Sex Differences in Brain and Behavior

Experience Days for Children

  • The School of Psychology conducts experience days for primary school children during every half-term holiday.

  • These days work as an outreach program to engage young students and provide valuable data collection for research purposes.

  • The program is looking for volunteers interested in research and working with children; those interested can inquire via the provided QR code.

Congenital Adrenal Hyperplasia (CRH)

  • Our last lecture covered individuals with Congenital Adrenal Hyperplasia (CRH), a genetic condition leading to increased testosterone levels due to adrenal gland activity. This condition offers insights into hormonal influences on development.

  • In 46 XY embryos, the effect of CRH may be minimal if testosterone levels are already within the typical male range.

  • However, 46 XX embryos with CRH experience significantly elevated testosterone levels, leading to virilization, which provides a natural model to study the effects of androgens on development.

Question: 46 XX Female with CRH Assigned Male at Birth

  • If assigned male at birth, it's typically due to male-appearing external genitalia; however, internal genitalia remain female (ovaries, uterus, fallopian tubes).

  • The extra testosterone from CRH maintains the Wolffian system but does not fully suppress the Mullerian system, leading to mixed internal anatomy.

  • These individuals, though living as males, are typically infertile because they possess ovaries, a uterus, and fallopian tubes alongside some male internal genitalia.

5-Alpha Reductase

  • 5-alpha reductase is the enzyme that converts testosterone to DHT (dihydrotestosterone), crucial for male genitalia development during early development.

  • At puberty, high testosterone levels can interact with androgen receptors, specifically DHT receptors, to further develop the penis and scrotum.

  • It’s important to differentiate between 5-alpha reductase deficiency and CRH; the adrenal gland does not produce more testosterone in 5-alpha reductase deficiency, whereas in CRH, it does, leading to different developmental pathways.

Gender Differentiation and Brain Development

  • Discussion of gender differentiation during development, deviations from typical patterns, and their consequences, focusing on the role of prenatal testosterone levels.

  • The discussion shifts from bodily differentiation to brain differentiation, emphasizing that the brain itself undergoes sex-specific differentiation during development.

  • Acknowledging clear, repeatable statistical sex differences in brain structure, brain function, and behavior.

  • Behavior is viewed as a function of the brain, linking neural substrates to observable actions.

Sources of Sex Differences

When seeking the origins of sex differences, particularly in humans, consider these areas:

Hormones

  • Hormones, differing between sexes, can significantly influence brain and behavior, as seen during development and puberty, leading to both organizational and activational effects.

Genetics

  • Genetic differences (XX vs. XY chromosomes) and their effects on the brain can contribute to sex differences, particularly traits requiring two X chromosomes or Y chromosome genes. These genetic underpinnings can influence neural development and function.

Environment

  • Environmental influences significantly impact the brain and behavior, potentially more than hormones or genetics. Cultural and social environments can lead to behavioral differences between sexes, which, in turn, can affect brain structure and function.

  • Example: Hair length is cited as a culturally determined behavior, with statistical sex disparities not rooted in genetics or hormones.

  • The behavior changes the brain.

  • Example: Professional musicians exhibit brain differences due to constant practice, indicating neural plasticity.

  • Example: London taxi drivers develop larger posterior hippocampi due to memorizing city maps, confirmed by studies tracking brain changes during training.

  • Cultural norms imposing behavioral differences between sexes can result in brain differences. Differences in the brain do not always mean they are due to genetics or hormones; they can be due to environmental factors such as cultural and social environments.

Considerations

  • When observing sex differences, consider potential sources, including genetics, hormones, and environmental factors, to provide a comprehensive understanding.

Mouse Studies: Separating Genetic and Hormonal Effects

  • In mice, the cultural component can be minimized, allowing for separating hormonal from genetic influences on sex differences. Researchers use the "four core genotypes" to separate the SRY gene from the Y chromosome.

Experimental Setups

  • Typical female mouse: ovaries, low testosterone, and female genes.

  • Modified mouse (SRY removed): ovaries, no early testosterone, but other Y-chromosome genes are present.

  • XX with added SRY: Genetically female but with testes and testosterone.

  • XY with added SRY: Testes and testosterone, replicating natural males.

Insights

  • This manipulation reveals sex differences due to early testosterone or independent of testosterone. Demonstrates that some sex differences are purely genetic, others are purely hormonal, and many involve interactions between the two.

Genetic Manipulation - Crispr CAS9

  • Genetic manipulation in mice has become very standard using Crispr Cas9, a revolutionary gene-editing technique.

  • Crispr CAS9 comprises enzymes that can cut DNA in a specific place by giving them the right guide mRNAs.

  • Amazing what they can do these days, but not with every animal.

  • People are now doing human gene therapy for people that have specific genetic disorders, and it's starting to work, offering potential cures for previously untreatable conditions.

Human Studies: Leveraging Natural Variations and Transitions

  • Ethical constraints prevent experimental genetic manipulation in humans. Instead, researchers study conditions like complete androgen insensitivity syndrome (CAIS) and congenital adrenal hyperplasia (CRH) to discern hormonal and genetic effects.

