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