The DOI matches its Crossref record; 36 of the 36 references it cites were found in a registry or an index; 16 of the 30 sources its claims cite were checked for support.
Intranasal Oxytocin in Children and Adolescents with Autism Spectrum Disorder
Open accessAbstract
BACKGROUND: Experimental 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. METHODS: We 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. RESULTS: Of 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. CONCLUSIONS: This 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.).
Overview
AI snapshot
Written from the paper’s full text.
TL;DR
In a 24-week, placebo-controlled phase 2 trial in children and adolescents with autism spectrum disorder, daily intranasal oxytocin did not improve social withdrawal or other social/cognitive outcomes compared with placebo. Adverse-event incidence and severity were similar between groups.
Key findings
- Primary outcome: least-squares mean change from baseline on the ABC modified Social Withdrawal subscale was −3.7 with oxytocin and −3.5 with placebo (difference, −0.2; 95% CI, −1.5 to 1.0; P=0.61).
- Secondary outcomes generally did not differ: SRS-2 Social Motivation T-score difference 0.9 (95% CI, −1.0 to 2.9); Sociability Factor difference 0.6 (95% CI, −1.8 to 3.1); SB5 Abbreviated IQ difference 0.1 (95% CI, −2.9 to 3.0).
- Subgroup differences were also nonsignificant: fluent verbal speech difference 0.3 (95% CI, −1.4 to 2.1); minimal verbal fluency difference −0.9 (95% CI, −2.7 to 1.0).
- Adverse events occurred in 82% of oxytocin participants and 83% of placebo participants; one serious adverse event was considered related to oxytocin (sedation while driving leading to a motor vehicle accident at 48 IU daily).
Methods
- Investigator-initiated, randomized, double-blind, parallel-group, placebo-controlled phase 2 trial conducted at seven academic sites from August 2014 through June 2017; participants were children and adolescents 3 to 17 years of age meeting DSM-5 criteria for autism spectrum disorder.
- Of 355 screened, 290 were enrolled and randomly assigned 1:1, stratified by age group and verbal fluency, to intranasal oxytocin or placebo; target total daily dose was 48 IU, with flexible dosing from 8 to 80 IU over 24 weeks.
- Primary outcome was the ABC-mSW; secondary outcomes were SRS-2-SM, Sociability Factor, and SB5 Abbreviated IQ. Efficacy used a modified intention-to-treat population (277 participants) and mixed-effect repeated-measures models; no prespecified adjustment for multiple comparisons for secondary, exploratory, or sensitivity outcomes.
Limitations
- The paper states that the ABC-mSW has not been validated, no minimum baseline score was required for enrollment, and the flexible-dose strategy differed from previous trials.
- The paper notes uncertainty about intranasal oxytocin absorption, brain penetration, and time course, and that the formulation differed from the Novartis Syntocinon product used in some prior trials.
- The paper states that the 24-week treatment period might attenuate an initial early response to oxytocin; it also reports no prespecified adjustment for multiple comparisons for secondary, exploratory, or sensitivity outcomes.
Model-written summary. Check it against the paper before relying on it.
Integrity signals
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Verification
Claims the paper makes
16 of 30 cited sources checked · 10 supported · 0 flagged · accuracy not yet measured
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“Several trials have shown that a single dose of intranasal oxytocin enhanced performance on measures of social cognition10,11 or motivation,12–14 as compared with placebo, in persons with autism spectrum disorder.”
