., Akil, H. and Bunney, W. E.  (2006).  Mitochondrial related gene expression changes are sensitive to agonal-pH state: Implications for brain disorders.  Mol. Psychiatry.  11: 615, 663-679.  PMID: 16636682. PDF

Karssen*, A. M., Li*, J. Z., Her, S., Patel, P. D., Meng, F., Evans, S. J., Vawter, M. P., Tomita, H., Choudary, P. V., Bunney, Jr., W. E., Jones, E. G., Watson, S. J., Akil, H., Myers, R. M., Schatzberg, A. F. and Lyons, D. M.  (2006).  Application of microarray technology in primate behavioral neuroscience research.  Methods.  38: 227-234.  (*co-first authors).  PMID: 16469505. PDF

Evans, S. J., Choudary, P. V., Neal, C. R., Li, J. Z., Vawter, M. P., Tomita, H., Lopez, J. F., Thompson, R. C., Meng, F., Stead, J. D., Walsh, D. M., Myers, R. M., Bunney, W. E., Watson, S. J., Jones, E. G. and Akil, H.  (2004).  Dysregulation of the fibroblast growth factor system in major depression.  Proc. Natl. Acad. Sci. USA. 101: 15506-15511.  PMID: 15483108. PDF

Vawter, M. P., Evans, S., Choudary, P., Tomita, H., Meador-Woodruff, J., Molnar, M., Li, J., Lopez, J. F., Myers, R., Cox, D., Watson, S. J., Akil, H., Jones, E. G., Bunney, W. E.  (2004).  Gender-specific gene expression in post-mortem human brain: Localization to sex chromosomes.  Neuropsychopharmacology.  29: 373-384. PDF

Li, J., Nguyen, L., Gleason, C. Lotspeich, L., Spiker, D., Risch, N. and Myers, R. M.  (2004).  Lack of evidence for an association between WNT2 and RELN polymorphisms and autism.  Amer. J. Med. Genet.: Neuropsych. Genet. 126B: 51-57.  PMID: 15048648. PDF

Tomita, H., Vawter, M. P., Walsh, D. M., Evan, S., Choudary, P. V., Li, J., Overman,  K., Atz, M., Myers, R. M., Jones, E. G., Watson, S. J., Akil, H. and Bunney, W. E.  (2004).  Effect of agonal and postmortem factors on microarray expression profile: quality control methods in microarray analyses of postmortem human brain.  Biol. Psychiatry. 55: 346-352.  PMID: 14960286. PDF

Bunney, W. E., Bunney, B. G., Vawter, M. P., Tomita, H., Li, J., Evans, S. J., Choudary, P. V., Myers, R. M., Jones, E. G., Watson, S. J., Akil, H.  (2003). Microarray technology: a review of new strategies to discover candidate vulnerability genes in psychiatric disorders.  Am. J. Psychiatry.  160: 657-666. PDF

Evans S. J., Choudary, P. V., Vawter, M. P., Li, J., Meador-Woodruff, J. H., Lopez, J. F., Burke, S. M., Thompson, R. C., Myers, R. M., Jones, E. G., Bunney, W. E., Watson, S. J., and Akil, H.  (2003).  DNA microarray analysis of functionally discrete human brain regions reveals divergent transcriptional profiles.  Neurobiol. Dis. 14: 240-250. PDF

Spiker, D., Lotspeich, L. J., Dimiceli, S., Myers, R. M. and Risch, N.  (2002).  Behavioral variation in autism multiplex families: Evidence for a continuous severity gradient.  Amer. J. Med. Genet.: Neuropsychiatric Genet. 114: 129-136.  PMID: 11857572. PDF

Li, J., Tabor, H., Gleason, C., Nguyen, L., Lotspeich, L., Spiker, D., Risch, N. and Myers, R. M.  (2002).  Lack of association between HoxA1 and HoxB1 gene variants and autism in 110 multiplex families.  Amer. J. Med. Genet.: Neuropsychiatric Genet.  114: 24-30. PDF

