Welcome to From the Spectrum Podcast. This is
a podcast about autism. It is my goal to explain
what is autism. I plan to use a mixture of scientific
literature, personal experience, and opinion.
With opinion, I will explain why I feel the way
I do and give examples. I will provide links
to various references for each episode. For each
episode, we will discuss various aspects of autism.
The From the Spectrum podcast will mostly avoid
causes of autism, and I will try to avoid the
increase of diagnoses of late. This is like playing
tug of war with barbed wire. and I don't think
I want to travel down that path. For today's
episode, we will explore the roles of oxytocin
and vasopressin with human development, human
socialness, and the implications to autism. We
will briefly do some time traveling to understand
the phylogenetics of oxytocin and vasopressin.
We will expand on some components of the excitation
inhibition balance, discuss more serotonin, dopamine,
and the line between socialness and anxiety,
while connecting many brain regions and functions
previously discussed. For today's episode, we
have several objectives. 1. Introduce oxytocin
and vasopressin. 2. Prepare to discuss vast differences
found between female and male autistics in a
future episode. 3. To prepare. for the episode
on autism and relationships. Four, to expand
on the excitation inhibition phenomena that is
very worthy in autism. And finally, number five,
to learn more about what is autism. Oxytocin
and vasopressin. Oxytocin is commonly known as
a love hormone and that's true. Both oxytocin
and vasopressin are unique and dynamic parts
of our biology. The phylogeny of oxytocin and
vasopressin date back 700 million years ago and
is found in many different species through evolution.
Primarily, back then, there were lower vertebrates.
Back before, humans and more complex organisms
were found on Earth. This hormone is vasotocin.
You can see a combination of vasopressin and
oxytocin. We could cover a lot here because of
the amount of history, but we can't. We can't
cover everything regarding our topic in modern
humans, development, and autism. However, the
division of vasotocin into vasopressin and oxytocin
appears to help create more complex organisms
like humans. Oxytocin and vasopressin are both
peptides and hormones and have three modes of
transmission. They have three methods of getting
around the body. One is endocrine, so a hormone.
Hormones use the blood to transport and hormones
are very slow acting, especially compared to
cellular functions. Hormones act more to change
us and build us based on experiences over time.
The second mode is paracrine released in dendrites
and cell bodies and into cerebrospinal fluid
or CSF. The CSF is a method to check levels of
oxytocin or vasopressin in the body. This is
a very challenging test. Not only the spinal
tap is challenging, but finding accurate amounts
of oxytocin and vasopressin. Now you can do it
maybe in a lab draw, a blood draw, but it's hard
to capture them because one, they have a short
half -life. They don't hang around in the body.
And two, you're likely only to see metabolites.
It won't be a very accurate test. So a more accurate
test is the spinal tap, and that's not necessarily
a feasible thing, something that people want
to do. The third is synaptic release, used for
transporting to other brain regions. This is
the neuropeptide or neurotransmitter type. Okay,
so what are peptides? Peptides are a chain of
protein collections. Oxytocin and vasopressin
are very fascinating whereby they are very similar
and they have a smaller complex or smaller collection
of proteins. Each oxytocin and vasopressin each
contain nine proteins. These are very special
types of proteins. Amino acids. We've discussed
some amino acids like tryptophan and tyrosine.
Those are aromatic amino acids. Remember, serotonin
comes from tryptophan and dopamine, epinephrine,
norepinephrine, and melanin comes from tyrosine.
And remember our discussion on these special
amino acids the aromatic amino acids that need
280 nanometer wavelength light which is UVB light
to activate and think about how our light environment
has changed let's say from modern day and all
the different light sources to the 1930s just
a change between that time frame when autism
was first kind of observed remember Leo Kanner
and Hans Asperger now let's think about modern
day to let's say 200 years ago when things like
autism and Alzheimer's didn't even exist this
part of the environment and how our human biology
is created with photoreceptors and such is going
to be crucial. We will discuss serotonin and
dopamine more in a little bit. Human biology
loves these proteins. Oxytocin and vasopressin
share seven of the nine proteins. So only two
proteins make these two different. But remember
the evolution. In complex organisms, they separated,
they divided. But still today, in smaller or
lower complex, less complex organisms, they still
remain one. Okay, taking a brief step towards
the upstream. of the neuropeptide. We're going
to go just a little bit upstream. These neuropeptides
come from two cell types. Magnocellular and parvocellular.
I first learned about these while studying the
eyes. Magnocellular provides information about
large and fast objects. They are low spatial
and high temporal, meaning low space, high time,
fast time. And do not pick up color. They are
color blind. Parvo Cellular provides information
about small and slow objects and does see color.
