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Mol Autism. 2015 Jun 05;6:33. doi: 10.1186/s13229-015-0024-1. eCollection 2015.

Sex differences in brain plasticity: a new hypothesis for sex ratio bias in autism.

Molecular autism

Laurent Mottron, Pauline Duret, Sophia Mueller, Robert D Moore, Baudouin Forgeot d'Arc, Sebastien Jacquemont, Lan Xiong

Affiliations

  1. Centre d'excellence en Troubles envahissants du dévelopement de l'Université de Montréal (CETEDUM), Montréal, Canada.
  2. Hôpital Rivière-des-Prairies, Département de Psychiatrie, Montréal, Canada.
  3. Centre de Recherche de l'Institut Universitaire en Santé Mentale de Montréal, Québec, Canada.
  4. Department of Psychiatry, University of Montreal, Québec, Canada.
  5. Département de Biologie, École Normale Supérieure de Lyon, Lyon, CEDEX 07 France.
  6. Institute of Clinical Radiology, University Hospitals, Munich, Germany.
  7. Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Charlestown, MA 02129 USA.
  8. Harvard University, Center for Brain Science, Cambridge, MA 02138 USA.
  9. Department of Health Sciences, University of Montreal, Montreal, Canada.
  10. College of Applied Health Sciences, University of Illinois, Urbana-Champaign, USA.
  11. Centre de recherche, Centre Hospitalier Universitaire Sainte Justine, Montréal, Canada.
  12. Service of Medical Genetics, University Hospital of Lausanne, University of Lausanne, Lausanne, 1011 Switzerland.

PMID: 26052415 PMCID: PMC4456778 DOI: 10.1186/s13229-015-0024-1

Abstract

Several observations support the hypothesis that differences in synaptic and regional cerebral plasticity between the sexes account for the high ratio of males to females in autism. First, males are more susceptible than females to perturbations in genes involved in synaptic plasticity. Second, sex-related differences in non-autistic brain structure and function are observed in highly variable regions, namely, the heteromodal associative cortices, and overlap with structural particularities and enhanced activity of perceptual associative regions in autistic individuals. Finally, functional cortical reallocations following brain lesions in non-autistic adults (for example, traumatic brain injury, multiple sclerosis) are sex-dependent. Interactions between genetic sex and hormones may therefore result in higher synaptic and consecutively regional plasticity in perceptual brain areas in males than in females. The onset of autism may largely involve mutations altering synaptic plasticity that create a plastic reaction affecting the most variable and sexually dimorphic brain regions. The sex ratio bias in autism may arise because males have a lower threshold than females for the development of this plastic reaction following a genetic or environmental event.

Keywords: Autism spectrum; Enhanced perceptual functioning; Male bias; Perceptual associative cortex; Regional plasticity; Sex ratio; Sexual dimorphism; Synaptic plasticity

