Clustering autism: Using neuroanatomical differences in 26 mouse models to gain insight into the heterogeneity

J. Ellegood; E. Anagnostou; B. A. Babineau; J. N. Crawley; L. Lin; M. Genestine; E. Dicicco-Bloom; J. K Y Lai; J. A. Foster; O. Peñagarikano; D. H. Geschwind; L. K. Pacey; D. R. Hampson; C. L. Laliberté; A. A. Mills; E. Tam; L. R. Osborne; M. Kouser; F. Espinosa-Becerra; Z. Xuan; C. M. Powell; A. Raznahan; D. M. Robins; N. Nakai; J. Nakatani; T. Takumi; M. C. Van Eede; T. M. Kerr; C. Muller; R. D. Blakely; J. Veenstra-Vander Weele; R. M. Henkelman; J. P. Lerch

doi:10.1038/mp.2014.98

Clustering autism: Using neuroanatomical differences in 26 mouse models to gain insight into the heterogeneity

J. Ellegood, E. Anagnostou, B. A. Babineau, J. N. Crawley, L. Lin, M. Genestine, E. Dicicco-Bloom, J. K Y Lai, J. A. Foster, O. Peñagarikano, D. H. Geschwind, L. K. Pacey, D. R. Hampson, C. L. Laliberté, A. A. Mills, E. Tam, L. R. Osborne, M. Kouser, F. Espinosa-Becerra, Z. XuanC. M. Powell, A. Raznahan, D. M. Robins, N. Nakai, J. Nakatani, T. Takumi, M. C. Van Eede, T. M. Kerr, C. Muller, R. D. Blakely, J. Veenstra-Vander Weele, R. M. Henkelman, J. P. Lerch

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Abstract

Autism is a heritable disorder, with over 250 associated genes identified to date, yet no single gene accounts for >1-2% of cases. The clinical presentation, behavioural symptoms, imaging and histopathology findings are strikingly heterogeneous. A more complete understanding of autism can be obtained by examining multiple genetic or behavioural mouse models of autism using magnetic resonance imaging (MRI)-based neuroanatomical phenotyping. Twenty-six different mouse models were examined and the consistently found abnormal brain regions across models were parieto-temporal lobe, cerebellar cortex, frontal lobe, hypothalamus and striatum. These models separated into three distinct clusters, two of which can be linked to the under and over-connectivity found in autism. These clusters also identified previously unknown connections between Nrxn1α, En2 and Fmr1; Nlgn3, BTBR and Slc6A4; and also between X monosomy and Mecp2. With no single treatment for autism found, clustering autism using neuroanatomy and identifying these strong connections may prove to be a crucial step in predicting treatment response.

Original language	English (US)
Pages (from-to)	118-125
Number of pages	8
Journal	Molecular psychiatry
Volume	20
Issue number	1
DOIs	https://doi.org/10.1038/mp.2014.98
State	Published - Feb 5 2015

ASJC Scopus subject areas

Molecular Biology
Cellular and Molecular Neuroscience
Psychiatry and Mental health

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Ellegood, J., Anagnostou, E., Babineau, B. A., Crawley, J. N., Lin, L., Genestine, M., Dicicco-Bloom, E., Lai, J. K. Y., Foster, J. A., Peñagarikano, O., Geschwind, D. H., Pacey, L. K., Hampson, D. R., Laliberté, C. L., Mills, A. A., Tam, E., Osborne, L. R., Kouser, M., Espinosa-Becerra, F., ... Lerch, J. P. (2015). Clustering autism: Using neuroanatomical differences in 26 mouse models to gain insight into the heterogeneity. Molecular psychiatry, 20(1), 118-125. https://doi.org/10.1038/mp.2014.98

Ellegood, J, Anagnostou, E, Babineau, BA, Crawley, JN, Lin, L, Genestine, M, Dicicco-Bloom, E, Lai, JKY, Foster, JA, Peñagarikano, O, Geschwind, DH, Pacey, LK, Hampson, DR, Laliberté, CL, Mills, AA, Tam, E, Osborne, LR, Kouser, M, Espinosa-Becerra, F, Xuan, Z, Powell, CM, Raznahan, A, Robins, DM, Nakai, N, Nakatani, J, Takumi, T, Van Eede, MC, Kerr, TM, Muller, C, Blakely, RD, Veenstra-Vander Weele, J, Henkelman, RM & Lerch, JP 2015, 'Clustering autism: Using neuroanatomical differences in 26 mouse models to gain insight into the heterogeneity', Molecular psychiatry, vol. 20, no. 1, pp. 118-125. https://doi.org/10.1038/mp.2014.98

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title = "Clustering autism: Using neuroanatomical differences in 26 mouse models to gain insight into the heterogeneity",

abstract = "Autism is a heritable disorder, with over 250 associated genes identified to date, yet no single gene accounts for >1-2% of cases. The clinical presentation, behavioural symptoms, imaging and histopathology findings are strikingly heterogeneous. A more complete understanding of autism can be obtained by examining multiple genetic or behavioural mouse models of autism using magnetic resonance imaging (MRI)-based neuroanatomical phenotyping. Twenty-six different mouse models were examined and the consistently found abnormal brain regions across models were parieto-temporal lobe, cerebellar cortex, frontal lobe, hypothalamus and striatum. These models separated into three distinct clusters, two of which can be linked to the under and over-connectivity found in autism. These clusters also identified previously unknown connections between Nrxn1α, En2 and Fmr1; Nlgn3, BTBR and Slc6A4; and also between X monosomy and Mecp2. With no single treatment for autism found, clustering autism using neuroanatomy and identifying these strong connections may prove to be a crucial step in predicting treatment response.",

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AU - Anagnostou, E.

AU - Babineau, B. A.

AU - Crawley, J. N.

AU - Lin, L.

AU - Genestine, M.

AU - Dicicco-Bloom, E.

AU - Lai, J. K Y

AU - Foster, J. A.

AU - Peñagarikano, O.

AU - Geschwind, D. H.

AU - Pacey, L. K.

AU - Hampson, D. R.

AU - Laliberté, C. L.

AU - Mills, A. A.

AU - Tam, E.

AU - Osborne, L. R.

AU - Kouser, M.

AU - Espinosa-Becerra, F.

AU - Xuan, Z.

AU - Powell, C. M.

AU - Raznahan, A.

AU - Robins, D. M.

AU - Nakai, N.

AU - Nakatani, J.

AU - Takumi, T.

AU - Van Eede, M. C.

AU - Kerr, T. M.

AU - Muller, C.

AU - Blakely, R. D.

AU - Veenstra-Vander Weele, J.

AU - Henkelman, R. M.

AU - Lerch, J. P.

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Clustering autism: Using neuroanatomical differences in 26 mouse models to gain insight into the heterogeneity

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