They are high spatial and low temporal. Magnocellular
peptides release large quantities in the central
and peripheral nervous system. This peripheral
path will come into play later when we discuss
intranasal oxytocin as a treatment option. Whereas
parvocellular releases small quantities in the
central nervous system. In large part, to support
reward processes, social cognition, and pair
bonding. Downstream, Magnocellular is responsible
for parental attachment, buffering, fear and
anxiety, and emotional or affective empathy.
Remember, we've discussed that. And hypersensitivity.
Parvocellular is responsible for various other
types of attachment. outside of the parental
attachment, such as peer -to -peer, now we're
getting somewhere, and cognitive flexibility
and social recognition memory, cognitive empathy,
being able to understand others without knowing,
just by looking at them, that so -called theory
of mind, and lack of social motivation. So that's
Magnocellular and Parvocellular. Now, these distinct
pathways to a single molecule, the idea is the
parallel paths for processing the social information
allows a single molecule, such as the oxytocin,
to encode multiple types of behaviors. And in
my opinion, this is a huge finding. This was
released in 2020. Furthermore, this idea of the
Magnocellular and Parvocellular paths is new.
Around 2015 or so, when this was really mentioned
in the scientific literature, a keynote or To
show appreciation, a researcher from Johns Hopkins
does excellent work on this. Her last name is
Dolan, I believe. Okay, back to oxytocin and
vasopressin. Oxytocin is central to human reproduction
and evolution, transforming us into complex organisms.
especially the nervous system, specifically socialness
and cognition. The peptides have connections
with making us upright through evolution. Remember,
humans are one of the few or the only species
completely upright and oxytocin has a role with
that. and developing our large cortex, the area
of the brain above the imaginary line that we've
previously discussed from the eyes to the back
of the head. Remember, our heads extend up unlike
any other species. It's fully developed. Also,
connections with our coranium This complex human
brain then gives us social sensitivity, complex
thinking capacities, and language. Speech and
language comes after song and dance. Correct.
It was song and dance first and then speech and
language through our evolution. The pair bonding
allows us to sustain our species, the connection
of reproduction, birthing process, and mother
-child relationships. Lastly, it supports healing
and is an antioxidant and anti -inflammatory,
all crucial across the lifespan. Just a note.
Veso and vasopressin means vessel. Vasopressin
has many functions related to the circulatory
system. A sidebar. If you have ever felt light
-headed, maybe you stood up too fast or you're
straining too much or too hard, that is vasovagal.
Vessels. and the vagus nerve, a major cranium
nerve for regulating and acting on the parasympathetic
side of the nervous system, the calming side.
Vasopressin has vast roles in blood pressure,
sodium regulation, and interacting with water.
Vasopressin is seen more in males than females.
and it does interact with that crude stress system
and fear, anxiety, and aggression. Anyway, oxytocin
and vasopressin, by the way of the magnocellular
and parvocellular, are released in the hypothalamus.
Remember, we've discussed the hypothalamus at
least a few times. Oxytocin and vasopressin are
transported by dendrites and axons. Remember
how cells connect and communicate to each other
and remember the genetic and protein implications
covered in episode 3. Oxytocin is distributed
to sensory areas of the brain and large part
for social relevant stimuli. Oxytocin mediates
communication in the amygdala. Remember the amygdala
mostly from autism and anxiety episode. Oxytocin
mediates fear response and coping between two
subdivisions in the amygdala. And oxytocin is
used for synaptic transmission between the BNST,
the bad nucleus of the stria terminalis and the
hypothalamus. More from the autism and anxiety
episode. Remember those two connections, the
amygdala to the bad stria terminalis was consistent
in those three dynamic structures and components
that we covered in the autism. and anxiety episode.
Oxytocin also interacts closely to dopamine and
serotonin those two neuromodulators previously
discussed. Remember dopamine is wanting and serotonin
is having. Oxytocin also interacts with GABA.
Remember the excitation is glutamate. The inhibition
is GABA. So this makes up that EI, that EI imbalance
that is constant and consistent. Perhaps the
most consistent thing in autism research about
biology is this imbalance of excitation and inhibition.
We will discuss more on GABA, the inhibition
part. Also, oxytocin Increases trust. Remember
that the root of that pair bonding and mother
-child development. So some overall trust. Some
empathy. Remember we discussed the two types
of empathy from Magnocellular and Parvocellular.
And eye contact. Oxytocin is related to eye contact.
