What does science really say about sex differences?
Oxytocin, a humane and feminine hormone
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Some research
Sex influences on the neurobiology of learning and memory.
Andreano JM, Cahill L.
Learn Mem. 2009 Mar 24;16(4):248-66. Print 2009.
Center for the Neurobiology of Learning and Memory, Department of Neurobiology and Behavior, University of California, Irvine, CA 92697-3800, USA.
In essentially every domain of neuroscience, the generally implicit assumption that few, if any, meaningful differences exist between male and female brain function is being challenged. Here we address how this development is influencing studies of the neurobiology of learning and memory. While it has been commonly held that males show an advantage on spatial tasks, and females on verbal tasks, there is increasing evidence that sex differences are more widespread than previously supposed. Differing performance between the sexes have been observed on a number of common learning tasks in both the human and animal literature, many neither purely spatial nor verbal. We review sex differences reported in various areas to date, while attempting to identify common features of sexually dimorphic tasks, and to place these differences in a neurobiological context. This discussion focuses on studies of four classes of memory tasks for which sex differences have been frequently reported: spatial, verbal, autobiographical, and emotional memory. We conclude that the female verbal advantage extends into numerous tasks, including tests of spatial and autobiographical abilities, but that a small but significant advantage may exist for general episodic memory. We further suggest that for some tasks, stress evokes sex differences, which are not normally observed, and that these differences are mediated largely by interactions between stress and sex hormones.
Sex-linked neuroanatomical basis of human altruistic cooperativeness
Yamasue H, Abe O, Suga M, Yamada H, Rogers MA, Aoki S, Kato N, Kasai K.
Cereb Cortex. 2008 Oct;18(10):2331-40. Epub 2008 Jan 29.
Department of Neuropsychiatry, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
Human altruistic cooperativeness, one of the most important components of our highly organized society, is along with a greatly enlarged brain relative to body size a spectacular outlier in the animal world. The "social-brain hypothesis" suggests that human brain expansion reflects an increased necessity for information processing to create social reciprocity and cooperation in our complex society. The present study showed that the young adult females (n = 66) showed greater Cooperativeness as well as larger relative global and regional gray matter volumes (GMVs) than the matched males (n = 89), particularly in the social-brain regions including bilateral posterior inferior frontal and left anterior medial prefrontal cortices. Moreover, in females, higher cooperativeness was tightly coupled with the larger relative total GMV and more specifically with the regional GMV in most of the regions revealing larger in female sex-dimorphism. The global and most of regional correlations between GMV and Cooperativeness were significantly specific to female. These results suggest that sexually dimorphic factors may affect the neurodevelopment of these "social-brain" regions, leading to higher cooperativeness in females. The present findings may also have an implication for the pathophysiology of autism; characterized by severe dysfunction in social reciprocity, abnormalities in social-brain, and disproportionately low probability in females.
Oxytocin, sexually dimorphic features of the social brain, and autism.
Yamasue H, Kuwabara H, Kawakubo Y, Kasai K.
Psychiatry Clin Neurosci. 2009 Apr;63(2):129-40.
Department of Neuropsychiatry, Graduate School of Medicine, University of Tokyo, Tokyo, Japan. yamasue-tky@umin.ac.jp
The common features of autism spectrum disorder, a highly heritable representative pervasive developmental disorder with significant heterogeneity and multiple-genetic factors, are severe dysfunction in social reciprocity, abnormalities in social brain regions, and disproportionately low probability in the female gender. Concomitantly, certain domains of mental function, such as emotional memory and social reciprocity, show a significant sex difference. In addition, recent neuroimaging studies have shown significant sexual dimorphisms in neuroanatomical correlates of social cognition. Recently, some sexually dimorphic factors, including oxytocin, vasopressin, and genes linked with the x-chromosome, have received attention because of their possible contribution to mental development especially in the social cognitive domain. Taking this evidence together, it is hypothesized that a sexually dimorphic factor associated with social reciprocity could affect characteristics of autism spectrum disorder including dysfunction in social reciprocity, abnormalities in social brain regions, and disproportionately low probability in female gender. This review article overviews sexual dimorphisms in clinical features of autism spectrum disorder, in normal social cognition, and in social brain function and structure. The association of oxytocin with sexual dimorphisms, social reciprocity, neural correlates of social cognition, and the pathogenesis of autism spectrum disorder were further summarized. Recent studies have suggested that oxytocin plays a role in social attachment in experimental animals, in enhancing social interactive ability in human adults, and in the pathogenesis of autism spectrum disorder. Thus, the ongoing accumulated evidence suggests that oxytocin deserves to be examined as a candidate that causes the sexually dimorphic aspect of human social reciprocity, social brain development and the pathogenesis of autism spectrum disorder.
