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Sex Differences in Autism Spectrum Disorder: a Review

  • Sex and Gender Issues in Behavioral Health (CN Epperson, Section Editor)
  • Published:
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Abstract

Purpose of Review

Neurodevelopmental disorders disproportionately affect males. The mechanisms underlying male vulnerability or female protection are not known and remain understudied. Determining the processes involved is crucial to understanding the etiology and advancing treatment of neurodevelopmental disorders. Here, we review current findings and theories that contribute to male preponderance of neurodevelopmental disorders, with a focus on autism.

Recent Findings

Recent work on the biological basis of the male preponderance of autism and other neurodevelopmental disorders includes discussion of a higher genetic burden in females and sex-specific gene mutations or epigenetic changes that differentially confer risk to males or protection to females. Other mechanisms discussed are sex chromosome and sex hormone involvement. Specifically, fetal testosterone is involved in many aspects of development and may interact with neurotransmitter, neuropeptide, or immune pathways to contribute to male vulnerability. Finally, the possibilities of female underdiagnosis and a multi-hit hypothesis are discussed.

Summary

This review highlights current theories of male bias in developmental disorders. Topics include environmental, genetic, and epigenetic mechanisms; theories of sex chromosomes, hormones, neuroendocrine, and immune function; underdiagnosis of females; and a multi-hit hypothesis.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance

  1. Butler M, Rafi S, Hossain W, Stephan D, Manzardo A. Whole exome sequencing in females with autism implicates novel and candidate genes. Int J Mol Sci. 2015;16(1):1312–35. https://doi.org/10.3390/ijms16011312.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Geschwind DH. Genetics of autism spectrum disorders. Trends Cogn Sci NIH Public Access. 2011;15(9):409–16. https://doi.org/10.1016/j.tics.2011.07.003.

    Article  Google Scholar 

  3. Christensen DL, Baio J, Braun KVN, Bilder D, Charles J, Constantino JN, et al. Prevalence and characteristics of autism spectrum disorder among children aged 8 years—autism and developmental disabilities monitoring network, 11 sites, United States, 2012. MMWR Surveill Summ. 2016;65(3):1–23. https://doi.org/10.15585/mmwr.ss6503a1.

    Article  PubMed  Google Scholar 

  4. Werling DM, Geschwind DH. Sex differences in autism spectrum disorders. Curr Opin Neurol. 2013;26(2):146–53. https://doi.org/10.1097/WCO.0b013e32835ee548.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Carayol J, Schellenberg GD, Dombroski B, Genin E, Rousseau F, Dawson G. Autism risk assessment in siblings of affected children using sex-specific genetic scores. Mol. Autism. 2011;2(1):17. https://doi.org/10.1186/2040-2392-2-17.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Steeb H, Ramsey JM, Guest PC, Stocki P, Cooper JD, Rahmoune H, et al. Serum proteomic analysis identifies sex-specific differences in lipid metabolism and inflammation profiles in adults diagnosed with Asperger syndrome. Mol. Autism. 2014;5(1):4. https://doi.org/10.1186/2040-2392-5-4.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  7. Sato D, Lionel AC, Leblond CS, Prasad A, Pinto D, Walker S, et al. SHANK1 deletions in males with autism spectrum disorder. Am J Hum Genet. 2012;90(5):879–87. https://doi.org/10.1016/j.ajhg.2012.03.017.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Tropeano M, Ahn JW, Dobson RJB, Breen G, Rucker J, Dixit A, et al. Male-biased autosomal effect of 16p13.11 copy number variation in neurodevelopmental disorders. Liu C, editor. PLoS One. 2013;8(4):e61365. https://doi.org/10.1371/journal.pone.0061365.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Tropeano M, Howley D, Gazzellone MJ, Wilson CE, Ahn JW, Stavropoulos DJ, et al. Microduplications at the pseudoautosomal SHOX locus in autism spectrum disorders and related neurodevelopmental conditions. J Med Genet. 2016;53(8):536–47. https://doi.org/10.1136/jmedgenet-2015-103621.

    Article  PubMed  Google Scholar 

  10. • Mitra I, Tsang K, Ladd-Acosta C, Croen LA, Aldinger KA, Hendren RL, et al. Pleiotropic mechanisms indicated for sex differences in autism. Flint J, editor. PLoS Genet. 2016;12:e1006425. A study of single nucleotide polymorphisms uncovered no excess genetic load in females, contradicting much previous data, but pointed to sex-specific mutations, specifically on the X chromosome, that may contribute to male prevalence in autism.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  11. Werling DM, Parikshak NN, Geschwind DH. Gene expression in human brain implicates sexually dimorphic pathways in autism spectrum disorders. Nat Commun. 2016;7 https://doi.org/10.1038/ncomms10717.

  12. • McCarthy MM, Wright CL. Convergence of sex differences and the neuroimmune system in autism spectrum disorder. Biol Psychiatry. 2017;81(5):402–10. An important developmental difference between males and females involves immune function. A number of immune mechanims are discussed that could confer male risk to neurodevelopmental disorders. https://doi.org/10.1016/j.biopsych.2016.10.004.

    Article  CAS  PubMed  Google Scholar 

  13. Tylee DS, Espinoza AJ, Hess JL, Tahir MA, SY MC, Rim JK, et al. RNA sequencing of transformed lymphoblastoid cells from siblings discordant for autism spectrum disorders reveals transcriptomic and functional alterations: evidence for sex-specific effects. Autism Res. 2017;10(3):439–55. https://doi.org/10.1002/aur.1679.

    Article  PubMed  Google Scholar 

  14. Wing L. Sex ratios in early childhood autism and related conditions. Psychiatry Res. 1981;5(2):129–37. https://doi.org/10.1016/0165-1781(81)90043-3.

    Article  CAS  PubMed  Google Scholar 

  15. • Kreiser NL, White SW. ASD in females: are we overstating the gender difference in diagnosis? Clin Child Fam Psychol Rev. Springer US. 2014;17:67–84. This review explores sociocultural factors and sex differences in manifestation that may affect females with neurodevelopmental disorders and how they may contribute to their underdiagnosis.

    Article  Google Scholar 

  16. Tsai L, Stewart MA, August G. Implication of sex differences in the familial transmission of infantile autism. J Autism Dev Disord. Kluwer Academic Publishers-Plenum Publishers; 1981;11:165–73.

  17. Sanders SJ, Ercan-Sencicek AG, Hus V, Luo R, Murtha MT, Moreno-De-Luca D, et al. Multiple recurrent de novo CNVs, including duplications of the 7q11.23 Williams syndrome region, are strongly associated with autism. Neuron. 2011;70(5):863–85. https://doi.org/10.1016/j.neuron.2011.05.002.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Sanders SJ, He X, Willsey AJ, Ercan-Sencicek AG, Samocha KE, Cicek AE, et al. Insights into autism Spectrum disorder genomic architecture and biology from 71 risk loci. Neuron. 2015;87(6):1215–33. https://doi.org/10.1016/j.neuron.2015.09.016.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Jacquemont S, Coe BP, Hersch M, Duyzend MH, Krumm N, Bergmann S, et al. A higher mutational burden in females supports a “female protective model” in neurodevelopmental disorders. Am J Hum Genet. 2014;94(3):415–25. https://doi.org/10.1016/j.ajhg.2014.02.001.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. • Desachy G, Croen LA, Torres AR, Kharrazi M, Delorenze GN, Windham GC, et al. Increased female autosomal burden of rare copy number variants in human populations and in autism families. Mol Psychiatry. 2015;20(2):170–5. In support of a Female Protective Effect, a meta-analysis found increased large, rare autosomal copy number variant mutations in female family members of autistic individuals compared to those in control families. https://doi.org/10.1038/mp.2014.179.

    Article  CAS  PubMed  Google Scholar 

  21. Gilman SR, Iossifov I, Levy D, Ronemus M, Wigler M, Vitkup D. Rare de novo variants associated with autism implicate a large functional network of genes involved in formation and function of synapses. Neuron. 2011;70(5):898–907. https://doi.org/10.1016/j.neuron.2011.05.021.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Levy D, Ronemus M, Yamrom B, Lee Y, Leotta A, Kendall J, et al. Rare de novo and transmitted copy-number variation in autistic spectrum disorders. Neuron. 2011;70(5):886–97. https://doi.org/10.1016/j.neuron.2011.05.015.

    Article  CAS  PubMed  Google Scholar 

  23. Schumann CM, Sharp FR, Ander BP, Stamova B. Possible sexually dimorphic role of miRNA and other sncRNA in ASD brain. Mol Autism BioMed Central. 2017;8(1):4. https://doi.org/10.1186/s13229-017-0117-0.

    Article  Google Scholar 

  24. Dworzynski K, Ronald A, Bolton P, Happé F. How different are girls and boys above and below the diagnostic threshold for autism spectrum disorders? J Am Acad Child Adolesc Psychiatry. 2012;51

  25. Robinson EB, Lichtenstein P, Anckarsäter H, Happé F, Ronald A. Examining and interpreting the female protective effect against autistic behavior. Proc Natl Acad Sci U S A. 2013;110(13):5258–62. https://doi.org/10.1073/pnas.1211070110.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Werling DM, Geschwind DH. Understanding sex bias in autism spectrum disorder. Proc Natl Acad Sci U S A. 2013;110(13):4868–9. https://doi.org/10.1073/pnas.1301602110.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Palmer N, Beam A, Agniel D, Eran A, Manrai A, Spettell C, et al. Association of sex with recurrence of autism spectrum disorder among siblings. JAMA Pediatr. 2017.