References

  1. Psychoneuroendocrinology. 2008 Jul;33(6):728-40 - PubMed
  2. Ann Clin Psychiatry. 2009 Jul-Sep;21(3):132-47 - PubMed
  3. Brain Res. 2011 Mar 22;1380:42-77 - PubMed
  4. J Neurosci. 2014 Nov 19;34(47):15779-92 - PubMed
  5. Am J Hum Genet. 2014 May 1;94(5):677-94 - PubMed
  6. Nat Genet. 2011 Jun;43(6):585-9 - PubMed
  7. J Neurosci. 2009 Dec 16;29(50):15684-93 - PubMed
  8. Am J Med Genet B Neuropsychiatr Genet. 2011 Jun;156B(4):484-9 - PubMed
  9. Am J Hum Genet. 2012 May 4;90(5):879-87 - PubMed
  10. Hippocampus. 2015 Mar;25(3):309-28 - PubMed
  11. Neurosurgery. 2007 Aug;61(2):345-50; discussion 350-1 - PubMed
  12. Nature. 2011 Apr 28;472(7344):437-42 - PubMed
  13. J Am Acad Child Adolesc Psychiatry. 2012 Aug;51(8):788-97 - PubMed
  14. Proc Natl Acad Sci U S A. 2006 May 23;103(21):8024-9 - PubMed
  15. Nature. 2011 Oct 26;478(7370):483-9 - PubMed
  16. J Neurosurg. 2005 May;102(5):856-63 - PubMed
  17. Science. 2007 Apr 20;316(5823):445-9 - PubMed
  18. J Neurotrauma. 2014 Oct 15;31(20):1744-9 - PubMed
  19. Autism Res. 2010 Oct;3(5):280-5 - PubMed
  20. Physiol Behav. 2015 Jan;138:13-20 - PubMed
  21. Brain. 2005 Sep;128(Pt 9):2146-53 - PubMed
  22. Nature. 2011 Nov 02;479(7371):33-5 - PubMed
  23. Nat Rev Neurol. 2012 Mar 27;8(5):255-63 - PubMed
  24. Neurosci Biobehav Rev. 2003 Jan-Mar;27(1-2):3-18 - PubMed
  25. J Head Trauma Rehabil. 2014 Sep-Oct;29(5):E1-8 - PubMed
  26. Prog Brain Res. 2009;175:219-37 - PubMed
  27. PLoS Genet. 2014 Sep 04;10(9):e1004580 - PubMed
  28. J Autism Dev Disord. 1982 Dec;12(4):317-30 - PubMed
  29. PLoS One. 2014 Jun 12;9(6):e90405 - PubMed
  30. JAMA. 2011 Nov 9;306(18):2001-10 - PubMed
  31. Nat Neurosci. 2011 Jun;14(6):677-83 - PubMed
  32. Neuroimage. 2009 Oct 15;48(1):37-49 - PubMed
  33. Neurosurg Focus. 2000 Jan 15;8(1):e5 - PubMed
  34. Neuron. 2008 Oct 23;60(2):201-14 - PubMed
  35. Expert Rev Neurother. 2009 Sep;9(9):1341-59 - PubMed
  36. Cereb Cortex. 2015 Sep;25(9):2383-94 - PubMed
  37. Mol Cell Biol. 2006 Dec;26(23):9105-15 - PubMed
  38. Hum Brain Mapp. 2014 May;35(5):2073-98 - PubMed
  39. Neuroimage. 2013 Nov 15;82:200-7 - PubMed
  40. Nature. 2012 Apr 04;485(7397):237-41 - PubMed
  41. Neuroscientist. 2011 Oct;17(5):575-91 - PubMed
  42. PLoS Genet. 2012;8(4):e1002635 - PubMed
  43. Mol Psychiatry. 2015 Mar;20(3):369-76 - PubMed
  44. Cell. 2008 Oct 31;135(3):401-6 - PubMed
  45. Am J Med Genet B Neuropsychiatr Genet. 2013 Dec;162B(8):889-97 - PubMed
  46. Cereb Cortex. 2003 Sep;13(9):943-9 - PubMed
  47. Proc Natl Acad Sci U S A. 2010 Mar 9;107(10):4734-9 - PubMed
  48. Proc Natl Acad Sci U S A. 2001 Mar 13;98(6):3525-30 - PubMed
  49. Neuron. 2013 Feb 6;77(3):586-95 - PubMed
  50. Brain. 2011 Jun;134(Pt 6):1623-34 - PubMed
  51. Neurosci Biobehav Rev. 2012 Jan;36(1):604-25 - PubMed
  52. Neuropsychopharmacology. 2008 Mar;33(4):901-12 - PubMed
  53. Nat Commun. 2014 Aug 21;5:4742 - PubMed