§ Intranasal Oxytocin in Children and Adolescents with Autism Spectrum Disorder > Abstract > CONCLUSIONS
What the sources say
- Not checked — no full text of the sourcecites [10] Guastella AJ, Einfeld SL, Gray KM, Intranasal oxytocin improves emotion recognition for youth with autism spectrum disorders. Biol Psychiatry 2010; 67: 692– 4. 19897177 source
- Not checked — no full text of the sourcecites [11] Watanabe T, Abe O, Kuwabara H, Mitigation of sociocommunicational deficits of autism through oxytocin-induced recovery of medial prefrontal activity: a randomized trial. JAMA Psychiatry 2014; 71: 166– 75. 24352377 source
- Supportedcites [12] Kanat M, Spenthof I, Riedel A, van Elst LT, Heinrichs M, Domes G. Restoring effects of oxytocin on the attentional preference for faces in autism. Transl Psychiatry 2017; 7(4): e1097. 28418399 PMC5416705 source
The Methods and Results (pages unavailable in our copy) describe a single-dose, placebo-controlled trial in people with ASD. Oxytocin significantly increased their attention to faces compared with houses in the 500-ms condition, supporting this paper as one of the cited trials showing improved social attentional preference. (LLM, conf=0.88)
- Supportedcites [13] Andari E, Duhamel J-R, Zalla T, Herbrecht E, Leboyer M, Sirigu A. Promoting social behavior with oxytocin in high-functioning autism spectrum disorders. Proc Natl Acad Sci U S A 2010; 107: 4389– 94. 20160081 PMC2840168 source
The citation is attached to the motivation portion of the sentence. Materials and Methods describes a single intranasal dose of oxytocin or placebo in participants with high-functioning autism spectrum disorder; the Results report greater engagement with a cooperative player under oxytocin than under placebo. This paper supports its contribution to the cited group of trials, not the number of trials as a whole. (LLM, conf=0.92)
- Not checked — no full text of the sourcecites [14] Althaus M, Groen Y, Wijers AA, Noltes H, Tucha O, Hoekstra PJ. Oxytocin enhances orienting to social information in a selective group of high-functioning male adults with autism spectrum disorder. Neuropsychologia 2015; 79: Pt A: 53– 69. 26498227 source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesThe cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Small, randomized, controlled trials of intranasal oxytocin administered for 4 to 24 weeks in persons with autism spectrum disorder have had equivocal results with regard to oxytocin-associated improvements in social functioning, social cognition, or social attention.18–21”
§ Intranasal Oxytocin in Children and Adolescents with Autism Spectrum Disorder > Abstract > CONCLUSIONS
What the sources say
- Partly supportedcites [18] Parker KJ, Oztan O, Libove RA, Intranasal oxytocin treatment for social deficits and biomarkers of response in children with autism. Proc Natl Acad Sci U S A 2017; 114: 8119– 24. 28696286 PMC5544319 sourceExperimental — accuracy not yet measured
Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
- Supportedcites [19] Watanabe T, Kuroda M, Kuwabara H, Clinical and neural effects of six-week administration of oxytocin on core symptoms of autism. Brain 2015; 138: 3400– 12. 26336909 source
Split into 2 atoms — 2 confirmed, 0 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
- Not checked — no full text of the sourcecites [20] Yamasue H, Okada T, Munesue T, Effect of intranasal oxytocin on the core social symptoms of autism spectrum disorder: a randomized clinical trial. Mol Psychiatry 2020; 25: 1849– 58. 29955161 source
- Supportedcites [21] Anagnostou E, Soorya L, Chaplin W, Intranasal oxytocin versus placebo in the treatment of adults with autism spectrum disorders: a randomized controlled trial. Mol Autism 2012; 3: 16. 23216716 PMC3539865 source
Split into 2 atoms — 2 confirmed, 0 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“There is uncertainty regarding absorption, brain penetration, and time course of effects with intranasal oxytocin35,36 that may be amplified by differences among specific preparations of intranasal oxytocin.”
