Special Topics: Genetics, Neurobiology, and Pathophysiology of Psychiatric Disorders

Readings

LEC #	TOPICS	READINGS
1	General introduction “Genome-wide association studies for complex traits: consensus, uncertainty and challenges.” Reading assignment handed out.
2	Bipolar disorder	Vieta E., and T. Suppes. “Bipolar II Disorder: Arguments for and Against A Distinct Diagnostic Entity.” Bipolar Disorders 10 (2008): 163-78. Strakowski S. M., M. P. Delbello, and C. M. Adler. “The Functional Neuroanatomy of Bipolar Disorder: A Review of Neuroimaging Findings.” Mol Psychiatry 10 (2005): 105-16.
3	Psychosis, Schizophrenia	Satcher, David, MD, PhD. “Schizophrenia.” In Mental Health: A Report of the Surgeon General. United States Department of Health and Human Services Center for Mental Health Services - Substance Abuse and Mental Health Services Administration site. 1999. Freedman, Robert. “Schizophrenia.” The N Engl J Med 349, no. 18 (2003): 1738-49. Lisman, John E., J. T. Coyle, and R. W. Green, et al. “Circuit-Based Framework for Understanding Neurotransmitter and Risk Gene Interactions in Schizophrenia.” Trends in Neurosciences 31, no. 5 (2008): 234-42. Kane, John, G. Honigfeld, and J. Singer, et al. “Clozapine for the Treatment-Resistant Schizophrenic.” Arch Gen Psychiatry 45 (1988): 789-96. Carlson, Gabrielle A., and F. K. Goodwin. “The Stages of Mania.” Arch Gen Psychiatry 28 (1973): 221-28.
4	Genetics of psychiatric disorder	Ferreira, Manuel A. R., M. C. O’Donovan, and Y. A. Meng, et al. “Collaborative Genome-Wide Association Analysis Supports a Role for ANK3 and CACNA1C in Bipolar Disorder.” Nature Genetics 40, no. 9 (September, 2008): 1056-58. The International Schizophrenia Consortium. “Rare Chromosomal Deletions and Duplications Increase Risk of Schizophrenia.” Nature 455 (September 11, 2008): 237-41.
5	DISC1	Ross, Christopher A., R. L. Margolis, and S. A. J. Reading, et al. “Neurobiology of Schizophrenia.” Neuron 52 (October 5, 2006): 139-53. Chubb, J. E., N. J. Bradshaw, and D. C. Soares, et al. “The DISC Locus in Psychiatric Illness.” Molecular Psychiatry 13 (2008): 36-64.
6	Ca++ signaling	Greer, P. L., and M. E. Greenberg. “From Synapse to Nucleus: Calcium-dependent Gene Transcription in the Control of Synapse Development and Function.” Neuron 59 (September 25, 2008): 846-60. Yingxi L., B. L. Bolldgood, and J. L. Hauser, et al. “Activity-dependent Regulation of Inhibitory Synapse Development by Npas4.” Nature 455 (October 30, 2008): 1198-1204.
7	Literature discussion: neurogenesis and depression	Nestler, E. J., M. Barrot, S., and R. J. DiLeone, et al. “Neurobiology of Depression.” Neuron 34 (March 28, 2002): 13-25. Zhao, C., W. Deng, and F. H. Gage. “Mechanisms and Functional Implications of Adult Neurogenesis.” Cell 132 (February 22, 2002): 645-60. Malberg, J. E., A. J. Eisch, and E. J. Nestler, et al. “Chronic Antidepressant Treatment Increases Neurogenesis in Adult Rat Hippocampus.” J Neurosci 20, no. 24 (December 15, 2000): 9104-10. Sahay, A., and R. Hen. “Adult Hippocampal Neurogenesis in Depression.” Nature Neuroscience 10, no. 9 (September, 2007): 1110-15. Santarelli, L., M. Saxe, and C. Gross, et al. “Requirement of Hippocampal Neurogenesis for the Behavioral Effects of Antidepressants.” Science 301 (August 8, 2003): 805-9.
8	Lithium and GSK3 hypothesis	Mitchell, P. B., and D. Hadzi-Pavlovic. “Lithium Treatment for Bipolar Disorder.” Bulletin of the World Health Organization 78, no. 4 (2000): 515-19. Klein, P. S., and D. A. Melton. “A Molecular Mechanism for the Effect of Lithium on Development.” Proc Natl Acad Sci 93 (August 1996): 8455-59. Beaulieu, Jean-Martin, T. D. Sotnikova, and Wei-Dong Yao, et al. “Lithium Antagonizes Dopamine-Dependent Behaviors Mediated by an AKT. Glycogen Synthase Kinase 3 Signaling Cascade.” PNAS 101, no. 14 (April 6, 2004): 5099-5104.
9	Behavioral assays “Overview of animal models of Schizophrenia.” Reading assignment handed out. “Different behaviors and different strains: potential new ways to model bipolar disorder.” Reading assignment handed out. “The ascent of mouse: advances in modelling human depression and anxiety.” Reading assignment handed out.