  28. Werling DM, Geschwind DH. Recurrence rates provide evidence for sex-differential, familial genetic liability for autism spectrum disorders in multiplex families and twins. Mol. Autism. 2015;6(1):27. https://doi.org/10.1186/s13229-015-0004-5.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Turner TN, Sharma K, Oh EC, Liu YP, Collins RL, Sosa MX, et al. Loss of δ-catenin function in severe autism. Nature. 2015;520(7545):51–6. https://doi.org/10.1038/nature14186.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Goin-Kochel RP, Abbacchi A, Constantino JN, Autism Genetic Resource Exchange Co. Lack of evidence for increased genetic loading for autism among families of affected females. Autism. 2007;11(3):279–86. https://doi.org/10.1177/1362361307076857.

    Article  PubMed  Google Scholar 

  31. Messinger DS, Young GS, Webb SJ, Ozonoff S, Bryson SE, Carter A, et al. Early sex differences are not autism-specific: a baby siblings research consortium (BSRC) study. Mol. Autism. 2015;6(1):32. https://doi.org/10.1186/s13229-015-0027-y.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Ziats MN, Rennert OM. Sex-biased gene expression in the developing brain: implications for autism spectrum disorders. Mol. Autism. 2013;4(1):10. https://doi.org/10.1186/2040-2392-4-10.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Shi L, Zhang Z, Su B. Sex biased gene expression profiling of human brains at major developmental stages. Sci Rep. 2016;6(1):21181. https://doi.org/10.1038/srep21181.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Kim KC, Choi CS, Kim J-W, Han S-H, Cheong JH, Ryu JH, et al. MeCP2 modulates sex differences in the postsynaptic development of the valproate animal model of autism. Mol Neurobiol. 2016;53(1):40–56. https://doi.org/10.1007/s12035-014-8987-z.

    Article  CAS  PubMed  Google Scholar 

  35. Bhatnagar S, Zhu X, Ou J, Lin L, Chamberlain L, Zhu LJ, et al. Genetic and pharmacological reactivation of the mammalian inactive X chromosome. Proc Natl Acad Sci U S A. 2014;111(35):12591–8. https://doi.org/10.1073/pnas.1413620111.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Viveros M-P, Mendrek A, Paus T, López-Rodríguez AB, Marco EM, Yehuda R, et al. A comparative, developmental, and clinical perspective of neurobehavioral sexual dimorphisms. Front Neurosci. Frontiers Media SA. 2012;6:84.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Schwarz JM, McCarthy MM. Cellular mechanisms of estradiol-mediated masculinization of the brain. J Steroid Biochem Mol Biol. 2008;109(3-5):300–6. https://doi.org/10.1016/j.jsbmb.2008.03.012.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. McCarthy MM. How it’s made: organisational effects of hormones on the developing brain. J Neuroendocrinol. 2010;22(7):736–42. https://doi.org/10.1111/j.1365-2826.2010.02021.x.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Baron-Cohen S, Knickmeyer RC, Belmonte MK. Sex differences in the brain: implications for explaining autism. Science. 2005;310(5749):819–23. https://doi.org/10.1126/science.1115455.

    Article  CAS  PubMed  Google Scholar 

  40. Woolley CS, McEwen BS. Estradiol mediates fluctuation in hippocampal synapse density during the estrous cycle in the adult rat. J Neurosci. 1992;12(7):2549–54.

    CAS  PubMed  Google Scholar 

  41. Calizo LH, Flanagan-Cato LM. Estrogen selectively regulates spine density within the dendritic arbor of rat ventromedial hypothalamic neurons. J Neurosci. 2000;20(4):1589–96.

    CAS  PubMed  Google Scholar 

  42. Amateau SK, McCarthy MM. A novel mechanism of dendritic spine plasticity involving estradiol induction of prostaglandin-E2. J Neurosci. 2002;22(19):8586–96.

    CAS  PubMed  Google Scholar 

  43. Schoch H, Kreibich AS, Ferri SL, White RS, Bohorquez D, Banerjee A, et al. Sociability deficits and altered amygdala circuits in mice lacking Pcdh10, an autism associated gene. Biol Psychiatry. 2017;81(3):193–202. https://doi.org/10.1016/j.biopsych.2016.06.008.

    Article  CAS  PubMed  Google Scholar 

  44. Hutsler JJ, Zhang H. Increased dendritic spine densities on cortical projection neurons in autism spectrum disorders. Brain Res. 2010;1309:83–94. https://doi.org/10.1016/j.brainres.2009.09.120.

    Article  CAS  PubMed  Google Scholar 

  45. Tang G, Gudsnuk K, Kuo S-H, Cotrina ML, Rosoklija G, Sosunov A, et al. Loss of mTOR-dependent macroautophagy causes autistic-like synaptic pruning deficits. Neuron. 2014;83(5):1131–43. https://doi.org/10.1016/j.neuron.2014.07.040.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Irwin SA, Patel B, Idupulapati M, Harris JB, Crisostomo RA, Larsen BP, et al. Abnormal dendritic spine characteristics in the temporal and visual cortices of patients with fragile-X syndrome: a quantitative examination. Am J Med Genet. 2001;98(2):161–7. https://doi.org/10.1002/1096-8628(20010115)98:2<161::AID-AJMG1025>3.0.CO;2-B.

    Article  CAS  PubMed  Google Scholar 

  47. Comery TA, Harris JB, Willems PJ, Oostra BA, Irwin SA, Weiler IJ, et al. Abnormal dendritic spines in fragile X knockout mice: maturation and pruning deficits. Proc Natl Acad Sci U S A. 1997;94(10):5401–4. https://doi.org/10.1073/pnas.94.10.5401.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Kwon C-H, Luikart BW, Powell CM, Zhou J, Matheny SA, Zhang W, et al. Pten regulates neuronal arborization and social interaction in mice. Neuron. 2006;50(3):377–88. https://doi.org/10.1016/j.neuron.2006.03.023.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Wright EC, Johnson SA, Hao R, Kowalczyk AS, Greenberg GD, Ordoñes Sanchez E, et al. Exposure to extrinsic stressors, social defeat or bisphenol A, eliminates sex differences in DNA methyltransferase expression in the amygdala. J Neuroendocrinol. 2017;29.

  50. Gámez-Del-Estal MM, Contreras I, Prieto-Pérez R, Ruiz-Rubio M. Epigenetic effect of testosterone in the behavior of C. elegans. A clue to explain androgen-dependent autistic traits? Front Cell Neurosci. 2014;8:69. https://doi.org/10.3389/fncel.2014.00069.

    PubMed  PubMed Central  Google Scholar 

  51. • Baron-Cohen S, Auyeung B, Nørgaard-Pedersen B, Hougaard DM, Abdallah MW, Melgaard L, et al. Elevated fetal steroidogenic activity in autism. Mol Psychiatry. 2015;20(3):369–76. Males with autism spectrum disorders had elevated fetal levels of progesterone, 17α-hydroxy-progesterone, androstenedione and testosterone in amniotic samples compared to those of typically developing controls, providing a possible mechanism for the male bias in autism. https://doi.org/10.1038/mp.2014.48.

    Article  CAS  PubMed  Google Scholar 

  52. Cox KH, Quinnies KM, Eschendroeder A, Didrick PM, Eugster EA, Rissman EF. Number of X-chromosome genes influences social behavior and vasopressin gene expression in mice. Psychoneuroendocrinology. 2015;51:271–81. https://doi.org/10.1016/j.psyneuen.2014.10.010.

    Article  CAS  PubMed  Google Scholar 

  53. Printzlau F, Wolstencroft J, Skuse DH. Cognitive, behavioral, and neural consequences of sex chromosome aneuploidy. J Neurosci Res. 2017;95(1-2):311–9. https://doi.org/10.1002/jnr.23951.

    Article  CAS  PubMed  Google Scholar 

  54. Tartaglia NR, Wilson R, Miller JS, Rafalko J, Cordeiro L, Davis S, et al. Autism spectrum disorder in males with sex chromosome aneuploidy. J Dev Behav Pediatr. 2017;38(3):197–207. https://doi.org/10.1097/DBP.0000000000000429.

    Article  PubMed  Google Scholar 

  55. Baron-Cohen S, Lombardo MV, Auyeung B, Ashwin E, Chakrabarti B, Knickmeyer R. Why are autism spectrum conditions more prevalent in males? PLoS Biol. 2011;9(6):e1001081. https://doi.org/10.1371/journal.pbio.1001081.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Lombardi LM, Baker SA, Zoghbi HY. MECP2 disorders: from the clinic to mice and back. J Clin Invest. 2015;125(8):2914–23. https://doi.org/10.1172/JCI78167.