 Spiker, D., Lotspeich, L. J., Dimiceli, S., Szatmari, P., Myers, R. M. and Risch, N.  (2001).  Birth order effects on nonverbal IQ scores in autism multiplex families.  J. Autism Devel. Disord. 31: 449-460.  PMID: 11794410. PDF

Salmon, B., Hallmayer, J., Rogers, T., Kalaydijieva, L., Peterson, P. B., Nicholas, P., Pingree, C., McMahon, W., Spiker, D., Lotspeich, L., Kraemer, H., McCague, P., Dimiceli,S., Nouri, N., Pitts, T., Yang, J., Hinds, D., Myers, R. M. and Risch, N. (1999).  Absence of linkage and linkage disequilibrium to chromosome 15q11-q13 markers in 139 multiplex families with autism.  Amer. J. Med. Genet. 88: 551-556.

Li, Z., Karlovich, C. A., Fish, M., Scott, M. P. and Myers, R. M. (1999).  A putative Drosophila homolog of the Huntington disease gene.  Hum. Molec. Genet. 8: 1807-1815. PDF

Risch, N., Spiker, D., Lotspeich, L., Nouri, N., Hinds, D., Hallmayer, J., et al. and Myers, R. M.  (1999).  A genomic screen for autism: Evidence for a multi-locus etiology.  Am. J. Hum. Genet. 65: 493-507. PDF

Rogers, T., Kalaydijieva, L., Hallmayer, J., et al., Risch, N. and Myers, R. M.  (1999).  Exclusion of linkage to the HLA region in ninety multiplex families with autism.  J. Autism and Develop. Disorders 29: 195-201.

Shelbourne, P. F., Killeen, N., Hevner, R. F., Johnston, H. M., Tecott, L., Lewandoski, M., Ennis, M., Ramirez, L., Li, A., Iannicola, C., Littman, D. R. and Myers, R. M. (1999).  A Huntington’s disease CAG expansion at the muring Hdh locus is unstable and associated with behavioural abnormalities in mice. Hum. Molec. Genet. 8: 763-774. PDF

Usdin, M., Shelbourne, P. F., Myers, R. M. and Madison, D. V. (1999).  Impaired synaptic plasticity in mice carrying the Huntington’s disease mutation.  Hum. Molec. Genet. 8: 839-846. PDF

Karlovich, C. A., John, R. M., Ramirez, L., Stainier, D. Y. R. and Myers, R. M. (1998).  Characterization of the Huntington disease (HD) gene homolog in the zebrafish Danio rerio.  Gene 217: 117-125.

Jou, Y.-S. and Myers, R. M. (1995).  Evidence from antibody studies that the CAG-repeat in the Huntington disease gene is expressed in the protein.  Hum. Mol. Genet.  4:  465-469.

Law,  A., Richard, C. W., Cottingham, R. W., Lathrop, G. M., Cox, D. R. and Myers, R. M.  (1992).  Genetic linkage analysis of bipolar affective disorder in an Old Order Amish pedigree.  Hum. Genet.  88: 562-568.

Pritchard, C. A., Cox, D. R. and Myers, R. M. (1991).  Invited editorial: The end in sight for Huntington disease?  Amer. J. Hum. Genet. 49: 1-6.

Pritchard, C. A., Casher, D., Bull, L., Cox, D. R. and Myers, R. M.  (1990).  A cloned DNA segment from the telomeric region of human chromosome 4p is not detectably rearranged in Huntington disease patients.  Proc. Natl. Acad. Sci. USA.  87: 7309-7313. PDF

Pritchard, C. A., Cox, D. R. and Myers, R. M. (1989).  Methylation at the Huntington disease-linked D4S95 locus.  Amer. J. Hum. Genet. 45: 335-336. PDF

Cox, D. R., Pritchard, C. A., Uglum, E., Casher, D., Kobori, J., and Myers, R. M.  (1989).  Segregation of the Huntington disease region of human chromosome 4 in a somatic cell hybrid.  Genomics 4: 397-407.

Pritchard, C. A., Casher, D., Uglum, E., Cox, D. R., and Myers, R. M.  (1989).  Isolation and field- inversion gel electrophoresis analysis of DNA markers located close to the Huntington disease gene.  Genomics 4: 408-418.