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Behavioral and Brain Sciences Behavioral and Brain Sciences

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Heterogeneity and hypothesis testing in neuropsychiatric illness

Published online by Cambridge University Press:  26 June 2008

Curtis K. Deutsch ,
Wesley W. Ludwig  and
William J. McIlvane
Curtis K. Deutsch
Affiliation:
Eunice Kennedy Shriver Center, University of Massachusetts Medical School (UMMS), Waltham, MA 02452, and Psychobiology Program, Harvard Medical School, Boston, MA 02115
Wesley W. Ludwig
Affiliation:
Neuroregeneration Laboratories, McLean Hospital, Mailman Research Center, Belmont, MA 02478
William J. McIlvane
Affiliation:
Eunice Kennedy Shriver Center, University of Massachusetts Medical School (UMMS) MRDDRC, Office of the Director, Waltham, MA 02452. curtis.deutsch@umassmed.eduwludwig@mclean.harvard.eduwilliam.mcilvane@umassmed.edu
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Abstract

The confounding effects of heterogeneity in biological psychiatry and psychiatric genetics have been widely discussed in the literature. We suggest an approach in which heterogeneity may be put to use in hypothesis testing, and may find application in evaluation of the Crespi & Badcock (C&B) imprinting hypothesis. Here we consider three potential sources of etiologic subtypes for analysis.

Type
Open Peer Commentary
Information
Behavioral and Brain Sciences , Volume 31 , Issue 3 , June 2008 , pp. 266 - 267
Copyright
Copyright © Cambridge University Press 2008