    Article  PubMed  PubMed Central  Google Scholar 

  57. Skuse DH. Imprinting, the X-chromosome, and the male brain: explaining sex differences in the liability to autism. Pediatr Res. 2000;47(1):9–16. https://doi.org/10.1203/00006450-200001000-00006.

    Article  CAS  PubMed  Google Scholar 

  58. Schaafsma SM, Pfaff DW. Etiologies underlying sex differences in autism spectrum disorders. Front Neuroendocrinol. 2014;35(3):255–71. https://doi.org/10.1016/j.yfrne.2014.03.006.

    Article  PubMed  Google Scholar 

  59. Gockley J, Willsey AJ, Dong S, Dougherty JD, Constantino JN, Sanders SJ. The female protective effect in autism spectrum disorder is not mediated by a single genetic locus. Mol Autism. 2015;6(1):25. https://doi.org/10.1186/s13229-015-0014-3.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  60. Gong X, Bacchelli E, Blasi F, Toma C, Betancur C, Chaste P, et al. Analysis of X chromosome inactivation in autism spectrum disorders. Am J Med Genet Part B Neuropsychiatr Genet. 2008;147B(6):830–5. https://doi.org/10.1002/ajmg.b.30688.

    Article  Google Scholar 

  61. Jamain S, Quach H, Quintana-Murci L, Betancur C, Philippe A, Gillberg C, et al. Y chromosome haplogroups in autistic subjects. Mol Psychiatry. 2002;7(2):217–9. https://doi.org/10.1038/sj.mp.4000968.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Serajee FJ, Mahbubul Huq AHM. Association of Y chromosome haplotypes with autism. J Child Neurol. 2009;24(10):1258–61. https://doi.org/10.1177/0883073809333530.

    Article  PubMed  Google Scholar 

  63. Barona M, Kothari R, Skuse D, Micali N. Social communication and emotion difficulties and second to fourth digit ratio in a large community-based sample. Mol. Autism. 2015;6(1):68. https://doi.org/10.1186/s13229-015-0063-7.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  64. Eriksson JM, Lundström S, Lichtenstein P, Bejerot S, Eriksson E. Effect of co-twin gender on neurodevelopmental symptoms: a twin register study. Mol. Autism. 2016;7(1) https://doi.org/10.1186/s13229-016-0074-z.

  65. Kung KTF, Spencer D, Pasterski V, Neufeld S, Glover V, O’Connor TG, et al. No relationship between prenatal androgen exposure and autistic traits: convergent evidence from studies of children with congenital adrenal hyperplasia and of amniotic testosterone concentrations in typically developing children. J Child Psychol Psychiatry 2016.

  66. Falter CM, Plaisted KC, Davis G. Visuo-spatial processing in autism—testing the predictions of extreme male brain theory. J Autism Dev Disord. 2008;38(3):507–15. https://doi.org/10.1007/s10803-007-0419-8.

    Article  PubMed  Google Scholar 

  67. van Honk J, Schutter DJ, Bos PA, Kruijt A-W, Lentjes EG, Baron-Cohen S. Testosterone administration impairs cognitive empathy in women depending on second-to-fourth digit ratio. Proc Natl Acad Sci. 2011;108(8):3448–52. https://doi.org/10.1073/pnas.1011891108.

    Article  PubMed  PubMed Central  Google Scholar 

  68. Whitehouse AJO, Maybery MT, Hart R, Mattes E, Newnham JP, Sloboda DM, et al. Fetal androgen exposure and pragmatic language ability of girls in middle childhood: implications for the extreme male-brain theory of autism. Psychoneuroendocrinology. 2010;35(8):1259–64. https://doi.org/10.1016/j.psyneuen.2010.02.007.

    Article  PubMed  Google Scholar 

  69. Voracek M, Dressler SG. High (feminized) digit ratio (2D, 4D) in Danish men: a question of measurement method? Hum Reprod. 2006;21(5):1329–31. https://doi.org/10.1093/humrep/dei464.

    Article  PubMed  Google Scholar 

  70. Guyatt AL, Heron J, BLC K, Golding J, Rai D. Digit ratio and autism spectrum disorders in the Avon longitudinal study of parents and children: a birth cohort study. BMJ Open. 2015;5(8):e007433. https://doi.org/10.1136/bmjopen-2014-007433.

    Article  PubMed  PubMed Central  Google Scholar 

  71. Al-Zaid FS, Alhader AA, AL-Ayadhi LY. The second to fourth digit ratio (2D,4D) in Saudi boys with autism: a potential screening tool. Early Hum Dev. 2015;91(7):413–5. https://doi.org/10.1016/j.earlhumdev.2015.04.007.

    Article  PubMed  Google Scholar 

  72. Park BY, Lee BK, Burstyn I, Tabb LP, Keelan JA, Whitehouse AJO, et al. Umbilical cord blood androgen levels and ASD-related phenotypes at 12 and 36 months in an enriched risk cohort study. Mol. Autism. 2017;8(1):3. https://doi.org/10.1186/s13229-017-0118-z.

    Article  PubMed  PubMed Central  Google Scholar 

  73. Nowack N, Wittsiepe J, Kasper-Sonnenberg M, Wilhelm M, Schölmerich A. Influence of low-level prenatal exposure to PCDD/fs and PCBs on empathizing, systemizing and autistic traits: results from the Duisburg birth cohort study. Carpenter DO, editor. PLoS One. 2015;10(6):e0129906. https://doi.org/10.1371/journal.pone.0129906.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  74. Auyeung B, Ahluwalia J, Thomson L, Taylor K, Hackett G, O’Donnell KJ, et al. Prenatal versus postnatal sex steroid hormone effects on autistic traits in children at 18 to 24 months of age. Mol. Autism. 2012;3(1):17. https://doi.org/10.1186/2040-2392-3-17.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Ruta L, Ingudomnukul E, Taylor K, Chakrabarti B, Baron-Cohen S. Increased serum androstenedione in adults with autism spectrum conditions. Psychoneuroendocrinology. 2011;36(8):1154–63. https://doi.org/10.1016/j.psyneuen.2011.02.007.

    Article  CAS  PubMed  Google Scholar 

  76. Takagishi H, Takahashi T, Yamagishi T, Shinada M, Inukai K, Tanida S, et al. Salivary testosterone levels and autism-spectrum quotient in adults. Neuro Endocrinol. Lett. 2010;31(6):837–41.

    CAS  PubMed  Google Scholar 

  77. Geier DA, Geier MR. A prospective assessment of androgen levels in patients with autistic spectrum disorders: biochemical underpinnings and suggested therapies. Neuro Endocrinol Lett. 2007;28(5):565–73.

    CAS  PubMed  Google Scholar 

  78. Pohl A, Cassidy S, Auyeung B, Baron-Cohen S. Uncovering steroidopathy in women with autism: a latent class analysis. Mol. Autism. 2014;5(1):27. https://doi.org/10.1186/2040-2392-5-27.

    Article  PubMed  PubMed Central  Google Scholar 

  79. Ingudomnukul E, Baron-Cohen S, Wheelwright S, Knickmeyer R. Elevated rates of testosterone-related disorders in women with autism spectrum conditions. Horm Behav. 2007;51(5):597–604. https://doi.org/10.1016/j.yhbeh.2007.02.001.

    Article  CAS  PubMed  Google Scholar 

  80. Tordjman S, Ferrari P, Sulmont V, Duyme M, Roubertoux P. Androgenic activity in autism. Am J Psychiatry. 1997;154(11):1626–7.

    Article  CAS  PubMed  Google Scholar 

  81. Crider A, Thakkar R, Ahmed AO, Pillai A. Dysregulation of estrogen receptor beta (ERβ), aromatase (CYP19A1), and ER co-activators in the middle frontal gyrus of autism spectrum disorder subjects. Mol. Autism. 2014;5(1):46. https://doi.org/10.1186/2040-2392-5-46.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  82. Sarachana T, Xu M, Wu R-C, Hu VW. Sex hormones in autism: androgens and estrogens differentially and reciprocally regulate RORA, a novel candidate gene for autism. PLoS One. 2011;6(2):e17116. https://doi.org/10.1371/journal.pone.0017116.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Hu VW, Sarachana T, Kim KS, Nguyen A, Kulkarni S, Steinberg ME, et al. Gene expression profiling differentiates autism case-controls and phenotypic variants of autism spectrum disorders: evidence for circadian rhythm dysfunction in severe autism. Autism Res. 2009;2(2):78–97. https://doi.org/10.1002/aur.73.

