Update on Oxytocin and Vasopressin in Autism

A nebulizer as a better means of delivering vasopressin?

 

Previous posts: 

https://www.epiphanyasd.com/search/label/Oxytocin

https://www.epiphanyasd.com/search/label/Vasopressin

One key, often unaddressed feature of autism is hormonal dysfunction in the brain. Oxytocin and vasopressin are two closely related hormones that significantly affect social behavior, an area frequently disrupted in those with autism. Interestingly, this challenge is often most troubling in individuals with milder forms of autism, as they are more acutely aware of their differences in social interactions. While serotonin dysfunctions also play a key role, today’s post focuses on the impact of oxytocin and vasopressin.

 

 Today we are in the top right - central hormonal dysfunction

Here is a very recent article on a Vasopressin trial:

Vasopressin Boosts Social Skills Without Aggression in Autism

Summary: New research shows that supplementing vasopressin levels in low-social rhesus monkeys improves social behavior and facial recognition without triggering aggression. The findings suggest vasopressin deficiency may underlie social difficulties seen in autism spectrum disorder (ASD).

Monkeys given vasopressin became more responsive to prosocial cues and better at remembering faces, critical skills often impaired in ASD. This work opens new avenues for precision therapies aimed at addressing core social deficits in autism rather than just managing symptoms.

Key Facts:

·    Social Gains Without Aggression: Vasopressin improved prosocial behavior and facial memory without increasing aggression.

·    Biological Link to ASD: Low-social monkeys naturally mirror some social impairments seen in humans with autism.

·    Therapeutic Potential: Vasopressin supplementation could offer a future targeted treatment for core social deficits in ASD.

For years, Florida Tech’s Catherine Talbot, an assistant professor of psychology, has worked to understand the sociality of male rhesus monkeys and how low-social monkeys can serve as a model for humans with autism.

Her most recent findings show that replenishing a deficient hormone, vasopressin, helped the monkeys become more social without increasing their aggression—a discovery that could change autism treatment. 

In a research paper published in the journal PNAS, Talbot and researchers with Stanford, the University of California, Davis and the California National Primate Research Center explored vasopressin, a hormone that is known to contribute to mammalian social behavior, as a potential therapeutic treatment that may ultimately help people with autism better function in society.

Previous work from this research group had found that vasopressin levels are lower in their low-social rhesus monkey model, as well as in a select group of people with ASD.

Previous studies testing vasopressin in rodents had found that increased hormone levels caused more aggression. As a result, researchers warned against administering vasopressin as a treatment, Talbot said.

However, she argued that in those studies, vasopressin induced aggression in contexts where aggression is the socially appropriate response, such as guarding mates in their home territory, so the hormone may promote species-typical behavior.

She also noted that the previous studies tested vasopressin in “neurotypical” rodents, as opposed to animals with low-social tendencies.

“It may be that individuals with the lowest levels of vasopressin may benefit the most from it—that is the step forward toward precision medicine that we now need to study,” Talbot said.

In her latest paper, Talbot and her co-authors tested how low-social monkeys with low vasopressin levels and high autistic-like trait burden responded to vasopressin supplementation to make up for their natural deficiency. They administered the hormone through a nebulizer, into which the monkeys could opt.

For a few minutes each week, the monkeys voluntarily held their faces up to a nebulizer to receive their dose while sipping white grape juice—a favorite among the monkeys, Talbot said.

After administering the hormone and verifying that it increased vasopressin levels in the central nervous system, the researchers wanted to see how the monkeys responded to both affiliative and aggressive stimuli by showing them videos depicting these behaviors.

They also compared their ability to recognize and remember new objects and faces, which is another important social skill.

They found that normally low-social monkeys do not respond to social communication and were better at recognizing and remembering objects compared to faces, similar to some humans diagnosed with ASD. When the monkeys were given vasopressin, they began reciprocating affiliative, pro-social behaviors, but not aggression.

It also improved their facial recognition memory, making it equivalent to their recognition memory of objects.