§ Intranasal Oxytocin in Children and Adolescents with Autism Spectrum Disorder > DISCUSSION
What the sources say
- Partly supportedcites [35] Lee MR, Shnitko TA, Blue SW, Labeled oxytocin administered via the intranasal route reaches the brain in rhesus macaques. Nat Commun 2020; 11: 2783. 32494001 PMC7270110 sourceExperimental — accuracy not yet measured
The Discussion (page not provided) says the extent and regional distribution of brain penetration need further study and that the two-hour sampling interval limits what can be inferred about timing. But the paper demonstrates brain penetration in rhesus macaques; it does not directly assess the time course of oxytocin’s effects or establish uncertainty about absorption. The claim is therefore supported only in part. (LLM, conf=0.85)
- Not checked — no full text of the sourcecites [36] Benner S, Aoki Y, Watanabe T, Neurochemical evidence for differential effects of acute and repeated oxytocin administration. Mol Psychiatry 2021; 26: 710– 20. 30262887 source
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes- Partly supported
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“These results have been supported by functional neuroimaging studies involving persons with autism spectrum disorder, which have shown differences in regional brain activation in response to social stimuli after the administration of intranasal oxytocin, as compared with placebo.11,15–17”
§ Intranasal Oxytocin in Children and Adolescents with Autism Spectrum Disorder > Abstract > CONCLUSIONS
What the sources say
- Not checked — no full text of the sourcecites [11] Watanabe T, Abe O, Kuwabara H, Mitigation of sociocommunicational deficits of autism through oxytocin-induced recovery of medial prefrontal activity: a randomized trial. JAMA Psychiatry 2014; 71: 166– 75. 24352377 source
- Supportedcites [15] Gordon I, Vander Wyk BC, Bennett RH, Oxytocin enhances brain function in children with autism. Proc Natl Acad Sci U S A 2013; 110: 20953– 8. 24297883 PMC3876263 source
The Results section reports greater brain activation during social versus nonsocial judgments after intranasal oxytocin than after placebo in children and adolescents with ASD. It also identifies regional increases in activation. The supplied copy does not specify a page number. (LLM, conf=0.94)
- Supportedcites [16] Kruppa JA, Gossen A, Oberwelland Weiß E, Neural modulation of social reinforcement learning by intranasal oxytocin in male adults with high-functioning autism spectrum disorder: a randomized trial. Neuropsychopharmacology 2019; 44: 749– 56. 30390065 PMC6372686 source
The ROI analysis (page not available in our copy) reports a significant interaction between social feedback and treatment in the left nucleus accumbens. In adults with ASD, the association between reward-prediction-error signals and activation during social versus nonsocial feedback differed under oxytocin but not placebo. (LLM, conf=0.92)
- Supportedcites [17] Greene RK, Spanos M, Alderman C, The effects of intranasal oxytocin on reward circuitry responses in children with autism spectrum disorder. J Neurodev Disord 2018; 10: 12. 29587625 PMC5870086 source
The Results (Functional activation analyses; page unavailable) report significantly decreased right frontal-pole activation during social reward outcomes after intranasal oxytocin compared with placebo in children and adolescents with ASD. The paper notes that this was the only significant activation change in its social-reward comparisons; the claim does not specify the direction or extent of the differences. (LLM, conf=0.90)
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesThe cited sources support only part of this claim — read each source’s verdict below.
In the paper
“One previous trial showed a significant benefit of intranasal oxytocin therapy on the SRS-2 total score only when the baseline plasma oxytocin level was incorporated into the analysis.18”
§ Intranasal Oxytocin in Children and Adolescents with Autism Spectrum Disorder > DISCUSSION
What the sources say
- Partly supportedcites [18] Parker KJ, Oztan O, Libove RA, Intranasal oxytocin treatment for social deficits and biomarkers of response in children with autism. Proc Natl Acad Sci U S A 2017; 114: 8119– 24. 28696286 PMC5544319 sourceExperimental — accuracy not yet measured
In “Evaluation of Biomarker Inclusion in the Statistical Model” (page not available), the SRS Total Raw Score treatment effect was nonsignificant without pretreatment biomarkers; “Effects of OXT Treatment on Social Abilities” reports a significant effect with them included. But the comparison added both pretreatment blood oxytocin and a receptor gene-expression measure, so it does not establish that incorporating oxytocin alone produced the significant result. (LLM, conf=0.86)
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes- Partly supported
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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).”
- Also stated in: § EFFICACY · plain
“Across the 24 weeks of the trial, 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 (difference, −0.2 points; 95% confidence interval [CI], −1.5 to 1.0; P = 0.61).”
- Also stated in: § DISCUSSION · boosted
“our randomized, controlled trial showed no significant difference between oxytocin and placebo, each administered daily for 24 weeks, in the least-squares mean change from baseline in the score on the ABC-mSW scale”
§ Intranasal Oxytocin in Children and Adolescents with Autism Spectrum Disorder > Abstract > RESULTS
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Rests on an assumption: The modified ABC Social Withdrawal subscale (ABC-mSW) is a valid measure of social interaction in children and adolescents with autism spectrum disorder for the purpose of this trial.
