Men Really are From Mars Women Really are From Venus

hello everyone

thank you for listening to my talk today

so in 1992 a best-selling book was

written by john gray

american author and relationship

counselor the main idea behind this book

was that the most common relationship

problems between men and women

were the result of innate psychological

differences between the sexes

to describe this he used a metaphor men

are from mars

and women are from venus in which he

stated that men and women

come from different planets and that we

are acclimated

to our own planets society and customs

but not to those of the other planet

now one of the topics discussed as to

why men and women come from different

planets

is the idea that we respond to stressful

stimuli

differently a very simple example of

this would be

when stress maybe women want to talk

about our feelings

whereas men may want to be left alone

but as a neuroscientist one of the first

questions that pops into my head

is why what is the biological basis

for these differences in behavior and

this brings me to what i want to talk to

you about today

is the idea that from a fundamental

biological perspective

men and women really are different or to

use the metaphor

men really are from mars and women

really are from venus

and yet we know so very little about

biological sex differences

in behavior health and disease

and this begs the answer to another two

questions

why do we know so little and does it

even really matter

so to begin to answer these questions i

want to talk a little bit

about neuropsychiatric disorders

something i know a little bit about

now the connection may not be

immediately clear but please bear with

me for a moment

so in neuropsychiatry for most of these

disorders

we haven’t exactly done the best job at

finding novel

therapeutic efficacious drugs

oh sure over the past couple decades

we’ve actually done okay

in improving the side effect profile of

these drugs

but in the grand scheme of things they

actually don’t work much better

in improving symptoms let’s take

depression for example

depression is a heterogeneous disorder

that can be very difficult to treat

we have drugs that work some of the time

they have side effects some worse than

others

and they can take a very long time to

work

in those that do respond and in those

that don’t

it can often take many trials with many

different drugs

before we find one that works if we even

find one that works

and let’s not forget that relapse is

always a serious concern

in depression clearly in this case

a one drug fits all strategy does not

work

now in our defense as a pre-clinical

researcher

we try we really really try

we are passionate about what we do we

come to

work every day and with the help of

amazing staff

and fabulous trainees we run our

experiments

looking for mechanisms of disease the

identification

of novel therapeutic targets and we test

the safety

and efficacy of novel compounds

we’re doing everything right

but are we really did you know

that women live longer than men but also

suffer from more chronic illnesses

delayed

diagnoses misdiagnoses

and also suffer from more drug side

effects than men do

let’s go back to our example of

depression

women are twice as likely to develop

depression

and they also suffer from heightened

stress susceptibility

which is a major risk factor for

depression

there’s even evidence to suggest that

men and women respond

to antidepressants differently

so again i have to ask the question

what’s the biological basis for these

differences

well unfortunately i can’t give you that

answer

and the reason that i can’t give you

that answer is because

we simply don’t know and one of the main

reasons that we don’t know

is because historically preclinical

research

which studies mechanisms of disease have

predominantly used

male subjects and this male

centric research is by no means

restricted to depression

now this was a study that examined

10 biological disciplines and what they

were looking for

was how much of this research included

males

females or both

what they found was in eight out of the

ten disciplines

there was a significant male bias

disciplines that included physiology

pharmacology

endocrinology behavior

neuroscience was actually one of the

worst culprits with

five studies done in males for every one

that was done in females now when we

look at the data as a whole

we can see that almost 50 percent of

studies

only use males in their research

19 didn’t even disclose

what sex was being used

25 actually did use both males and

females and they should be applauded

but of these the majority did not even

examine the sex

as an experimental variable

so this study is from 2018 let’s fast

forward

to 2020. see if we’re doing any better

so this study did the same thing where

they looked at

inclusivity of males and females in

research but they focused on

neuroscience studies

both pre-clinical and clinical

so when we look at the pre-clinical

studies in the rats and mice

we’re not doing any better about 75

percent of these studies used either

only males

or they used both sexes but not did not

examine sex

as a significant experimental variable

now the clinical studies did a little

better and that they were

more likely to include both men and

women in their research

but again same problem they did not look

at sex as an important

biological variable so if there are

important sex differences in behavior

health and disease how are we going to

know what they are

if we never actually study it

so this appears to be where we’re at

with the big iceberg representing

what we know about men in health

research in health research

disease and behavior and the small

iceberg representing what we know about

women

so how did we get to this place

how is it that we have focused all our

attention

on the males well there have been a few

assumptions that have been made over the

years that have led us here

the first assumption is that when we

