WEBVTT 00:00:03.520 --> 00:00:08.199 Welcome to From the Spectrum Podcast. This is 00:00:08.199 --> 00:00:13.140 a podcast about autism. It is my goal to explain 00:00:13.140 --> 00:00:18.879 what is autism. I plan to use a mixture of scientific 00:00:18.879 --> 00:00:22.879 literature, personal experience, and opinion. 00:00:23.839 --> 00:00:27.219 With opinion, I will explain why I feel the way 00:00:27.219 --> 00:00:32.200 I do and give examples. I will provide links 00:00:32.200 --> 00:00:36.659 to various references for each episode. For each 00:00:36.659 --> 00:00:40.780 episode, we will discuss various aspects of autism. 00:00:42.799 --> 00:00:46.060 The From the Spectrum podcast will mostly avoid 00:00:46.060 --> 00:00:50.740 causes of autism, and I will try to avoid the 00:00:50.740 --> 00:00:55.079 increase of diagnoses of late. This is like playing 00:00:55.079 --> 00:00:58.630 tug of war with barbed wire. and I don't think 00:00:58.630 --> 00:01:03.770 I want to travel down that path. For today's 00:01:03.770 --> 00:01:09.269 episode, we will explore the roles of oxytocin 00:01:09.269 --> 00:01:14.989 and vasopressin with human development, human 00:01:14.989 --> 00:01:20.430 socialness, and the implications to autism. We 00:01:20.430 --> 00:01:24.170 will briefly do some time traveling to understand 00:01:24.170 --> 00:01:29.400 the phylogenetics of oxytocin and vasopressin. 00:01:30.319 --> 00:01:35.260 We will expand on some components of the excitation 00:01:35.260 --> 00:01:42.200 inhibition balance, discuss more serotonin, dopamine, 00:01:43.019 --> 00:01:46.459 and the line between socialness and anxiety, 00:01:47.400 --> 00:01:51.439 while connecting many brain regions and functions 00:01:51.439 --> 00:01:57.019 previously discussed. For today's episode, we 00:01:57.019 --> 00:02:04.000 have several objectives. 1. Introduce oxytocin 00:02:04.000 --> 00:02:10.639 and vasopressin. 2. Prepare to discuss vast differences 00:02:10.639 --> 00:02:16.240 found between female and male autistics in a 00:02:16.240 --> 00:02:22.469 future episode. 3. To prepare. for the episode 00:02:22.469 --> 00:02:28.590 on autism and relationships. Four, to expand 00:02:28.590 --> 00:02:33.409 on the excitation inhibition phenomena that is 00:02:33.409 --> 00:02:39.889 very worthy in autism. And finally, number five, 00:02:40.110 --> 00:02:48.610 to learn more about what is autism. Oxytocin 00:02:48.610 --> 00:02:54.449 and vasopressin. Oxytocin is commonly known as 00:02:54.449 --> 00:03:00.650 a love hormone and that's true. Both oxytocin 00:03:00.650 --> 00:03:04.590 and vasopressin are unique and dynamic parts 00:03:04.590 --> 00:03:09.770 of our biology. The phylogeny of oxytocin and 00:03:09.770 --> 00:03:15.650 vasopressin date back 700 million years ago and 00:03:15.650 --> 00:03:19.509 is found in many different species through evolution. 00:03:21.199 --> 00:03:25.180 Primarily, back then, there were lower vertebrates. 00:03:26.199 --> 00:03:30.099 Back before, humans and more complex organisms 00:03:30.099 --> 00:03:35.840 were found on Earth. This hormone is vasotocin. 00:03:36.879 --> 00:03:41.719 You can see a combination of vasopressin and 00:03:41.719 --> 00:03:46.500 oxytocin. We could cover a lot here because of 00:03:46.500 --> 00:03:50.860 the amount of history, but we can't. We can't 00:03:50.860 --> 00:03:54.340 cover everything regarding our topic in modern 00:03:54.340 --> 00:03:59.759 humans, development, and autism. However, the 00:03:59.759 --> 00:04:06.580 division of vasotocin into vasopressin and oxytocin 00:04:06.580 --> 00:04:10.960 appears to help create more complex organisms 00:04:10.960 --> 00:04:18.000 like humans. Oxytocin and vasopressin are both 00:04:18.000 --> 00:04:23.160 peptides and hormones and have three modes of 00:04:23.160 --> 00:04:26.540 transmission. They have three methods of getting 00:04:26.540 --> 00:04:33.579 around the body. One is endocrine, so a hormone. 