- Also stated in: § EFFICACY · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Sensitivity analyses that used least-squares mean changes from baseline in scores from the original ABC Lethargy–Social Withdrawal subscale showed results that did not differ appreciably between the trial groups (Table 2).”
- Also stated in: § DISCUSSION · plain
“A sensitivity analysis of the least-squares mean changes from baseline in scores on the original ABC Lethargy–Social Withdrawal subscale provided results similar to that for the primary outcome”
§ Intranasal Oxytocin in Children and Adolescents with Autism Spectrum Disorder > RESULTS > EFFICACY
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes- Also stated in: § DISCUSSION · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“However, a benefit with oxytocin therapy was not observed when the analysis was limited to the subgroup of participants with a baseline ABC-mSW score of at least 11.”
§ Intranasal Oxytocin in Children and Adolescents with Autism Spectrum Disorder > DISCUSSION
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Rests on an assumption: The modified ABC Social Withdrawal subscale (ABC-mSW) is a valid measure of social interaction in children and adolescents with autism spectrum disorder for the purpose of this trial.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This 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.”
- Also stated in: § DISCUSSION · plain
“we found that 24 weeks of daily intranasal oxytocin treatment, as compared with placebo, did not improve social interaction or other measures of social function related to autism spectrum disorder.”
§ Intranasal Oxytocin in Children and Adolescents with Autism Spectrum Disorder > Abstract > CONCLUSIONS
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Rests on an assumption: The modified ABC Social Withdrawal subscale (ABC-mSW) is a valid measure of social interaction in children and adolescents with autism spectrum disorder for the purpose of this trial.
- Also stated in: § DISCUSSION · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The point estimate of the least-squares mean change from baseline in the SRS-2-SM T-score was −4.5 in the oxytocin group and −5.4 in the placebo group (difference, 0.9 points; estimated 95% CI, −1.0 to 2.9).”
- Also stated in: § RESULTS · plain
“Secondary outcomes generally did not differ between the trial groups.”
§ Intranasal Oxytocin in Children and Adolescents with Autism Spectrum Disorder > RESULTS > EFFICACY
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes- Also stated in: § RESULTS · plain
- Probably not a substantial claim. 16
- It may state two separate claims as one. 21
- The quote only partly states this claim. 1
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Some, but not all, studies have shown reduced plasma oxytocin levels in children with autism spectrum disorder.6”
§ Intranasal Oxytocin in Children and Adolescents with Autism Spectrum Disorder > Abstract > CONCLUSIONS
What the sources say
- Partly supportedcites [6] Rutigliano G, Rocchetti M, Paloyelis Y, Peripheral oxytocin and vasopressin: biomarkers of psychiatric disorders? A comprehensive systematic review and preliminary meta-analysis. Psychiatry Res 2016; 241: 207– 20. 27183106 sourceExperimental — accuracy not yet measured
Section 3.2.2 (p. not available) reports a negative pooled estimate for plasma oxytocin in ASD, substantial variation between studies, and no statistically significant overall difference. Table 1 (p. not available) identifies plasma studies involving children with ASD, but the available passages do not state which individual studies found reduced levels and which did not. (LLM, conf=0.74)
Strength:hedged· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Decreased oxytocin-receptor density has been found in the ventral pallidum of postmortem brain tissue obtained from a few persons with autism spectrum disorder.9”
§ Intranasal Oxytocin in Children and Adolescents with Autism Spectrum Disorder > Abstract > CONCLUSIONS
What the sources say
- Supportedcites [9] Freeman SM, Palumbo MC, Lawrence RH, Smith AL, Goodman MM, Bales KL. Effect of age and autism spectrum disorder on oxytocin receptor density in the human basal forebrain and midbrain. Transl Psychiatry 2018; 8: 257. 30514927 PMC6279786 source
The Results (page not provided) report significantly lower oxytocin-receptor binding in the ventral pallidum of ASD specimens than in typically developing specimens. The Materials and methods section identifies the specimens as postmortem human brain tissue and reports 22 ASD specimens, consistent with the claim’s description of a small group. (LLM, conf=0.94)