Brain sex differences and hormone influences: a moving experience?
Tobet S, Knoll JG, Hartshorn C, Aurand E, Stratton M, Kumar P, Searcy B, McClellan K.
J Neuroendocrinol. 2009 Mar;21(4):387-92. Review.
Sex differences in cell positions in the developing hypothalamus, and steroid hormone influences on cell movements in vitro, suggest that cell migration may be one target for early molecular actions that impact brain development and sexual differentiation.
Females follow a more "compact" early human brain development model than males. A case-control study of preterm neonates.
Vasileiadis GT, Thompson RT, Han VK, Gelman N. Pediatr Res. 2009 Nov;66(5):551-5.
The cerebral volume and the cortical folding area (FA), defined as the surface area of the interface between cortical gray and white matter, were compared between males and females. Females had smaller cerebra than males even after removing the influence of overall size differences between the subjects. The cortical FA increased in relation to volume by a power of 4/3 in both groups. Females had larger cortical FA compared with males with similar cerebral volumes. The study provides in vivo evidence of sexually dimorphic early human brain development. The relatively more "compact" female model may well relate to sex differences in neural circuitry and cognitive domains.
It is not all hormones: alternative explanations for sexual differentiation of the brain.
Davies W, Wilkinson LS. Brain Res. 2006 Dec 18;1126(1):36-45. Epub 2006 Nov 13.
The Babraham Institute, Babraham Research Campus, Babraham, Cambridge CB2 4AT, UK. william.davies@bbsrc.ac.uk
Males and females of many species differ with regard to neurodevelopment, ongoing brain function and behavior. For many years, it was assumed that these differences primarily arose due to hormonal masculinization of the male brain (and to a lesser extent hormonal feminization of the female brain). Recent elegant experiments in model systems have revealed that, while gonadal hormones undoubtedly play an important role in sexual differentiation of the brain, they are not the only possible mechanism for this phenomenon. In the present review, we discuss the concept that genes residing upon the sex chromosomes (which are asymmetrically inherited between males and females) may influence sexually dimorphic neurobiology directly, and suggest possible mechanisms. Future work will be directed towards understanding the extent and specificity with which sex-linked genes and hormones define brain structure and function, and towards elucidating potential interactions between the two mechanisms. Ultimately, it is hoped that such studies will provide insights into why men and women are differentially vulnerable to certain mental disorders, and will enable the development of effective sex-tailored therapeutics.
also see
The organizational-activational hypothesis as the foundation for a unified theory of sexual differentiation of all mammalian tissues.
Arnold AP. Horm Behav. 2009 May;55(5):570-8.
PET and MRI show differences in cerebral asymmetry and functional connectivity between homo- and heterosexual subjects.
Savic I, Lindström P.
Proc Natl Acad Sci U S A. 2008 Jul 8;105(27):9403-8. Epub 2008 Jun 16.
Stockholm Brain Institute, Department of Clinical Neuroscience, Karolinska Institute, 171 76 Stockholm, Sweden. ivanka.savic-berglund@ki.se
Comment in:
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Proc Natl Acad Sci U S A. 2008 Nov 11;105(45):E82; author reply E83.
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Proc Natl Acad Sci U S A. 2008 Nov 18;105(46):E86.
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Proc Natl Acad Sci U S A. 2008 Jul 29;105(30):10273-4.