    Article  PubMed  PubMed Central  Google Scholar 

  84. Hu VW, Frank BC, Heine S, Lee NH, Quackenbush J. Gene expression profiling of lymphoblastoid cell lines from monozygotic twins discordant in severity of autism reveals differential regulation of neurologically relevant genes. BMC Genomics. 2006;7(1):118. https://doi.org/10.1186/1471-2164-7-118.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  85. Nguyen A, Rauch TA, Pfeifer GP, Hu VW. Global methylation profiling of lymphoblastoid cell lines reveals epigenetic contributions to autism spectrum disorders and a novel autism candidate gene, RORA, whose protein product is reduced in autistic brain. FASEB J. 2010;24(8):3036–51. https://doi.org/10.1096/fj.10-154484.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Hu VW, Sarachana T, Sherrard RM, Kocher KM. Investigation of sex differences in the expression of RORA and its transcriptional targets in the brain as a potential contributor to the sex bias in autism. Mol Autism. 2015;6:7.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  87. Hoffman EJ, Turner KJ, Fernandez JM, Cifuentes D, Ghosh M, Ijaz S, et al. Estrogens suppress a behavioral phenotype in zebrafish mutants of the autism risk gene, CNTNAP2. Neuron. 2016;89(4):725–33. https://doi.org/10.1016/j.neuron.2015.12.039.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Macrì S, Biamonte F, Romano E, Marino R, Keller F, Laviola G. Perseverative responding and neuroanatomical alterations in adult heterozygous reeler mice are mitigated by neonatal estrogen administration. Psychoneuroendocrinology. 2010;35(9):1374–87. https://doi.org/10.1016/j.psyneuen.2010.03.012.

    Article  PubMed  CAS  Google Scholar 

  89. Xu XJ, Zhang HF, Shou XJ, Li J, Jing WL, Zhou Y, et al. Prenatal hyperandrogenic environment induced autistic-like behavior in rat offspring. Physiol Behav. 2015;138:13–20. https://doi.org/10.1016/j.physbeh.2014.09.014.

    Article  CAS  PubMed  Google Scholar 

  90. Hatanaka Y, Wada K, Kabuta T. Abnormal instability, excess density, and aberrant morphology of dendritic spines in prenatally testosterone-exposed mice. Neurochem Int. 2015;85–86:53–8.

    Article  PubMed  CAS  Google Scholar 

  91. Gur RC, Gur RE. Complementarity of sex differences in brain and behavior: from laterality to multimodal neuroimaging. J Neurosci Res. 2017;95(1-2):189–99. https://doi.org/10.1002/jnr.23830.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Ashwin C, Ricciardelli P, Baron-Cohen S. Positive and negative gaze perception in autism spectrum conditions. Soc Neurosci. 2009;4(2):153–64. https://doi.org/10.1080/17470910802337902.

    Article  PubMed  Google Scholar 

  93. Tan DW, Russell-Smith SN, Simons JM, Maybery MT, Leung D, Ng HLH, et al. Perceived gender ratings for high and low scorers on the autism-spectrum quotient consistent with the extreme male brain account of autism. McCormick CM, editor. PLoS One. 2015;10(7):e0131780. https://doi.org/10.1371/journal.pone.0131780.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  94. Baron-Cohen S, Cassidy S, Auyeung B, Allison C, Achoukhi M, Robertson S, et al. Attenuation of typical sex differences in 800 adults with autism vs. 3,900 controls. Hu VW, editor. PLoS One. 2014;9(7):e102251. https://doi.org/10.1371/journal.pone.0102251.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  95. Øien RA, Hart L, Schjølberg S, Wall CA, Kim ES, Nordahl-Hansen A, et al. Parent-endorsed sex differences in toddlers with and without ASD: utilizing the M-CHAT. J Autism Dev Disord. 2017;47(1):126–34. https://doi.org/10.1007/s10803-016-2945-8.

    Article  PubMed  Google Scholar 

  96. Gilmore JH, Lin W, Prastawa MW, Looney CB, Vetsa YSK, Knickmeyer RC, et al. Regional gray matter growth, sexual dimorphism, and cerebral asymmetry in the neonatal brain. J Neurosci. 2007;27(6):1255–60. https://doi.org/10.1523/JNEUROSCI.3339-06.2007.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Courchesne E, Campbell K, Solso S. Brain growth across the life span in autism: age-specific changes in anatomical pathology. Brain Res. 2011;1380:138–45. https://doi.org/10.1016/j.brainres.2010.09.101.

    Article  CAS  PubMed  Google Scholar 

  98. Beacher FD, Minati L, Baron-Cohen S, Lombardo MV, Lai M-C, Gray MA, et al. Autism attenuates sex differences in brain structure: a combined voxel-based morphometry and diffusion tensor imaging study. Am J Neuroradiol. 2012;33(1):83–9. https://doi.org/10.3174/ajnr.A2880.

    Article  CAS  PubMed  Google Scholar 

  99. Ecker C, Andrews DS, Gudbrandsen CM, Marquand AF, Ginestet CE, Daly EM, et al. Association between the probability of autism spectrum disorder and normative sex-related phenotypic diversity in brain structure. JAMA Psychiatry. 2017;74(4):329–38. https://doi.org/10.1001/jamapsychiatry.2016.3990.

    Article  PubMed  Google Scholar 

  100. Ypma RJF, Moseley RL, Holt RJ, Rughooputh N, Floris DL, Chura LR, et al. Default mode hypoconnectivity underlies a sex-related autism spectrum. Biol psychiatry Cogn Neurosci Neuroimaging. 2016;1(4):364–71. https://doi.org/10.1016/j.bpsc.2016.04.006.

    Article  PubMed  PubMed Central  Google Scholar 

  101. Bejerot S, Eriksson JM, Bonde S, Carlström K, Humble MB, Eriksson E. The extreme male brain revisited: gender coherence in adults with autism spectrum disorder. Br J Psychiatry. 2012;201(02):116–23. https://doi.org/10.1192/bjp.bp.111.097899.

    Article  PubMed  Google Scholar 

  102. Beacher FDCC, Radulescu E, Minati L, Baron-Cohen S, Lombardo M V, Lai M-C, et al. Sex differences and autism: brain function during verbal fluency and mental rotation. Tsakiris M, editor. PLoS One. Public Libr Sci; 2012;7:e38355.

  103. Cauda F, Geda E, Sacco K, D’Agata F, Duca S, Geminiani G, et al. Grey matter abnormality in autism spectrum disorder: an activation likelihood estimation meta-analysis study. J Neurol Neurosurg Psychiatry BioMed Central. 2011;82(12):1304–13. https://doi.org/10.1136/jnnp.2010.239111.

    Article  Google Scholar 

  104. Jung M, Mody M, Saito DN, Tomoda A, Okazawa H, Wada Y, et al. Sex differences in the default mode network with regard to autism Spectrum traits: a resting state fMRI study. Stamatakis EA, editor. PLoS One. 2015;10(11):e0143126. https://doi.org/10.1371/journal.pone.0143126.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  105. Alaerts K, Swinnen SP, Wenderoth N. Sex differences in autism: a resting-state fMRI investigation of functional brain connectivity in males and females. Soc Cogn Affect Neurosci. Oxford University Press. 2016;11:1002–16.

    Article  PubMed  PubMed Central  Google Scholar 

  106. Lai M-C, Lombardo MV, Suckling J, Ruigrok ANV, Chakrabarti B, Ecker C, et al. Biological sex affects the neurobiology of autism. Brain. 2013;136(9):2799–815. https://doi.org/10.1093/brain/awt216.

    Article  PubMed  PubMed Central  Google Scholar 

  107. Barth C, Villringer A, Sacher J. Sex hormones affect neurotransmitters and shape the adult female brain during hormonal transition periods. Front Neurosci. 2015;9:37.

    Article  PubMed  PubMed Central  Google Scholar 

  108. Cai J, Ding L, Zhang J-S, Xue J, Wang L-Z. Elevated plasma levels of glutamate in children with autism spectrum disorders. Neuroreport. 2016;27(4):272–6. https://doi.org/10.1097/WNR.0000000000000532.

    Article  CAS  PubMed  Google Scholar 

  109. Bredewold R, Schiavo JK, van der Hart M, Verreij M, Veenema AH. Dynamic changes in extracellular release of GABA and glutamate in the lateral septum during social play behavior in juvenile rats: implications for sex-specific regulation of social play behavior. Neuroscience. 2015;307:117–27. https://doi.org/10.1016/j.neuroscience.2015.08.052.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Won H, Lee H-R, Gee HY, Mah W, Kim J-I, Lee J, et al. Autistic-like social behaviour in Shank2-mutant mice improved by restoring NMDA receptor function. Nature. 2012;486(7402):261–5. https://doi.org/10.1038/nature11208.

    Article  CAS  PubMed  Google Scholar 

  111. Toft AKH, Lundbye CJ, Banke TG. Dysregulated NMDA-receptor signaling inhibits long-term depression in a mouse model of fragile X syndrome. J Neurosci. 2016;36(38):9817–27. https://doi.org/10.1523/JNEUROSCI.3038-15.2016.

    Article  CAS  PubMed  Google Scholar 

  112. Burket JA, Benson AD, Tang AH, Deutsch SI. NMDA receptor activation regulates sociability by its effect on mTOR signaling activity. Prog. Neuro-Psychopharmacology Biol Psychiatry. 2015;60:60–5.

