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Course Prerequisites:  

Basic knowledge of genetics  and cognitive and behavioral measures in addition to understanding elements of neuroimaging and neuroanatomy
    Course Description:  

There will be 4 lectures, each 2.5 hours:

1) Organic causes of autism: This course will review known genetic or medical causes of autism and will describe gene, brain, and behavioral relationships related to these causes. We will review the medical workup of children who present with autism and what is known about biological markers and environmental toxicology. Treatment issues will be addressed.

2) X-linked mental retardation including fragile X syndrome and FXTAS: New genes associated with X-linked mental retardation and their neurobiology will be presented. Overlap and commonalities of function will be emphasized. Fragile X syndrome and the fragile X-associated tremor ataxia syndrome (FXTAS) will be detailed including gene, brain, behavior relationships and treatment issues.

3) Microdeletion syndromes, fetal alcohol syndrome and sex chromosomal disorders: The behavioral and cognitive phenotypes and molecular-clinical correlations in Williams syndrome, velocardiofacial syndrome, Smith Magenis syndrome, Prader-Willi Syndrome, Angelman syndrome and sex chromosomal disorders will be described. Commonalities in molecular mechanisms will be emphasized. Fetal alcohol syndrome will also be reviewed as a model of environmental toxicity leading to mental retardation.

4) Psychopharmacological Interventions: We will review currently available psychopharmacological interventions that impact dopamine, norepinephrine, serotonin and glutamate systems. The differences regarding responses to different psychopharmacological agents in the syndromes we have previously discussed will be presented. Finally new psychopharmacological interventions developed for specific disorders will be presented, such as metabotropic glutamate receptor 5 (mGluR5) inhibitors in fragile X.



REQUIRED READING LIST:

Bardoni, B. and J. L. Mandel (2002). "Advances in understanding of fragile X pathogenesis and FMRP function, and in identification of X linked mental retardation genes." Curr Opin in Genetics & Development 12: 284-293.  

Bearden, C. E., P. P. Wang, et al. (2002). "Williams syndrome cognitive profile also characterizes Velocardiofacial/DiGeorge syndrome." Am J Med Genet 114(6): 689-92. 

Chelly, J. (2000). "MRX Review." American Journal of Medical Genetics 94: 364-366. 

De Leersnyder, H., J. L. Bresson, et al. (2003). "Beta 1-adrenergic antagonists and melatonin reset the clock and restore sleep in a circadian disorder, Smith-Magenis syndrome." J Med Genet 40(1): 74-8. 

des Portes, V., Hagerman, R.J., Hendren, R.L. (2003). Pharmacotherapy. Autism Spectrum Disorders: A research review for practitioners. S. Ozonoff, Rogers, S.J., Hendren, R.L. Arlington, American Psychiatric Publishing, Inc.: 161-187.  

Filipek, P. A., P. J. Accardo, et al. (2000). "Practice parameter: Screening and diagnosis of autism. Report of the Quality Standards Subcommittee of the American Academy of Neurology and the Child Neurology Society." Neurology 55: 468-479.

Hagerman, P. J. and R. J. Hagerman (2004). "The fragile-X premutation: a maturing perspective." Am J Hum Genet 74(5): 805-16. 

Hagerman, R. J. (1999). Fetal Alcohol Syndrome. Neurodevelopmental Disorders: Diagnosis and Treatment. New York, Oxford University Press: 3-59.

Hagerman, R. J. (1999). Sex Chromosome Aneuploidy in Females. Neurodevelopmental Disorders: Diagnosis and Treatment. New York, Oxford University Press: 207-241.

Hagerman, R. J. (1999). Sex Chromosome Aneuploidy in Males. Neurodevelopmental Disorders: Diagnosis and Treatment. New York, Oxford University Press: 173-206.

Goldstone, A. P. (2004). "Prader-Willi syndrome: advances in genetics, pathophysiology and treatment." Trends Endocrinol Metab 15(1): 12-20. 