Cerebral responses to putative pheromones and objects of sexual attraction were recently found to differ between homo- and heterosexual subjects. Although this observation may merely mirror perceptional differences, it raises the intriguing question as to whether certain sexually dimorphic features in the brain may differ between individuals of the same sex but different sexual orientation. We addressed this issue by studying hemispheric asymmetry and functional connectivity, two parameters that in previous publications have shown specific sex differences. Ninety subjects [25 heterosexual men (HeM) and women (HeW), and 20 homosexual men (HoM) and women (HoW)] were investigated with magnetic resonance volumetry of cerebral and cerebellar hemispheres. Fifty of them also participated in PET measurements of cerebral blood flow, used for analyses of functional connections from the right and left amygdalae. HeM and HoW showed a rightward cerebral asymmetry, whereas volumes of the cerebral hemispheres were symmetrical in HoM and HeW. No cerebellar asymmetries were found. Homosexual subjects also showed sex-atypical amygdala connections. In HoM, as in HeW, the connections were more widespread from the left amygdala; in HoW and HeM, on the other hand, from the right amygdala. Furthermore, in HoM and HeW the connections were primarily displayed with the contralateral amygdala and the anterior cingulate, in HeM and HoW with the caudate, putamen, and the prefrontal cortex. The present study shows sex-atypical cerebral asymmetry and functional connections in homosexual subjects. The results cannot be primarily ascribed to learned effects, and they suggest a linkage to neurobiological entities.
Brain response to putative pheromones in lesbian women
Berglund H, Lindström P, Savic I.
Proc Natl Acad Sci U S A. 2006 May 23;103(21):8269-74. Epub 2006 May 16.
Department of Medicine, and Stockholm Brain Institute, Karolinska University Hospital, Karolinska Institutet, 171 76 Stockholm, Sweden.
Erratum in:
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Proc Natl Acad Sci U S A. 2006 Jul 18;103(29):11098.
The progesterone derivative 4,16-androstadien-3-one (AND) and the estrogen-like steroid estra-1,3,5(10),16-tetraen-3-ol (EST) are candidate compounds for human pheromones. In previous positron emission tomography studies, we found that smelling AND and EST activated regions primarily incorporating the sexually dimorphic nuclei of the anterior hypothalamus, that this activation was differentiated with respect to sex and compound, and that homosexual men processed AND congruently with heterosexual women rather than heterosexual men. These observations indicate involvement of the anterior hypothalamus in physiological processes related to sexual orientation in humans. We expand the information on this issue in the present study by performing identical positron emission tomography experiments on 12 lesbian women. In contrast to heterosexual women, lesbian women processed AND stimuli by the olfactory networks and not the anterior hypothalamus. Furthermore, when smelling EST, they partly shared activation of the anterior hypothalamus with heterosexual men. These data support our previous results about differentiated processing of pheromone-like stimuli in humans and further strengthen the notion of a coupling between hypothalamic neuronal circuits and sexual preferences.
My brain is bigger than yours (and more autistic): Sexual dimorphism of brain developmental trajectories during childhood and adolescence.
Lenroot RK, Gogtay N, Greenstein DK, Wells EM, Wallace GL, Clasen LS, Blumenthal JD, Lerch J, Zijdenbos AP, Evans AC, Thompson PM, Giedd JN.
Neuroimage. 2007 Jul 15;36(4):1065-73. Epub 2007 Apr 6.
Child Psychiatry Branch of the National Institute of Mental Health, NIMH/CHP 10 Center Drive, Bethesda, MD 20814-9692, USA. lenrootr@mail.nih.gov
Human total brain size is consistently reported to be approximately 8-10% larger in males, although consensus on regionally specific differences is weak. Here, in the largest longitudinal pediatric neuroimaging study reported to date (829 scans from 387 subjects, ages 3 to 27 years), we demonstrate the importance of examining size-by-age trajectories of brain development rather than group averages across broad age ranges when assessing sexual dimorphism. Using magnetic resonance imaging (MRI) we found robust male/female differences in the shapes of trajectories with total cerebral volume peaking at age 10.5 in females and 14.5 in males. White matter increases throughout this 24-year period with males having a steeper rate of increase during adolescence. Both cortical and subcortical gray matter trajectories follow an inverted U shaped path with peak sizes 1 to 2 years earlier in females. These sexually dimorphic trajectories confirm the importance of longitudinal data in studies of brain development and underline the need to consider sex matching in studies of brain development.
