title: Beyond sex differences: new approaches for thinking about variation in brain structure and function.
abstract: In the study of variation in brain structure and function that might relate to sex and gender, language matters because it frames our research questions and methods. In this article, we offer an approach to thinking about variation in brain structure and function that pulls us outside the sex differences formulation. We argue that the existence of differences between the brains of males and females does not unravel the relations between sex and the brain nor is it sufficient to characterize a population of brains. Such characterization is necessary for studying sex effects on the brain as well as for studying brain structure and function in general. Animal studies show that sex interacts with environmental, developmental and genetic factors to affect the brain. Studies of humans further suggest that human brains are better described as belonging to a single heterogeneous population rather than two distinct populations. We discuss the implications of these observations for studies of brain and behaviour in humans and in laboratory animals. We believe that studying sex effects in context and developing or adopting analytical methods that take into account the heterogeneity of the brain are crucial for the advancement of human health and well-being.
authors.affiliation: School of Psychological Sciences, Tel-Aviv University, Ramat Aviv, Tel-Aviv, Israel Sagol School of Neuoroscience, Tel-Aviv University, Ramat Aviv, Tel-Aviv, Israel djoel@post.tau.ac.il.
authors.forename: Daphna
authors.initials: D
authors.lastname: Joel
authors.affiliation: Department of Molecular Biology, Cell and Biochemistry, Brown University, Providence, RI, USA.
authors.forename: Anne
authors.initials: A
authors.lastname: Fausto-Sterling
mesh_terms: D000818:Animals; D001921:Brain / Q000033:anatomy & histology* / Q000502:physiology*; D001931:Brain Mapping; D005260:Female; D006801:Humans; D008297:Male; D017594:Publication Bias; D012737:Sex Factors
keywords: brain; gender; sex
references.citation: PLoS One. 2009;4(1):e3675
references.pmid: 19180242
references.citation: Trends Cogn Sci. 2013 Nov;17(11):550-1
references.pmid: 24176517
references.citation: Biol Sex Differ. 2012 Aug 21;3(1):19
references.pmid: 22908911
references.citation: J Adolesc Health. 2002 Apr;30(4 Suppl):49-58
references.pmid: 11943575
references.citation: Physiol Behav. 1986;36(5):793-9
references.pmid: 3714855
references.citation: PLoS One. 2015;10(6):e0128102
references.pmid: 26069955
references.citation: Front Neuroendocrinol. 2009 Jan;30(1):1-9
references.pmid: 19028515
references.citation: Proc Natl Acad Sci U S A. 2015 Dec 15;112(50):15468-73
references.pmid: 26621705
references.citation: Behav Brain Res. 1998 May;92(2):205-13
references.pmid: 9638962
references.citation: Am Psychol. 2005 Sep;60(6):581-92
references.pmid: 16173891
references.citation: Hum Brain Mapp. 2010 May;31(5):758-69
references.pmid: 19957268
references.citation: Mol Neurobiol. 2009 Oct;40(2):166-82
references.pmid: 19653136
references.citation: Rev Bras Psiquiatr. 2011 Dec;33(4):390-9
references.pmid: 22189930
references.citation: Endocrinology. 2006 May;147(5):2506-17
references.pmid: 16455779
references.citation: Int J Epidemiol. 2003 Aug;32(4):652-7
references.pmid: 12913047
references.citation: Womens Health (Lond Engl). 2011 Nov;7(6):663-74; quiz 675-6
references.pmid: 22040208
references.citation: Arch Sex Behav. 1975 Jul;4(4):405-20
references.pmid: 808193
references.citation: Neurochem Res. 1995 May;20(5):509-19
references.pmid: 7643957
references.citation: Schizophr Bull. 2014 Jul;40(4):729-36
references.pmid: 24860087
references.citation: Neurosci Biobehav Rev. 2014 Mar;40:1-5
references.pmid: 24456941
references.citation: Nature. 2011 Oct 27;478(7370):483-9
references.pmid: 22031440
references.citation: Neuropharmacology. 2013 Dec;75:426-36
references.pmid: 23994757
references.citation: Horm Behav. 2009 May;55(5):589-96
references.pmid: 19446075
references.citation: J Clin Endocrinol Metab. 2000 May;85(5):2034-41
references.pmid: 10843193
references.citation: Biol Sex Differ. 2012 Dec 17;3(1):27
references.pmid: 23244600
references.citation: Front Integr Neurosci. 2011 Sep 20;5:57
references.pmid: 21960961
references.citation: Brain Res Rev. 2009 Oct;61(2):49-59
references.pmid: 19406148
references.citation: Nature. 2014 May 15;509(7500):282-3
references.pmid: 24834516
references.citation: Br J Psychiatry. 2012 Aug;201:116-23
references.pmid: 22500012
references.citation: J Neurosci. 2012 Jan 11;32(2):674-80
references.pmid: 22238103
references.citation: Neuroscience. 2015 Feb 26;287:78-92
references.pmid: 25528062
references.citation: Prog Neuropsychopharmacol Biol Psychiatry. 2001 Aug;25(6):1203-26
references.pmid: 11474841