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References

Brock, J., Brown, C., Boucher, J. & Rippon, G. (2002) The temporal binding deficit hypothesis of autism. Development and Psychopathology 142(2):209–24.Google Scholar
Butler, M. G., Dasouki, M. J., Zhou, X. P., Talebizadeh, Z., Brown, M., Takahashi, T. N., Miles, J. H., Wang, C. H., Stratton, R., Pilarski, R. & Eng, C. (2005) Subset of individuals with autism spectrum disorders and extreme macrocephaly associated with germline PTEN tumour suppressor gene mutations. Journal of Medical Genetics 42:318–21.CrossRefGoogle ScholarPubMed
Christian, S. L., Fantes, J. A., Mewborn, S. K., Huang, B. & Ledbetter, D. H. (1999) Large genomic duplicons map to sites of instability in the Prader-Willi/Angelman syndrome chromosome region (15q11–q13). Human Molecular Genetics 8(6):1025–37.CrossRefGoogle Scholar
Clifford, S., Dissanayake, C., Bui, Q. M., Huggins, R., Taylor, A. K. & Loesch, D. Z. (2007) Autism spectrum phenotype in male and females with fragile X full mutation and permutation. Journal of Autism and Developmental Disorders 37(4):738–47.CrossRefGoogle Scholar
Deutsch, C. K. (1998) Emergent properties of brain development and function. In: Perspectives on fundamental processes in intellectual functioning: A survey of research approaches, vol. 2, ed. Soraci, S. A. & McIlvane, W. J., pp. 168–85. Ablex.Google Scholar
Fanous, A. H. & Kendler, K. S. (2005) Genetic heterogeneity, modifier genes, and quantitative phenotypes in psychiatric illness: Searching for a framework. Molecular Psychiatry 10(1):6–13.CrossRefGoogle ScholarPubMed
Fine, S. E, Weissman, A., Gerdes, M., Pinto-Martin, J., Zackai, E. H., McDonald-McGinn, D. M. & Emanuel, B. S. (2005) Autism spectrum disorders and symptoms in children with molecularly confirmed 22q11.2 deletion syndrome. Journal of Autism and Developmental Disorders 35(4):461–70.CrossRefGoogle ScholarPubMed
Geschwind, D. H. & Levitt, P. (2007) Autism spectrum disorders: Developmental disconnection syndromes. Current Opinion in Neurobiology 17(1):103–11.CrossRefGoogle ScholarPubMed
Havlovicova, M., Novotna, D, Kocarek, E, Novotna, K, Bendova, S, Petrak, B, Hrdlicka, M. & Sedlacek, Z. (2007) A girl with Neurofibromatosis type 1, atypical autism and mosaic ring chromosome 17. American Journal of Medical Genetics 143A:76–81.CrossRefGoogle ScholarPubMed
Iafrate, A. J., Feuk, L., Rivera, M. N., Listewnik, M. L., Donahoe, P. K., Qi, Y., Scherer, S. W. & Lee, C. (2004) Detection of large-scale variation in the human genome. Nature Genetics 36(9):949–51.CrossRefGoogle ScholarPubMed
Johansson, M., Wentz, E., Fernell, E., Stromland, K., Miller, M. & Gillberg, C. (2001) Autistic spectrum disorders in Mobius sequence: A comprehensive study of 25 individuals. Developmental Medicine and Child Neurology 43(5):338–45.CrossRefGoogle ScholarPubMed
Just, M. A., Cherkassky, V. L., Keller, T. A. & Minshew, N. J. (2004) Cortical activation and synchronization during sentence comprehension in high-functioning autism: Evidence of underconnectivity. Brain 127:1811–21.CrossRefGoogle ScholarPubMed
Lord, C., Leventhal, B. L. & Cook, E. H. Jr. (2001) Quantifying the phenotype in autism spectrum disorders. American Journal of Medical Genetics 105(1):36–38.3.0.CO;2-4>CrossRefGoogle ScholarPubMed
Matthysse, S., Levy, D. L., Kinney, D., Deutsch, C., Lajonchere, C., Yurgelun-Todd, D., Woods, B. & Holzman, P. S (1992) Gene expression in mental illness: A navigation chart to future progress. Journal of Psychiatric Research 26(4):461–73.CrossRefGoogle ScholarPubMed
McCaffery, P. & Deutsch, C. K. (2005) Macrocephaly and the control of brain growth in autistic disorders. Progress in Neurobiology 77:38–56.CrossRefGoogle ScholarPubMed
McClellan, J. M., Susser, E. & King, M. C. (2007) Schizophrenia: A common disease caused by multiple rare alleles. British Journal of Psychiatry 190:194–99.CrossRefGoogle ScholarPubMed
Perry, G. H., Tchinda, J., McGrath, S. D., Zhang, J., Picker, S. R., Cáceres, A. M., Iafrate, A. J., Tyler-Smith, C., Scherer, S. W., Eichler, E. E., Stone, A. C. & Lee, C. (2006) Hotspots for copy number variation in chimpanzees and humans. Proceedings of the National Academy of Sciences USA 103(21):8006–11.CrossRefGoogle ScholarPubMed
Peters, S. U., Beaudet, A. L., Madduri, N. & Bacino, C. A. (2004) Autism in Angelman syndrome: Implications for autism research. Clinical Genetics 66(6):530–36.CrossRefGoogle ScholarPubMed
Rippon, G., Brock, J., Brown, C. & Boucher, J. (2007) Disordered connectivity in the autistic brain: Challenges for the “new psychophysiology.” International Journal of Psychophysiology 63(2):164–72.CrossRefGoogle Scholar
Ropers, H. H. (2007) New perspectives for the elucidation of genetic disorders. American Journal of Human Genetics 81(2):199–207.CrossRefGoogle ScholarPubMed
Rubenstein, J. L. & Merzenich, M. M. (2003) Model of autism: Increased ratio of excitation/inhibition in key neural systems. Genes, Brain, and Behavior 2:255–67.CrossRefGoogle ScholarPubMed
Sebat, J., Lakshmi, B., Malhotra, D., Troge, J., Lese-Martin, C., Walsh, T., Yamrom, B., Yoon, S., Krasnitz, A., Kendall, J., Leotta, A., Pai, D., Zhang, R., Lee, Y. H., Hicks, J., Spence, S. J., Lee, A. T., Puura, K., Lehtimäki, T., Ledbetter, D., Gregersen, P. K., Bregman, J., Sutcliffe, J. S., Jobanputra, V., Chung, W., Warburton, D., King, M. C., Skuse, D., Geschwind, D. H., Gilliam, T. C., Ye, K. & Wigler, M. (2007) Strong association of de novo copy number mutations with autism. Science 316(5823):445–49.CrossRefGoogle ScholarPubMed
Sebat, J., Lakshmi, B., Troge, J., Alexander, J., Young, J., Lundin, P., Månér, S., Massa, H., Walker, M., Chi, M., Navin, N., Lucito, R., Healy, J., Hicks, J., Ye, K., Reiner, A., Gilliam, T. C., Trask, B., Patterson, N., Zetterberg, A. & Wigler, M. (2004) Large-scale copy number polymorphism in the human genome. Science 305(5683):525–28.CrossRefGoogle ScholarPubMed
Smalley, S. L. (1998) Autism and tuberous sclerosis. Journal of Autism and Developmental Disorders 28(5):407–14.CrossRefGoogle ScholarPubMed
Spence, S. J., Cantor, R. M., Chung, L., Kim, S., Geschwind, D. H., Alarcón, M. (2006) Stratification based on language-related endophenotypes in autism: Attempt to replicate reported linkage. American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics 141(6):591–98.CrossRefGoogle Scholar
Tierney, E., Nwokoro, N. A., Porter, F. D., Freund, L. S., Ghuman, J. K. & Kelley, R. (2001) Behavior phenotype in the RSH/Smith-Lemli-Opitz syndrome. American Journal of Medical Genetics 98(2):191–200.3.0.CO;2-M>CrossRefGoogle ScholarPubMed
Wassink, T. H., Brzustowicz, L. M., Bartlett, C. W., Szatmari, P. (2004) The search for autism disease genes. Mental Retardation and Developmental Disabilities Research Reviews 10(4):272–83.CrossRefGoogle ScholarPubMed
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