look at our experimental data

females are more variable than males

and this is owed to hormonal variation

across the easter cycle and this jumps

right into the second assumption

that if we use females in our research

they have to be staged

which means that for every parameter

that we look at

we need to know what stage in the easter

cycle

these animals are in now i’m not

up here arguing that female hormones

don’t have biological effects of course

they have biological effects

but guess what male hormones have

biological effects too

and as it turns out recent studies have

shown

that in fact there is little to no

differences

in variability between males

and unstaged females and i’m just going

to give you one example here

so again we’re looking at neuroscience

studies

and here they examined differences in

experimental vari

data variability between males and

unstaged females

across various methodological approaches

and as you can see clearly there is

variability in the females

and it is likely that female hormones

actually contributed to this variability

but males also showed variability

why are we so much less concerned about

what contributes

to this variability

and this leads us to the last assumption

now when we incorporate

females into our research of course we

have to

increase the number of animals that are

used

this does lead to increased costs

but it is assumed that it also delays

progress

but if there are important biological

sex differences

isn’t it important that we know what

they are and if we knew this

wouldn’t this in fact increase

progress

so i’m up here talking to you about

inclusivity

in pre-clinical research and yes

i might talk a good talk but i also walk

the log

and i want to show you some of my own

research which will help

reinforce why we need to use both

sexes now one of the things that

i work on is brain waves

this is electrical activity in the brain

that is critical

to communication both between brain

regions

and within brain regions importantly

these brain wave patterns are highly

coupled

to behavioral states and disease states

and in my research i look at sex

differences in these brain wave patterns

in the context of neuropsychiatric

disorders

now brain waves are made up from various

frequencies

as shown and in our research

we look at sex-dependent effects of

stress

on these brain wave patterns and the

relationship

to the development of depression-like

behaviors

now when we take rats and we expose them

to very mild stressors

over the course of a long period of time

they develop these depression-like

behaviors

but what we notice is that some animals

are susceptible to the stress and so far

as they develop these behaviors

much sooner we call these rats

stress susceptible and they are

different

from those animals that develop the

depression-like behaviors later

which we call stress resilient

so one of the parameters that we can

look at

when examining these brain wave patterns

is something that we call spectral power

and to put it very simply spectral power

is related to the amplitude of the wave

now we when we looked at female animals

that were exposed to these stressors

we saw that those that were stressed

susceptible

actually showed a decrease in theta

power

and an increase in delta power across a

number of regions

in the brain we did not see this

in the females that were stress

resilient

when we looked at the male animals the

first thing we noticed

is that they they took twice as long to

develop these depression-like behaviors

so they were already showing a

resilience to the stress that the

females did not have

however when we compared the susceptible

and the resilient males

we found no stress dependent changes

in these brain wave patterns that could

distinguish between these two groups

so another parameter that we could look

at is something called

coherence and again in very simple terms

this is related to how well

two brain waves synchronize

when we looked at the females we saw a

widespread

decrease in theta coherence across

multiple brain regions in the stress

susceptible

animals only

we did not see this in the stress

susceptible males

in fact when we looked at the stress

susceptible males we found

no brainwave signatures that we could

use to actually identify them

what we did see was a change in the

resilient males when they were exposed

to stress

and this was a widespread increase

in gamma coherence

so what does this tell us it tells us

that even though

males and females may have behaviors

that look

the same the underlying mechanisms

that regulate these behaviors is in fact

different and it gets better

we actually went back in time because we

wanted to see

how these brain wave patterns changed

upon initial exposure to stress

we found that these changes occurred

relatively early

and in fact we could use them to predict

with

high accuracy which animals

were going to develop the

depression-like behaviors

sooner or later so we could identify

the stress-resilient and

stress-susceptible animals

in a sex-dependent way before these

behaviors developed

and what’s even more remarkable when we

looked at the females and the females

only they showed

very unique signatures that we could use

to identify

those animals that were stressed

susceptible or stress resilient

before they were even exposed to the

stress

we were very excited about this because

we thought not

only can we use sex-dependent brainwave

signatures

as biomarkers for established depression

but maybe we can also use them

to identify those that have increased

depression vulnerability and this could

lead to

increased monitoring and early

interventions

as necessary so this brings me to the

end of the talk and if there’s one thing

i hope that you get from that

this is that inclusivity is very

important

and although i’ve spoken about it in the

context of pre-clinical research

it really is important in everything we

do

when we are inclusive we enrich the

lives

of everybody thank you

you