Mol Autism. 2015 Jul 04;6:42. doi: 10.1186/s13229-015-0035-y. eCollection 2015.
Sex differences in cortical volume and gyrification in autism.
Molecular autism
Marie Schaer, John Kochalka, Aarthi Padmanabhan, Kaustubh Supekar, Vinod Menon
Affiliations
Affiliations
- Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA 94305 USA.
- Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA 94305 USA ; Program in Neuroscience, Stanford University School of Medicine, Stanford, CA 94305 USA ; Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, USA.
PMID: 26146534
PMCID: PMC4491212 DOI: 10.1186/s13229-015-0035-y
Abstract
BACKGROUND: Male predominance is a prominent feature of autism spectrum disorders (ASD), with a reported male to female ratio of 4:1. Because of the overwhelming focus on males, little is known about the neuroanatomical basis of sex differences in ASD. Investigations of sex differences with adequate sample sizes are critical for improving our understanding of the biological mechanisms underlying ASD in females.
METHODS: We leveraged the open-access autism brain imaging data exchange (ABIDE) dataset to obtain structural brain imaging data from 53 females with ASD, who were matched with equivalent samples of males with ASD, and their typically developing (TD) male and female peers. Brain images were processed with FreeSurfer to assess three key features of local cortical morphometry: volume, thickness, and gyrification. A whole-brain approach was used to identify significant effects of sex, diagnosis, and sex-by-diagnosis interaction, using a stringent threshold of p < 0.01 to control for false positives. Stability and power analyses were conducted to guide future research on sex differences in ASD.
RESULTS: We detected a main effect of sex in the bilateral superior temporal cortex, driven by greater cortical volume in females compared to males in both the ASD and TD groups. Sex-by-diagnosis interaction was detected in the gyrification of the ventromedial/orbitofrontal prefrontal cortex (vmPFC/OFC). Post-hoc analyses revealed that sex-by-diagnosis interaction was driven by reduced vmPFC/OFC gyrification in males with ASD, compared to females with ASD as well as TD males and females. Finally, stability analyses demonstrated a dramatic drop in the likelihood of observing significant clusters as the sample size decreased, suggesting that previous studies have been largely underpowered. For instance, with a sample of 30 females with ASD (total n = 120), a significant sex-by-diagnosis interaction was only detected in 50 % of the simulated subsamples.
CONCLUSIONS: Our results demonstrate that some features of typical sex differences are preserved in the brain of individuals with ASD, while others are not. Sex differences in ASD are associated with cortical regions involved in language and social function, two domains of deficits in the disorder. Stability analyses provide novel quantitative insights into why smaller samples may have previously failed to detect sex differences.
Keywords: Cerebral morphometry; Cortical volume; Females; Gyrification; Neuroimaging; Sex differences
References
- Hum Brain Mapp. 1999;8(4):272-84 - PubMed
- Cereb Cortex. 2000 Sep;10(9):866-72 - PubMed
- Proc Natl Acad Sci U S A. 2000 Sep 26;97(20):11050-5 - PubMed
- J Autism Dev Disord. 2000 Jun;30(3):205-23 - PubMed
- Neuroimage. 2001 Sep;14(3):685-700 - PubMed
- Dev Med Child Neurol. 2002 Jan;44(1):4-16 - PubMed
- Neuron. 2002 Jan 31;33(3):341-55 - PubMed
- Neurology. 2002 Mar 12;58(5):695-701 - PubMed
- Trends Cogn Sci. 2002 Jun 1;6(6):248-254 - PubMed
- Arch Gen Psychiatry. 2002 Sep;59(9):809-16 - PubMed
- Brain Lang. 2003 Feb;84(2):264-72 - PubMed
- Am J Hum Genet. 2004 Dec;75(6):1117-23 - PubMed
- Neuropsychologia. 2006;44(3):445-53 - PubMed
- Nature. 2006 Mar 30;440(7084):676-9 - PubMed
- Neuroimage. 2006 Aug 1;32(1):180-94 - PubMed
- Neuroimage. 2006 Dec;33(4):1093-103 - PubMed
- Neurology. 2006 Nov 28;67(10):1818-22 - PubMed
- J Autism Dev Disord. 2007 Jan;37(1):86-97 - PubMed
