lecture 19 - the genetics of sex differences in behaviour Flashcards
(32 cards)
Why study sex differences?
- Relevant to everyone
- Relevant to many different
areas of psychology eg most adults in prison are males, developmental psychology - Most brain disorders show
some sort of sex bias
Sex and Gender
Sex differences: ‘variations in biology between men and
women’
Gender differences: ‘differences between men and women,
both in terms of biology and self-representation as male or
female (or both/neither), as shaped by the environment’
studying sex differences is challenging as theres a wide variety of sex chromosome variants out there and people can differ in their levels of hormones and its very complicated to define sex, its very difficult or even more difficult to define gender
artistotle
‘Woman is |more compassionate than man|, more easily
moved to tears, at the same time is more jealous, more
querulous, more apt to scold and to strike. She is,
furthermore, |more prone to despondency| and less hopeful
than the man, more void of shame or self-respect, more false
of speech, more deceptive and of |more retentive memory|’
Aristotle, Historia Animalium
‘Do you not know I am a woman? |When I think,
I must speak’|
William Shakespeare, As You Like It
most of it is nonsense but elements of truth to the parts with lines around
on average
Generally, male and female behaviour and cognition is equivalent
However, on average, there are some notable sex differences :
Miller and Halpern (2014) TICS 18(1): 37-45
- Language acquisition - Age of 2.5 /3 female vocab double size of males
- Physical aggression - Males higher in aggression and behavioural disinhibition
- Behavioural disinhibition
- sexual preference - vast majority of males will be exclusively or predominantly sexually attracted to females and majority of females will be predominately or exclusively attracted to males
On average …
Females>males on tasks:
* requiring rapid access to, and use of,
phonological and semantic information in
long-term memory
* requiring production and comprehension of
complex prose
* assessing fine motor skills
* assessing perceptual speed
More ‘cross-talk’ between hemispheres: greater Redundancy - so if a male and a female suffer the same severity of unilateral stroke on one side of the brain the females cognitive function will tend to be less impaired than the males because their cognitive resources are more evenly dirstributed across both hemispheres of the brain whereas in males cognitive resources tend to be more lateralised. so damage to one side of the brain has more profound effects in males and the recovery from stroke tends to be worse on average.
females can also discriminate better between two slightly different stimuli so their sense of persception is slightly better than males also can discriminate between two smells better than males
Males>females on tasks:
- requiring transformations in
visuospatial working memory eg showed someone a 3D shape and asked them to imagine what it looks like rotated males tend to be better at those sorts of tasks - assessing motor skills involved in aiming
- involving spatiotemporal responding
- involving fluid reasoning especially in abstract scientific/ mathematical domains
males show greater variablity in IQ than females
mean IQ of males and females is the same = 100
more variability in males as there is an excess of males down at the lower end of IQ at below 70 but there is also an excess of males at higher end of IQ range of about 130
Males also show greater variability in brain size
Sex differences in brain structure
- Male brain bigger from 2 weeks of age (more cortical neurons more glutamatergic cortical neurons , Kelava et al., (2022)
Nature 602:112-116); female brain has a more developed neuropil early on in life
neuropil = bits of the brain which are relavelively depleted for cell bodies but are enriched for synaptic connections - Female brain matures more rapidly
- Females have a larger Wernicke’s area (involved in comprehension of communication) , orbitofrontal cortex (involved in assessing the rewarding or punishing values of particular stimuli is particularly important in social function, inhibiting your brain), corpus callosum (why have greater hemispheric redundancy),
hippocampus. Males have larger amygdala (involved in fear response processing and understanding comprehension of fear in other individuals) , fronto-medial cortex - Male brain wired ‘front-to-back’; female brain wired
‘left-to right’ - might explain why females have a greater degree of hemispheric redundancy - Sex differences in brain function e.g. fMRI
Ingalhalikar et al (2014) PNAS 111(2):823-828
Many sexually dimorphic brain regions regulate sex-specific physiology/behaviour
e.g. regions of hypothalamus regulate hormonal control of:
* sexual attraction
* ovulation
* pregnancy
* milk letdown
* vaginal contraction during birth
* mother-offspring bonding/suckling
* social & affiliative behaviours
* reactivity to stress
Key issues in sex differences research
- Small effect sizes with considerable overlap
- Temporal specificity - differences early in life but at adult hood differences no longer present
- Effects of menstrual cycle
- Differences in test performance modulated by context - conforming to sex specific stereotypes if told going to be identified by sex
- Studies in model organisms generally use males - assumption was that females have menstrual cycle constantly changing their behaviour it would be very variable so people tended to focus on males but it doesnt have that big of an effect and males have a testosterone hormonal cycle - both are used now
- Differences in brain structure do not necessarily predict behavioural differences
- ‘Differences are not deficiencies’ (Diane Halpern, former APA President)
- Most psychological studies performed in WEIRD (Western, Educated, Industrialized, Rich
and Democratic) populations
physical differences between sexes
Differences supported by evidence may be used to support prejudicial beliefs and
discriminatory actions against one sex
* Differences may arise due to social conditioning or ascertainment/selection bias
head of Harvard said females have less intrinsic aptitude for science than men - taking the idea that on average men outperform females on tasks of abstract scientific reasoning and saying women are worse than men but in science some aspects women are better than men and some men are better than women
