Okay. So now what we’re going
to do is we’re going to
start going a little bit deeper into
each specific state that I talked about.
We’ll start with schizophrenia.
And so we know that schizophrenia
has a very strong genetic link
and you can be genetically
predisposed to this disorder.
So the way we always figure this
out is through twin studies
and we looked at both monozygotic
and dizygotic twins.
And in twin studies, we know
that if one twin has it,
it’s a 50% chance that the other will have
it or some type of form of schizophrenia.
We know that genetics provides
a biological predisposition
and environmental stressors
can elicit the onset.
So, in English,
if it runs in your family,
so if your father or your
mother or your grandfather
or grandparents have it,
it's passed on through genes and you might
be what I like to say is prewired for it.
It doesn’t necessarily mean
you’re going to get it,
but you’re prewired or you have the
predisposition to potentially get it.
And if the appropriate environmental
stressors or triggers are there,
you can initiate the disease
or the onset of the disease.
So there are a lot of debates sort of
in the community around what causes it
and I don’t think anybody
agrees on the exact cause,
but we do agree that there’s
a strong genetic link,
you would be predisposed and there
are things in the environment around
you that might trigger or activate
that expression of the disease.
Now, there’s a dopamine hypothesis of the
disease and when you see terms like this,
what they’re trying to do is
understand and express the underlying
mechanism behind why they think
this disease is being expressed.
This theory is still obviously
up for debate, but it’s been
around for long enough where I
would say there’s merit to it.
And the dopamine hypothesis states that
some of the positive symptoms that
we’re seeing are due to an over
expression or overabundance of dopamine
and you also can have
So even if you have, say, the same
amount of dopamine that you normally do
but the receptors that are going to bind
to the dopamine are hypersensitive,
you would still have an
and along with the hyperactivation
of the temporal lobe.
So collectively, these things
all revolve around dopamine
and this would explain some of the
positive symptoms that we’re seeing.
Now, the negative symptoms are
believed to be linked to the
hypofunctioning of the frontal lobes,
also this something
called brain atrophy,
which is when the brain is actually
smaller than a compared cohort,
and we also have something called
a decrease in convolution.
So convolution is, if you look at an
image of the brain it has all those with
the folds and all that kind of wormy
looking exterior structures of the cortex
that the level of complexity of folding
or convolution is an expression of
complexity or knowledge state, so how
much information is actually there.
So the less convoluted or smooth
the brain is, the worse off it is.
So you want your brain to be
nice and convoluted and folded
because that represents a
higher degree of functioning.
Now, moving on to depression, we’re going
to look at some of the biology behind that.
And to do that, we’re going to have to revisit
this image I’m sure you’ve seen before
in the biology sections or some of the
other modules that we’ve already covered
and we’re looking at what’s
happening at the synaptic
cleft or synaptic junction
between two neurons
and this is outlining the process
of synaptic transmission.
So typically, a chemical, electric
chemical signal is initiating
from a presynaptic neuron, so
what we’re seeing on the top,
and it’s going to pass the signal down
to the receiving postsynaptic side.
So a couple of points that we’re going to
highlight here, we have neurotransmitters,
which are encased in
synaptic vesicles, and these
transmitters can include things
like dopamine, GABA, glutamate.
And when the appropriate
signal comes, which would
be an action potential
coming down in axon,
it would open voltage-gated
and that influx of calcium
would trigger these
vesicles to fuse to
the presynaptic side,
release their contents, which would be
in this case let’s say it’s dopamine,
cause the release of
dopamine, and that dopamine
is going to travel across
the synaptic cleft,
which is the gap between the presynaptic
neuron and the postsynaptic neuron,
and that the transmitter will
interact with a receptor,
and we call those postsynaptic
receptors because of its location.
Once activated, that would open ion channels
and allow the signal then to pass on
and the electrical signal gets converted
down to the postsynaptic neuron.
So this really quickly high overview of the
process of synaptic transmission is what
happens in a quote unquote “normal individual”
or let’s say a non-depressed individual.
in individuals with depression we see that
this process gets altered or gets skewed.
So again, we’re getting back
to genetics, we know that this
driver of depression
is genetically linked.