And now, dangerous science! X-linked genes and mental functioning.
Hum Mol Genet. 2005 Apr 15;14 Spec No 1:R27-32.
Skuse DH.
Behavioural and Brain Sciences Unit, Institute of Child Health, London, UK. dskuse@ich.ucl.ac.uk
The X-chromosome has played a crucial role in the development of sexually selected characteristics for over 300 million years. During that time it has accumulated a disproportionate number of genes concerned with mental functions. Evidence is emerging, from studies of both humans and mice, for a general influence upon intelligence (as indicated by the large number of X-linked mental retardation syndromes). In addition, there is evidence for relatively specific effects of X-linked genes on social-cognition and emotional regulation. Sexually dimorphic processes could be influenced by several mechanisms. First, a small number of X-linked genes are apparently expressed differently in male and female brains in mouse models. Secondly, many human X-linked genes outside the X-Y pairing pseudoautosomal regions escape X-inactivation. Dosage differences in the expression of such genes (which might comprise at least 20% of the total) are likely to play an important role in male-female neural differentiation. To date, little is known about the process but clues can be gleaned from the study of X-monosomic females who are haploinsufficient for expression of all non-inactivated genes relative to 46,XX females. Finally, from studies of both X-monosomic humans (45,X) and mice (39,X), we are learning more about the influences of X-linked imprinted genes upon brain structure and function. Surprising specificity of effects has been described in both species, and identification of candidate genes cannot now be far off.
Is it about reading maps, or about putting yourself in other's shoes? Males and females scan maps similarly, but give directions differently
MacFadden A, Elias L, Saucier D.
Brain Cogn. 2003 Nov;53(2):297-300.
Consistent with earlier research, males made more references to NSEW when giving directions, whereas females referred mainly to left/right turns and landmarks along each route. However, these reporting biases were not related to differences in how the groups explored the maps, as females did not spend more time looking at landmarks, nor did either group spend more time looking at Euclidean cues.
An evolutionary perspective of sex-typed toy preferences: pink, blue, and the brain
Alexander GM.
Arch Sex Behav. 2003 Feb;32(1):7-14.
The epigenetics of sex differences in the brain
McCarthy MM, Auger AP, Bale TL, De Vries GJ, Dunn GA, Forger NG, Murray EK, Nugent BM, Schwarz JM, Wilson ME. J Neurosci. 2009 Oct 14;29(41):12815-23.
Department of Physiology and Program in Neuroscience, University of Maryland School of Medicine, Baltimore, Maryland 21201-1559, USA.
Epigenetic changes in the nervous system are emerging as a critical component of enduring effects induced by early life experience, hormonal exposure, trauma and injury, or learning and memory. Sex differences in the brain are largely determined by steroid hormone exposure during a perinatal sensitive period that alters subsequent hormonal and nonhormonal responses throughout the lifespan. Steroid receptors are members of a nuclear receptor transcription factor superfamily and recruit multiple proteins that possess enzymatic activity relevant to epigenetic changes such as acetylation and methylation. Thus steroid hormones are uniquely poised to exert epigenetic effects on the developing nervous system to dictate adult sex differences in brain and behavior. Sex differences in the methylation pattern in the promoter of estrogen and progesterone receptor genes are evident in newborns and persist in adults but with a different pattern. Changes in response to injury and in methyl-binding proteins and steroid receptor coregulatory proteins are also reported. Many steroid-induced epigenetic changes are opportunistic and restricted to a single lifespan, but new evidence suggests endocrine-disrupting compounds can exert multigenerational effects. Similarly, maternal diet also induces transgenerational effects, but the impact is sex specific. The study of epigenetics of sex differences is in its earliest stages, with needed advances in understanding of the hormonal regulation of enzymes controlling acetylation and methylation, coregulatory proteins, transient versus stable DNA methylation patterns, and sex differences across the epigenome to fully understand sex differences in brain and behavior.