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“In persons without known developmental or psychiatric disorders, the use of intranasal oxytocin increases social affiliation, social memory, and empathy.2–5”
§ Intranasal Oxytocin in Children and Adolescents with Autism Spectrum Disorder > Abstract > CONCLUSIONS
What the sources say
- Partly supportedcites [2] Kosfeld M, Heinrichs M, Zak PJ, Fischbacher U, Fehr E. Oxytocin increases trust in humans. Nature 2005; 435: 673– 6. 15931222 sourceExperimental — accuracy not yet measured
The Subjects section describes healthy male students who received intranasal oxytocin or placebo; significant psychiatric illness was an exclusion criterion. The Abstract and LETTERS report increased trust in social interactions, which supports the social-affiliation aspect, but the paper does not report increases in social memory or empathy. (LLM, conf=0.90)
- Not checked — no full text of the sourcecites [3] Domes G, Heinrichs M, Michel A, Berger C, Herpertz SC. Oxytocin improves “mind-reading” in humans. Biol Psychiatry 2007; 61: 731– 3. 17137561 source
- Not checked — no full text of the sourcecites [4] De Dreu CKW, Greer LL, Handgraaf MJJ, The neuropeptide oxytocin regulates parochial altruism in intergroup conflict among humans. Science 2010; 328: 1408– 11. 20538951 source
- Partly supportedcites [5] Bartz JA, Zaki J, Bolger N, Oxytocin selectively improves empathic accuracy. Psychol Sci 2010; 21: 1426– 8. 20855907 PMC6634294 sourceExperimental — accuracy not yet measured
The Method and Results (page unavailable) describe healthy men given intranasal oxytocin and show improved empathic accuracy only among those with lower baseline social proficiency. The paper does not report increases in social affiliation or social memory, and its Discussion explicitly cautions against treating oxytocin as a universal social enhancer. (LLM, conf=0.90)
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“In animals, oxytocin increases social approach and social memory,1 both of which are impaired in persons with autism.”
§ Intranasal Oxytocin in Children and Adolescents with Autism Spectrum Disorder > Abstract > CONCLUSIONS
What the sources say
- Supportedcites [1] Insel TR. The challenge of translation in social neuroscience: a review of oxytocin, vasopressin, and affiliative behavior. Neuron 2010; 65: 768– 79. 20346754 PMC2847497 source
In “AVP and Affiliation” (page unavailable), the review reports that oxytocin increases partner-preference formation in female prairie voles, supporting the social-approach point. In “OT and Maternal Behavior” (page unavailable), it reports profound social amnesia in mice lacking oxytocin; the autism section also identifies social deficits and reports improved social memory after oxytocin treatment. (LLM, conf=0.88)
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Elevated promoter methylation in OXTR has also been reported in persons with autism spectrum disorder, as compared with controls.8”
§ Intranasal Oxytocin in Children and Adolescents with Autism Spectrum Disorder > Abstract > CONCLUSIONS
What the sources say
- Supportedcites [8] Gregory SG, Connelly JJ, Towers AJ, Genomic and epigenetic evidence for oxytocin receptor deficiency in autism. BMC Med 2009; 7: 62. 19845972 PMC2774338 source
The Results section, “Hypermethylation of residues critical for OXTR gene silencing are associated with autism,” reports significantly higher methylation at three OXTR promoter CpG sites in blood samples from individuals with autism than in controls. The Results section on temporal cortex tissue also reports significant hypermethylation at four sites in autism cases versus matched controls. (LLM, conf=0.94)
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
- Supported
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“There were no other clinically meaningful changes in vital signs, height, clinical laboratory assessments, or electrocardiographic findings in either group.”
§ Intranasal Oxytocin in Children and Adolescents with Autism Spectrum Disorder > RESULTS > SAFETY
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Among participants with fluent verbal speech, the between-group difference in the least-squares mean change from baseline was 0.3 (95% CI, −1.4 to 2.1); among participants with minimal verbal fluency, the between-group difference in the least-squares mean change from baseline was −0.9 (95% CI, −2.7 to 1.0).”