00:04:34.199 --> 00:04:38.980 Hormones use the blood to transport and hormones 00:04:38.980 --> 00:04:44.540 are very slow acting, especially compared to 00:04:44.540 --> 00:04:50.129 cellular functions. Hormones act more to change 00:04:50.129 --> 00:04:54.689 us and build us based on experiences over time. 00:04:55.910 --> 00:05:01.209 The second mode is paracrine released in dendrites 00:05:01.209 --> 00:05:05.910 and cell bodies and into cerebrospinal fluid 00:05:05.910 --> 00:05:14.410 or CSF. The CSF is a method to check levels of 00:05:14.410 --> 00:05:18.629 oxytocin or vasopressin in the body. This is 00:05:18.629 --> 00:05:22.850 a very challenging test. Not only the spinal 00:05:22.850 --> 00:05:26.870 tap is challenging, but finding accurate amounts 00:05:26.870 --> 00:05:31.089 of oxytocin and vasopressin. Now you can do it 00:05:31.089 --> 00:05:35.329 maybe in a lab draw, a blood draw, but it's hard 00:05:35.329 --> 00:05:38.790 to capture them because one, they have a short 00:05:38.790 --> 00:05:42.750 half -life. They don't hang around in the body. 00:05:43.110 --> 00:05:46.670 And two, you're likely only to see metabolites. 00:05:46.959 --> 00:05:52.480 It won't be a very accurate test. So a more accurate 00:05:52.480 --> 00:05:56.379 test is the spinal tap, and that's not necessarily 00:05:56.379 --> 00:05:59.060 a feasible thing, something that people want 00:05:59.060 --> 00:06:04.939 to do. The third is synaptic release, used for 00:06:04.939 --> 00:06:09.000 transporting to other brain regions. This is 00:06:09.000 --> 00:06:14.180 the neuropeptide or neurotransmitter type. Okay, 00:06:14.360 --> 00:06:19.290 so what are peptides? Peptides are a chain of 00:06:19.290 --> 00:06:24.449 protein collections. Oxytocin and vasopressin 00:06:24.449 --> 00:06:28.889 are very fascinating whereby they are very similar 00:06:28.889 --> 00:06:33.350 and they have a smaller complex or smaller collection 00:06:33.350 --> 00:06:39.829 of proteins. Each oxytocin and vasopressin each 00:06:39.829 --> 00:06:44.350 contain nine proteins. These are very special 00:06:44.350 --> 00:06:49.730 types of proteins. Amino acids. We've discussed 00:06:49.730 --> 00:06:54.930 some amino acids like tryptophan and tyrosine. 00:06:55.649 --> 00:07:01.750 Those are aromatic amino acids. Remember, serotonin 00:07:01.750 --> 00:07:06.730 comes from tryptophan and dopamine, epinephrine, 00:07:06.810 --> 00:07:11.069 norepinephrine, and melanin comes from tyrosine. 00:07:11.670 --> 00:07:14.509 And remember our discussion on these special 00:07:14.649 --> 00:07:19.910 amino acids the aromatic amino acids that need 00:07:19.910 --> 00:07:27.269 280 nanometer wavelength light which is UVB light 00:07:27.269 --> 00:07:32.529 to activate and think about how our light environment 00:07:32.529 --> 00:07:36.790 has changed let's say from modern day and all 00:07:36.790 --> 00:07:42.290 the different light sources to the 1930s just 00:07:42.290 --> 00:07:46.009 a change between that time frame when autism 00:07:46.009 --> 00:07:49.589 was first kind of observed remember Leo Kanner 00:07:49.589 --> 00:07:54.490 and Hans Asperger now let's think about modern 00:07:54.490 --> 00:07:59.350 day to let's say 200 years ago when things like 00:07:59.350 --> 00:08:04.509 autism and Alzheimer's didn't even exist this 00:08:04.509 --> 00:08:08.740 part of the environment and how our human biology 00:08:08.740 --> 00:08:12.319 is created with photoreceptors and such is going 00:08:12.319 --> 00:08:18.079 to be crucial. We will discuss serotonin and 00:08:18.079 --> 00:08:23.779 dopamine more in a little bit. Human biology 00:08:23.779 --> 00:08:29.839 loves these proteins. Oxytocin and vasopressin 00:08:29.839 --> 00:08:35.659 share seven of the nine proteins. So only two 00:08:35.659 --> 00:08:40.379 proteins make these two different. But remember 00:08:40.379 --> 00:08:45.600 the evolution. In complex organisms, they separated, 00:08:45.879 --> 00:08:51.080 they divided. But still today, in smaller or 00:08:51.080 --> 00:08:55.059 lower complex, less complex organisms, they still 00:08:55.059 --> 00:09:02.240 remain one. Okay, taking a brief step towards 00:09:02.240 --> 00:09:06.309 the upstream. of the neuropeptide. We're going 00:09:06.309 --> 00:09:10.990 to go just a little bit upstream. These neuropeptides 00:09:10.990 --> 00:09:17.809 come from two cell types. Magnocellular and parvocellular. 00:09:18.870 --> 00:09:22.169 I first learned about these while studying the 00:09:22.169 --> 00:09:27.509 eyes. Magnocellular provides information about 00:09:27.509 --> 00:09:32.080 large and fast objects. They are low spatial 00:09:32.080 --> 00:09:36.759 and high temporal, meaning low space, high time, 00:09:37.159 --> 00:09:41.379 fast time. And do not pick up color. They are 00:09:41.379 --> 00:09:45.980 color blind. Parvo Cellular provides information 00:09:45.980 --> 00:09:51.059 about small and slow objects and does see color. 