Sex Differences - Pt. 2

Sex differentiation in the brain

• There are structural and functional sex differences in the brain

• These can be due to:

  • Hormones (activational and organizational)

  • Genetics (genes on sex chromosomes)

• Environment (e.g. peers, culture,…)

Sex differentiation in mice - genotypes

·      XXSry Testes

·      XY-Sry Testes

·      XX Ovaries

·      XY- Ovaries

Sex differentiation in mice - gonadal effects

• Sex behaviour,

• LH secretion,

• Aggression

• Nociception

Sex differentiation in mice - Sex chromosome effects

• Habit formation

• Alcohol preference

• Aggression

• Nociception

Measuring sex differentiation in the brain - humans

• No experimental manipulations possible

• Information can be gathered from:

  • Congenital Adrenal Hyperplasia in 46,XX

  • Complete Androgen Insensitivity in 46,XY

o   Hormone treatment in transgender individuals

Measuring behavioural sex differences in the brain

Toy preferences

Evidence for sex-typical toys - monkeys

·      Infant vervet monkeys show sex-typical choices

o   Females played with dolls

o   Males playing with a toy car

Evidence for sex-typical toys - Congenital Adrenal Hyperplasia

46,XX → masculine toy preferences

46,XY → feminine toy preferences

Correlation between play style and prenatal testosterone

Measuring sex differences in spatial perception

Mental rotation tasks

Sex differences in spatial mental rotation tasks

• Men tend to be faster

• CAH 46,XX individuals perform better than non-CAH 46,XX individuals

• CAIS 46,XY individuals are indistinguishable from non-CAIS 46,XX individuals

  Suggests a role of testosterone in spatial mental rotation

Sex differences in spatial rotation and perceptual speed

• CAH 46,XX individuals better at mental rotation

• Non-CAH 46,XX better at perceptual speed

Structural differences in the brain - males

• Male brains are ~ 10% larger

• Males have larger white matter volume & subcortical structures

Structural differences in the brain - females

• Female cortex is thicker (more grey matter)

Structural differences in the brain - CAIS

·      46,XY individuals have some features that are masculine (genetics), and some that are feminine (hormones or environment)

·      Sex differences in the brain are complex and specific, and due to many different causes

Sexual orientation - gynophile

90-95% of human males are attracted to human females exclusively

Sexual orientation - androphile

85-90% of human females are attracted to human males exclusively

Swaab & Hofman 1988

Suprachiasmatic Nucleus (SCN) larger in androphile individuals

Levay 1991

INAH-3 smaller in androphile individuals

Allen & Gorski 1992

Anterior commissure larger in androphile individuals

Conclusion of evidence for sex differences in the brain

• Could be causal to sexual orientation

• Could also be purely correlation, as indicators of other mechanisms (hormonal, genetic)

• Could be consequence of sexual orientation

Experiential/cultural effects on sexual orientation

• Influences on brain development (e.g. what you’re exposed to in childhood)

• Effects of practice (e.g. you are better at what you spend more time doing)

• Social effects (expectations, stereotypes,…)

HOWEVER – little to NO evidence that this affects sexual orientation

Experience and Sexual Orientation

• Most people feel their sexual orientation has always been this way

• No good evidence to support effects of parenting, learning, etc.

• Evidence from other species

Sexual orientation in sheep

• 8% of male sheep are exclusively interested in other males

• Sexually Dimorphic Nucleus (SDN) of preoptic area is smaller in these males

• Size of SDN is influenced by developmental T levels

Activational hormonal effects on sexual orientation

• Prenatal hormones correlate with sexual orientation

• No correlation with sexual orientation in later life, only sexual motivation

Organisational role of hormones on sexual orientation

High T in boys for two periods of development:

• Weeks 8-24 of pregnancy

  • Early: external genitalia

  • Late: brain differentiation

• First 3 months after birth

  • potential further brain differentiation

It is possible that sexual orientation develops during this period

Why is it difficult to test prenatal hormone levels?