- Also stated in: § DISCUSSION · plain
“The absence of between-group differences in outcomes was similar among participants with fluent verbal communication and among those with minimal verbal communication”
§ Intranasal Oxytocin in Children and Adolescents with Autism Spectrum Disorder > RESULTS > EFFICACY
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one. The quote only partly states this claim.
- Rests on an assumption: The modified ABC Social Withdrawal subscale (ABC-mSW) is a valid measure of social interaction in children and adolescents with autism spectrum disorder for the purpose of this trial.
- Also stated in: § DISCUSSION · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Three serious adverse events occurred during the trial. One serious adverse event was considered by the investigators to be related to oxytocin: sedation while driving that led to a motor vehicle accident while the participant was taking a total daily dose of 48 IU.”
§ Intranasal Oxytocin in Children and Adolescents with Autism Spectrum Disorder > RESULTS > SAFETY
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The oxytocin group had higher incidences of increased appetite (16%, vs. 10% in the placebo group), increased energy (10% vs. 3%), restlessness (8% vs. 2%), subjective weight loss (7% vs. 3%), increased thirst (6% vs. 3%), inattention (6% vs. 3%), and myalgia (3% vs. 1%) (Table S7).”
§ Intranasal Oxytocin in Children and Adolescents with Autism Spectrum Disorder > RESULTS > SAFETY
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The incidence and severity of adverse events were similar in the two groups.”
- Also stated in: § SAFETY · plain
“Adverse events occurred in 82% of the participants in the oxytocin group and in 83% of those in the placebo group (Table 3).”
§ Intranasal Oxytocin in Children and Adolescents with Autism Spectrum Disorder > Abstract > RESULTS
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Also stated in: § SAFETY · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In the safety population, four participants in the oxytocin group and three in the placebo group discontinued the trial regimen owing to adverse events. Most of the discontinuations in the oxytocin group were related to irritability or aggression; only one of the discontinuations in the placebo group was due to behavioral causes (increased libido with impulsivity).”
§ Intranasal Oxytocin in Children and Adolescents with Autism Spectrum Disorder > RESULTS > SAFETY
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The point estimate of the least-squares mean change from baseline in the Sociability Factor score was −7.7 in the oxytocin group and −8.3 in the placebo group (difference, 0.6 points; 95% CI, −1.8 to 3.1).”
§ Intranasal Oxytocin in Children and Adolescents with Autism Spectrum Disorder > RESULTS > EFFICACY
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The mean weight gain was 1.6±2.2 kg in the oxytocin group and 2.3±2.8 kg in the placebo group.”
§ Intranasal Oxytocin in Children and Adolescents with Autism Spectrum Disorder > RESULTS > SAFETY
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“All the efficacy analyses were performed with the use of a modified intention-to-treat approach that included all the participants who had undergone randomization, received oxytocin or placebo for at least 1 day, and had both a baseline and at least one postbaseline ABC-mSW score.”
§ Intranasal Oxytocin in Children and Adolescents with Autism Spectrum Disorder > METHODS > STATISTICAL ANALYSIS
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“We conducted an investigator-initiated, randomized, double-blind, parallel-group, placebo-controlled trial of daily, flexible-dose intranasal oxytocin treatment in children and adolescents with autism spectrum disorder.”
- Also stated in: § PARTICIPANTS · plain
“At each visit, the trial physician, who was unaware of the participant’s trial-group assignment, completed a physical examination, systematically elicited a history of adverse events, verified concomitant treatments, and, at visits after the baseline visit, assessed current symptoms of autism spectrum disorder using the Clinical Global Impressions Scale of Improvement.”
§ Intranasal Oxytocin in Children and Adolescents with Autism Spectrum Disorder > METHODS > TRIAL DESIGN AND OVERSIGHT
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim. It may state two separate claims as one.