00:09:51.980 --> 00:09:58.740 They are high spatial and low temporal. Magnocellular 00:09:58.740 --> 00:10:02.580 peptides release large quantities in the central 00:10:02.580 --> 00:10:06.519 and peripheral nervous system. This peripheral 00:10:06.519 --> 00:10:10.379 path will come into play later when we discuss 00:10:10.379 --> 00:10:16.659 intranasal oxytocin as a treatment option. Whereas 00:10:16.659 --> 00:10:20.519 parvocellular releases small quantities in the 00:10:20.519 --> 00:10:24.980 central nervous system. In large part, to support 00:10:24.980 --> 00:10:29.159 reward processes, social cognition, and pair 00:10:29.159 --> 00:10:34.379 bonding. Downstream, Magnocellular is responsible 00:10:34.379 --> 00:10:39.440 for parental attachment, buffering, fear and 00:10:39.440 --> 00:10:43.840 anxiety, and emotional or affective empathy. 00:10:44.460 --> 00:10:48.460 Remember, we've discussed that. And hypersensitivity. 00:10:49.639 --> 00:10:53.460 Parvocellular is responsible for various other 00:10:53.460 --> 00:10:56.980 types of attachment. outside of the parental 00:10:56.980 --> 00:11:02.019 attachment, such as peer -to -peer, now we're 00:11:02.019 --> 00:11:06.080 getting somewhere, and cognitive flexibility 00:11:06.080 --> 00:11:11.940 and social recognition memory, cognitive empathy, 00:11:12.399 --> 00:11:16.620 being able to understand others without knowing, 00:11:17.759 --> 00:11:20.360 just by looking at them, that so -called theory 00:11:20.360 --> 00:11:26.269 of mind, and lack of social motivation. So that's 00:11:26.269 --> 00:11:31.950 Magnocellular and Parvocellular. Now, these distinct 00:11:31.950 --> 00:11:39.250 pathways to a single molecule, the idea is the 00:11:39.250 --> 00:11:44.029 parallel paths for processing the social information 00:11:44.029 --> 00:11:48.909 allows a single molecule, such as the oxytocin, 00:11:49.570 --> 00:11:54.149 to encode multiple types of behaviors. And in 00:11:54.149 --> 00:11:57.889 my opinion, this is a huge finding. This was 00:11:57.889 --> 00:12:04.809 released in 2020. Furthermore, this idea of the 00:12:04.809 --> 00:12:10.190 Magnocellular and Parvocellular paths is new. 00:12:11.629 --> 00:12:16.389 Around 2015 or so, when this was really mentioned 00:12:16.389 --> 00:12:22.840 in the scientific literature, a keynote or To 00:12:22.840 --> 00:12:26.759 show appreciation, a researcher from Johns Hopkins 00:12:26.759 --> 00:12:31.139 does excellent work on this. Her last name is 00:12:31.139 --> 00:12:37.539 Dolan, I believe. Okay, back to oxytocin and 00:12:37.539 --> 00:12:44.279 vasopressin. Oxytocin is central to human reproduction 00:12:44.279 --> 00:12:50.659 and evolution, transforming us into complex organisms. 00:12:51.210 --> 00:12:57.610 especially the nervous system, specifically socialness 00:12:57.610 --> 00:13:02.610 and cognition. The peptides have connections 00:13:02.610 --> 00:13:07.809 with making us upright through evolution. Remember, 00:13:09.049 --> 00:13:14.409 humans are one of the few or the only species 00:13:14.409 --> 00:13:19.029 completely upright and oxytocin has a role with 00:13:19.029 --> 00:13:26.559 that. and developing our large cortex, the area 00:13:26.559 --> 00:13:31.120 of the brain above the imaginary line that we've 00:13:31.120 --> 00:13:33.960 previously discussed from the eyes to the back 00:13:33.960 --> 00:13:39.299 of the head. Remember, our heads extend up unlike 00:13:39.299 --> 00:13:45.360 any other species. It's fully developed. Also, 00:13:45.600 --> 00:13:51.039 connections with our coranium This complex human 00:13:51.039 --> 00:13:55.919 brain then gives us social sensitivity, complex 00:13:55.919 --> 00:14:01.179 thinking capacities, and language. Speech and 00:14:01.179 --> 00:14:07.139 language comes after song and dance. Correct. 