barbie in 2000s that said maths class is hard - social factor
it’s not all nurture: some brain sex differences may be
hard-wired and present across species
studies -
- sexually dimorphic gene expression in mouse brain precedes gonadal differentiation - theres differences in gene expression in mammalian brains
- sex differences in rhesus monkey toy preferences parallel those of children - male monkeys prefer playing with the truck and the female monkeys prefer playing with the doll - makes sense in terms of evolution for females but why male monkeys are interested in trucks is uncertain could be to do with the wheels
Sex differences in neurodevelopmental and psychiatric disorders
- Prevalence
(biology/ascertainment?) - ADHD is four time more commonly diagnosed in males than in females, autism with learning disability is 3 times more common in males, autism without learning disability is 10 more commonly diagnosed in males, dependency disorders also more common in males but when females are diagnosed with these disorders they tend to progress through addiction much more rapidly than males, females are diagnosed more frequently with affective disorders eg anxiety, panic disorders, depression, PTSD - may be biological component or social or environment reasons - Age-at-onset - Sz develops late teens / early twenties in males and late 20s and early 30s in females
- Disorder subtypes
and co-morbidities - for ADHD females with it will tend to present co-morbidities with anxiety, depression etc and males with externalising disorders, aggressive disorders, conduct disorders, oppositional defiant disorder - Clinical course - clinical course in sz is more severe in males than females
- Underlying neurobiology
- Response to therapy - antidepressants activity can be modulated by sex differences in the acidity of the stomach, sex differences in transit time, females have more adipose tissue, more fat tissue in their body where the drug can be stored and released, sex differences in the expression of enzymes in the liver that metabolise drugs like antidepressants - all these factors influence the extent to which drugs are metabolised in the body and the extent to which they work to alleviate the symptoms of conditions like depression
prevalence rates of particular psychological conditions can also be affected by Ascertainment bias/differential rates of diagnosis
- More overt and disruptive behaviours - eg males with autism are more aggressive and disruptive in class so this may be identified by parents and teachers.
- Closer conformation to the diagnostic norm - when people like connie and Asperger were defining what autism is that were doing so on the basis of largely male bias samples so you will overdiagnose males relative to females \
- More abstract (i.e. noteworthy) obsessions - Males with autism may have more odd obsessesions eg trainspotting that stand out whereas in females this is not the case as much there obsessions may be celebrities which doesnt stand out as much
- More effective ‘masking’ strategies in females - change their behaviour in order to fit in with their neurotypical peers
Mechanisms underlying sexual differentiation of the brain
Sex differences in brain/behaviour must
ultimately be due to differences in sex
chromosome complement
Three differences between the sexes:
* Y chromosome in males only
* Two X’s in females vs. one in males
* Parental origin of X’s
male
X (always from mum)
Y (always from dad)
female
X (from mum)
X (from dad)
Nettie stevens
geneticist that discovered sex is determined by XX AND XY chromosome . discovery was falsely credited to her colleague E.B Wilson. Stevens published her paper first and her work was eventually shown to be more correct but for years she was described as a ‘lab technician’.
the human X and Y chromosomes
X chromosome
* ~155 million basepairs in size
* Contains ~1500 genes, many involved in neurodevelopment
- average size chromosome
- enriched for genes important in brain development and brain function - theres a diproportionate number of genes on X chromosome that are expressed in the brain at some point to the Y chromosome
https://www.nature.com/articles/s41593-021-00890-w
Y chromosome
* ~60 million basepairs in size
* Contains ~350 (pseudo)genes; 78 protein-coding
- third of size of X chromosome
* Most genes involved in sperm production; some expressed in brain
a high density of X-lined genes for general cognitive ability - a run-away process shaping human evolution?
Male-limited expression of genes on Y chromosome
- SRY (Sex-determining Region on Y) can influence brain development/function indirectly via
gonadal hormones - fundamentally causes differences between males and females
- The gene was identified as the testis-determining factor in the early 1990s:
- XY, XXY and XXXY subjects all male
- Sry-transgenic XX mice sterile males - these mice looked like males but were sterile, had testes and bigger than females - proof that the SRY gene that confirmed maleness
- Translocation of part of Y chromosome containing SRY to X chromosome can cause XX
male syndrome - Rare XY females with mutations of SRY so it doenst work properly (Swyer syndrome) so they appear as females
what does SRY do
- SRY expression during embryogenesis causes bipotential gonads to differentiate into testes rather than ovaries
- Androgens (testosterone) secreted from Leydig cells of the testis following stimulation by
luteinising hormone from pituitary gland which is then metabolised to more potty forms like Dihydrotestosterone
testosterone circles in the blood of males it binds to androgen receptors within the cells of target tissues and once it binds that complex then moves to the nucleus of those cells where it can regulate gene expression. within the cells in these target tissues things like prostate glands, various aspects, various regions of the brain etc can initiate a program of gene expression which confer sort of maleness in those tissues
Main pathway in humans
Testosterone —-
- via 5(alpha) -reductase to Dihydrotestosterone (DHT)
- Estradiol
- Androgen receptors in
target tissues
Dihydrotestosterone (DHT) links to –
Androgen receptors in
target tissues which links to
Brain gene expression changes via
‘Masculinisation’
Estradiol links to –
Oestrogen receptors in
target tissues which links to Brain gene expression changes
diagram in notes - clearer
androgens
Androgen receptors are highly concentrated in sexually dimorphic brain regions e.g.