Face memory. and generosity. These peptides decreases
activity of negative emotional experiences. And
guess where? The amygdala, the anterior cingulate
cortex, and the insula. All areas from autism
and adaptive responses episode. The peptides
increase responses for automatic and effortful
emotional regulation in the medial prefrontal
cortex, also the region of interest in autism
and adaptive responses episode. The peptides
targets motivational and rewarding regions by
initiating and sustaining socialness by acting
on the ventral tegmental area. Remember from
Autism and Anxiety, the Autism and Anxiety episode,
the VTA is the spot for providing valence or
attaching how we feel in that moment, in that
environment. Hopefully, this is all coming together
now. Oxytocin also targets three of the four
areas in the striatum. The putamen and caudate,
which is the dorsal part of the striatum. The
putamen and caudate is responsible for stimulus
response memories. Remember, we've discussed
stimulants responses. Those reflexive actions
all humans do. in response to something in the
environment, the external stimuli. The stimulus
response intends to return the individual back
to homeostasis, back to the comfort that they
prefer, that they've learned, that they've developed
through neuroplasticity, returning us as the
living organism back to comfort. And remember,
One, because our nervous system mostly just responds
based on who we are, based on our lifetime of
neuroplasticity. And two, change is hard. Change
is hard because the nervous system doesn't like
to work. It likes to reflexively respond, pass
things on to what it knows, how it knows. how
it knows how to operate, acting in a way it knows.
See, this is more than a discussion on autism.
This is human life. We are who we are. A brief
note, a brief review of this study comparing
autistics and non -autistics, reward processing,
altered in large part at the cellular level with
the autism group the autistic groups using two
activities the first one is monetary rewards
found in the ventral striatum remember the ventral
striatum in large part is the nucleus accumbens
our hotspot for rewards and the ACC which we
discussed in depth a previous episode and the
prefrontal cortex and the second activity was
reduced activity in the striatum during positive
socialness for instance seeing smiling faces
and remember theory of mind also called cognitive
empathy which we discussed earlier this is a
super deficit But effective empathy is not. It
is a possible superpower. We will discuss more
on that in the future. So you can see from the
study the differences between autistics and non
-autistics and how different brain regions are
activated based on those two activities. Receiving
monetary rewards and experiencing positive socialness.
This lack of reward attached to socialness prevents
social learning opportunities as far back as
that critical period. And if you understand the
social phenotypes of autism, they are very, how
do I say they are behind or uneducated and poor.
things like loud and soft tone, porosity, when
and how to join and end a conversation, speaking
too much on a specific topic, despite obvious,
well, to others, not so much for us, obvious,
this interest in the topic by the listener. In
addition, to these areas, there are hypo -connectivity
to downstream or connecting brain regions used
in socialness, providing more proof and insight
on what causes the autistic phenotypes, explaining
what and who we are. This is giving you understanding
to maybe calm any tendency. of wanting to change
someone with autism because they are different
than you. I did not say, you can't help them
build social skills. I would not say that. However,
if an autistic prefers being less active in socialness,
the so -called autistic aloneness. Remember the
paper by Leo Kanner. That first paper on autism
released in 1943, he highlighted this quite extensively.
Be mindful. Autism gives us the ability to be
comfortable within ourselves. And this is a path
for developing tremendous superpowers. In autism,
data exists on lower levels of peripheral and
central oxytocin and deficient and altered expression
of oxytocin receptors in both animal and human
research. In addition, data also show the lower
plasma oxytocin are present in children and not
so much adolescent or adult autistics. This critical
in the role of oxytocin and development. I think
this is a good finding in correlation a meta
-analysis using 18 studies examined and determined
this finding and that was released in 2021. Oxytocin
and serotonin. Oxytocin and serotonin appears
to be the driving force in the role of supporting
anxiety -like features and supports socialness.
The dorsal raffae, the raffae is the brain serotonin,
receives oxytocin fibers and the raffae has oxytocin
receptors. This action causes a release of serotonin,
specifically to frontal brain regions. And remember,
serotonin's role in active versus passive coping.
In contrast, studies show genetically removing
this connection after childbirth resulted in
offspring loss. Remember the developmental roles.