00:14:07.519 --> 00:14:12.399 It was song and dance first and then speech and 00:14:12.399 --> 00:14:18.279 language through our evolution. The pair bonding 00:14:18.279 --> 00:14:24.220 allows us to sustain our species, the connection 00:14:24.220 --> 00:14:29.320 of reproduction, birthing process, and mother 00:14:29.320 --> 00:14:35.440 -child relationships. Lastly, it supports healing 00:14:35.440 --> 00:14:40.139 and is an antioxidant and anti -inflammatory, 00:14:41.259 --> 00:14:48.009 all crucial across the lifespan. Just a note. 00:14:48.950 --> 00:14:54.850 Veso and vasopressin means vessel. Vasopressin 00:14:54.850 --> 00:14:58.190 has many functions related to the circulatory 00:14:58.190 --> 00:15:04.710 system. A sidebar. If you have ever felt light 00:15:04.710 --> 00:15:08.690 -headed, maybe you stood up too fast or you're 00:15:08.690 --> 00:15:13.570 straining too much or too hard, that is vasovagal. 00:15:13.950 --> 00:15:18.279 Vessels. and the vagus nerve, a major cranium 00:15:18.279 --> 00:15:22.480 nerve for regulating and acting on the parasympathetic 00:15:22.480 --> 00:15:27.240 side of the nervous system, the calming side. 00:15:28.940 --> 00:15:33.019 Vasopressin has vast roles in blood pressure, 00:15:33.460 --> 00:15:37.440 sodium regulation, and interacting with water. 00:15:38.820 --> 00:15:42.799 Vasopressin is seen more in males than females. 00:15:43.240 --> 00:15:47.320 and it does interact with that crude stress system 00:15:47.320 --> 00:15:55.759 and fear, anxiety, and aggression. Anyway, oxytocin 00:15:55.759 --> 00:15:59.700 and vasopressin, by the way of the magnocellular 00:15:59.700 --> 00:16:03.899 and parvocellular, are released in the hypothalamus. 00:16:04.559 --> 00:16:08.200 Remember, we've discussed the hypothalamus at 00:16:08.200 --> 00:16:15.330 least a few times. Oxytocin and vasopressin are 00:16:15.330 --> 00:16:19.850 transported by dendrites and axons. Remember 00:16:19.850 --> 00:16:23.690 how cells connect and communicate to each other 00:16:23.690 --> 00:16:27.269 and remember the genetic and protein implications 00:16:27.269 --> 00:16:33.590 covered in episode 3. Oxytocin is distributed 00:16:33.590 --> 00:16:38.590 to sensory areas of the brain and large part 00:16:38.590 --> 00:16:45.070 for social relevant stimuli. Oxytocin mediates 00:16:45.070 --> 00:16:50.289 communication in the amygdala. Remember the amygdala 00:16:50.289 --> 00:16:56.649 mostly from autism and anxiety episode. Oxytocin 00:16:56.649 --> 00:17:01.330 mediates fear response and coping between two 00:17:01.330 --> 00:17:07.710 subdivisions in the amygdala. And oxytocin is 00:17:07.710 --> 00:17:14.779 used for synaptic transmission between the BNST, 00:17:15.400 --> 00:17:18.579 the bad nucleus of the stria terminalis and the 00:17:18.579 --> 00:17:23.299 hypothalamus. More from the autism and anxiety 00:17:23.299 --> 00:17:28.099 episode. Remember those two connections, the 00:17:28.099 --> 00:17:32.420 amygdala to the bad stria terminalis was consistent 00:17:32.420 --> 00:17:38.160 in those three dynamic structures and components 00:17:38.160 --> 00:17:42.730 that we covered in the autism. and anxiety episode. 00:17:43.630 --> 00:17:48.690 Oxytocin also interacts closely to dopamine and 00:17:48.690 --> 00:17:53.769 serotonin those two neuromodulators previously 00:17:53.769 --> 00:17:59.849 discussed. Remember dopamine is wanting and serotonin 00:17:59.849 --> 00:18:05.869 is having. Oxytocin also interacts with GABA. 00:18:07.670 --> 00:18:12.250 Remember the excitation is glutamate. The inhibition 00:18:12.250 --> 00:18:18.089 is GABA. So this makes up that EI, that EI imbalance 00:18:18.089 --> 00:18:21.769 that is constant and consistent. Perhaps the 00:18:21.769 --> 00:18:25.130 most consistent thing in autism research about 00:18:25.130 --> 00:18:30.529 biology is this imbalance of excitation and inhibition. 00:18:31.009 --> 00:18:34.809 We will discuss more on GABA, the inhibition 00:18:34.809 --> 00:18:42.049 part. Also, oxytocin Increases trust. Remember 00:18:42.049 --> 00:18:45.089 that the root of that pair bonding and mother 00:18:45.089 --> 00:18:51.250 -child development. So some overall trust. Some 00:18:51.250 --> 00:18:54.589 empathy. Remember we discussed the two types 00:18:54.589 --> 00:18:59.950 of empathy from Magnocellular and Parvocellular. 00:19:00.910 --> 00:19:06.009 And eye contact. Oxytocin is related to eye contact. 