Risk factors of sampling amniotic fluid

Measuring prenatal hormone levels

• Correlations with measured prenatal hormones

• Correlations with adult correlates of prenatal hormones

• Conditions with varying prenatal hormone levels

  • Congenital Adrenal Hyperplasia (CAH)

  • Androgen Insensitivity Syndrome

Evaluating evidence for prenatal hormone levels

• Indirect evidence, no longitudinal study (collecting prenatal hormones and tracking the sexual orientation of these individuals later in life)

• Atypical early hormonal development (Congenital Adrenal Hyperplasia): more testosterone, more likely to have different sexual orientation

Verbal abilities and sexual orientation

Better in androphile men than gynophile men

Visuo-spatial performance and sexual orientation

Worse in androphile men than gynophile men

Mental rotation and sexual orientation

• Faster in gynophile women than in androphile women

• HOWEVER, effect of type of play in childhood

2D/4D ratios

The measurement of the length of the index finger (second digit) compared to the length of the ring finger (fourth digit)

Sexual orientation in 2D/4D ratios

• Male: 0.95, Female 0.97

• Early testosterone dependent

• Masculine presenting lesbians have more masculine 2D/4D

Swift-Gallant et al. (2021)

• 2D/4D correlates with gender non-conformity

No consistent finding in androphile men, but may differ between sub-groups

Oto-acoustic emissions

·      When stimulated with a click, ears make a sound back

Sexual orientation and oto-acoustic emissions

·      This is louder and more frequent in women (and females of other species)

·      Early T- dependent in other species

·      Gynophile women’s OAEs closer to gynophile men’s than androphile women’s

46 XY – Androgen Insensitivity Syndrome - sexual orientation

• Look outwardly female

• More likely to be androphilic

• Not being able to respond to testosterone may cause this

46XX - Congenital Adrenal Hyperplasia - sexual orientation

More likely to identify as gynophile.

Summary of evidence for hormonal sexual orientation

Points towards prenatal testosterone as a factor in developing as a gynophile adult.

Twin studies and sexual orientation

Minority sexual orientation

•       Higher concordance in monozygotic than dizygotic twins

•       Estimates from 30-100%

•       Possibly higher concordance for women than men

Indicates genetic effects

Genetic mapping and sexual orientation

Androphilic men often have androphilic maternal uncles

• Suggests an X-chromosome inheritance pattern

• A region of the X-chromosome has been identified as related to sexual orientation

• Regions on other chromosomes have also been identified

Concerns over sexual orientation - evolutionary perspective

Idea that there can’t be a genetic basis of sexual orientation if it is not evolutionarily beneficial.

Explanation for maintaining genes for homosexuality - Heterozygote advantage

Sickle cell anaemia

• One recessive gene for sickle cell anaemia mutation = advantage at fighting malaria.

Explanation for maintaining genes for homosexuality - Kin selection

• If there were a gene that leads to sexual orientation in men, a man who is homosexual may help raise his sister’s offspring

• Gene would stay in population through maternal line.

  • Study shows that people with homosexual siblings have more children.

 

Fraternal birth order effect on sexual orientation

• Odds of having an androphyllic boy increase depending on how many boys a mother has already given birth to.

• Half Ps were homosexual, and half were straight

• Trend was there, and this has been replicated many times.

Maternal immune hypothesis - Bogaert et al., 2017

• Mother’s immune response to protein neuroligin 4 Y-linked

• Predicts probability of having male-oriented son

Gender identity and sex differences

• Larger sex difference than sexual orientation

• Does not seem to be binary

• Childhood gender dysphoria does not always continue after puberty (does for ~40%)

Genetic predispositions to gender dysphoria - Fernández et al. (2018)

• Study in Spain – Transgender individuals vs Cisgender individuals

• (n=2000)

• Particular alleles associated with gender dysphoria

Genetic predispositions for trans women - Fernández et al. (2018)

• Long version of estrogen receptor beta

• Endenacin version of estrogen receptor alpha

Genetic predispositions for trans men - Fernández et al. (2018)

• Short version of estrogen receptor beta

• Long version of androgen receptor

Brain differences in trans women

MtF individuals show more feminine cortical thickness and white matter in some brain areas

Brain differences in trans men

FtM individuals show more masculine basal ganglia and some white matter tracts

Brain differences - cis vs trans

• Some aspects of brain anatomy are similar between trans men and women, but different to cis men and women

Possible that differences are due to difficulty living with gender dysphoria