NeuRA Talks – Freedom from schizophrenia by Professor Cyndi Shannon Weickert

so thanks for coming tonight
I’m going to talk to you about schizophrenia schizophrenia is one of
the most severe and disabling of all mental illnesses schizophrenia is
particularly devastating because it strikes someone when they’re young and
it robs people of their full potential in life the treatments that we have for
schizophrenia can dampen down the hallucinations and the delusions but
they often leave people unemployed ignored overweight and alone clearly we
need to do better so you may know of the famous rock band the Beach Boys and this
is Brian Wilson the co-founder of the Beach Boys a singer and a songwriter
considered a musical genius Brian actually became paranoid and got
confused and withdrew from his family and friends while writing the last Beach
Boys album called smile he was later diagnosed with
schizophrenia and what I think is really interesting about Brian’s story is the
brain was essentially developing normally through childhood and
adolescence and in he was an early success in the band having many songs
that made it into the top 40 however when schizophrenia struck he
actually became unable to pursue his career in music and he feels that
actually his schizophrenia was caused by drug exposure so in his case it seems
like there was an outside event that may have triggered schizophrenia in a
parallel story here in Australia you may have heard of the band the Sonny boys
and one of the singers the lead singer songwriter
Jeremy Oxley was also an early success and this band
actually developed a cult following in the early 1980s but Jeremy became
unpredictable he drank heavily he was drew from family and friends and
he too got the diagnosis of schizophrenia what I think is most
interesting about Jeremy’s and Brian’s story is that even though they suffered
from schizophrenia remarkably decades later both of these men have appeared on
stage again producing music so this reminds me to tell you of the 20% of
people that get the diagnosis with schizophrenia who seemed to somewhat
miraculously and spontaneously recover and it reminds us to remember that the
human brain has a lot of resilience built in and it suggests that there’s
not some deep-seated problem in the brains of people suffering from
schizophrenia that can never be fixed it actually suggests schizophrenia could be
reversible and it offers us hope however for my research I was interested in
studying those people that 80% who failed to recover who fail to be able to
hold down jobs who fail to be able to form many meaningful social
relationships I wanted to study those individuals that are estranged from
society and I wanted to study these people because my twin brother was one
of them he actually was diagnosed with schizophrenia when he was 17 years old
and he failed to respond well to the medications so I dedicated my life at
that time to try to figure out what possibly could have gone wrong in his
brain at the cellular level in an effort to find better ways to treat him to help
him so my approach was to study the human brain itself on the biological
level so here’s a side view of human brain and you can see it’s highly
convoluted there’s many bumps and there’s many grooves in the human brain
this outer covering the brain is called the cerebral cortex and it’s actually
expanded in humans it takes up a lot of real estate and this is the area of the
brain that’s thought to be responsible for abstract thinking for creativity for
emotional language for the things that make us uniquely human and it’s an area
that’s thought to be impacted and those that suffer from schizophrenia we have
been studying the human brain for over a hundred years at the cellular level and
there’s over a hundred thousand scholarly articles written on
schizophrenia yet the mystery of what causes
schizophrenia has not yet been solved tonight what I’m going to share with you
is that I think it’s going to be the biggest breakthrough in schizophrenia
research history and I’m not kidding so hopefully pay attention and I’m going
to actually first have to teach you a little bit about how the human brain is
organized and teaching you how its organized on a cellular level so we
can’t put the whole brain under the microscope we have to study the human
brain and smaller and smaller bits so buckle up we’re going to look at the
human brain a greater and greater magnification so we can look at the
cells together and we can try to puzzle out what’s happening so the first thing
we do is studying the human brain is we actually cut it from north to south like
this so when we cut it from north to south and we lay it flat what you can
see is that these are this is the outer covering here called the cerebral cortex
remember that’s where a lot of the uniquely human functions exist but what
you’ll notice is that pinkish tan bit that runs around the outside can also be
found deeper in the brain but then we also have these lighter bits here and
you may have heard the distinction between gray matter and white matter so
we’re going to actually focus on this cerebral cortex and we can only look at
a tiny chunk at a time because it’s only a very small section that will fit under
the microscope so when we focus on a small section of cerebral cortex the
gray matter and we stain it and we put it under a microscope what does it look