00:19:06.750 --> 00:19:14.569 Face memory. and generosity. These peptides decreases 00:19:14.569 --> 00:19:19.230 activity of negative emotional experiences. And 00:19:19.230 --> 00:19:24.390 guess where? The amygdala, the anterior cingulate 00:19:24.390 --> 00:19:30.529 cortex, and the insula. All areas from autism 00:19:30.529 --> 00:19:35.430 and adaptive responses episode. The peptides 00:19:35.430 --> 00:19:40.849 increase responses for automatic and effortful 00:19:40.849 --> 00:19:44.970 emotional regulation in the medial prefrontal 00:19:44.970 --> 00:19:49.869 cortex, also the region of interest in autism 00:19:49.869 --> 00:19:56.630 and adaptive responses episode. The peptides 00:19:56.630 --> 00:20:01.210 targets motivational and rewarding regions by 00:20:01.210 --> 00:20:06.109 initiating and sustaining socialness by acting 00:20:06.109 --> 00:20:11.599 on the ventral tegmental area. Remember from 00:20:11.599 --> 00:20:16.839 Autism and Anxiety, the Autism and Anxiety episode, 00:20:17.420 --> 00:20:22.480 the VTA is the spot for providing valence or 00:20:22.480 --> 00:20:26.799 attaching how we feel in that moment, in that 00:20:26.799 --> 00:20:31.759 environment. Hopefully, this is all coming together 00:20:31.759 --> 00:20:37.609 now. Oxytocin also targets three of the four 00:20:37.609 --> 00:20:43.130 areas in the striatum. The putamen and caudate, 00:20:43.849 --> 00:20:47.829 which is the dorsal part of the striatum. The 00:20:47.829 --> 00:20:51.970 putamen and caudate is responsible for stimulus 00:20:51.970 --> 00:20:56.710 response memories. Remember, we've discussed 00:20:56.710 --> 00:21:01.809 stimulants responses. Those reflexive actions 00:21:01.809 --> 00:21:05.819 all humans do. in response to something in the 00:21:05.819 --> 00:21:11.039 environment, the external stimuli. The stimulus 00:21:11.039 --> 00:21:15.299 response intends to return the individual back 00:21:15.299 --> 00:21:19.160 to homeostasis, back to the comfort that they 00:21:19.160 --> 00:21:22.960 prefer, that they've learned, that they've developed 00:21:22.960 --> 00:21:28.200 through neuroplasticity, returning us as the 00:21:28.200 --> 00:21:33.259 living organism back to comfort. And remember, 00:21:33.390 --> 00:21:38.809 One, because our nervous system mostly just responds 00:21:38.809 --> 00:21:44.829 based on who we are, based on our lifetime of 00:21:44.829 --> 00:21:51.789 neuroplasticity. And two, change is hard. Change 00:21:51.789 --> 00:21:54.430 is hard because the nervous system doesn't like 00:21:54.430 --> 00:21:59.410 to work. It likes to reflexively respond, pass 00:21:59.410 --> 00:22:02.960 things on to what it knows, how it knows. how 00:22:02.960 --> 00:22:07.819 it knows how to operate, acting in a way it knows. 00:22:10.059 --> 00:22:13.819 See, this is more than a discussion on autism. 00:22:14.619 --> 00:22:21.359 This is human life. We are who we are. A brief 00:22:21.359 --> 00:22:25.660 note, a brief review of this study comparing 00:22:25.660 --> 00:22:30.599 autistics and non -autistics, reward processing, 00:22:31.019 --> 00:22:35.920 altered in large part at the cellular level with 00:22:35.920 --> 00:22:39.720 the autism group the autistic groups using two 00:22:39.720 --> 00:22:44.119 activities the first one is monetary rewards 00:22:44.119 --> 00:22:48.160 found in the ventral striatum remember the ventral 00:22:48.160 --> 00:22:51.980 striatum in large part is the nucleus accumbens 00:22:51.980 --> 00:22:58.880 our hotspot for rewards and the ACC which we 00:22:58.880 --> 00:23:03.170 discussed in depth a previous episode and the 00:23:03.170 --> 00:23:08.250 prefrontal cortex and the second activity was 00:23:08.250 --> 00:23:13.190 reduced activity in the striatum during positive 00:23:13.190 --> 00:23:18.009 socialness for instance seeing smiling faces 00:23:18.009 --> 00:23:22.769 and remember theory of mind also called cognitive 00:23:22.769 --> 00:23:28.190 empathy which we discussed earlier this is a 00:23:28.190 --> 00:23:34.549 super deficit But effective empathy is not. It 00:23:34.549 --> 00:23:38.589 is a possible superpower. We will discuss more 00:23:38.589 --> 00:23:42.910 on that in the future. So you can see from the 00:23:42.910 --> 00:23:47.410 study the differences between autistics and non 00:23:47.410 --> 00:23:50.869 -autistics and how different brain regions are 00:23:50.869 --> 00:23:55.109 activated based on those two activities. Receiving 00:23:55.109 --> 00:24:01.440 monetary rewards and experiencing positive socialness. 