    Article  CAS  Google Scholar 

  113. Lee E-J, Lee H, Huang T-N, Chung C, Shin W, Kim K, et al. Trans-synaptic zinc mobilization improves social interaction in two mouse models of autism through NMDAR activation. Nat Commun. 2015;6:7168. https://doi.org/10.1038/ncomms8168.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Duffney LJ, Zhong P, Wei J, Matas E, Cheng J, Qin L, et al. Autism-like deficits in Shank3-deficient mice are rescued by targeting actin regulators. Cell Rep. 2015;11(9):1400–13. https://doi.org/10.1016/j.celrep.2015.04.064.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. Belmonte MK, Cook EH, Anderson GM, Rubenstein JLR, Greenough WT, Beckel-Mitchener A, et al. Autism as a disorder of neural information processing: directions for research and targets for therapy1. Mol Psychiatry. 2004;9(7):646–63. https://doi.org/10.1038/sj.mp.4001499.

    Article  CAS  PubMed  Google Scholar 

  116. Shuffrey LC, Guter SJ, Delaney S, Jacob S, Anderson GM, Sutcliffe JS, et al. Is there sexual dimorphism of hyperserotonemia in autism spectrum disorder? Autism Res. 2017;10(8):1417–23. https://doi.org/10.1002/aur.1791.

    Article  PubMed  Google Scholar 

  117. Imwalle DB, Gustafsson J-Å, Rissman EF. Lack of functional estrogen receptor β influences anxiety behavior and serotonin content in female mice. Physiol Behav. 2005;84(1):157–63. https://doi.org/10.1016/j.physbeh.2004.11.002.

    Article  CAS  PubMed  Google Scholar 

  118. Fink G, Sumner B, Rosie R, Wilson H, McQueen J. Androgen actions on central serotonin neurotransmission: relevance for mood, mental state and memory. Behav Brain Res. 1999;105(1):53–68. https://doi.org/10.1016/S0166-4328(99)00082-0.

    Article  CAS  PubMed  Google Scholar 

  119. Estes ML, McAllister AK. Immune mediators in the brain and peripheral tissues in autism spectrum disorder. Nat Rev Neurosci. 2015;16(8):469–86. https://doi.org/10.1038/nrn3978.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  120. Roved J, Westerdahl H, Hasselquist D. Sex differences in immune responses: hormonal effects, antagonistic selection, and evolutionary consequences. Horm Behav. 2017;88:95–105. https://doi.org/10.1016/j.yhbeh.2016.11.017.

    Article  CAS  PubMed  Google Scholar 

  121. Lenz KM, Nugent BM, Haliyur R, McCarthy MM, et al. J. Neurosci. NIH Public Access. 2013;33:2761–72.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  122. Schwarz E, Guest PC, Rahmoune H, Wang L, Levin Y, Ingudomnukul E, et al. Sex-specific serum biomarker patterns in adults with Asperger’s syndrome. Mol Psychiatry. 2011;16(12):1213–20. https://doi.org/10.1038/mp.2010.102.

    Article  CAS  PubMed  Google Scholar 

  123. Suzuki K, Sugihara G, Ouchi Y, Nakamura K, Futatsubashi M, Takebayashi K, et al. Microglial activation in young adults with autism spectrum disorder. JAMA Psychiatry. 2013;70(1):49–58. https://doi.org/10.1001/jamapsychiatry.2013.272.

    Article  PubMed  Google Scholar 

  124. Gupta S, Ellis SE, Ashar FN, Moes A, Bader JS, Zhan J, et al. Transcriptome analysis reveals dysregulation of innate immune response genes and neuronal activity-dependent genes in autism. Nat Commun. 2014;5:5748. https://doi.org/10.1038/ncomms6748.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  125. Xuan, ICY, Hampson DR. Gender-dependent effects of maternal immune activation on the behavior of mouse offspring. Baudry M, editor PLoS One 2014;9:e104433, 8, DOI: https://doi.org/10.1371/journal.pone.0104433.

  126. Custódio CS, Mello, BSF, Filho, AJMC, de Carvalho Lima CN, Cordeiro RC, Miyajima F, et al. Neonatal immune challenge with lipopolysaccharide triggers long-lasting sex- and age-related behavioral and immune/neurotrophic alterations in mice: relevance to autism spectrum disorders. Mol Neurobiol. 2017.

  127. Turano A, Lawrence JH, Schwarz JM. Activation of neonatal microglia can be influenced by other neural cells. Neurosci Lett. 2017;657:32–7. https://doi.org/10.1016/j.neulet.2017.07.052.

    Article  CAS  PubMed  Google Scholar 

  128. Coretti L, Cristiano C, Florio E, Scala G, Lama A, Keller S, et al. Sex-related alterations of gut microbiota composition in the BTBR mouse model of autism spectrum disorder. Sci Rep. 2017;7:45356. https://doi.org/10.1038/srep45356.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  129. Basil P, Li Q, Dempster EL, Mill J, Sham P-C, Wong CCY, et al. Prenatal maternal immune activation causes epigenetic differences in adolescent mouse brain. Transl Psychiatry. 2014;4(9):e434. https://doi.org/10.1038/tp.2014.80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  130. Hanamsagar R, Alter MD, Block CS, Sullivan H, Bolton JL, Bilbo SD. Generation of a microglial developmental index in mice and in humans reveals a sex difference in maturation and immune reactivity. Glia. 2017;65(9):1504–20. https://doi.org/10.1002/glia.23176.

    Article  PubMed  Google Scholar 

  131. Schulkin J. Autism and the amygdala: an endocrine hypothesis. Brain Cogn. 2007;65(1):87–99. https://doi.org/10.1016/j.bandc.2006.02.009.

    Article  PubMed  Google Scholar 

  132. Kosfeld M, Heinrichs M, Zak PJ, Fischbacher U, Fehr E. Oxytocin increases trust in humans. Nature. 2005;435(7042):673–6. https://doi.org/10.1038/nature03701.

    Article  CAS  PubMed  Google Scholar 

  133. Zak P, Kurzban R, Matzner W. Oxytocin is associated with human trustworthiness. Horm Behav. 2005;48(5):522–7. https://doi.org/10.1016/j.yhbeh.2005.07.009.

    Article  CAS  PubMed  Google Scholar 

  134. Baumgartner T, Heinrichs M, Vonlanthen A, Fischbacher U, Fehr E. Oxytocin shapes the neural circuitry of trust and trust adaptation in humans. Neuron. 2008;58(4):639–50. https://doi.org/10.1016/j.neuron.2008.04.009.

    Article  CAS  PubMed  Google Scholar 

  135. Petrovic P, Kalisch R, Singer T, Dolan RJ. Oxytocin attenuates affective evaluations of conditioned faces and amygdala activity. J Neurosci. 2008;28(26):6607–15. https://doi.org/10.1523/JNEUROSCI.4572-07.2008.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  136. Buchheim A, Heinrichs M, George C, Pokorny D, Koops E, Henningsen P, et al. Oxytocin enhances the experience of attachment security. Psychoneuroendocrinology. 2009;34(9):1417–22. https://doi.org/10.1016/j.psyneuen.2009.04.002.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  137. Savaskan E, Ehrhardt R, Schulz A, Walter M, Schächinger H. Post-learning intranasal oxytocin modulates human memory for facial identity. Psychoneuroendocrinology. 2008;33(3):368–74. https://doi.org/10.1016/j.psyneuen.2007.12.004.

    Article  CAS  PubMed  Google Scholar 

  138. White-Traut R, Watanabe K, Pournajafi-Nazarloo H, Schwertz D, Bell A, Carter CS. Detection of salivary oxytocin levels in lactating women. Dev Psychobiol. 2009;51(4):367–73. https://doi.org/10.1002/dev.20376.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  139. Domes G, Heinrichs M, Michel A, Berger C, Herpertz SC. Oxytocin improves “mind-reading” in humans. Biol Psychiatry. 2007;61(6):731–3. https://doi.org/10.1016/j.biopsych.2006.07.015.

    Article  CAS  PubMed  Google Scholar 

  140. Ozsoy S, Esel E, Kula M. Serum oxytocin levels in patients with depression and the effects of gender and antidepressant treatment. Psychiatry Res. 2009;169(3):249–52. https://doi.org/10.1016/j.psychres.2008.06.034.

    Article  CAS  PubMed  Google Scholar 

  141. Bale TL, Dorsa DM. Regulation of oxytocin receptor messenger ribonucleic acid in the ventromedial hypothalamus by testosterone and its metabolites. Endocrinology. 1995;136(11):5135–8. https://doi.org/10.1210/endo.136.11.7588251.

    Article  CAS  PubMed  Google Scholar 

  142. Bale TL, Dorsa DM, Johnston CA. Oxytocin receptor mRNA expression in the ventromedial hypothalamus during the estrous cycle. J Neurosci. 1995;15(7 Pt 1):5058–64.

    CAS  PubMed  Google Scholar 

  143. de Kloet ER, Voorhuis DA, Boschma Y, Elands J. Estradiol modulates density of putative “oxytocin receptors” in discrete rat brain regions. Neuroendocrinology. 1986;44(4):415–21. https://doi.org/10.1159/000124680.

    Article  PubMed  Google Scholar 

  144. Quiñones-Jenab V, Jenab S, Ogawa S, Adan RA, Burbach JP, Pfaff DW. Effects of estrogen on oxytocin receptor messenger ribonucleic acid expression in the uterus, pituitary, and forebrain of the female rat. Neuroendocrinology. 1997;65(1):9–17. https://doi.org/10.1159/000127160.