amygdala, medial pre-optic area, paraventricular nucleus, anteroventral periventricular
nucleus, temporal cortex
Androgens can affect masculinisation:
* in critical pre- and perinatal periods (organisational effects = growth effects that tend to happen early on in life whereby the gross structure of the brain is est so these organisational effects tend to be large and irreversible, makes gross structure of brain different in males to females):
- genital virilization (4-6 weeks gestation),
- gender determination (2nd trimester),
- increase <4-6 months postnatally (unknown function)
- in later postnatal life e.g. during puberty (activational effects where the androgens are transiently expressed and can influence brain structure and brain function more subtly than the organisational effects so can effect things like synaptogenisis and the extent to which you get connectivity between various regions in the brain so the effects are more subtle than organisational effects and can also be reversible)
schematic in notes
The E-S or ‘Extreme Male Brain’ Theory of ASCs (autism spectrum conditions)
- Developed by Simon Baron-Cohen in 1990s
- Males and females differ with regard to
‘systemising’ (S) (understanding how the subcomponents of systems interacted with one another in particular ways to generate a sort of gestalt output eg how football fixtures and football tables worked - males are better) and ‘empathising’ (E) (females are better - understanding that other people have different opinions and different views and might potentially act different to you)
behaviours (and underlying neural substrates) - in autism people tended to present an extreme version of these differences
- in autism people tended to present an extreme version of these differences
Autism posited to represent an extreme of the male pattern (impaired empathising,
enhanced systemising)
Simon developed a questionnaire called the autism quotient to assess these sort of behaviours - females have high empathising scores and low systematising scores and males have high systematising scores and lower empathising scores
Simon thought people with autism are exposed to factors that normally confer maleness during development. Thought people with autism exposed to high level of androgens during development. he tested this in a few ways.
simons tests
-Some evidence that in utero testosterone levels may correlate with later male behaviours
and autistic traits
* However, indirect measures (2D:4D finger length ratio) or small sample sizes from amniotic
fluid samples
- in males the ring finger is longer than the index finger and in females they are roughly the same length due to the function of the fact that you have different concentrations of the androgen receptors in each of those fingers and the fingers grow at different rates depending upon their exposure to androgens during early life
- the more extreme the 2D to 4D ratio the higher the levels of testosterone and androgens you’ve been exposed to during prenatal life
- he found that people with autism had a particularly low 2D to 4D ratio indicating that potentially they had been exposed to particularly high levels of androgens prenatally which was consistent with his idea
- Genes involved? - also evidence that you can see an association between autism and genetic variance within genes which are important in the metabolism, production, reception of androgens - support Simon’s ideas
As levels of testosterone exposed to prenatally increased so did level of autistic traits
another study he did was he took some mothers who were about to give brith and they were undergoing amniocentesis so they took samples of amniotic fluid from these pregnant mums and looked at testosterone levels and waited for the mums to give birth and the kids to grow up then assessed the kids for autistic traits and found that the levels of testosterone that the kids were exposed to prenatally increased the levels of autism related traits during childhood
- positive correlation between amount of testosterone exposed to prenatally and level of autistic traits consistent with idea that exposure to high levels of androgens prenatally might predispose you to autism/ autism related traits
issues with interpreting this
- population of women undergoing aminocentisis tend to be slightly older than normal and that tends to be a risk of having children with chromosomal abnormalities so whether these findings can be generalised to the population is open to debate
Experiments in guinea pigs in 1950s (castration/supplementation) gave rise to the dogma
that:
‘gonadal hormonal factors are chiefly
responsible for sexual differentiation of
the brain’
- if you take a male guinea pig and chop off its testicles, it reduces its levels of androgens and then it tends to become less aggressive and tends not to be as interested in bouncing females, etc
- if you take a female guinea pig inject it with a testosterone tend to become more aggressive, start to ,mate with females etc
* New data have suggested that sex-linked genes may act directly on the brain and
contribute to sexually dimorphic phenotypes independently of hormones
‘Gynandromorphic birds’
genes are also important and they have direct impacts on brain function
‘Gynandromorphic birds’ - the zebra finch it’s right half of its body has the male characteristic plumage there has got a little Testicle and in his head has a male song socket in its brain but the left-hand side of the body has typical female plumage found, has a little ovary and in its brain on the left hand side has female specific circuit - every cell in this birds body is surrounded by the same level of hormones so it’s not hormones that are explaining these sex differences - but on male side of body cells have bird equivalent of XY chromosome and other side has bird equivalent of XX - so implied it must be the chromsomes and genes on those chromosomes that are directly influencing the biology and presentation of the bird