00:24:02.720 --> 00:24:07.079 This lack of reward attached to socialness prevents 00:24:07.079 --> 00:24:12.180 social learning opportunities as far back as 00:24:12.180 --> 00:24:16.200 that critical period. And if you understand the 00:24:16.200 --> 00:24:21.799 social phenotypes of autism, they are very, how 00:24:21.799 --> 00:24:27.839 do I say they are behind or uneducated and poor. 00:24:28.970 --> 00:24:35.569 things like loud and soft tone, porosity, when 00:24:35.569 --> 00:24:41.430 and how to join and end a conversation, speaking 00:24:41.430 --> 00:24:46.470 too much on a specific topic, despite obvious, 00:24:46.470 --> 00:24:51.329 well, to others, not so much for us, obvious, 00:24:51.589 --> 00:24:56.950 this interest in the topic by the listener. In 00:24:56.950 --> 00:25:02.210 addition, to these areas, there are hypo -connectivity 00:25:02.210 --> 00:25:06.369 to downstream or connecting brain regions used 00:25:06.369 --> 00:25:11.869 in socialness, providing more proof and insight 00:25:11.869 --> 00:25:16.829 on what causes the autistic phenotypes, explaining 00:25:16.829 --> 00:25:22.789 what and who we are. This is giving you understanding 00:25:22.789 --> 00:25:28.359 to maybe calm any tendency. of wanting to change 00:25:28.359 --> 00:25:32.440 someone with autism because they are different 00:25:32.440 --> 00:25:37.779 than you. I did not say, you can't help them 00:25:37.779 --> 00:25:43.460 build social skills. I would not say that. However, 00:25:43.839 --> 00:25:49.480 if an autistic prefers being less active in socialness, 00:25:50.240 --> 00:25:54.240 the so -called autistic aloneness. Remember the 00:25:54.240 --> 00:25:58.039 paper by Leo Kanner. That first paper on autism 00:25:58.039 --> 00:26:03.119 released in 1943, he highlighted this quite extensively. 00:26:05.000 --> 00:26:08.900 Be mindful. Autism gives us the ability to be 00:26:08.900 --> 00:26:13.700 comfortable within ourselves. And this is a path 00:26:13.700 --> 00:26:19.839 for developing tremendous superpowers. In autism, 00:26:20.259 --> 00:26:24.970 data exists on lower levels of peripheral and 00:26:24.970 --> 00:26:30.930 central oxytocin and deficient and altered expression 00:26:30.930 --> 00:26:36.609 of oxytocin receptors in both animal and human 00:26:36.609 --> 00:26:42.710 research. In addition, data also show the lower 00:26:42.710 --> 00:26:48.210 plasma oxytocin are present in children and not 00:26:48.210 --> 00:26:54.109 so much adolescent or adult autistics. This critical 00:26:54.160 --> 00:26:58.859 in the role of oxytocin and development. I think 00:26:58.859 --> 00:27:02.880 this is a good finding in correlation a meta 00:27:02.880 --> 00:27:07.119 -analysis using 18 studies examined and determined 00:27:07.119 --> 00:27:14.440 this finding and that was released in 2021. Oxytocin 00:27:14.440 --> 00:27:19.579 and serotonin. Oxytocin and serotonin appears 00:27:19.579 --> 00:27:24.019 to be the driving force in the role of supporting 00:27:24.019 --> 00:27:29.119 anxiety -like features and supports socialness. 00:27:30.500 --> 00:27:35.880 The dorsal raffae, the raffae is the brain serotonin, 00:27:36.279 --> 00:27:41.700 receives oxytocin fibers and the raffae has oxytocin 00:27:41.700 --> 00:27:48.059 receptors. This action causes a release of serotonin, 00:27:48.140 --> 00:27:52.660 specifically to frontal brain regions. And remember, 00:27:52.920 --> 00:27:56.740 serotonin's role in active versus passive coping. 00:27:58.559 --> 00:28:02.759 In contrast, studies show genetically removing 00:28:02.759 --> 00:28:07.759 this connection after childbirth resulted in 00:28:07.759 --> 00:28:12.359 offspring loss. Remember the developmental roles. 00:28:13.400 --> 00:28:17.680 The impaired nursing increased aggression and 00:28:17.680 --> 00:28:24.079 behavior complications. When oxytocin and serotonin 00:28:24.079 --> 00:28:29.140 work in concert, it provides a perception of 00:28:29.140 --> 00:28:34.539 rewarding socialness occurring. In other words, 00:28:34.880 --> 00:28:39.019 when socialness is rewarding, coordinated activity 00:28:39.019 --> 00:28:43.980 of oxytocin and serotonin is required. And it 00:28:43.980 --> 00:28:47.460 goes to that ventral striatum area, the nucleus 00:28:47.460 --> 00:28:53.470 accumbens. Said differently, a lack of oxytocin 00:28:53.470 --> 00:28:59.069 prevents social enjoyment. And now, just a brief 00:28:59.069 --> 00:29:03.549 note, when we discuss female versus male autistics, 00:29:05.230 --> 00:29:08.589 the nucleus accumbens and oxytocin is gonna be 00:29:08.589 --> 00:29:16.309 huge. This was a huge finding. Anyway, data