    Article  PubMed  Google Scholar 

  145. Schumacher M, Coirini H, Pfaff DW, McEwen BS. Behavioral effects of progesterone associated with rapid modulation of oxytocin receptors. Science. 1990;250(4981):691–4. https://doi.org/10.1126/science.2173139.

    Article  CAS  PubMed  Google Scholar 

  146. Miller M, Bales KL, Taylor SL, Yoon J, Hostetler CM, Carter CS, et al. Oxytocin and vasopressin in children and adolescents with autism spectrum disorders: sex differences and associations with symptoms. Autism Res. 2013;6(2):91–102. https://doi.org/10.1002/aur.1270.

    Article  PubMed  PubMed Central  Google Scholar 

  147. Bodo C, Rissman EF. New roles for estrogen receptor beta in behavior and neuroendocrinology. Front Neuroendocrinol. 2006;27(2):217–32. https://doi.org/10.1016/j.yfrne.2006.02.004.

    Article  CAS  PubMed  Google Scholar 

  148. Devidze N, Mong JA, Jasnow AM, Kow L-M, Pfaff DW. Sex and estrogenic effects on coexpression of mRNAs in single ventromedial hypothalamic neurons. Proc Natl Acad Sci. 2005;102(40):14446–51. https://doi.org/10.1073/pnas.0507144102.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  149. Guastella AJ, Hickie IB. Oxytocin treatment, circuitry, and autism: a critical review of the literature placing oxytocin into the autism context. Biol Psychiatry. 2016;79(3):234–42. https://doi.org/10.1016/j.biopsych.2015.06.028.

    Article  CAS  PubMed  Google Scholar 

  150. Modahl C, Green L, Fein D, Morris M, Waterhouse L, Feinstein C, et al. Plasma oxytocin levels in autistic children. Biol Psychiatry. 1998;43(4):270–7. https://doi.org/10.1016/S0006-3223(97)00439-3.

    Article  CAS  PubMed  Google Scholar 

  151. Green L, Fein D, Modahl C, Feinstein C, Waterhouse L, Morris M. Oxytocin and autistic disorder: alterations in peptide forms. Biol Psychiatry. 2001;50(8):609–13. https://doi.org/10.1016/S0006-3223(01)01139-8.

    Article  CAS  PubMed  Google Scholar 

  152. Guastella AJ, Einfeld SL, Gray KM, Rinehart NJ, Tonge BJ, Lambert TJ, et al. Intranasal oxytocin improves emotion recognition for youth with autism spectrum disorders. Biol Psychiatry. 2010;67(7):692–4. https://doi.org/10.1016/j.biopsych.2009.09.020.

    Article  CAS  PubMed  Google Scholar 

  153. Guastella AJ, Gray KM, Rinehart NJ, Alvares GA, Tonge BJ, Hickie IB, et al. The effects of a course of intranasal oxytocin on social behaviors in youth diagnosed with autism spectrum disorders: a randomized controlled trial. J Child Psychol Psychiatry. 2015;56(4):444–52. https://doi.org/10.1111/jcpp.12305.

    Article  PubMed  Google Scholar 

  154. Andari E, Duhamel J-R, Zalla T, Herbrecht E, Leboyer M, Sirigu A. Promoting social behavior with oxytocin in high-functioning autism spectrum disorders. Proc Natl Acad Sci U S A. 2010;107(9):4389–94. https://doi.org/10.1073/pnas.0910249107.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  155. Aiello TP, Whitaker-Azmitia PM. Sexual differentiation and the neuroendocrine hypothesis of autism. Anat Rec (Hoboken). 2011;294(10):1663–70. https://doi.org/10.1002/ar.21251.

    Article  CAS  Google Scholar 

  156. Simpson EA, Paukner A, Sclafani V, Kaburu SSK, Suomi SJ, Ferrari PF. Acute oxytocin improves memory and gaze following in male but not female nursery-reared infant macaques. Psychopharmacology. 2017;234(3):497–506. https://doi.org/10.1007/s00213-016-4480-x.

    Article  CAS  PubMed  Google Scholar 

  157. Feng C, Hackett PD, DeMarco AC, Chen X, Stair S, Haroon E, et al. Oxytocin and vasopressin effects on the neural response to social cooperation are modulated by sex in humans. Brain Imaging Behav. 2015;9(4):754–64. https://doi.org/10.1007/s11682-014-9333-9.

    Article  PubMed  Google Scholar 

  158. Carter C. Sex differences in oxytocin and vasopressin: implications for autism spectrum disorders? Behav Brain Res. 2007;176(1):170–86. https://doi.org/10.1016/j.bbr.2006.08.025.

    Article  CAS  PubMed  Google Scholar 

  159. Johnson ZV, Young LJ. Oxytocin and vasopressin neural networks: implications for social behavioral diversity and translational neuroscience. Neurosci Biobehav Rev. 2017;76(Pt A):87–98. https://doi.org/10.1016/j.neubiorev.2017.01.034.

    Article  CAS  PubMed  Google Scholar 

  160. Israel S, Lerer E, Shalev I, Uzefovsky F, Reibold M, Bachnermelman R, et al. Molecular genetic studies of the arginine vasopressin 1a receptor (AVPR1a) and the oxytocin receptor (OXTR) in human behaviour: from autism to altruism with some notes in between. Adv. Vasopressin Oxytocin &#x2014; From Genes to Behav. to Dis. Elsevier; 2008. p. 435–49.

  161. Bangasser DA, Curtis A, BAS R, Bethea TT, Parastatidis I, Ischiropoulos H, et al. Sex differences in corticotropin-releasing factor receptor signaling and trafficking: potential role in female vulnerability to stress-related psychopathology. Mol Psychiatry. 2010;15(9):896–904. https://doi.org/10.1038/mp.2010.66.

    Article  CAS  Google Scholar 

  162. Bao A-M, Swaab DF. Gender difference in age-related number of corticotropin-releasing hormone-expressing neurons in the human hypothalamic paraventricular nucleus and the role of sex hormones. Neuroendocrinology. 2007;85(1):27–36. https://doi.org/10.1159/000099832.

    Article  CAS  PubMed  Google Scholar 

  163. Corbett BA, Mendoza S, Abdullah M, Wegelin JA, Levine S. Cortisol circadian rhythms and response to stress in children with autism. Psychoneuroendocrinology. 2006;31(1):59–68. https://doi.org/10.1016/j.psyneuen.2005.05.011.

    Article  CAS  PubMed  Google Scholar 

  164. Taylor JL, Corbett BA. A review of rhythm and responsiveness of cortisol in individuals with autism spectrum disorders. Psychoneuroendocrinology. 2014;49:207–28. https://doi.org/10.1016/j.psyneuen.2014.07.015.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  165. Veenit V, Riccio O, Sandi C. CRHR1 links peripuberty stress with deficits in social and stress-coping behaviors. J Psychiatr Res. 2014;53:1–7. https://doi.org/10.1016/j.jpsychires.2014.02.015.

    Article  PubMed  Google Scholar 

  166. Lai M-C, Lombardo MV, Pasco G, Ruigrok ANV, Wheelwright SJ, Sadek SA, et al. A behavioral comparison of male and female adults with high functioning autism spectrum conditions. PLoS One. 2011;6(6):e20835. https://doi.org/10.1371/journal.pone.0020835.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  167. Giarelli E, Wiggins LD, Rice CE, Levy SE, Kirby RS, Pinto-Martin J, et al. Sex differences in the evaluation and diagnosis of autism spectrum disorders among children. Disabil Health J. 2010;3(2):107–16. https://doi.org/10.1016/j.dhjo.2009.07.001.

    Article  PubMed  Google Scholar 

  168. Solomon M, Miller M, Taylor SL, Hinshaw SP, Carter CS. Autism symptoms and internalizing psychopathology in girls and boys with autism spectrum disorders. J Autism Dev Disord. 2012;42(1):48–59. https://doi.org/10.1007/s10803-011-1215-z.

    Article  PubMed  Google Scholar 

  169. May T, Cornish K, Rinehart N. Does gender matter? A one year follow-up of autistic, attention and anxiety symptoms in high-functioning children with autism spectrum disorder. J Autism Dev Disord. Springer US. 2014;44:1077–86.

    Article  PubMed  Google Scholar 

  170. Hartley SL, Sikora DM. Sex differences in autism spectrum disorder: an examination of developmental functioning, autistic symptoms, and coexisting behavior problems in toddlers. J Autism Dev Disord. 2009;39(12):1715–22. https://doi.org/10.1007/s10803-009-0810-8.

    Article  PubMed  PubMed Central  Google Scholar 

  171. Begeer S, Mandell D, Wijnker-Holmes B, Venderbosch S, Rem D, Stekelenburg F, et al. Sex differences in the timing of identification among children and adults with autism spectrum disorders. J Autism Dev Disord. 2013;43(5):1151–6. https://doi.org/10.1007/s10803-012-1656-z.

    Article  PubMed  Google Scholar 

  172. Rutherford M, McKenzie K, Johnson T, Catchpole C, O’Hare A, McClure I, et al. Gender ratio in a clinical population sample, age of diagnosis and duration of assessment in children and adults with autism spectrum disorder. Autism. 2016;20(5):628–34. https://doi.org/10.1177/1362361315617879.