In other words, vasopressin “rescued” low-social monkeys’ ability to respond prosocially to others and to remember new faces. The treatment was successful—vasopressin selectively improved the social cognition of these low-social monkeys.

“It was really exciting to see this come to fruition after pouring so much work into this project and overcoming so many challenges,” Talbot said of her findings.

One of Talbot’s co-authors has already begun translating this work to cohorts of autism patients. She expects more clinical trials to follow.

 

The original paper: 

Nebulized vasopressin penetrates CSF and improves social cognition without inducing aggression in a rhesus monkey model of autism

  

  

A review/update of all the previous posts on vasopressin and oxytocin: 

Plasma vs CSF Levels of hormones

It is relatively straightforward to measure hormone levels in a blood sample. However, plasma levels of oxytocin and vasopressin do not reliably reflect the levels in the brain. Brain hormone levels are best measured via cerebrospinal fluid (CSF), which requires a lumbar puncture. Studies have consistently shown that both oxytocin and vasopressin levels are reduced in the CSF of individuals with autism. These reductions highlight potential deficiencies in the central signaling pathways of these hormones.

 

Dysfunctional Receptors

The dysfunction in autism may not only involve reduced hormone levels but also abnormalities in their receptors.

• Oxytocin Receptors (OXTR): Variations in the oxytocin receptor gene have been linked to autism, potentially leading to reduced receptor sensitivity or signaling efficiency. Dysfunctional oxytocin receptors can impair bonding, trust, and other social behaviors.
• Vasopressin Receptors: Vasopressin exerts its effects through several receptor subtypes:
• V1a Receptors: Involved in social behavior regulation.
• V1b (also known as V3) Receptors: Primarily located in the anterior pituitary, these receptors influence the release of adrenocorticotropic hormone (ACTH) and are implicated in stress responses.
• V2 Receptors: Regulate water retention in the kidneys.

Alterations in these receptors, especially V1a and V1b, may contribute to the social and stress-related symptoms observed in autism.

 

Therapeutic Options and Their Limitations

Addressing these hormonal and receptor dysfunctions offers promising avenues for therapeutic intervention, though challenges remain:

• Increasing Hormone Levels in the Brain. Enhancing oxytocin or vasopressin concentrations in the brain could improve social behaviors. Measuring the efficacy of these interventions is difficult because CSF sampling is invasive.
• Receptor Activation. Drugs designed to activate oxytocin or vasopressin receptors directly could bypass issues with hormone levels. However, such therapies need precise targeting to avoid side effects and ensure effectiveness.

 

Delivery Methods

Various delivery methods have been explored to introduce oxytocin or vasopressin into the body:

Intranasal Spray: Widely researched, intranasal delivery targets the brain directly via the nasal mucosa. However, this method is challenging because the drug is not meant to be inhaled into the lungs. Instead, it must cross the nasal membrane or travel along the olfactory or trigeminal nerves directly to the brain. Only specific molecules can effectively cross the blood-brain barrier, typically those that are small and lipophilic. Stanford University has conducted groundbreaking work using intranasal vasopressin in autism, demonstrating potential improvements in social behavior. However, many commercially available nasal sprays may lose their effectiveness because the active hormones degrade during transit if not properly chilled.

Nebulizer: Recent studies have investigated the use of nebulized vasopressin, delivering the hormone in aerosol form for inhalation. This method may offer more consistent dosing and better absorption while avoiding the challenges of nasal delivery.

Tablet by Mouth: Oral administration faces challenges because these hormones can degrade in the digestive system and may not cross the blood-brain barrier effectively. Vasopressin, for instance, cannot be taken orally due to rapid degradation. However, desmopressin, a synthetic analog of vasopressin, is orally bioavailable and can be used to treat conditions like diabetes insipidus.

Interestingly, desmopressin appears to help some individuals with autism, possibly due to its effects on water retention and central nervous system signaling. The nasal spray form of desmopressin offers rapid absorption compared to tablets, but tablets provide more convenient and consistent dosing.