  54. Am J Med Genet B Neuropsychiatr Genet. 2011 Apr;156B(3):255-74 - PubMed
  55. Behav Brain Funct. 2006 Oct 16;2:34 - PubMed
  56. Neuroscientist. 2016 Feb;22(1):46-60 - PubMed
  57. Nat Neurosci. 2015 Feb;18(2):302-9 - PubMed
  58. Curr Opin Neurobiol. 2005 Apr;15(2):225-30 - PubMed
  59. Neural Regen Res. 2013 Sep 15;8(26):2432-40 - PubMed
  60. Front Hum Neurosci. 2010 Dec 21;4:224 - PubMed
  61. Biol Psychiatry. 2005 May 1;57(9):991-8 - PubMed
  62. Cereb Cortex. 2011 May;21(5):1134-46 - PubMed
  63. Hum Brain Mapp. 2012 Apr;33(4):849-60 - PubMed
  64. Cereb Cortex. 2008 Apr;18(4):763-70 - PubMed
  65. Genomics. 1999 Dec 15;62(3):540-3 - PubMed
  66. BMC Med. 2013 Feb 27;11:54 - PubMed
  67. J Autism Dev Disord. 2006 Jan;36(1):27-43 - PubMed
  68. Neurosci Biobehav Rev. 2013 Feb;37(2):209-28 - PubMed
  69. Mol Neurobiol. 2016 Jan;53(1):40-56 - PubMed
  70. Prog Brain Res. 2011;191:211-31 - PubMed
  71. Hum Brain Mapp. 2012 Jul;33(7):1553-81 - PubMed
  72. Autism Res. 2015 Feb;8(1):82-93 - PubMed
  73. Brain Res. 2009 Mar 25;1262:48-63 - PubMed
  74. Cell. 2013 Nov 21;155(5):1008-21 - PubMed
  75. Neuron. 2013 Jan 23;77(2):259-73 - PubMed
  76. Mol Autism. 2014 Apr 09;5:27 - PubMed
  77. Neuroimage Clin. 2015 Apr 30;8:267-80 - PubMed
  78. Cereb Cortex. 2007 Feb;17(2):457-65 - PubMed
  79. Int J Dev Neurosci. 2015 Feb;40:15-23 - PubMed
  80. J Neurosci. 2008 Feb 13;28(7):1697-708 - PubMed
  81. Nature. 2014 Nov 13;515(7526):216-21 - PubMed
  82. J Autism Dev Disord. 2009 Dec;39(12):1715-22 - PubMed
  83. Neuroscientist. 2002 Dec;8(6):524-31 - PubMed
  84. Mol Autism. 2013 Oct 11;4(1):39 - PubMed
  85. Mol Psychiatry. 2016 Feb;21(2):169-77 - PubMed
  86. Cell. 2011 Jul 22;146(2):247-61 - PubMed
  87. Brain Res. 2006 Aug 9;1104(1):160-74 - PubMed
  88. Neurosci Biobehav Rev. 2012 Apr;36(4):1292-313 - PubMed
  89. Am J Med Genet B Neuropsychiatr Genet. 2012 Jan;159B(1):5-12 - PubMed
  90. Trends Cogn Sci. 2002 Jun 1;6(6):248-254 - PubMed
  91. Neuroreport. 2006 Jul 31;17(11):1103-6 - PubMed
  92. Mamm Genome. 2004 Jan;15(1):41-52 - PubMed
  93. Neuron. 2011 Jun 9;70(5):886-97 - PubMed
  94. Curr Opin Neurobiol. 2007 Feb;17(1):43-52 - PubMed
  95. Nat Neurosci. 2004 Aug;7(8):799-800 - PubMed
  96. PLoS One. 2013 May 10;8(5):e63131 - PubMed
  97. Mol Psychiatry. 2009 Jun;14(6):558-61 - PubMed
  98. Neuron. 2003 Feb 20;37(4):555-8 - PubMed
  99. Brain. 2004 Aug;127(Pt 8):1811-21 - PubMed
  100. Nature. 2014 Nov 13;515(7526):209-15 - PubMed
  101. Trends Neurosci. 2010 Jun;33(6):285-91 - PubMed
  102. Annu Rev Genomics Hum Genet. 2007;8:109-29 - PubMed
  103. Brain. 2013 Sep;136(Pt 9):2799-815 - PubMed
  104. Hum Genet. 2006 Apr;119(3):267-75 - PubMed
  105. Proc Natl Acad Sci U S A. 2013 Mar 26;110(13):5258-62 - PubMed
  106. Physiol Behav. 2011 Aug 3;104(2):242-7 - PubMed
  107. Horm Metab Res. 2012 Jul;44(8):577-86 - PubMed
  108. J Neurosci. 2005 Aug 10;25(32):7385-92 - PubMed
