Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Comment
  • Published:

Vasopressin deficiency: a hypothesized driver of both social impairment and fluid imbalance in autism spectrum disorder

Molecular Psychiatry (2024)Cite this article

Subjects

Scientific naming conventions are often idiosyncratic. For example, biological processes have acquired names after a physician who described a syndrome (Alois Alzheimer), the resemblance of a structure to a common item (sella turcica or Turkish saddle), or a function a molecule is observed to mediate (growth hormone). Although these names may be useful for initial characterization, they can also create confusion (e.g., when a biological entity receives multiple names) or be misleading (e.g., when critical aspects of a molecule’s function are overlooked because it is named after a different, unrelated action).

We believe that arginine vasopressin (AVP), also known as anti-diuretic hormone (ADH), is one such “casualty.” Its dual scientific names – suggesting important effects on blood pressure maintenance and renal water regulation – have made integrating knowledge of AVP’s diverse functions across disciplines challenging. Moreover, because this molecule was named for its peripheral actions – twice! – its function in the central nervous system as a key regulator of mammalian social behavior was insufficiently studied for decades.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on SpringerLink
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

References

  1. Rigney N, de Vries GJ, Petrulis A, Young LJ. Oxytocin, Vasopressin, and Social Behavior: From Neural Circuits to Clinical Opportunities. Endocrinology. 2022;163:bqac111.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Caldwell HK, Lee HJ, Macbeth AH, Young WS 3rd. Vasopressin: behavioral roles of an “original” neuropeptide. Prog Neurobiol. 2008;84:1–24.

    Article  CAS  PubMed  Google Scholar 

  3. Insel TR, O’Brien DJ, Leckman JF. Oxytocin, vasopressin, and autism: is there a connection? Biol Psychiatry. 1999;45:145–57.

    Article  CAS  PubMed  Google Scholar 

  4. Parker KJ, Garner JP, Oztan O, Tarara ER, Li J, Sclafani V, et al. Arginine vasopressin in cerebrospinal fluid is a marker of sociality in nonhuman primates. Sci Transl Med. 2018;10:eaam9100.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Oztan O, Garner JP, Constantino JN, Parker KJ. Neonatal CSF vasopressin concentration predicts later medical record diagnoses of autism spectrum disorder. Proc Natl Acad Sci USA. 2020;117:10609–13.

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  6. Oztan O, Garner JP, Partap S, Sherr EH, Hardan AY, Farmer C, et al. Cerebrospinal fluid vasopressin and symptom severity in children with autism. Ann Neurol. 2018;84:611–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Parker KJ, Oztan O, Libove RA, Mohsin N, Karhson DS, Sumiyoshi RD, et al. A randomized placebo-controlled pilot trial shows that intranasal vasopressin improves social deficits in children with autism. Sci Transl Med. 2019;11:eaau7356.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Raja M, Azzoni A, Giammarco V. Diabetes Insipidus and Polydipsia in a Patient with Asperger’s Disorder and an Empty Sella: A Case Report. J Autism Dev Disord. 1998;28:235–9.

    Article  CAS  PubMed  Google Scholar 

  9. Brugnara M, Gaudino R, Tedeschi S, Syrèn ML, Perrotta S, Maines E, et al. Type III Bartter-like syndrome in an infant boy with Gitelman syndrome and autosomal dominant familial neurohypophyseal diabetes insipidus. J Pediatr Endocrinol Metab. 2014;27:971–5.

    Article  CAS  PubMed  Google Scholar 

  10. Paul MJ, Peters NV, Holder MK, Kim AM, Whylings J, Terranova JI, et al. Atypical Social Development in Vasopressin-Deficient Brattleboro Rats. eNeuro. 2016;3:ENEURO.0150–15.2016.

    Article  PubMed  Google Scholar 

  11. Mills R, Wing L. Excessive drinking of fluids in children and adults on the autism spectrum: a brief report. Adv Autism. 2015;1:51–60.

    Article  Google Scholar 

  12. Terai K, Munesue T, Hiratani M. Excessive water drinking behavior in autism. Brain Dev. 1999;21:103–6.

    Article  CAS  PubMed  Google Scholar 

  13. Rowland GH. Polydipsia in Adults with Learning Disabilities: Prevalence, Presentation and Aetiology. Br J Dev Disabil. 1999;45:52–62.