on 00:29:16.309 --> 00:29:21.410 various modeled organisms and humans show various 00:29:21.410 --> 00:29:25.849 oxytocin and serotonin connections including 00:29:25.849 --> 00:29:30.130 in the prefrontal cortex, that area that makes 00:29:30.130 --> 00:29:36.109 us the superior species on earth, and the amygdala, 00:29:36.769 --> 00:29:43.269 the striatal areas, and interesting, serotonin 00:29:43.269 --> 00:29:47.779 regulates the release of oxytocin in one of the 00:29:47.779 --> 00:29:54.799 areas of the hypothalamus. So three things of 00:29:54.799 --> 00:29:59.539 interest here. One, the reward processing. Two, 00:29:59.799 --> 00:30:04.700 the fear response. And three, the social -emotional 00:30:04.700 --> 00:30:11.839 processing. Doxytocin and dopamine. The roles 00:30:11.839 --> 00:30:15.980 in dopamine primarily stick to the main roles 00:30:15.980 --> 00:30:20.380 of dopamine. That is, connecting brain regions 00:30:20.380 --> 00:30:27.299 based on wanting, motivation, and craving. What 00:30:27.299 --> 00:30:32.339 you find rewarding and aspects of cognitive processing 00:30:32.339 --> 00:30:38.480 and sensory gating. This is a good one. Remember 00:30:38.480 --> 00:30:42.759 dopamine is a neuromodulator and it conducts 00:30:42.759 --> 00:30:47.259 whole systems. It turns things on, turns certain 00:30:47.259 --> 00:30:49.880 brain regions on or whole systems throughout 00:30:49.880 --> 00:30:54.640 the body. It activates them and it turns things 00:30:54.640 --> 00:30:59.799 off. Little brain regions or entire systems, 00:31:00.160 --> 00:31:05.119 biological systems, it inactivates them and it 00:31:05.119 --> 00:31:08.460 regulates action through the nervous system. 00:31:09.160 --> 00:31:13.559 Dopamine has two receptor types. Dopamine has 00:31:13.559 --> 00:31:18.519 five total receptors broken down into two types. 00:31:19.380 --> 00:31:23.740 D1 is excitation, and that's dopamine receptor 00:31:23.740 --> 00:31:30.400 one and five. And D2 is inhibition. These are 00:31:30.400 --> 00:31:36.099 dopamine receptors two, three, and four. D2 type 00:31:36.099 --> 00:31:41.920 receptors are inhibition. So, Now we will introduce 00:31:41.920 --> 00:31:49.079 GABA, which is inhibition. In autism, dysregulation 00:31:49.079 --> 00:31:53.819 of GABA receptors exists in the data. Remember 00:31:53.819 --> 00:31:56.579 one of those components or reasons that gives 00:31:56.579 --> 00:32:01.420 us the EI imbalance. Remember a critical role 00:32:01.420 --> 00:32:06.099 of GABA, which is inhibitory, turning things 00:32:06.099 --> 00:32:10.049 off or quieting the brain. One of GABA's main 00:32:10.049 --> 00:32:16.009 roles is regulating sensations via that thalamocortical 00:32:16.009 --> 00:32:22.009 path. These abnormal GABA receptors are also 00:32:22.009 --> 00:32:25.710 found in seizures, remember the closeness to 00:32:25.710 --> 00:32:31.349 epilepsy, and learning disabilities, and our 00:32:31.349 --> 00:32:35.789 primary topic in social and cognitive dysfunctions. 00:32:37.200 --> 00:32:42.640 The excitation inhibition needs both oxytocin 00:32:42.640 --> 00:32:48.700 and GABA for a proper balance. For the developing 00:32:48.700 --> 00:32:52.339 brain, these components are critical for proper 00:32:52.339 --> 00:32:58.039 development. A study shows aberrations in these 00:32:58.039 --> 00:33:05.759 areas are a cause of autistic phenotypes. Also, 00:33:05.920 --> 00:33:10.480 abnormal GABA development in the dopaminergic 00:33:10.480 --> 00:33:14.019 areas of the brain is our region of interest. 00:33:15.599 --> 00:33:19.940 This expands on some dysfunction of the excitation 00:33:19.940 --> 00:33:24.339 and inhibition balance and offers a topic in 00:33:24.339 --> 00:33:29.779 recent research of pathophysiology of autism. 00:33:31.960 --> 00:33:36.369 In addition, neurogenesis the development of 00:33:36.369 --> 00:33:42.289 neurons. Remember, cells divide and neurite growth 00:33:42.289 --> 00:33:46.990 and synapsis formation involve many factors. 00:33:47.769 --> 00:33:51.230 Nothing's singular. These neuropeptides alongside 00:33:51.230 --> 00:33:58.789 GABA are critical for these roles. Okay, before 00:33:58.789 --> 00:34:03.250 we end, I just want to cover intranasal oxytocin. 