like so we’ll zoom in higher on that square and what you can see here is this
is the outer part of the brain and we have a layer one here and then we can
see a lot of brown dots going from layer two down to layer six all the way to the
white matter which is if you get deep enough devoid of those brown dots
altogether so let’s take an even higher view
zooming in even more at just one layer of the human cerebral cortex and what I
hope you can see is that they’re smaller rounder brown dots and there is some
bigger triangular shaped with these little caps on them so we have large
neurons and small neurons so the brown dots are called neurons and this is what
we tend to focus on the neuronal cells of the brain and this focus on neurons
it’s because they’re the most obvious cells of the brain they’re the largest
cells of the brain and we think about neurons there’s a hundred billion
neurons in your brain now let’s put this in context okay there’s actually more
neurons in your brain than there are people alive on the planet today and
each one of these neurons has 7,000 connections so it’s like each person
having 7,000 Facebook friends that they’re in constant communication with
so you can imagine the amazing capacity for information processing and
information overload so when we actually take a further a closer look at these
cells and think about them and our models of pathology and we can look at
this drawing that was made to depict the large cells and in the purple and the
smaller cells in the orange and the pink drawing that was made by my graduate
student Laura glass we can see an image that a lot of neuroscientists trying to
understand mental illness will have is their worldview of the brain that’s
because these neurons as I said we’re larger and they dominate our thinking
and it’s also because the medicines that we use to treat people with major mental
illness work on transporters and receptors that these neurons actually
can synthesize chemicals that act on these receptors and transporters and
think of dopamine and serotonin okay those are chemicals that are produced by
neurons and all the drugs in psychiatry did today work on these neurotransmitter
systems but now I think this hyper focus on neurons was actually barking up the
wrong tree so why do I think that well let’s take another look at this
microscopic picture let’s set aside the neurons for a while and instead let’s
return to this image so if we try to subtract out all those brown cells those
brown neurons what you can see is in between the brown cells there’s these
fainter bluer cells these fainter bluer cells were just thought to be brain glue
and not really doing much they’re called brain glia however we now know that
these brain glia are really important in sensing trauma to the brain and they can
actually become reactive when there is brain damage and what I’ve actually
found is the pathology within these glial cells is far greater than the
pathology within the neurons themselves so we’ll look at these glial cells in a
different light so when we actually stain the tissue for these glial cells
we can see how beautiful they are they have this star shaped morphology they have many processes and now we see the neurons as the fainter purpley blue
cells in the background so when the glia cells damage they become
hypertrophied and they react so we have to actually add the glial cells to our
model of thinking about the cells that are found in the human brain
not only neurons that have received all the attention but also the glial cells so I found greater pathology in the glial cells and in certain people I
found that the glia took on an angry morphology that they got hypertrophied
and I also found that there were more distress signals that could be produced
by glial cells called cytokines and we were the first lab in the world actually
fine increased distress signals in the brains of people with schizophrenia
compared to controls so that implicates the glial cells so if we actually think
about this what’s happening in the brain then you can ask what is the consequence
of these increased distress signals and now for you to appreciate how we use
that insight to then carry the research forward I’m going to return to my
anatomy lesson I’m going to teach you about a third kind of cell in the brain
so this is just really to remember to focus on the glial cells and this is
typically how we view the brain I started out like this we view the brain
devoid of any vasculature blood vessels no does that make sense the brain we
know is the biggest user of glucose and it’s the biggest user of blood oxygen
and so the brain is utterly dependent on being constantly bathed and surrounded
by human blood so instead of looking at the brain from this point of view and
thinking about the brain tissue we could instead think about the human brain as a
basket of blood vessels constantly being bathed by the blood and probably a
better picture of what this looks like if we blow it up actually is that the
brain tissue and the blood vessels are in constant two-way communication with
one another so back to what I said that there’s
actually distress signals coming from the glia we hypothesize that that would
have an effect on the blood vessels so if we go back to our diagram and instead
we change our perspective I think if we’re really going to understand the
