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Dose-dependent social-cognitive effects of intranasal oxytocin delivered with novel Breath Powered device in adults with autism spectrum disorder: a randomized placebo-controlled double-blind crossover trial.

ABSTRACT: The neuropeptide oxytocin has shown promise as a treatment for symptoms of autism spectrum disorders (ASD). However, clinical research progress has been hampered by a poor understanding of oxytocin's dose-response and sub-optimal intranasal delivery methods. We examined two doses of oxytocin delivered using a novel Breath Powered intranasal delivery device designed to improve direct nose-to-brain activity in a double-blind, crossover, randomized, placebo-controlled trial. In a randomized sequence of single-dose sessions, 17 male adults with ASD received 8 international units (IU) oxytocin, 24IU oxytocin or placebo followed by four social-cognitive tasks. We observed an omnibus main effect of treatment on the primary outcome measure of overt emotion salience as measured by emotional ratings of faces (?2=0.18). Compared to placebo, 8IU treatment increased overt emotion salience (P=0.02, d=0.63). There was no statistically significant increase after 24IU treatment (P=0.12, d=0.4). The effects after 8IU oxytocin were observed despite no significant increase in peripheral blood plasma oxytocin concentrations. We found no significant effects for reading the mind in the eyes task performance or secondary outcome social-cognitive tasks (emotional dot probe and face-morphing). To our knowledge, this is the first trial to assess the dose-dependent effects of a single oxytocin administration in autism, with results indicating that a low dose of oxytocin can significantly modulate overt emotion salience despite minimal systemic exposure.

SUBMITTER: Quintana DS

PROVIDER: S-EPMC5584522 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

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Dose-dependent social-cognitive effects of intranasal oxytocin delivered with novel Breath Powered device in adults with autism spectrum disorder: a randomized placebo-controlled double-blind crossover trial.

Quintana D S DS Westlye L T LT Hope S S Nærland T T Elvsåshagen T T Dørum E E Rustan Ø Ø Valstad M M Rezvaya L L Lishaugen H H Stensønes E E Yaqub S S Smerud K T KT Mahmoud R A RA Djupesland P G PG Andreassen O A OA

Translational psychiatry 20170523 5

The neuropeptide oxytocin has shown promise as a treatment for symptoms of autism spectrum disorders (ASD). However, clinical research progress has been hampered by a poor understanding of oxytocin's dose-response and sub-optimal intranasal delivery methods. We examined two doses of oxytocin delivered using a novel Breath Powered intranasal delivery device designed to improve direct nose-to-brain activity in a double-blind, crossover, randomized, placebo-controlled trial. In a randomized sequenc ...[more]

PMID: 28534875

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Project description:There are no effective medications for the treatment of social cognition/function deficits in autism spectrum disorder (ASD), and adult intervention literature in this area is sparse. Emerging data from animal models and genetic association studies as well as early, single-dose intervention studies suggest that the oxytocin system may be a potential therapeutic target for social cognition/function deficits in ASD. The primary aim of this study was to examine the safety/therapeutic effects of intranasal oxytocin versus placebo in adults with ASD, with respect to the two core symptom domains of social cognition/functioning and repetitive behaviors.This was a pilot, randomized, double-blind, placebo-controlled, parallel design trial of intranasal oxytocin versus placebo in 19 adults with ASD (16 males; 33.20 ± 13.29 years). Subjects were randomized to 24 IU intranasal oxytocin or placebo in the morning and afternoon for 6 weeks. Measures of social function/cognition (the Diagnostic Analysis of Nonverbal Accuracy) and repetitive behaviors (Repetitive Behavior Scale Revised) were administered. Secondary measures included the Social Responsiveness Scale, Reading-the-Mind-in-the-Eyes Test and the Yale Brown Obsessive Compulsive Scale - compulsion subscale and quality of life (World Health Organization Quality of Life Questionnaire - emotional/social subscales). Full-information maximum-likelihood parameter estimates were obtained and tested using mixed-effects regression analyses.Although no significant changes were detected in the primary outcome measures after correcting for baseline differences, results suggested improvements after 6 weeks in measures of social cognition (Reading-the-Mind-in-the-Eyes Test, p = 0.002, d = 1.2), and quality of life (World Health Organization Quality of Life Questionnaire - emotion, p = 0.031, d = 0.84), both secondary measures. Oxytocin was well tolerated and no serious adverse effects were reported.This pilot study suggests that there is therapeutic potential to daily administration of intranasal oxytocin in adults with ASD and that larger and longer studies are warranted.NCT00490802.