    Article  Google Scholar 

  14. Pan CG 58 - Polyuria and Urinary Incontinence. In: Kliegman RM, Toth H, Bordini BJ, Basel D, editors. Nelson Pediatric Symptom-Based Diagnosis: Common Diseases and their Mimics (Second Edition). Elsevier: Philadelphia, 2023, pp 1106–13.e1101.

  15. von Gontard A, Pirrung M, Niemczyk J, Equit M. Incontinence in children with autism spectrum disorder. J Pediatr Urol. 2015;11:264.e261–264.e267.

    Google Scholar 

  16. Mayes SD, Calhoun S, Bixler EO, Vgontzas AN. Sleep Problems in Children with Autism, ADHD, Anxiety, Depression, Acquired Brain Injury, and Typical Development. Sleep Med Clin. 2009;4:19–25.

    Article  Google Scholar 

  17. Christ-Crain M, Bichet DG, Fenske WK, Goldman MB, Rittig S, Verbalis JG, et al. Diabetes insipidus. Nat Rev Dis Prim. 2019;5:54.

    Article  PubMed  Google Scholar 

  18. Zeidan J, Fombonne E, Scorah J, Ibrahim A, Durkin MS, Saxena S, et al. Global prevalence of autism: A systematic review update. Autism Res. 2022;15:778–90.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Oztan O, Talbot CF, Argilli E, Maness AC, Simmons SM, Mohsin N, et al. Autism-associated biomarkers: test-retest reliability and relationship to quantitative social trait variation in rhesus monkeys. Mol Autism. 2021;12:50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Mutter CM, Smith T, Menze O, Zakharia M, Nguyen H. Diabetes Insipidus: Pathogenesis, Diagnosis, and Clinical Management. Cureus. 2021;13:e13523.

    PubMed  PubMed Central  Google Scholar 

  21. Fenske W, Refardt J, Chifu I, Schnyder I, Winzeler B, Drummond J, et al. A Copeptin-Based Approach in the Diagnosis of Diabetes Insipidus. N Engl J Med. 2018;379:428–39.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The writing of this manuscript was supported, in part, by funding from the National Institutes of Health (HD091972; KJP and AYH), the Department of Defense (W81XWH-21-1-0210; KJP), and the Truong-Tan Broadcom Endowment (KJP). No funding source was involved in the writing of this report or in the decision to submit it for publication.

Author information

Authors and Affiliations

  1. 401 Quarry Road, Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, 94305, USA

    Lauren Clarke, Antonio Y. Hardan & Karen J. Parker

  2. 1265 Welch Road, Department of Medicine, Division of Endocrinology, Stanford University, Stanford, CA, 94305, USA

    Neil Gesundheit

  3. 675 Nelson Rising Lane, Department of Neurology, University of California, San Francisco, CA, 94158, USA

    Elliott H. Sherr

  4. 300 Pasteur Drive, Department of Comparative Medicine, Stanford University, Stanford, CA, 94305, USA

    Karen J. Parker

Authors
  1. Lauren Clarke
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Neil Gesundheit
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Elliott H. Sherr
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Antonio Y. Hardan
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Karen J. Parker
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

All authors contributed to the conceptualization of this manuscript. LC and KJP performed the literature review and wrote the first draft of the manuscript. NG, EHS, and AYH reviewed the manuscript and provided critical editorial feedback on it. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Karen J. Parker.

Ethics declarations

Competing interests

LC, NG, and EHS have no interests to declare. AYH declares consulting fees from Quadrant Bio, IAMA therapeutics, and Beaming Health. AYH and KJP are receiving Vasostrict from Endo International free of charge for use in an investigator-initiated, NIH-funded phase IIb clinical trial that is evaluating the safety and efficacy of vasopressin treatment to improve social abilities in children with ASD. The Board of Trustees of the Leland Stanford Junior University has filed patent applications related to data reviewed herein: PCT/US2019/019029 (“Methods for diagnosing and determining severity of an autism spectrum disorder”) and PCT/US2019/041250 (“Intranasal Vasopressin Treatment for Social Deficits in Children with Autism”). These patents have not been granted, nor licensed, and no author is receiving financial compensation at this time.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Clarke, L., Gesundheit, N., Sherr, E.H. et al. Vasopressin deficiency: a hypothesized driver of both social impairment and fluid imbalance in autism spectrum disorder. Mol Psychiatry (2024). https://doi.org/10.1038/s41380-024-02497-6

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1038/s41380-024-02497-6

Search

Advanced search

Quick links