- Philos Trans R Soc Lond B Biol Sci. 2007 Apr 29;362(1480):671-8 - PubMed
- J Am Acad Child Adolesc Psychiatry. 2007 Apr;46(4):515-23 - PubMed
- Behav Res Methods. 2007 May;39(2):175-91 - PubMed
- Eur Psychiatry. 2008 Jun;23(4):289-99 - PubMed
- Neuropsychologia. 2008 Apr;46(5):1349-62 - PubMed
- IEEE Trans Med Imaging. 2008 Feb;27(2):161-70 - PubMed
- J Neurosci. 2008 Apr 2;28(14):3586-94 - PubMed
- Arch Gen Psychiatry. 2008 Aug;65(8):946-54 - PubMed
- J Autism Dev Disord. 2009 May;39(5):693-705 - PubMed
- Dev Med Child Neurol. 2009 Sep;51(9):746-53 - PubMed
- Neurosci Biobehav Rev. 2009 Sep;33(8):1198-203 - PubMed
- Biol Psychiatry. 2009 Nov 15;66(10):942-9 - PubMed
- J Neurosci. 2010 Sep 1;30(35):11576-85 - PubMed
- Mol Psychiatry. 2011 Dec;16(12):1213-20 - PubMed
- Prog Brain Res. 2010;186:3-12 - PubMed
- Disabil Health J. 2010 Apr;3(2):107-16 - PubMed
- Soc Cogn Affect Neurosci. 2012 Feb;7(2):160-72 - PubMed
- J Child Psychol Psychiatry. 2011 Jun;52(6):631-44 - PubMed
- Arch Gen Psychiatry. 2011 Apr;68(4):409-18 - PubMed
- Behav Brain Funct. 2011 May 14;7:13 - PubMed
- Radiology. 2011 Aug;260(2):521-30 - PubMed
- J Neurol Neurosurg Psychiatry. 2011 Dec;82(12):1304-13 - PubMed
- PLoS Biol. 2011 Jun;9(6):e1001081 - PubMed
- Soc Cogn Affect Neurosci. 2012 Nov;7(8):871-80 - PubMed
- Psychol Med. 2012 Jun;42(6):1329-37 - PubMed
- AJNR Am J Neuroradiol. 2012 Jan;33(1):83-9 - PubMed
- Neurosci Biobehav Rev. 2012 Mar;36(3):1043-59 - PubMed
- J Neurosci. 2012 Jan 11;32(2):674-80 - PubMed
- Neuroimage. 2012 Aug 15;62(2):774-81 - PubMed
- Br J Dev Psychol. 2012 Jun;30(Pt 2):326-43 - PubMed
- Soc Cogn Affect Neurosci. 2013 Aug;8(6):694-701 - PubMed
- Neuroimage. 2012 Nov 15;63(3):1443-53 - PubMed
- Brain. 2012 Sep;135(Pt 9):2711-25 - PubMed
- Magn Reson Imaging. 2013 Apr;31(3):366-75 - PubMed
- J Neurodev Disord. 2012 Jun 27;4(1):10 - PubMed
- Res Dev Disabil. 2013 Jan;34(1):413-22 - PubMed
- PLoS One. 2012;7(11):e50064 - PubMed
- Soc Cogn Affect Neurosci. 2014 Mar;9(3):367-77 - PubMed
- Soc Cogn Affect Neurosci. 2014 Apr;9(4):520-8 - PubMed
- J Neurosci. 2013 Feb 13;33(7):2761-72 - PubMed
- Autism Res. 2013 Apr;6(2):78-90 - PubMed
- Int J Psychol. 2013;48(6):1230-6 - PubMed
- Neuroimage. 2013 Nov 15;82:200-7 - PubMed
- Mol Psychiatry. 2014 Jun;19(6):659-67 - PubMed
- JAMA Psychiatry. 2013 Aug;70(8):869-79 - PubMed
- Brain. 2013 Sep;136(Pt 9):2799-815 - PubMed
- Front Hum Neurosci. 2013 Aug 06;7:430 - PubMed
- J Autism Dev Disord. 2014 Mar;44(3):627-35 - PubMed
- Biol Psychiatry. 2014 Sep 1;76(5):405-11 - PubMed
- Am J Med Genet B Neuropsychiatr Genet. 2013 Oct;162B(7):742-50 - PubMed
- Front Hum Neurosci. 2013 Oct 30;7:733 - PubMed
- Proc Natl Acad Sci U S A. 2013 Dec 24;110(52):20953-8 - PubMed
- Neuroimage. 2014 May 15;92:225-36 - PubMed
- Neurosci Biobehav Rev. 2014 Feb;39:34-50 - PubMed
- Mol Autism. 2014 Feb 17;5(1):13 - PubMed
- MMWR Surveill Summ. 2014 Mar 28;63(2):1-21 - PubMed
- Brain. 2014 Jun;137(Pt 6):1772-80 - PubMed
- Front Neuroendocrinol. 2014 Aug;35(3):255-71 - PubMed
- Neuropsychology. 2014 Jul;28(4):605-12 - PubMed
- Mol Psychiatry. 2015 Mar;20(3):369-76 - PubMed
- Front Behav Neurosci. 2014 May 16;8:181 - PubMed
- J Neurosci. 2014 Jun 18;34(25):8488-98 - PubMed
- Mol Autism. 2014 Jun 11;5:35 - PubMed
- Cereb Cortex. 2015 Dec;25(12):4740-7 - PubMed
- J Autism Dev Disord. 2015 Mar;45(3):766-77 - PubMed
- Cereb Cortex. 2015 Oct;25(10):3613-28 - PubMed
- Cereb Cortex. 2016 Apr;26(4):1440-52 - PubMed
- Mol Neurobiol. 2016 Jan;53(1):40-56 - PubMed
- J Am Acad Child Adolesc Psychiatry. 2015 Jan;54(1):11-24 - PubMed
- Eur Child Adolesc Psychiatry. 1992 Apr;1(2):89-99 - PubMed
- Cereb Cortex. 1995 Jan-Feb;5(1):56-63 - PubMed
- J Autism Dev Disord. 1994 Oct;24(5):659-85 - PubMed
- J Autism Dev Disord. 1993 Jun;23(2):217-27 - PubMed
- Psychiatry Res. 1995 Sep 29;61(3):129-35 - PubMed
- Arch Neurol. 1997 Feb;54(2):171-6 - PubMed
- Neuroimage. 1999 Feb;9(2):179-94 - PubMed
- Neuroimage. 1999 Feb;9(2):195-207 - PubMed
Publication Types
Grant support