So if there’s depression
in your family,
in your immediate family members, your
mom, your dad, your brothers and sisters,
the likelihood that you would
get it would be higher
than a matched cohort of individuals who
don’t have it running in their family.
So what’s causing it and
where are we seeing it?
What we’re seeing issues are in the transmitter
levels in certain specific structures of
the brain including the frontal lobe, the
cerebellum, the hippocampus, and few others.
So these are just some of the
large ones that come up,
but we’ll know that there’s an inappropriate
level or amount of either transmitter
or receptor or reuptake of the
neurotransmitter and that’s leading
to some of the issues that we’re
seeing leading to depression.
So there’s the monoamine hypothesis of
the disease and there are three kind of
real monoamines that come up: dopamine,
serotonin, and norepinephrine.
And so, inappropriate levels
of any these or a combination
of these would lead to the
expression of depression.
And so a lot of the antidepressants
that are out there
that have been designed and
formulated and identified
work around the premise of modulating or
reestablishing the appropriate level of either
of these or all of these collectively, so
dopamine, serotonin, and norepinephrine.
So you should definitely know that
for your MCAT, is you need to know
the different transmitters that would be
behind regulating and causing depression.
Alzheimer’s disease is a
disease I would say that is
most highly expressed
in elderly folk
and it’s the most prevalent form of
dementia characterized by memory loss.
So depression is a catchall
term that’s used to
represent a couple of
So, you know, and not to belittle the
disease, but you might hear people saying,
you know, “My grandparent
is losing it,”
or “My parents are losing
and they’re forgetting
things and they don’t
know where they are.
I tell them something one day and
they forget it the next day.”
So that generalized, those generalized
characteristics would outline dementia.
Alzheimer’s is a little
bit more specific
and it is the most prevalent, like
we’re saying, form of dementia.
So anterograde amnesia is one
of the key characteristics
of that and that’s the inability
to form new memories.
So let’s break down that
term anterograde amnesia.
Amnesia I think we all
understand that means
a sort of memory loss
and forgetting things.
So anterograde means that you’re
forgetting things from this point forward
versus, say, something like
retrograde amnesia, where
you’re forgetting things
that you’ve already learned.
So you’re forgetting things that have
happened since where we’re looking right now.
So, we know that Alzheimer’s
is also a cortical disease
affecting the outermost layer
of the brain, the cortex.
The cortex is what we’re mentioning
with the convolution and the folding,
so it’s actually impacting specific
areas on that outer cortex,
which is where we know a lot
of that function happens.
in terms of the pathogenesis of the
disease or what’s causing the disease,
our understanding is
actually still evolving.
And, you know, I was fortunate enough to
actually do some research in the area.
And back even 10, 15 years
ago when this was happening,
there was still the idea of like, "Well,
what’s actually causing the disease?"
So what we’ve at least
collectively agreed upon is that
there’s an increase in the amount and
level of something called beta-amyloid.
And beta-amyloid is a very sticky
substance and it can stick upon itself
and it creates these things
called beta-amyloid plaques
tangles or NTs.
And, you know, for a long time they
weren’t really quite sure what they do,
but the working hypothesis
is that the plaques,
more specifically the tangles create
what we call synaptic clutter.
So if you go back to the previous diagram
that we had of the synaptic junction with
the pre and postsynaptic neuron and the
synaptic cleft and we had transmitter moving,
the idea is these tangles can actually get
in there and get into the cleft and block
and get in the way
and create garbage.
So it prevents the presynaptic neuron to
communicate with the postsynaptic neuron.
So if you imagine one
neuron trying to talk to
the other and you have
something in the way,
that signal will not be able to pass
and therefore you cannot communicate.
Now, let’s imagine in this scenario that
the information being passed is a memory.
So memory is going from the pre to post
and you need to access that memory.
All of a sudden, you have synaptic
clutter or garbage or NTs in the way
that are preventing that from happening,
there goes transmission of that memory.
So you now kind of lost a memory
or aren’t able to form a memory.
So that is sort of the working model
in a real, real brief abbreviated form
of how we think Alzheimer’s is
actually initiated and is expressed.
So abnormalities in the activity of
acetylcholine in the hippocampus,
is where the memory center of the
brain, is also believed to be involved.
So we have a combination of
beta-amyloid and we have an issue
and abnormality in levels of
acetylcholine in the hippocampus.
