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 fill 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 and 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. 4. To expand on the excitation and inhibition phenomena
that is very worthy in autism. And finally, number 5. 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 cerebral spinal 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
can be a lab draw or blood draw, but it's hard to capture them because they have a short
half life. They don't hang around in the body and 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 subnaptic
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 or epinephrine 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 the 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 neuropath
peptide. We're going to go just a little bit upstream. These neuropaths come from two cell
types. Magnosecular and Parvocellular. I first learned about these while studying the eyes.
Magnosecular 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. Parvocellular provides information about small and slow objects and does see
color. They are high spatial and low temporal. Magnosecular 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,
low cognition and pair bonding. Downstream, Magnosecular 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 Magnosecular 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 Magnosecular 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 John 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 their nervous system. Specifically, socialness and
cognition. The peptides have connections with making us upright through evolution. Remember,
our connections 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 curanium. 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 in 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 curanium 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 magnosecular 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 B and ST
that bad nucleus of the striaterminalis and the hypothalamus. More from the autism and
anxiety episode. Remember those two connections, the amygdala to the bad striaterminalis 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
neuro modulators previously discussed. Remember dopamine is one team and serotonin is having.
Oxytocin also interacts with GABA. Remember the excitation is glutamate. The inubition
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
magnosecular 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 stimulates 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 is 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 in 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 in the 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 is critical in the role of oxytocin in
development. I think this is a good finding and 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 and 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 going to 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.
Oxytocin 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 inoculates 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 1 and 5. And D2 is inhibition. These are dopamine receptors 2, 3, and 4.
D2 type receptors are inhibition. So, now we will introduce GABA, which is inhibition.
In autism, dysregulation of GABA receptors exist 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 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 super deficits, 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 and 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 magnosecular 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 area is responsible for the brain region,
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 magnosecular. If you are listening and enjoy the
episode or enjoy the podcast, feel free to leave a review or rating. And podcasting reviews, ratings,
and downloads are huge. And I very much appreciate your feedback. You can email me at info.fromthespectrum.com.
And thank you for listening to From the Spectrum podcast.