  • In CAIS, individuals have XY chromosomes but no sensitivity to testosterone, allowing researchers to identify traits due to XY chromosomes. In CRH, 46 XX individuals with high testosterone levels during development help differentiate traits due to genes vs. hormones.

  • Studying individuals undergoing hormone transitions offers insights into activation vs. organizational roles of hormones, further clarifying hormonal influences.

Caveats

  • These human conditions are not perfect experimental situations and are often confounded, especially regarding cultural and social environmental influences, complicating interpretations.

Behavioral Differences

  • Boys and girls have different toy preferences, suggesting early divergence in behavior. These preferences are often studied to understand the influence of hormones and socialization.

Monkey Study

  • A slightly controversial study involving vervet monkeys showed male monkeys tended to pick up the cars, and female monkeys picked up the dolls to play with, suggesting innate preferences that align with sex.

CRH Study

  • 46 XX individuals with CRH tend to have more masculine toy preferences, providing further evidence that androgen levels can influence behavior.

  • 46 XY individuals with androgen insensitivity syndrome tend to play with girls' toys, highlighting the role of androgen sensitivity in toy preference.

Play Style

  • Prenatal testosterone levels have also been correlated with play style. Females tend to be more feminine-typical, and males tend to be more masculine-typical, reflecting hormonal effects on behavior.

Mental Rotation

  • Spatial mental rotation involves mentally rotating objects to determine if they are the same or different. On average, men are slightly faster than women at this task.

  • 46 XX individuals were also faster than the 46 individuals.

Correlation

  • It increases after puberty, suggesting that maybe the testosterone at puberty also influences it. Experience plays a huge role; if boys are limited in the types of toys they play with, they tend to play more with toys that are more spatial. Whereas girls might play more across with different things than boys, they might have more experience with rotating things in space and, therefore, might get better at it from experience purely rather than from any kind of hormonal effect.

Structural Sex Differences in the Brain

  • Male brains are larger, even when adjusted for body size, which is a consistent finding across studies.

  • Female brains have a thicker cortical layer, potentially resulting in a similar total number of neurons.

  • Males have larger white matter volume (axons), facilitating efficient communication between brain regions.

  • Females have a larger corpus callosum (axons connecting the two hemispheres) which plays a role in interhemispheric communication. Sex differences are set up during embryonic development, influenced by hormones and environment throughout life.

  • But, it could be both the hormones and the environment since they have lived their whole lives being a woman.

Typical Sex Differences

  • In most traits, sex differences are statistical and population-level, not absolute. There is considerable overlap between sexes, highlighting individual variability.

Sexual Orientation

  • Sexual orientation is one of the most extreme sex differences that arises during development, influencing partner preference and behavior more broadly.

Stats

  • 90-95% of human males were giant a file (interested in being partnered with or having sex with a female).

  • Rafael (being interested in a romantic relationship). That is the better term should have used. Yeah, romantic relationship and or sex with a male.

  • Males as a population, there's more exclusive China files and are exclusive under files in females. If you look at the distribution, they look a bit like this.

SC and the Supercharismatic Nucleus

  • It is larger in Andrew file individuals. The biological clock.

H3

  • A nucleus that is somewhere in the hypothalamus, that's smaller and under five individuals.

Anterior Commissure

  • Another set of axons that runs between the two hemispheres, larger and under five individuals, larger in most females than males, but it turns out also larger and under file males.

  • I'd like to know if you're presented and maybe I biased you by now, but if you're presented with evidence that there are brain differences that map onto correlate with what sexual orientation you are, whether you're interested in male partners or in female partners, does that make you more likely to believe that sexual orientation has a biological basis?

Sources of Sex Differences

  • Cultural effects, hormonal effects. And I've split them here by activation or organizational effects, which you now know what that means or genetic effects. Yeah. Those are the four potential causal routes into any sex difference.

  • Is there any evidence that sexual orientation is experiential or cultural?

  • There's no good evidence for it, for sexual orientation. Most people, and I don't mean everybody feels that their sexual orientation, once they started thinking about it because, you know, small children usually don't even think about sexual orientation, has always been the same. They may have struggled with what is it, but it didn't just flip flop at some point.

Sheep

  • In sheep, about 8% of male sheep are other male sheep.

  • There's no way that cultural environment has any effect on these sheep's sexual orientation.

  • When we look in their brains, we do find that the male-oriented male sheep have a smaller sexually dimorphic nucleus, and the sexually dimorphic nucleus is called sexually dimorphic nucleus because it's bigger in males and females, in rats and sheep and any mammals they've looked at.

  • We also know from rat studies that the size of this STN is influenced by testosterone levels during embryonic development.

  • It is purely correlational because there's nothing that says the SDM is actually responsible for the sexual orientation. It just correlates. We do know that the testosterone is responsible for the SDM, but we don't have the link from that to the