10	CREB in addiction and depressive behaviors “Biological substrates of reward and aversion: a nucleus accumbens activity hypothesis.” Reading assignment handed out. “Understanding the neurobiological consequences of early exposure to psychotropic drugs: linking behavior with molecules.” Reading assignment handed out. “The mesolimbic dopamine reward circuit in depression.” Reading assignment handed out.
11	Literature discussion: the GABA System-I	Woo, Tsung-Ung, R. E. White, and D. S. Melchitzky, et al. “A Subclass of Prefrontal-Aminobutyric Acid Axon Terminals are Selectively Altered in Schizophrenia.” Proc Natl Acad Sci 95 (April 1998): 5341-5346. Lewis, D. A., D. A. Cruz, and D. S. Melchitzky, et al. “Lamina-Specific Deficits in Parvalbumin-Immunoreactive Varicosities in the Prefrontal Cortex of Subjects With Schizophrenia: Evidence for Fewer Projections From the Thalamus.” Am J Psychiatry 158 (2001): 1411-22. Lewis, D. A., and G. Gonzalez-Burgos. “Neuroplasticity of Neocortical Circuits in Schizophrenia.” Neuropsychopharmacology 33 (2008): 141-65. Wonders, C. P., and S. A. Anderson. “The Origin and Specification of Cortical Interneurons.” Neuroscience 7 (2006): 687-96. Anderson, S. A., D. D. Eisenstat, and L. Shi, et al. “Interneuron Migration from Basal Forebrain To Neocortex: Dependence on Dlx Genes.” Science 278 (October 17, 1997): 474-76. Lewis, D. A., D. W. Volk, and T. Hashimoto. “Selective Alterations in Prefrontal Cortical GABA Neurotransmission in Schizophrenia: A Novel Target for the Treatment of Working Memory Dysfunction.” Psychopharmacology 174 (2004): 143-50.
12	Literature discussion: the GABA System-II
13	Literature discussion: the glutamate hypothesis of Schizophrenia	Mohn, A. R., R. R. Gainetdinov, and M. G. Caron, et al. “Mice with Reduced NMDA Receptor Expression Display Behaviors Related to Schizophrenia.” Cell 98 (August 20, 1999): 427-36. Coyle, J. T., G. Tsai, and D. Goff. “Converging Evidence of NMDA Receptor Hupofunction in the Pathophysiology of Schizophrenia.” N Y Acad Sci 1003 (2003): 318-27. Lisman, J. E., J. T. Coyle, and R. W. Green, et al. “Circuit-Based Framework for Understanding Neurotransmitter and Risk Gene Interactions in Schizophrenia.” Trends in Neurosciences 31, no. 5 (April 7, 2008): 234-42. Homayoun H., and B. Moghaddam. “Orbitofrontal Cortex Neurons as a Common Target for Classic and Glutamatergic Antipsychotic Drugs.” PNAS 105, no. 46 (November 18, 2008): 18041-46. Homayoun H., and B. Moghaddam. “NMDA Receptor Hypofunction Produces Opposite Effects on Prefrontal Cortex Interneurons and Pyramidal Neurons.” J Neurosci 27, no. 43 (October 24, 2007): 11496-11500.
14	Literature discussion: the dopamine pathway and DARPP32	Beaulieu J. M., T. D. Sotnikova, and S. Marion, et al. “An Akt/Beta-Arrestin 2/PP2A Signaling Complex Mediates Dopaminergic Neurotransmission and Behavior.” Cell 122, no. 2 (July 29, 2005): 261-73. Gainetdinov, R. R., R. T. Premont, and L. M. Bohn, et al. “Desensitization of G Protein-Coupled Receptors and Neuronal Functions.” Annu Rev Neurosci 27 (2004): 107-44. Craddock, N., M. J. Owen, and M. C. O’Donovan. “The Catechol-O-Methyl Transferase (COMT) Gene as a Candidate for Psychiatric Phenotypes: Evidence and Lessons.” Molecular Psychiatry 11 (2006): 446-58. Drew, M. R., E. H. Simpson, and C. Kellendonk, et al. “Transient Overexpression of Striatal D2 Receptors Impairs Operant Motivation and Interval Timing.” J Neurosci 27, no. 29 (July 18, 2007): 7731-39. Svenningsson P., A. Nishi, and G. Fisone, et al. “DARPP-32: An Integrator of Neurotransmission.” Annu Rev Pharmacol Toxicol 44 (2004): 269-96. Kellendonk C., E. H. Simpson, and H. J. Polan, et al. “Transient and Selective Overexpression of Dopamine D2 Receptors in the Striatum Causes Persistent Abnormalities in Prefrontal Cortex Functioning.” Neuron 49 (February 16, 2006): 603-15. Ross, C. A., R. L. Margolis, and A. A. J. Reading, et al. “Neurobiology of Schizophrenia.” Neuron 52 (October 5, 2006): 139-53.