    Article  PubMed  Google Scholar 

  173. Irimia A, Torgerson CM, Jacokes ZJ, Van Horn JD. The connectomes of males and females with autism spectrum disorder have significantly different white matter connectivity densities. Sci Rep. 2017;7:46401. https://doi.org/10.1038/srep46401.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  174. Kirkovski M, Enticott PG, Maller JJ, Rossell SL, Fitzgerald PB. Diffusion tensor imaging reveals no white matter impairments among adults with autism spectrum disorder. Psychiatry Res Neuroimaging. 2015;233(1):64–72. https://doi.org/10.1016/j.pscychresns.2015.05.003.

    Article  PubMed  Google Scholar 

  175. Retico A, Giuliano A, Tancredi R, Cosenza A, Apicella F, Narzisi A, et al. The effect of gender on the neuroanatomy of children with autism spectrum disorders: a support vector machine case-control study. Mol Autism. 2016;7.

  176. Supekar K, Menon V. Sex differences in structural organization of motor systems and their dissociable links with repetitive/restricted behaviors in children with autism. Mol Autism. 2015;6(1) https://doi.org/10.1186/s13229-015-0042-z.

  177. Zeestraten EA, Gudbrandsen MC, Daly E, de Schotten MT, Catani M, Dell’Acqua F, et al. Sex differences in frontal lobe connectivity in adults with autism spectrum conditions. Transl Psychiatry. 2017;7(4):e1090. https://doi.org/10.1038/tp.2017.9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  178. Schaer M, Kochalka J, Padmanabhan A, Supekar K, Menon V. Sex differences in cortical volume and gyrification in autism. Mol Autism. 2015;6.

  179. Nordahl CW, Iosif A-M, Young GS, Perry LM, Dougherty R, Lee A, et al. Sex differences in the corpus callosum in preschool-aged children with autism spectrum disorder. Mol Autism. 2015;6(1):26. https://doi.org/10.1186/s13229-015-0005-4.

    Article  PubMed  PubMed Central  Google Scholar 

  180. Kirkovski M, Enticott PG, Hughes ME, Rossell SL, Fitzgerald PB. Atypical neural activity in males but not females with autism Spectrum disorder. J Autism Dev Disord. 2016;46(3):954–63. https://doi.org/10.1007/s10803-015-2639-7.

    Article  PubMed  Google Scholar 

  181. Ruskin DN, Fortin JA, Bisnauth SN, Masino SA. Ketogenic diets improve behaviors associated with autism spectrum disorder in a sex-specific manner in the EL mouse. Physiol Behav. 2017;168:138–45. https://doi.org/10.1016/j.physbeh.2016.10.023.

    Article  CAS  PubMed  Google Scholar 

  182. Van Wijngaarden-Cremers PJM, van Eeten E, Groen WB, Van Deurzen PA, Oosterling IJ, Van der Gaag RJ. Gender and age differences in the Core triad of impairments in autism spectrum disorders: a systematic review and meta-analysis. J Autism Dev Disord. 2014;44(3):627–35. https://doi.org/10.1007/s10803-013-1913-9.

    Article  PubMed  Google Scholar 

  183. Head AM, McGillivray JA, Stokes MA. Gender differences in emotionality and sociability in children with autism spectrum disorders. Mol. Autism. 2014;5(1):19. https://doi.org/10.1186/2040-2392-5-19.

    Article  PubMed  PubMed Central  Google Scholar 

  184. Backer van Ommeren T, Koot HM, Scheeren AM, Begeer S. Sex differences in the reciprocal behaviour of children with autism. Autism. 2017;21(6):795–803. https://doi.org/10.1177/1362361316669622.

    Article  PubMed  Google Scholar 

  185. Rynkiewicz A, Schuller B, Marchi E, Piana S, Camurri A, Lassalle A, et al. An investigation of the “female camouflage effect” in autism using a computerized ADOS-2 and a test of sex/gender differences. Mol. Autism. 2016;7(1):10. https://doi.org/10.1186/s13229-016-0073-0.

    Article  PubMed  PubMed Central  Google Scholar 

  186. Lai M-C, Lombardo M V., Ruigrok AN V., Chakrabarti B, Wheelwright SJ, Auyeung B, Allison C, MRC AIMS Consortium, Baron-Cohen S Cognition in males and females with autism: similarities and differences. Botbol M, editor PLoS One 2012;7:e47198, 10, DOI: https://doi.org/10.1371/journal.pone.0047198.

  187. Beggiato A, Peyre H, Maruani A, Scheid I, Rastam M, Amsellem F, et al. Gender differences in autism spectrum disorders: divergence among specific core symptoms. Autism Res. 2017;10(4):680–9. https://doi.org/10.1002/aur.1715.

    Article  PubMed  Google Scholar 

  188. Frazier TW, Georgiades S, Bishop SL, Hardan AY. Behavioral and cognitive characteristics of females and males with autism in the Simons simplex collection. J Am Acad Child Adolesc Psychiatry. 2014;53(3):329–340.e3. https://doi.org/10.1016/j.jaac.2013.12.004.

    Article  PubMed  Google Scholar 

  189. Koyama T, Kamio Y, Inada N, Kurita H. Sex differences in WISC-III profiles of children with high-functioning pervasive developmental disorders. J Autism Dev Disord. 2009;39(1):135–41. https://doi.org/10.1007/s10803-008-0610-6.

    Article  PubMed  Google Scholar 

  190. Sedgewick F, Hill V, Yates R, Pickering L, Pellicano E. Gender differences in the social motivation and friendship experiences of autistic and non-autistic adolescents. J Autism Dev Disord Springer US. 2016;46(4):1297–306. https://doi.org/10.1007/s10803-015-2669-1.

    Article  Google Scholar 

  191. Lehnhardt F-G, Falter CM, Gawronski A, Pfeiffer K, Tepest R, Franklin J, et al. Sex-related cognitive profile in autism Spectrum disorders diagnosed late in life: implications for the female autistic phenotype. J Autism Dev Disord. 2016;46(1):139–54. https://doi.org/10.1007/s10803-015-2558-7.

    Article  PubMed  Google Scholar 

  192. Kauschke C, van der Beek B, Kamp-Becker I. Narratives of girls and boys with autism spectrum disorders: gender differences in narrative competence and internal state language. J Autism Dev Disord. 2016;46(3):840–52. https://doi.org/10.1007/s10803-015-2620-5.

    Article  PubMed  Google Scholar 

  193. Reinhardt VP, Wetherby AM, Schatschneider C, Lord C. Examination of sex differences in a large sample of young children with autism spectrum disorder and typical development. J Autism Dev Disord. Springer US. 2015;45:697–706.

    Article  PubMed  PubMed Central  Google Scholar 

  194. Frazier TW, Hardan AY. Equivalence of symptom dimensions in females and males with autism. Autism. 2017;21(6):749–59. https://doi.org/10.1177/1362361316660066.

    Article  PubMed  Google Scholar 

  195. Harrop C, Gulsrud A, Kasari C. Does gender moderate core deficits in ASD? An investigation into restricted and repetitive behaviors in girls and boys with ASD. J. Autism Dev. Disord. Springer US. 2015;45(11):3644–55. https://doi.org/10.1007/s10803-015-2511-9.

    Article  Google Scholar 

  196. Pisula E, Pudło M, Słowińska M, Kawa R, Strząska M, Banasiak A, et al. Behavioral and emotional problems in high-functioning girls and boys with autism spectrum disorders: parents’ reports and adolescents’ self-reports. Autism. 2017;21(6):738–48. https://doi.org/10.1177/1362361316675119.

    Article  PubMed  Google Scholar 

  197. Grove R, Hoekstra RA, Wierda M, Begeer S. Exploring sex differences in autistic traits: a factor analytic study of adults with autism. Autism. 2017;21(6):760–8. https://doi.org/10.1177/1362361316667283.

    Article  PubMed  Google Scholar 

  198. Hiller RM, Young RL, Weber N. Sex differences in autism spectrum disorder based on DSM-5 criteria: evidence from clinician and teacher reporting. J Abnorm Child Psychol. Springer US. 2014;42:1381–93.

    Article  PubMed  Google Scholar 

  199. Howe YJ, O’Rourke JA, Yatchmink Y, Viscidi EW, Jones RN, Morrow EM. Female autism phenotypes investigated at different levels of language and developmental abilities. J Autism Dev Disord. Springer US. 2015;45:3537–49.

    Article  PubMed  PubMed Central  Google Scholar 

  200. Halladay AK, Bishop S, Constantino JN, Daniels AM, Koenig K, Palmer K, et al. Sex and gender differences in autism spectrum disorder: summarizing evidence gaps and identifying emerging areas of priority. Mol. Autism. 2015;6(1):36. https://doi.org/10.1186/s13229-015-0019-y.

    Article  PubMed  PubMed Central  Google Scholar 

  201. Jamison R, Bishop SL, Huerta M, Halladay AK. The clinician perspective on sex differences in autism spectrum disorders. Autism. 2017;21(6):772–84. https://doi.org/10.1177/1362361316681481.