Okay. So let’s move on to
the Parkinson’s disease
and this is a disease that’s associated
with some movement disorders.
And what’s happening here
is we’re seeing a disorder
because of the death
of a group of cells
that typically generate
the transmitter dopamine,
and there are two specific areas that we’re
talking about, one is the basal ganglia.
So you can see here
the basal ganglia.
It’s fairly deep in the brain, so this
isn’t something you see on the surface,
and we also have something
called the substantia nigra,
two very important structures that are
generating the transmitter dopamine.
And so deficiency in these areas of dopamine
is what’s causing Parkinson’s disease.
we’re going to work through
sort of this figure here.
On the left we have
a healthy patient,
and on the right we have a
patient with Parkinson’s.
So in a healthy patient,
you have the presynaptic
neuron and it would release
dopamine, the dopamine
would be captured by the
cells on the postsynaptic
side and you would have
your typical response.
In a PD patient, you have less dopamine
being released and therefore you’re not
activating enough of the receptors and
you start to see some of the issues.
And some of those symptoms that we’re
talking about are resting tremor,
which is when just sitting there doing
nothing you would see a hand shake,
slow movement, rigidity of
movements especially in the face.
So if you’re trying
to go grab a pen,
it seems like a lot of work to try and just
go grab your pen and it seems quite slow,
and you also have this
rigidity in the face.
So what we’re referring
to here is normally,
you know, people are quite animated when
they’re talking, some more than others,
but you know, you see movements of
the eyes, the face, the cheeks.
Individuals with Parkinson’s,
they seem like there is no expression
of movement in their face.
So they speak slow, their
face seems kind of rigid,
and this is again characteristic of the
fact that there’s not enough dopamine.
So an obvious solution would be, "Well, how
can I somehow increase levels of dopamine?"
So the easy answer is giving
something called L-Dopa,
which is sort of a precursor
form of dopamine.
Biochemically, we’re not going to get
in to all the specifics, but it gets
broken down to release dopamine and we
see an increase in levels of dopamine.
Well, recently they’ve come up with
agents that are dopamine agonists.
You can even have things that cause a
blockade of the reuptake of dopamine,
so that ends up staying in the
synaptic cleft a little bit longer.
So everything is pretty
much anchored on trying to
increase the amount of
dopamine that’s available.
we’re going to get into sort of a new
late breaking area, which is, you know,
we say new, but we’re looking at
about 10, 15 years of research,
and that is looking at stem cells to regenerate
neurons in the central nervous system.
So the central nervous system
is an area where you don’t see
a lot of regrowth of neurons,
especially in areas like the spine.
stem cells are undifferentiated cells that
are, you know, for a lack of a better term,
sort of blank slates and they really
haven’t decided what they’re going
to be just yet, so they have the
potential to be pretty much anything.
So looking at this figure
we have the stem cells.
They can go on to differentiate
and to becoming things like
a neuron, an astrocyte, an
So they can do a lot of
different things is the idea.
So neural stem cells have the capacity
to differentiate into anything, yes.
They could be put in the appropriate place
and become what we call a progenitor cell
and potentially migrate into
the area of deficiency.
So if we’re looking at, say,
Parkinson’s disease and we’re
seeing an issue with substantia
nigra or the basal --
the other areas where you don’t
have enough dopamine production,
you could put in a stem cell and the
stem cell would become a progenitor cell
and realize that it needs to become
a cell that producing dopamine.
And so you could work in diseases where
the deficiency is at the cellular level,
so things like Alzheimer’s,
Parkinson’s, and MS, where you need to
reestablish the appropriate
level of activity that’s being
modulated by the neuron and you
do that by looking at stem cells.
So obviously, you have two base camps,
those who believe that using stem cells
is dangerous because of its potential
to be used inappropriately.
Some are against how they’re harvested
because typically you get stem cells from --
or you can get stem cells
from aborted fetuses,
you can get them from excised
tissue from young children.
You could even get stem cells from
yourself in appropriate key areas
and reintroduce them to
where you need them.
But the whole process is barred
with a lot of adversity,
but I would say those that are
scientifically inclined agree
and say the general consensus these days
that stem cells, especially if you can do
something as impactful as addressing some of
these disorders, is really, really useful.