pathology what’s going on at the cellular level and the brains of people
with schizophrenia we have to change our perspective so this is what Laura has
drawn for you here instead we’re starting with the blood vessel and we
have the blood vessel surrounded by these cells cause endothelial cells that
help form those tubes and we have to add in the glia these green cells notice the
glia are contacting the blood vessels so it’s the end of the allele wall and the
blood vessels that actually form the blood-brain barrier and of course we
have the neurons here off in a distance because we recognize they’re still
important but we don’t think they’re necessarily the major protagonists in
this story so the way we think about blood in the brain cells is that the
blood the red blood cells carrying the oxygen and the white blood cells the
immune cells pictured here in yellow and blue and purple and pink flying by as
they’re cruising along like on some kind of highway through the brain but they’re
not stopping in to visit they’re not coming to have tea they’re just cruising
by and they’re not really able to gain entry into the brain because of this
blood-brain barrier however remember in schizophrenia the glia are angry and the
glia are producing these distress signals these distress signals I called
cytokines pictured here in yellow when you have more of them build up it’s
actually changing the endothelial cells it sends a signal so the endothelial
cells extend this purple protein in response to these distress signals now
the immune cells that are cruising by on the highway are being slowed they’re
being tethered they’re being captured they’re actually being stopped in some
cases and they’re actually being attracted to recognize that they need to trans-migrate across this wall this
blood-brain barrier to gain entry into the brain parenchyma so here you can see
a white blood cell now found in the brain and that is the major breakthrough
okay so we said there’s one kind of brain cell the neuron the second is the
glia the third is the endothelial cells but
now what I’m telling you there’s actually a fourth kind of cell in the
human brain in it’s increase in people with schizophrenia and those are the
immune cells they’re not really even brain cells at all but they’re in the
brain and what’s important the important breakthrough here is that they’re
actually outside the blood vessel and they’re in close proximity to the
neurons that they can mess them up so why is this important I want you to
think about a murder-mystery one that’s remained unsolved for a hundred years
and then all of a sudden a new suspect appears on the list and this individual
actually was there at the scene of the crime at the time the crime was
committed this is analogous to finding a whole new player in the neuropathology
of schizophrenia and this is why it’s a breakthrough this cell has gone
unrecognized by scientists in the past so now we have a new suspect a new
culprit that could be triggering schizophrenia why is it a breakthrough
number one it suggests the pathology could be within the immune cells
themselves and they actually can be triggering the psychosis and the problem
may not reside in the neurons number two it’s a breakthrough because none of the
medicines we use today to treat people with schizophrenia actually target the
immune system and number three is suggested for serious about curing
schizophrenia and our loved ones that we’re going to actually have to engage
immunologists on our team so why else is it a breakthrough because it
suggests whole new avenues for therapy it suggests we can dampen down the
immune system in a variety of ways and see if that brings about benefit we
could block entry of these immune cells into the brain to see if that’s going to
change things for people with schizophrenia and here at neuro we’ve
done just that we’ve just finished a clinical trial using a monoclonal
antibody to interleukin-1 beta this was actually led by my husband Tom Weichert
so stay tuned so I’ll be happy to take questions at the end thank you

6 thoughts on “NeuRA Talks – Freedom from schizophrenia by Professor Cyndi Shannon Weickert

  • Congratulations Dear Professor Weickert and Team. I want to take the opportunity to congratulate you and your husband both in your truth quest. Well done!! KEEP ON!! Your brief video is encouraging and provides the beginning to so many answers.
    It makes sense!!! I honor and salute your work. Such a breakthrough and future improved quality of life and care for those suffering. Please keep up the error free work and authentic life stand.
    As the facts unfold I look forward with hope to hearing of improved recovery paths forward. I speak as a mother,( who has the utmost respect for health professionals) ,of one son whose suffering was so great he remains with us as a memory and light and a second high achieving son who is now facing the same challenges. May revelation and truth flood your paths.
    (please let me know if if there is some way I can assist you.)

  • congratulations professor! awesome work. So many people suffer. Very very pleased to see such awesome work being done.

  • I am so happy that such people like you exist, keep up your important work in improving the suffering of people with schizophrenia and giving them a chance to have a life woth to live. I am so proud of you.

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