references.citation: FASEB J. 2016 Feb;30(2):519-24
references.pmid: 26514164
references.citation: Soc Sci Med. 2012 Jun;74(11):1667-74
references.pmid: 21803468
references.citation: Dev Neurobiol. 2007 Nov;67(13):1751-64
references.pmid: 17659594
references.citation: Neuroscience. 2004;126(4):849-57
references.pmid: 15207320
references.citation: J Pers Soc Psychol. 2013 Feb;104(2):385-407
references.pmid: 23088230
references.citation: Behav Brain Res. 2009 Nov 5;203(2):264-9
references.pmid: 19460405
references.citation: Am J Hum Biol. 2000 Mar;12(2):151-166
references.pmid: 11534012
references.citation: Neuroimage. 2016 Jan 1;124(Pt A):350-66
references.pmid: 26334947
references.citation: Am Psychol. 2015 Jan;70(1):10-20
references.pmid: 25581005
references.citation: J Neurosci. 2002 Feb 1;22(3):1027-33
references.pmid: 11826131
references.citation: Brain Res Dev Brain Res. 1995 Jan 14;84(1):55-61
references.pmid: 7720217
references.citation: Handb Exp Pharmacol. 2012;(214):107-26
references.pmid: 23027448
references.citation: Front Behav Neurosci. 2009 Aug 14;3:12
references.pmid: 19707539
references.citation: Pharmacol Rev. 2010 Jun;62(2):155-98
references.pmid: 20392807
references.citation: Biol Sex Differ. 2015 Aug 15;6:15
references.pmid: 26279833
references.citation: Annu Rev Clin Psychol. 2012;8:161-87
references.pmid: 22035243
references.citation: Front Hum Neurosci. 2014 Aug 28;8:650
references.pmid: 25221493
references.citation: Brain Cogn. 2010 Feb;72(1):46-55
references.pmid: 19913969
references.citation: Nat Genet. 2007 Jul;39(7 Suppl):S37-42
references.pmid: 17597780
references.citation: Cereb Cortex. 2009 Sep;19(9):1978-89
references.pmid: 19073626
references.citation: Annu Rev Psychol. 2014;65:373-98
references.pmid: 23808917
references.citation: J Neurochem. 2009 Jun;109(6):1733-44
references.pmid: 19383086
references.citation: J Comp Neurol. 1990 Dec 22;302(4):697-706
references.pmid: 1707064
references.citation: PLoS One. 2014;9(6):e99900
references.pmid: 24964040
references.citation: Neuroscience. 2008 Apr 9;152(4):959-69
references.pmid: 18329814
references.citation: J Comp Neurol. 2011 Oct 15;519(15):3061-84
references.pmid: 21618223
references.citation: PLoS One. 2008;3(5):e2170
references.pmid: 18478112
references.citation: Proc Natl Acad Sci U S A. 2014 Jan 14;111(2):823-8
references.pmid: 24297904
references.citation: Brain Res Dev Brain Res. 2000 Nov 30;124(1-2):43-52
references.pmid: 11113510
references.citation: Endocrinology. 2012 Jun;153(6):2551-5
references.pmid: 22434084
references.citation: J Neurosci. 2001 Aug 15;21(16):6292-7
references.pmid: 11487652
references.citation: Soc Sci Med. 2012 Jun;74(11):1817-24
references.pmid: 21724313
references.citation: Brain Res Dev Brain Res. 1992 Jul 24;68(1):125-31
references.pmid: 1521318
references.citation: Hippocampus. 2009 Jul;19(7):623-32
references.pmid: 19115376
references.citation: Neuroimage. 2009 Apr 15;45(3):1020-32
references.pmid: 19162200
references.citation: Neurosci Biobehav Rev. 2014 Feb;39:34-50
references.pmid: 24374381
references.citation: Psychol Sci. 2010 Oct;21(10):1494-501
references.pmid: 20807895
references.citation: Psychoneuroendocrinology. 1991;16(1-3):105-9
references.pmid: 1961834
references.citation: Dev Psychol. 2001 Jul;37(4):451-63
references.pmid: 11444482
references.citation: Nat Rev Neurosci. 2006 Jun;7(6):477-84
references.pmid: 16688123
references.citation: Expert Rev Neurother. 2011 Jul;11(7):951-9
references.pmid: 21721913
references.citation: Biol Psychiatry. 2007 Oct 15;62(8):847-55
references.pmid: 17544382
references.citation: Neuroendocrinology. 2003 Oct;78(4):234-40
references.pmid: 14583656
references.citation: J Pers. 1995 Sep;63(3):681-710
references.pmid: 7562367
references.citation: Brain Res. 2000 Feb 21;856(1-2):254-8
references.pmid: 10677635
references.citation: Br J Pharmacol. 2014 Oct;171(20):4620-35
references.pmid: 24758640
references.citation: Proc Natl Acad Sci U S A. 2015 Nov 3;112(44):13419-20
references.pmid: 26534989
references.citation: Horm Metab Res. 2012 Jul;44(8):607-18
references.pmid: 22581646
references.citation: J Neurosci. 2012 Feb 15;32(7):2241-7
references.pmid: 22396398
references.citation: Psychoneuroendocrinology. 2002 Jan-Feb;27(1-2):273-83
references.pmid: 11750783
references.citation: Nat Genet. 2012 Sep;44(9):981-90
references.pmid: 22885922
references.citation: Psychoneuroendocrinology. 2009 Dec;34 Suppl 1:S217-26
references.pmid: 19553026
references.citation: Int J Epidemiol. 2001 Aug;30(4):668-77
references.pmid: 11511581
references.citation: FASEB J. 2014 Jan;28(1):4-13
references.pmid: 24056086
references.citation: Front Neuroendocrinol. 2005 Sep;26(2):85-102
references.pmid: 16083951
references.citation: Neuroscience. 1997 Dec;81(3):689-97
references.pmid: 9316021
references.citation: Neuroscience. 2009 Aug 4;162(1):195-207
references.pmid: 19401219