00:34:03.420 --> 00:34:08.360 as a therapeutic option for autism or for those 00:34:08.360 --> 00:34:14.960 autistic phenotypes. Intranasal oxytocin administration 00:34:14.960 --> 00:34:18.780 penetrates the brain. It crosses the blood -brain 00:34:18.780 --> 00:34:24.079 barrier with capillary beds and induces cognitive, 00:34:24.880 --> 00:34:29.860 emotional, and behavioral changes mostly related 00:34:29.860 --> 00:34:35.420 to socialness. To no surprise, for that reason, 00:34:35.960 --> 00:34:40.840 data exists on testing intranasal oxytocin for 00:34:40.840 --> 00:34:47.280 autism superdeficits, social anxiety, increasing 00:34:47.280 --> 00:34:51.760 peer -to -peer capabilities, or said differently, 00:34:52.500 --> 00:34:56.960 acting on those roles oxytocin has in social 00:34:56.960 --> 00:35:04.780 functioning discussed earlier. The data on intranasal 00:35:04.780 --> 00:35:12.139 oxytocin is both inconsistent and low risk, meaning 00:35:12.139 --> 00:35:18.500 little to zero side effects. Criteria for the 00:35:18.500 --> 00:35:22.679 intranasal oxytocin include standardization of 00:35:22.679 --> 00:35:29.900 dosage, frequency, formulation, differences in 00:35:29.900 --> 00:35:35.130 sex, and devices used for administration. Two 00:35:35.130 --> 00:35:39.150 points to consider. There's an idea gender differences 00:35:39.150 --> 00:35:44.769 is a primary cause of the inconsistent data and 00:35:44.769 --> 00:35:49.050 intranasal oxytocin is shown to improve socialness 00:35:49.050 --> 00:35:54.389 or more precisely shown to suppress anxiety in 00:35:54.389 --> 00:35:58.650 healthy participants. The reason we will explore 00:35:58.650 --> 00:36:02.230 this option is because there is proof and it 00:36:02.230 --> 00:36:06.329 is in the so -called low risk category as a helpful 00:36:06.329 --> 00:36:11.230 option for autism. There are several things to 00:36:11.230 --> 00:36:16.889 know here, several takeaways to consider. One, 00:36:17.210 --> 00:36:23.170 studies do show improvements and a few meta -analysis 00:36:23.170 --> 00:36:29.170 confirm this. Intranasal oxytocin, this approach 00:36:29.369 --> 00:36:32.349 has been around for about 20 years now, I believe 00:36:32.349 --> 00:36:38.210 2003. So some data has collected. The second 00:36:38.210 --> 00:36:42.530 thing to consider is it is low risk and this 00:36:42.530 --> 00:36:46.409 ought to be a tremendous factor. If it works, 00:36:46.409 --> 00:36:52.690 it works. If it doesn't, okay, it doesn't. Three, 00:36:53.210 --> 00:36:58.610 it is unknown if intranasal mimics the endogenous 00:36:58.780 --> 00:37:03.920 amounts released in the brain. The dosage has 00:37:03.920 --> 00:37:11.559 to really be pinpointed. Four. There is a chance 00:37:11.559 --> 00:37:17.559 intranasal oxytocin activates broad serotonin 00:37:17.559 --> 00:37:22.139 across the brain. In other words, it might lack 00:37:22.139 --> 00:37:28.610 specificity. And lastly, number five. And this 00:37:28.610 --> 00:37:33.610 is a big one. Intranasal appears to target the 00:37:33.610 --> 00:37:37.769 magnocellular pathway, which is more peripheral. 00:37:38.809 --> 00:37:43.449 So it acts on hormones and it blunts stress responses 00:37:43.449 --> 00:37:48.949 in the hormonal systems such as cortisol. When 00:37:48.949 --> 00:37:54.230 in reality, the idea is acting on the central 00:37:54.230 --> 00:38:00.309 pathways that the areas responsible for the brain 00:38:00.309 --> 00:38:05.070 regions, that cellular activity. You want more 00:38:05.070 --> 00:38:10.309 neuropeptide or neurotransmitter and less hormone 00:38:10.309 --> 00:38:14.969 so it can target the nucleus accumbens. Remember, 00:38:15.230 --> 00:38:20.190 co -activating with serotonin and oxytocin to 00:38:20.190 --> 00:38:24.409 reach the nucleus accumbens. That is the primary 00:38:24.409 --> 00:38:30.940 target. And that works by the way of the parvocellular 00:38:30.940 --> 00:38:36.980 function or that parvocellular path and not the 00:38:36.980 --> 00:38:41.599 magnocellular. If you are listening and enjoy 00:38:41.599 --> 00:38:45.739 the episode or enjoy the podcast, feel free to 00:38:45.739 --> 00:38:50.659 leave a review or rating. In podcasting, reviews, 00:38:51.179 --> 00:38:55.360 ratings, and downloads are huge. And I very much 00:38:55.360 --> 00:39:01.239 appreciate your feedback. You can email me at 00:39:01.239 --> 00:39:10.420 info .fromthespectrumatgmail .com. And thank 00:39:10.420 --> 00:39:14.239 you for listening to From the Spectrum Podcast.