  109. Am J Hum Genet. 2004 Mar;74(3):552-7 - PubMed
  110. Neuropsychologia. 2011 Jan;49(2):254-63 - PubMed
  111. Brain. 2013 Jun;136(Pt 6):1956-67 - PubMed
  112. Proc Natl Acad Sci U S A. 2013 Mar 26;110(13):4868-9 - PubMed
  113. Neural Dev. 2015 Apr 03;10:10 - PubMed
  114. Proc Natl Acad Sci U S A. 2002 May 28;99(11):7746-50 - PubMed
  115. Nat Neurosci. 2011 Jan;14(1):19-21 - PubMed
  116. PLoS Genet. 2012;8(3):e1002556 - PubMed
  117. PLoS One. 2011 Feb 16;6(2):e17116 - PubMed
  118. J Child Neurol. 2005 Sep;20(9):736-40 - PubMed
  119. Brain Res Bull. 2004 Dec 15;64(4):303-8 - PubMed
  120. Proc Natl Acad Sci U S A. 2010 Sep 28;107(39):16988-93 - PubMed
  121. Nature. 2002 Dec 19-26;420(6917):788-94 - PubMed
  122. J Neurosci. 2013 Dec 4;33(49):19112-9 - PubMed
  123. Endocr Rev. 2014 Dec;35(6):961-91 - PubMed
  124. Pediatr Res. 2009 Jun;65(6):591-8 - PubMed
  125. Neuroreport. 2003 Feb 10;14(2):205-9 - PubMed
  126. Proc Natl Acad Sci U S A. 2007 Jul 31;104(31):12831-6 - PubMed
  127. J Neurochem. 2013 Mar;124(6):832-43 - PubMed
  128. Brain Res. 2011 Mar 22;1380:138-45 - PubMed
  129. J Neurosci. 2003 Oct 29;23(30):9752-60 - PubMed
  130. Neuroimage. 2013 Jan 1;64:671-84 - PubMed
  131. J Psychiatr Res. 2015 Sep;68:285-92 - PubMed
  132. Hum Brain Mapp. 2013 Oct;34(10):2524-37 - PubMed
  133. Neuropsychol Rev. 2014 Mar;24(1):16-31 - PubMed
  134. Mult Scler. 2014 Apr;20(4):451-7 - PubMed
  135. PLoS One. 2011;6(6):e20835 - PubMed
  136. Biol Res Nurs. 2004 Apr;5(4):299-310 - PubMed
  137. Front Neurosci. 2007 Oct 15;1(1):77-96 - PubMed
  138. J Autism Dev Disord. 2014 Mar;44(3):627-35 - PubMed
  139. Nat Genet. 2003 May;34(1):27-9 - PubMed
  140. Science. 2005 Nov 4;310(5749):819-23 - PubMed
  141. Brain Res Rev. 2008 Mar;57(2):386-97 - PubMed
  142. Trends Neurosci. 2013 May;36(5):275-84 - PubMed
  143. Nat Genet. 2010 Jun;42(6):489-91 - PubMed
  144. J Am Acad Child Adolesc Psychiatry. 2015 Jan;54(1):11-24 - PubMed
  145. Genome Res. 2015 Jan;25(1):142-54 - PubMed
  146. Pediatr Blood Cancer. 2014 Oct;61(10):1720-3 - PubMed
  147. Neuroimage Clin. 2014 Mar 25;4:593-603 - PubMed
  148. Science. 2012 Oct 5;338(6103):128-32 - PubMed
  149. Mol Autism. 2014 Mar 06;5(1):22 - PubMed
  150. Neuroscience. 2013 Jun 3;239:124-38 - PubMed
  151. Proc Natl Acad Sci U S A. 2014 Jan 14;111(2):823-8 - PubMed
  152. Mol Psychiatry. 2011 Oct;16(10):1039-47 - PubMed
  153. Cell Rep. 2013 Nov 14;5(3):567-72 - PubMed
  154. Proc Natl Acad Sci U S A. 2007 Feb 13;104(7):2454-9 - PubMed
  155. Neuroscience. 2013 Jun 3;239:46-66 - PubMed
  156. J Neurosci. 2011 May 11;31(19):7174-7 - PubMed
  157. Neuron. 2012 Apr 26;74(2):285-99 - PubMed
  158. Neuroreport. 2011 Mar 9;22(4):190-4 - PubMed
  159. Cereb Cortex. 2013 Apr;23(4):900-12 - PubMed
  160. Nature. 2012 Apr 29;486(7402):256-60 - PubMed
  161. Arch Gen Psychiatry. 2011 May;68(5):467-76 - PubMed
  162. Cereb Cortex. 2011 Feb;21(2):449-58 - PubMed