The impaired nursing increased aggression and
behavior complications. When oxytocin and serotonin
work in concert, it provides a perception of
rewarding socialness occurring. In other words,
when socialness is rewarding, coordinated activity
of oxytocin and serotonin is required. And it
goes to that ventral striatum area, the nucleus
accumbens. Said differently, a lack of oxytocin
prevents social enjoyment. And now, just a brief
note, when we discuss female versus male autistics,
the nucleus accumbens and oxytocin is gonna be
huge. This was a huge finding. Anyway, data on
various modeled organisms and humans show various
oxytocin and serotonin connections including
in the prefrontal cortex, that area that makes
us the superior species on earth, and the amygdala,
the striatal areas, and interesting, serotonin
regulates the release of oxytocin in one of the
areas of the hypothalamus. So three things of
interest here. One, the reward processing. Two,
the fear response. And three, the social -emotional
processing. Doxytocin and dopamine. The roles
in dopamine primarily stick to the main roles
of dopamine. That is, connecting brain regions
based on wanting, motivation, and craving. What
you find rewarding and aspects of cognitive processing
and sensory gating. This is a good one. Remember
dopamine is a neuromodulator and it conducts
whole systems. It turns things on, turns certain
brain regions on or whole systems throughout
the body. It activates them and it turns things
off. Little brain regions or entire systems,
biological systems, it inactivates them and it
regulates action through the nervous system.
Dopamine has two receptor types. Dopamine has
five total receptors broken down into two types.
D1 is excitation, and that's dopamine receptor
one and five. And D2 is inhibition. These are
dopamine receptors two, three, and four. D2 type
receptors are inhibition. So, Now we will introduce
GABA, which is inhibition. In autism, dysregulation
of GABA receptors exists in the data. Remember
one of those components or reasons that gives
us the EI imbalance. Remember a critical role
of GABA, which is inhibitory, turning things
off or quieting the brain. One of GABA's main
roles is regulating sensations via that thalamocortical
path. These abnormal GABA receptors are also
found in seizures, remember the closeness to
epilepsy, and learning disabilities, and our
primary topic in social and cognitive dysfunctions.
The excitation inhibition needs both oxytocin
and GABA for a proper balance. For the developing
brain, these components are critical for proper
development. A study shows aberrations in these
areas are a cause of autistic phenotypes. Also,
abnormal GABA development in the dopaminergic
areas of the brain is our region of interest.
This expands on some dysfunction of the excitation
and inhibition balance and offers a topic in
recent research of pathophysiology of autism.
In addition, neurogenesis the development of
neurons. Remember, cells divide and neurite growth
and synapsis formation involve many factors.
Nothing's singular. These neuropeptides alongside
GABA are critical for these roles. Okay, before
we end, I just want to cover intranasal oxytocin.
as a therapeutic option for autism or for those
autistic phenotypes. Intranasal oxytocin administration
penetrates the brain. It crosses the blood -brain
barrier with capillary beds and induces cognitive,
emotional, and behavioral changes mostly related
to socialness. To no surprise, for that reason,
data exists on testing intranasal oxytocin for
autism superdeficits, social anxiety, increasing
peer -to -peer capabilities, or said differently,
acting on those roles oxytocin has in social
functioning discussed earlier. The data on intranasal
oxytocin is both inconsistent and low risk, meaning
little to zero side effects. Criteria for the
intranasal oxytocin include standardization of
dosage, frequency, formulation, differences in
sex, and devices used for administration. Two
points to consider. There's an idea gender differences
is a primary cause of the inconsistent data and
intranasal oxytocin is shown to improve socialness
or more precisely shown to suppress anxiety in
healthy participants. The reason we will explore
this option is because there is proof and it
is in the so -called low risk category as a helpful
option for autism. There are several things to
know here, several takeaways to consider. One,
studies do show improvements and a few meta -analysis
confirm this. Intranasal oxytocin, this approach
has been around for about 20 years now, I believe
2003. So some data has collected. The second
thing to consider is it is low risk and this
ought to be a tremendous factor. If it works,
it works. If it doesn't, okay, it doesn't. Three,
it is unknown if intranasal mimics the endogenous
amounts released in the brain. The dosage has
to really be pinpointed. Four. There is a chance
intranasal oxytocin activates broad serotonin
across the brain. In other words, it might lack
specificity. And lastly, number five. And this
is a big one. Intranasal appears to target the
magnocellular pathway, which is more peripheral.
So it acts on hormones and it blunts stress responses
in the hormonal systems such as cortisol. When
in reality, the idea is acting on the central
pathways that the areas responsible for the brain
regions, that cellular activity. You want more
neuropeptide or neurotransmitter and less hormone
so it can target the nucleus accumbens. Remember,
co -activating with serotonin and oxytocin to
reach the nucleus accumbens. That is the primary
target. And that works by the way of the parvocellular
function or that parvocellular path and not the
magnocellular. If you are listening and enjoy
the episode or enjoy the podcast, feel free to
leave a review or rating. In podcasting, reviews,
ratings, and downloads are huge. And I very much
appreciate your feedback. You can email me at
info .fromthespectrumatgmail .com. And thank
you for listening to From the Spectrum Podcast.