    Article  PubMed  Google Scholar 

  202. Hiller RM, Young RL, Weber N. Sex differences in pre-diagnosis concerns for children later diagnosed with autism spectrum disorder. Autism. 2016;20(1):75–84. https://doi.org/10.1177/1362361314568899.

    Article  PubMed  Google Scholar 

  203. Charman T, Loth E, Tillmann J, Crawley D, Wooldridge C, Goyard D, et al. The EU-AIMS Longitudinal European Autism Project (LEAP): clinical characterisation. Mol. Autism. 2017;8(1):27. https://doi.org/10.1186/s13229-017-0145-9.

    Article  PubMed  PubMed Central  Google Scholar 

  204. Tsai P-C, Harrington RA, Lung F-W, Lee L-C. Disparity in report of autism-related behaviors by social demographic characteristics: findings from a community-based study in Taiwan. Autism. 2017;21(5):540–51. https://doi.org/10.1177/1362361316677024.

    Article  PubMed  Google Scholar 

  205. Murray AL, Allison C, Smith PL, Baron-Cohen S, Booth T, Auyeung B. Investigating diagnostic bias in autism spectrum conditions: an item response theory analysis of sex bias in the AQ-10. Autism Res. 2017;10(5):790–800. https://doi.org/10.1002/aur.1724.

    Article  PubMed  Google Scholar 

  206. Little LM, Wallisch A, Salley B, Jamison R. Do early caregiver concerns differ for girls with autism spectrum disorders? Autism. 2017;21(6):728–32. https://doi.org/10.1177/1362361316664188.

    Article  PubMed  Google Scholar 

  207. Cridland EK, Jones SC, Caputi P, Magee CA. Being a girl in a boys’ world: investigating the experiences of girls with autism spectrum disorders during adolescence. J Autism Dev Disord. 2014;44(6):1261–74. https://doi.org/10.1007/s10803-013-1985-6.

    Article  PubMed  Google Scholar 

  208. Mandy W, Tchanturia K. Do women with eating disorders who have social and flexibility difficulties really have autism? A case series. Mol. Autism. 2015;6(1):6. https://doi.org/10.1186/2040-2392-6-6.

    Article  PubMed  PubMed Central  Google Scholar 

  209. Bargiela S, Steward R, Mandy W. The experiences of late-diagnosed women with autism spectrum conditions: an investigation of the female autism phenotype. J Autism Dev Disord. 2016;46(10):3281–94. https://doi.org/10.1007/s10803-016-2872-8.

    Article  PubMed  PubMed Central  Google Scholar 

  210. Hull L, Petrides KV, Allison C, Smith P, Baron-Cohen S, Lai M-C, et al. “Putting on my best normal”: social camouflaging in adults with autism spectrum conditions. J Autism Dev Disord. 2017;47(8):2519–34. https://doi.org/10.1007/s10803-017-3166-5.

    Article  PubMed  PubMed Central  Google Scholar 

  211. Lai M-C, Lombardo MV, Ruigrok AN, Chakrabarti B, Auyeung B, Szatmari P, et al. Quantifying and exploring camouflaging in men and women with autism. Autism. 2017;21(6):690–702. https://doi.org/10.1177/1362361316671012.

    Article  PubMed  Google Scholar 

  212. Baldwin S, Costley D. The experiences and needs of female adults with high-functioning autism spectrum disorder. Autism. 2016;20(4):483–95. https://doi.org/10.1177/1362361315590805.

    Article  PubMed  Google Scholar 

  213. Dean M, Harwood R, Kasari C. The art of camouflage: gender differences in the social behaviors of girls and boys with autism spectrum disorder. Autism. 2017;21(6):678–89. https://doi.org/10.1177/1362361316671845.

    Article  PubMed  Google Scholar 

  214. • Schaafsma SM, Gagnidze K, Reyes A, Norstedt N, Månsson K, Francis K, et al. Sex-specific gene-environment interactions underlying ASD-like behaviors. Proc Natl Acad Sci U S A. 2017;114(6):1383–8. This paper discusses risk for autism as a three-hit hypothesis, in which the factors are environmental, genetic, and male sex, as a possible explanation for male preponderance. https://doi.org/10.1073/pnas.1619312114.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  215. Connors EJ, Shaik AN, Migliore MM, Kentner AC. Environmental enrichment mitigates the sex-specific effects of gestational inflammation on social engagement and the hypothalamic pituitary adrenal axis-feedback system. Brain Behav Immun. 2014;42:178–90. https://doi.org/10.1016/j.bbi.2014.06.020.

    Article  CAS  PubMed  Google Scholar 

  216. Edlow AG, Guedj F, Pennings JLA, Sverdlov D, Neri C, Bianchi DW. Males are from Mars, and females are from Venus: sex-specific fetal brain gene expression signatures in a mouse model of maternal diet-induced obesity. Am J Obstet Gynecol. 2016;214(5):623.e1–623.e10. https://doi.org/10.1016/j.ajog.2016.02.054.

    Article  Google Scholar 

  217. Foley KA, MacFabe DF, Kavaliers M, Ossenkopp K-P. Sexually dimorphic effects of prenatal exposure to lipopolysaccharide, and prenatal and postnatal exposure to propionic acid, on acoustic startle response and prepulse inhibition in adolescent rats: relevance to autism spectrum disorders. Behav Brain Res. 2015;278:244–56. https://doi.org/10.1016/j.bbr.2014.09.032.

    Article  CAS  PubMed  Google Scholar 

  218. Sadowski RN, Wise LM, Park PY, Schantz SL, Juraska JM. Early exposure to bisphenol A alters neuron and glia number in the rat prefrontal cortex of adult males, but not females. Neuroscience. 2014;279:122–31. https://doi.org/10.1016/j.neuroscience.2014.08.038.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  219. Angelakos CC, Watson AJ, O’Brien WT, Krainock KS, Nickl-Jockschat T, Abel T. Hyperactivity and male-specific sleep deficits in the 16p11.2 deletion mouse model of autism. Autism Res. 2017;10(4):572–84. https://doi.org/10.1002/aur.1707.

    Article  PubMed  Google Scholar 

  220. Tilot AK, Gaugler MK, Yu Q, Romigh T, Yu W, Miller RH, et al. Germline disruption of Pten localization causes enhanced sex-dependent social motivation and increased glial production. Hum Mol Genet. 2014;23(12):3212–27. https://doi.org/10.1093/hmg/ddu031.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  221. Amram N, Hacohen-Kleiman G, Sragovich S, Malishkevich A, Katz J, Touloumi O, et al. Sexual divergence in microtubule function: the novel intranasal microtubule targeting SKIP normalizes axonal transport and enhances memory. Mol Psychiatry. 2016;21(10):1467–76. https://doi.org/10.1038/mp.2015.208.

    Article  CAS  PubMed  Google Scholar 

  222. Magliaro C, Cocito C, Bagatella S, Merighi A, Ahluwalia A, Lossi L. The number of Purkinje neurons and their topology in the cerebellar vermis of normal and reln haplodeficient mouse. Ann Anat - Anat Anzeiger. 2016;207:68–75. https://doi.org/10.1016/j.aanat.2016.02.009.

    Article  Google Scholar 

  223. Perez-Pouchoulen M, Miquel M, Saft P, Brug B, Toledo R, Hernandez ME, et al. Prenatal exposure to sodium valproate alters androgen receptor expression in the developing cerebellum in a region and age specific manner in male and female rats. Int J Dev Neurosci. 2016;53:46–52. https://doi.org/10.1016/j.ijdevneu.2016.07.001.

    Article  CAS  PubMed  Google Scholar 

  224. Mowery TM, Wilson SM, Kostylev PV, Dina B, Buchholz JB, Prieto AL, et al. Embryological exposure to valproic acid disrupts morphology of the deep cerebellar nuclei in a sexually dimorphic way. Int J Dev Neurosci. 2015;40:15–23. https://doi.org/10.1016/j.ijdevneu.2014.10.003.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

This work was supported by NIMH grant R34MH104407 (Brodkin, PI), the Asperger Syndrome Program of Excellence at University of Pennsylvania (Brodkin, co-Director), and Simons Foundation (SFARI) grant 345034 (Abel, PI). We would like to thank Joseph F. Lynch III for his help editing the manuscript.

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  1. Department of Molecular Physiology and Biophysics, Iowa Neuroscience Institute, University of Iowa, Pappajohn Biomedical Discovery Building, 169 Newton Road, Iowa City, IA, 52242, USA

    Sarah L. Ferri & Ted Abel

  2. Center for Neurobiology and Behavior, Department of Psychiatry, Translational Research Laboratory, Perelman School of Medicine at the University of Pennsylvania, 125 South 31st Street, Room 2202, Philadelphia, PA, 19104-3403, USA

    Edward S. Brodkin

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This article is part of the Topical Collection on Sex and Gender Issues in Behavioral Health

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Ferri, S.L., Abel, T. & Brodkin, E.S. Sex Differences in Autism Spectrum Disorder: a Review. Curr Psychiatry Rep 20, 9 (2018). https://doi.org/10.1007/s11920-018-0874-2

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