Project description:INTRODUCTION:Anorexia nervosa (AN) is an eating disorder characterised by restriction of energy intake, fears of gaining weight and related body image disturbances. The oxytocinergic system has been proposed as a pathophysiological candidate for AN. Oxytocin is a neuropeptide involved in bodily processes (eg, breast feeding) and in the onset of social behaviours (eg, bonding). Studies investigating the effect of intranasal oxytocin (IN-OT) in AN showed that it can improve attentional bias for high-calorie food and fat bodies stimuli, and related stress. However, less is known about the effect of IN-OT on bodily awareness and body image distortions, key features of the disorder linked to its development, prognosis and maintenance. Here, we aim to investigate the effect of IN-OT on the perception of affective, C-tactile-optimal touch, known to be impaired in AN and on multisensory integration processes underlying a body ownership illusion (ie, rubber hand illusion). For exploratory purposes, we will also investigate the effect of IN-OT on another interoceptive modality, namely cardiac awareness and its relationship with affective touch. DESIGN, METHODS AND ANALYSIS:Forty women with AN and forty matched healthy controls will be recruited and tested in two separate sessions; self-administering IN-OT (40 IU) or placebo, intranasally, in a pseudo-randomised manner. The data from this double-blind, placebo-controlled, cross-over study will be analysed using linear mixed models that allow the use of both fixed (treatment levels) and random (subjects) effects in the same analysis. To address our main hypotheses, separate analyses will be run for the affective touch task, where the primary outcome dependent variable will be the pleasantness of the touch, and for the rubber hand illusion, where we will investigate multisensory integration quantified as subjective embodiment towards the rubber hand. In the latter, we will manipulate the synchronicity of touch and the size of the hand. ETHICS AND DISSEMINATION:Ethics approval has been obtained by National Research Ethics Service NRES Committee London (Queen's Square Committee, ref number 14/LO/1593). The results will be disseminated through conference presentations and publication in peer-reviewed journals.

Project description:Prader-Willi syndrome (PWS) is a rare, complex multisystem genetic disorder which includes hypothalamic dysfunction, hyperphagia, cognitive and behavioral problems, increased anxiety, and compulsive behaviors. Individuals with PWS have a deficit of oxytocin producing neurons in the paraventricular nucleus of the hypothalamus. Oxytocin plays a role in regulation of feeding behaviors, social interactions, and emotional reactivity, which are all issues that significantly affect the quality of life for individuals with this syndrome. We performed a double-blind, placebo-controlled, crossover study in 24 children with PWS at three academic institutions using 5 days of intranasal oxytocin (IN-OT) or 5 days of intranasal placebo spray, followed by a 4 week washout period, and then patients returned for 5 days of treatment with the alternate source. Questionnaires, including the Aberrant Behavior Checklist, Social Responsiveness Scale, Repetitive Behavior Scale - Revised, and the Hyperphagia Questionnaire, as well as Clinical Global Impression scales were administered. Blood testing for sodium, potassium, and glucose levels on days 2, 4, and 6, and a 24?hr diet recall. All scales factor improvement from Day 3 to Day 6 favored oxytocin over placebo. No single factor showed a statistically significant difference (P?<?0.05) between groups at Day 6. The drug effect appeared to be diminished at Day 14. There was no evidence of a difference between oxytocin and placebo in safety lab parameters, 60?min post dose vital signs, weight, or diet parameters. The results from this study suggest that low dose intranasal oxytocin is safe for individuals with PWS and may result in reduction in appetite drive, and improvements in socialization, anxiety, and repetitive behaviors. Further, long-term studies with a larger population of participants are necessary to confirm these findings. The results of this study are encouraging that oxytocin may be a safe and effective treatment for many of the issues that negatively impact individuals with PWS.

Project description:BackgroundExperimental studies and small clinical trials have suggested that treatment with intranasal oxytocin may reduce social impairment in persons with autism spectrum disorder. Oxytocin has been administered in clinical practice to many children with autism spectrum disorder.MethodsWe conducted a 24-week, placebo-controlled phase 2 trial of intranasal oxytocin therapy in children and adolescents 3 to 17 years of age with autism spectrum disorder. Participants were randomly assigned in a 1:1 ratio, with stratification according to age and verbal fluency, to receive oxytocin or placebo, administered intranasally, with a total target dose of 48 international units daily. The primary outcome was the least-squares mean change from baseline on the Aberrant Behavior Checklist modified Social Withdrawal subscale (ABC-mSW), which includes 13 items (scores range from 0 to 39, with higher scores indicating less social interaction). Secondary outcomes included two additional measures of social function and an abbreviated measure of IQ.ResultsOf the 355 children and adolescents who underwent screening, 290 were enrolled. A total of 146 participants were assigned to the oxytocin group and 144 to the placebo group; 139 and 138 participants, respectively, completed both the baseline and at least one postbaseline ABC-mSW assessments and were included in the modified intention-to-treat analyses. The least-squares mean change from baseline in the ABC-mSW score (primary outcome) was -3.7 in the oxytocin group and -3.5 in the placebo group (least-squares mean difference, -0.2; 95% confidence interval, -1.5 to 1.0; P = 0.61). Secondary outcomes generally did not differ between the trial groups. The incidence and severity of adverse events were similar in the two groups.ConclusionsThis placebo-controlled trial of intranasal oxytocin therapy in children and adolescents with autism spectrum disorder showed no significant between-group differences in the least-squares mean change from baseline on measures of social or cognitive functioning over a period of 24 weeks. (Funded by the National Institute of Child Health and Human Development; SOARS-B ClinicalTrials.gov number, NCT01944046.).

Dataset Information

Dose-dependent social-cognitive effects of intranasal oxytocin delivered with novel Breath Powered device in adults with autism spectrum disorder: a randomized placebo-controlled double-blind crossover trial.

Publications

Dose-dependent social-cognitive effects of intranasal oxytocin delivered with novel Breath Powered device in adults with autism spectrum disorder: a randomized placebo-controlled double-blind crossover trial.

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