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

J. Ellegood, E. Anagnostou, B. A. Babineau, Jacqueline 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

Research output: Contribution to journalArticle

117 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)118-125
Number of pages8
JournalMolecular Psychiatry
Volume20
Issue number1
DOIs
StatePublished - Feb 5 2015

Fingerprint

Autistic Disorder
Cluster Analysis
Behavioral Genetics
Neuroanatomy
Behavioral Symptoms
Cerebellar Cortex
Turner Syndrome
Frontal Lobe
Temporal Lobe
Genes
Hypothalamus
Magnetic Resonance Imaging
Brain
Therapeutics

ASJC Scopus subject areas

  • Molecular Biology
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience

Cite this

Clustering autism : Using neuroanatomical differences in 26 mouse models to gain insight into the heterogeneity. / Ellegood, J.; Anagnostou, E.; Babineau, B. A.; Crawley, Jacqueline; 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.; Xuan, Z.; Powell, C. M.; Raznahan, A.; Robins, D. M.; Nakai, N.; Nakatani, J.; Takumi, T.; Van Eede, M. C.; Kerr, T. M.; Muller, C.; Blakely, R. D.; Veenstra-Vander Weele, J.; Henkelman, R. M.; Lerch, J. P.

In: Molecular Psychiatry, Vol. 20, No. 1, 05.02.2015, p. 118-125.

Research output: Contribution to journalArticle

Ellegood, J, Anagnostou, E, Babineau, BA, Crawley, J, 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
Ellegood, J. ; Anagnostou, E. ; Babineau, B. A. ; Crawley, Jacqueline ; 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. ; Xuan, Z. ; Powell, C. M. ; Raznahan, A. ; Robins, D. M. ; Nakai, N. ; Nakatani, J. ; Takumi, T. ; Van Eede, M. C. ; Kerr, T. M. ; Muller, C. ; Blakely, R. D. ; Veenstra-Vander Weele, J. ; Henkelman, R. M. ; Lerch, J. P. / Clustering autism : Using neuroanatomical differences in 26 mouse models to gain insight into the heterogeneity. In: Molecular Psychiatry. 2015 ; Vol. 20, No. 1. pp. 118-125.
@article{8d5e4a6090ed4302ac5d48e4c9d04279,
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.",
author = "J. Ellegood and E. Anagnostou and Babineau, {B. A.} and Jacqueline Crawley and L. Lin and M. Genestine and E. Dicicco-Bloom and Lai, {J. K Y} and Foster, {J. A.} and O. Pe{\~n}agarikano and Geschwind, {D. H.} and Pacey, {L. K.} and Hampson, {D. R.} and Lalibert{\'e}, {C. L.} and Mills, {A. A.} and E. Tam and Osborne, {L. R.} and M. Kouser and F. Espinosa-Becerra and Z. Xuan and Powell, {C. M.} and A. Raznahan and Robins, {D. M.} and N. Nakai and J. Nakatani and T. Takumi and {Van Eede}, {M. C.} and Kerr, {T. M.} and C. Muller and Blakely, {R. D.} and {Veenstra-Vander Weele}, J. and Henkelman, {R. M.} and Lerch, {J. P.}",
year = "2015",
month = "2",
day = "5",
doi = "10.1038/mp.2014.98",
language = "English (US)",
volume = "20",
pages = "118--125",
journal = "Molecular Psychiatry",
issn = "1359-4184",
publisher = "Nature Publishing Group",
number = "1",

}

TY - JOUR

T1 - Clustering autism

T2 - Using neuroanatomical differences in 26 mouse models to gain insight into the heterogeneity

AU - Ellegood, J.

AU - Anagnostou, E.

AU - Babineau, B. A.

AU - Crawley, Jacqueline

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.

PY - 2015/2/5

Y1 - 2015/2/5

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84922229342&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84922229342&partnerID=8YFLogxK

U2 - 10.1038/mp.2014.98

DO - 10.1038/mp.2014.98

M3 - Article

C2 - 25199916

AN - SCOPUS:84922229342

VL - 20

SP - 118

EP - 125

JO - Molecular Psychiatry

JF - Molecular Psychiatry

SN - 1359-4184

IS - 1

ER -