Jacquemont, S., R. J. Hagerman, et al. (2003). "Fragile X Premutation Tremor/Ataxia Syndrome: Molecular, Clinical, and Neuroimaging Correlates." Am J Hum Genetics 72: 869-878.  

Itoh, M., M. Hayashi, et al. (2004). "Systemic growth hormone corrects sleep disturbance in Smith-Magenis syndrome." Brain Dev 26(7): 484-6. 

Loesch, D. Z., R. M. Huggins, et al. (2004). "Phenotypic variation and FMRP levels in fragile X." Ment Retard Dev Disabil Res Rev 10(1): 31-41. 

Peters, S., A. Beaudet, et al. (2004). "Autism in Angelman syndrome: implications for autism research." Clin Genet 66(6): 530-6.
 


OPTIONAL READING LIST:

Barnea-Goraly, N., V. Menon, et al. (2003). "Investigation of white matter structure in velocardiofacial syndrome: a diffusion tensor imaging study." Am J Psychiatry 160(10): 1863-9. 

De Smedt, B., A. Swillen, et al. (2003). "Pre-academic and early academic achievement in children with velocardiofacial syndrome (del22q11.2) of borderline or normal intelligence." Genet Couns 14(1): 15-29.

 Dykens, E. and B. Shah (2003). "Psychiatric disorders in Prader-Willi syndrome: epidemiology and management." CNS Drugs 17(3): 167-78.  

Feinstein, C., S. Eliez, et al. (2002). "Psychiatric disorders and behavioral problems in children with velocardiofacial syndrome: usefulness as phenotypic indicators of schizophrenia risk." Biol Psychiatry 51(4): 312-8. 

Galaburda, A. M., D. Holinger, et al. (2003). "[Williams syndrome. A summary of cognitive, electrophysiological, anatomofunctional, microanatomical and genetic findings]." Rev Neurol 36 Suppl 1: S132-7.  

Galaburda, A. M., D. P. Holinger, et al. (2002). "Williams syndrome: neuronal size and neuronal-packing density in primary visual cortex." Arch Neurol 59(9): 1461-7.  

Glaser, B., D. L. Mumme, et al. (2002). "Language skills in children with velocardiofacial syndrome (deletion 22q11.2)." J Pediatr 140(6): 753-8.   

Hirota, H., R. Matsuoka, et al. (2003). "Williams syndrome deficits in visual spatial processing linked to GTF2IRD1 and GTF2I on chromosome 7q11.23." Genet Med 5(4): 311-21.

Mandel, J. L. and J. Chelly (2004). "Monogenic X-linked mental retardation: is it as frequent as currently estimated? The paradox of the ARX (Aristaless X) mutations." Eur J Hum Genet 12(9): 689-93.

Maynard, T. M., G. T. Haskell, et al. (2002). "22q11 DS: genomic mechanisms and gene function in DiGeorge/velocardiofacial syndrome." Int J Dev Neurosci 20(3-5): 407-19.

Paul, B. M., J. Stiles, et al. (2002). "Face and place processing in Williams syndrome: evidence for a dorsal-ventral dissociation." Neuroreport 13(9): 1115-9. 

Schmitt, J. E., K. Watts, et al. (2002). "Increased gyrification in Williams syndrome: evidence using 3D MRI methods." Dev Med Child Neurol 44(5): 292-5.
 
Spadoni, E., P. Colapietro, et al. (2004). "Smith-Magenis syndrome and growth hormone deficiency." Eur J Pediatr 163(7): 353-8.  

Streissguth, A. P. and K. O'Malley (2000). "Neuropsychiatric implications and long-term consequences of fetal alcohol spectrum disorders." Semin Clin Neuropsychiatry 5(3): 177-90.

Streissguth, A. P., F. L. Bookstein, et al. (2004). "Risk factors for adverse life outcomes in fetal alcohol syndrome and fetal alcohol effects." J Dev Behav Pediatr 25(4): 228-38.

Vogels, A. and J. P. Fryns (2002). "The velocardiofacial syndrome: a review." Genet Couns 13(2): 105-13.