Probiotic by Mouth. Human research suggests that specific strains of Lactobacillus reuteri can stimulate oxytocin production. These probiotics may offer a novel and non-invasive therapeutic option to enhance oxytocin levels naturally. Biogaia Protectis is one such oxytocin-stimulating probiotic.

 

Recent Advances: Nebulized Vasopressin for Social Deficits in Autism

Research conducted by scientists from Florida Institute of Technology, Stanford, and other institutions has revealed that supplementing vasopressin in low-social rhesus monkeys improves social behaviors and facial recognition without increasing aggression. These findings highlight the potential of vasopressin as a precision therapy for addressing core social deficits in autism.

The study focused on low-social rhesus monkeys, which exhibit behaviors similar to certain social impairments observed in humans with autism. The researchers used a nebulizer to administer vasopressin, a non-invasive and targeted delivery method. The monkeys voluntarily inhaled the hormone while drinking grape juice, ensuring an effective and stress-free administration. The point to note is that monkeys need to breath through their nose for the therapy to work, hence the drink.

Key findings include:

• Improved Prosocial Behavior. Vasopressin enhanced affiliative behaviors and facial recognition memory in low-social monkeys without increasing aggression, addressing a common concern from earlier studies in neurotypical animals.
• Precision Medicine Potential. Researchers observed that individuals with the lowest vasopressin levels derived the greatest benefit, suggesting the importance of tailoring treatments to specific biological deficiencies.
• Successful Central Nervous System Targeting. The study verified that nebulized vasopressin reached the central nervous system, a critical factor for its efficacy in enhancing social cognition.

These results offer a promising path forward, especially since one of the study’s co-authors is already working on translating these findings to human trials. If successful, this approach could modernize autism treatment by targeting an underlying hormonal deficiencies.

 

Why approved therapies remain elusive

Despite the promising science, no therapies targeting oxytocin or vasopressin have yet gained widespread approval for treating autism. The reasons for this include:-

• Challenges in Delivery Systems. Ensuring that sufficient amounts of oxytocin or vasopressin reach the brain remains a significant hurdle. Many delivery systems, such as nasal sprays, face degradation of the active hormone during transit or storage, limiting their effectiveness.
• Variable Responses. Hormonal therapies may yield inconsistent results due to genetic differences, baseline hormone levels, or receptor functionality among individuals.
• Complexity of ASD. Autism is a highly heterogeneous condition with diverse underlying causes, making it challenging to develop a one-size-fits-all treatment.

 

Over-the-counter (OTC) therapies also face criticism for their lack of rigorous testing and quality control. Many users report limited or no benefits, likely due to suboptimal dosing, poor bioavailability, or degraded products. These failures underscore the need for precision medicine approaches and robust clinical evidence to guide treatment.

 

Conclusion

While hormonal and receptor dysfunctions involving oxytocin and vasopressin present significant hurdles, they also offer unique opportunities for targeted interventions. Current therapies and delivery methods are promising but require further refinement to maximize their effectiveness. Recent advances, such as the use of nebulized vasopressin, demonstrate the potential for precision therapies to address core social deficits in autism. Future research into the relationship between these hormones and autism may unlock more personalized and effective treatments, bringing hope to those affected by these challenges. 

Many people have a nebulizer at home - we have had one for 15 years. They are very simple to use, even with a young child with severe autism. If the vasopressin, or oxytocin therapy was once a week for 5 minutes it would be a simple process. The trick would be ensuring breathing through the nose, rather than mouth, which you would normally be encouraging for drugs to reach the lungs. With the monkeys they added a straw and a favourite drink.

Vasopressin has to be kept between 2 and 8 celsius (36-46F). So you would get it from the local pharmacy, measure the dose, add saline solution and turn on the nebulizer. Do not try to buy it online, it will not work! It looks they have already started using this method at Stanford.  

If it works on a rhesus monkey, there is a good chance it will work on your own little monkey—and, of course, for our many adult Aspie readers.