  163. Proc Natl Acad Sci U S A. 2007 Aug 14;104(33):13501-6 - PubMed
  164. Trends Genet. 2010 Aug;26(8):363-72 - PubMed
  165. Nature. 2011 May 25;474(7351):380-4 - PubMed
  166. Neuropharmacology. 2012 Nov;63(6):1028-41 - PubMed
  167. Neurosci Biobehav Rev. 2014 Feb;39:34-50 - PubMed
  168. J Neurosci. 2007 Oct 24;27(43):11725-35 - PubMed
  169. J Neurotrauma. 2010 Mar;27(3):527-39 - PubMed
  170. MMWR Surveill Summ. 2011 May 6;60(5):1-32 - PubMed
  171. J Neurochem. 2005 Aug;94(4):896-905 - PubMed
  172. Sci Rep. 2013;3:1139 - PubMed
  173. PLoS One. 2014 Aug 12;9(8):e103781 - PubMed
  174. Brain. 2002 Jul;125(Pt 7):1607-15 - PubMed
  175. Mol Psychiatry. 2013 Oct;18(10):1054-6 - PubMed
  176. Radiology. 2014 Sep;272(3):815-23 - PubMed
  177. Cell. 2013 Nov 21;155(5):997-1007 - PubMed
  178. PLoS One. 2013 Apr 17;8(4):e61493 - PubMed
  179. Neuron. 2013 Jan 23;77(2):209-11 - PubMed
  180. PLoS Biol. 2011 Jun;9(6):e1001081 - PubMed
  181. Mamm Genome. 2000 Oct;11(10):906-14 - PubMed
  182. Neurosci Biobehav Rev. 2014 Nov;47:735-52 - PubMed
  183. Neuron. 2011 Jun 9;70(5):863-85 - PubMed
  184. J Neurosci. 2012 Oct 24;32(43):14994-9 - PubMed
  185. Nature. 2012 Apr 04;485(7397):246-50 - PubMed
  186. Brain Struct Funct. 2013 Jul;218(4):929-42 - PubMed
  187. Exp Neurol. 2014 Mar;253:41-51 - PubMed
  188. Nucleic Acids Res. 2011 Jan;39(Database issue):D842-8 - PubMed
  189. Hum Brain Mapp. 2012 Jun;33(6):1470-89 - PubMed
  190. Neuroimage Clin. 2014 Feb 25;4:444-53 - PubMed
  191. Pediatr Res. 2002 Oct;52(4):576-9 - PubMed
  192. Neuron. 2005 Aug 4;47(3):339-52 - PubMed
  193. Neuroimage Clin. 2012 Nov 16;2:79-94 - PubMed
  194. Novartis Found Symp. 2003;251:149-66; discussion 166-76, 281-97 - PubMed
  195. Int J Dev Neurosci. 2005 Apr-May;23(2-3):143-52 - PubMed
  196. PLoS One. 2010 Mar 24;5(3):e9842 - PubMed
  197. Front Hum Neurosci. 2014 Jun 02;8:349 - PubMed
  198. Dev Med Child Neurol. 2005 Jan;47(1):10-8 - PubMed
  199. Cereb Cortex. 2016 Apr;26(4):1440-52 - PubMed
  200. J Neurosci. 2015 Apr 8;35(14):5837-50 - PubMed
  201. J Comp Neurol. 2013 Mar 1;521(4):894-911 - PubMed
  202. Neuron. 2013 Jan 23;77(2):235-42 - PubMed
  203. J Steroid Biochem Mol Biol. 2012 Aug;131(1-2):24-9 - PubMed
  204. Front Neural Circuits. 2008 Oct 29;2:4 - PubMed
  205. J Autism Dev Disord. 2015 May;45(5):1354-67 - PubMed
  206. Am J Sports Med. 2009 Sep;37(9):1699-704 - PubMed
  207. Sci Rep. 2013 Oct 09;3:2897 - PubMed
  208. J Neurophysiol. 2006 Oct;96(4):1734-45 - PubMed
  209. Mol Cell Neurosci. 2002 Feb;19(2):138-51 - PubMed
  210. J Neurosci. 2014 Mar 19;34(12):4228-38 - PubMed
  211. Neuroscience. 1997 Dec;81(3):689-97 - PubMed
  212. Biol Psychiatry. 2005 Jul 1;58(1):1-9 - PubMed
  213. Learn Mem. 2007 Oct 01;14 (10 ):693-702 - PubMed
  214. Neuroscience. 2013 Jun 3;239:271-9 - PubMed
  215. Am J Hum Genet. 2014 Mar 6;94(3):415-25 - PubMed

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