Journal of Neurology and Neuroscience

Keywords

Autism spectrum disorders; Saliva; Oxytocin; Social behavior; High functioning; Assessment

Introduction

Oxytocin is a Nona peptide synthesized in the hypothalamus which is known to influence maternal behavior, maternal aggression, pair bonding and sexual behaviors [1]. Oxytocin participates in the development of normal social bonds and in humans is involved in affiliate behaviors such as nursing, mating, social attachment, bonding, social memory and support, human trust and parental behavior [2]. Aberrations in this neurochemical system may contribute for developing independence and aloofness [3], thus there is a reason to believe that disturbances in oxytocin function may be responsible for some of the behavioral abnormalities associated with Autism Spectrum Disorders (ASD) [4].

Plasma, salivary and CSF oxytocin measurements in ASD have been done in the past. Though studies using saliva are limited, the technique is gaining popularity in the last few years. We searched on PubMed, for articles related to collection of salivary sample in children with ASD using key words oxytocin, autism, autism spectrum disorder, neuroendocrine, cortisol, salivary oxytocin and saliva. Relevant articles were then reviewed for appropriate information on collection methods for salivary sample in children with ASD.

Discussion

Salivary oxytocin is a reliable biomarker of peripheral oxytocin and oxytocin levels in plasma and saliva are comparable. Studies in parents of typical children have shown similar baseline levels of plasma and salivary oxytocin; and salivary oxytocin is known to be individually stable across observations [5]. Salivary and plasma oxytocin show medium level correlation [6,7] and therapeutic intranasal administration of oxytocin increases both plasma and salivary oxytocin [8,9]. These evidences have shown that salivary oxytocin can be considered as an alternative to drawing blood and ethical issues related to the same can be overcome [10]. It also can help to conduct experiments in real life situations in children with ASD were needles may not be feasible [11].

Collection methods

Salivary samples in adults and infants can be collected using salivettes [5,6,9]. Some studies have also used passive drool technique in adults [8]. Studies in high functioning ASD population have demonstrated that both passive drool and salivette methods are equally acceptable by children for collecting saliva [12]. Though adults and adolescents with high functioning ASD would cooperate, problems arise in very young children and in those with low functioning autism. Their ability to understand the methodology involved in collecting saliva using salivettes or passive drool method is limited. Many children with ASD are also known to have sensory issues commonly referred to as sensory defensiveness or sensory over reactivity [13] which is a hurdle in making them retain foreign objects like straw or sorbents in their mouth for 40-60 seconds for collecting saliva [5,6].

Other studies were salivary samples are collected for levels of cortisol, testosterone, etc have used methods like feed the frog technique, desensitizing the child and then rewarding after obtaining sample, collection using cotton dental rolls, collection by passive drool after stimulating the production by the use of sugarless chewing gum, etc [14-16] (Table 1).

Table 1: Saliva collection methods.

Conclusion

Lower levels of oxytocin in ASD have been demonstrated many times in adult patients but only few studies have been conducted in children and adolescents with ASD. Evidences imply possible beneficial effects of oxytocin administration on autistic social and communicative dysfunctions and their neural underpinnings. Newer techniques for collection of saliva in children with ASD will be promising as they will help monitor the oxytocin treatment outcome in a quantitative non clinical approach and would enhance the current research in oxytocin supplementation. However, further extensive large-scale studies and longitudinal clinical trials to identify neurogenetic mechanisms of the therapeutic effects of oxytocin are also needed [8,10,17]

Conflicting interest

The authors declare there is no conflict of interest.

References

1. Leckman JF, Herman AE(2002) Maternal behavior and developmental psychopathology. Biological psychiatry 51: 27-43.
2. Insel RT, Shapiro LE (1992) Oxytocin receptors and maternal behavior. Annals of the New York Academy of Sciences 652: 122-141.
3. Panksepp J (1993) Commentary on the possible role of oxytocin in autism. Journal of autism and developmental disorders 23: 567-569.
4. Susan G, Sally O, Lainhart J (2003) Brief report: pitocin induction in autistic and nonautistic individuals. Journal of autism and developmental disorders 33: 205-208.
5. Ruth F, Ilanit G, Schneiderman I, weisman O, Zagoory-Sharon O, et al. (2010) Natural variations in maternal and paternal care are associated with systematic changes in oxytocin following parent-infant contact. Psychoneuroendocrinology 35: 1133-1141.
6. Ruth F, Ilanit G, Zagoory-Sharon O(2010) The cross-generation transmission of oxytocin in humans. Hormones and behavior 58: 669-676.
7. Ruth F, Ilanit G,Zagoory-Sharon O(2011) Maternal and paternal plasma, salivary, and urinary oxytocin and parent-infant synchrony: considering stress and affiliation components of human bonding. Developmental science 14: 752-761.
8. Marinus VI, Ritu B, der Veen V, Grewen KM, Kranenburg MJB, et al. (2012) Elevated Salivary Levels of Oxytocin Persist More than 7 h after Intranasal Administration. Frontiers in neuroscience 6: 174.
9. Omri W, Zagoory-Sharon O, Feldman R, et al. (2012) Intranasal oxytocin administration is reflected in human saliva. Psychoneuroendocrinology 37: 1582-1586.
10. Ruth F, Ilanit G, Influs M, Gutbir T, Ebstein RP(2013) Parental Oxytocin and Early Caregiving Jointly Shape Children's Oxytocin Response and Social Reciprocity. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 38: 1154-1162.
11. Grewen M Karen, Davenport E Russell,Kathleen C Light (2010) An investigation of plasma and salivary oxytocin responses in breast- and formula-feeding mothers of infants. Psychophysiology 47: 625-632.
12. Putnam S.K, Lopata C, Fox J.D, Thomeer M.L, Rodgers J.D, et al. (2012) Comparison of saliva collection methods in children with high-functioning autism spectrum disorders: acceptability and recovery of cortisol [Research Support, U.S. Gov't, Non-P.H.S.]. Child psychiatry and human development 43: 560-573.
13. Cermak SA, Curtin C, Bandini LG (2010) Food selectivity and sensory sensitivity in children with autism spectrum disorders [Research Support, N.I.H, Extramural Research Support, U.S. Gov't, P.H.S.Review] Journal of the American Dietetic Association 110: 238-246.
14. De Andrés-García S, Moya-Albiol L, González-Bono E (2012) Salivary cortisol and immunoglobulin A: responses to stress as predictors of health complaints reported by caregivers of offspring with autistic spectrum disorder. Hormones and behavior 62: 464-474.
15. Gabriels RL, Agnew JA, Pan Zhaoxing, Holt KD, Ann R, et al. (2013) Elevated repetitive behaviors are associated with lower diurnal salivary cortisol levels in autism spectrum disorder. Biological psychology 93: 262-268.
16. Hollocks MJ, Patricia H, Andrew SP, Mizanur K, Emily S (2014) Differences in HPA-axis and heart rate responsiveness to psychosocial stress in children with autism spectrum disorders with and without co-morbid anxiety. Psychoneuroendocrinology 46: 32-45.
17. Ilanit G, Brent CVW, Randi HB, Cara C, Molly VL, et al. (2013) Oxytocin enhances brain function in children with autism. Proceedings of the National Academy of Sciences of the United States of America 110: 20953-20958.