- Also stated in: § PARTICIPANTS · plain
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Participants were randomly assigned in a 1:1 ratio, by means of a centralized randomization table, to receive intranasal oxytocin or matching intranasal placebo, with stratification according to verbal fluency (minimally verbal or fluently verbal, with the ability to perform ADOS-2 module 3 or 4 as an indication of fluent speech) and age group (3 to 6 years, 7 to 11 years, and 12 to 17 years).”
§ Intranasal Oxytocin in Children and Adolescents with Autism Spectrum Disorder > METHODS > PARTICIPANTS
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“The participants’ demographic characteristics, symptom severity, and use of concomitant medications were similar at baseline in the two trial groups (Tables 1 and S3).”
§ Intranasal Oxytocin in Children and Adolescents with Autism Spectrum Disorder > RESULTS > PARTICIPANTS
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“In the modified intention-to-treat population, 14 participants in the oxytocin group and 13 in the placebo group withdrew before week 24; thus, 90% of the participants in the modified intention-to-treat population (125 in each group) completed the trial (Fig. 1).”
§ Intranasal Oxytocin in Children and Adolescents with Autism Spectrum Disorder > RESULTS > PARTICIPANTS
Strength:plain· not yet calibratedn = 277Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“The placebo contained no oxytocin but was otherwise identical to the intranasal oxytocin product with respect to the other ingredients, volume, labeling, container system, and other features.”
§ Intranasal Oxytocin in Children and Adolescents with Autism Spectrum Disorder > METHODS > TRIAL DESIGN AND OVERSIGHT
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Of the 1939 ABC-mSW assessments that were expected if every participant in the modified intention-to-treat population completed all scheduled assessments, 128 (6.6%) were missing; the data were considered to be missing at random (Table S4).”
§ Intranasal Oxytocin in Children and Adolescents with Autism Spectrum Disorder > RESULTS > PARTICIPANTS
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“A total of 52% of the trial physicians, 49% of the primary caregivers, and 22 of the 44 participants who answered (50%) guessed the trial-group assignment correctly at the end of the trial.”
§ Intranasal Oxytocin in Children and Adolescents with Autism Spectrum Disorder > RESULTS > PARTICIPANTS
Strength:plain· not yet calibratedn = 44Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The highest concentration of the formulation used in our trial was 24 IU per 0.1 ml.”
§ Intranasal Oxytocin in Children and Adolescents with Autism Spectrum Disorder > DISCUSSION
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“The data and safety monitoring board reviewed unblinded safety data twice yearly.”
§ Intranasal Oxytocin in Children and Adolescents with Autism Spectrum Disorder > METHODS > SAFETY MONITORING
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“There was no prespecified plan for adjustment of confidence intervals to account for multiple comparisons for secondary, exploratory, or sensitivity outcomes. Results of these analyses are therefore reported as point estimates with 95% confidence intervals and cannot be used to infer definitive treatment effects.”
§ Intranasal Oxytocin in Children and Adolescents with Autism Spectrum Disorder > METHODS > STATISTICAL ANALYSIS
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“Many children with autism spectrum disorder are thought to have tried intranasal oxytocin therapy33 on the basis of putatively promising data.”
§ Intranasal Oxytocin in Children and Adolescents with Autism Spectrum Disorder > DISCUSSION
What the sources say
- Not checked — no full text of the sourcecites [33] Hopf KP, Madren E, Santianni KA. Use and perceived effectiveness of complementary and alternative medicine to treat and manage the symptoms of autism in children: a survey of parents in a community population. J Altern Complement Med 2016; 22: 25– 32. 26654976 PMC4739350 source
Strength:hedged· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“There was no commercial involvement in the trial.”
§ Intranasal Oxytocin in Children and Adolescents with Autism Spectrum Disorder > METHODS > TRIAL DESIGN AND OVERSIGHT
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Previous trials used 12 IU of oxytocin in children younger than 13 years of age and 24 IU once or twice daily in participants 13 years of age or older.”
§ Intranasal Oxytocin in Children and Adolescents with Autism Spectrum Disorder > DISCUSSION
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim. It may state two separate claims as one.
In the paper
“A meta-analysis has tentatively supported an association between autism spectrum disorder and polymorphisms in the oxytocin receptor gene, OXTR, but not at the level of genomewide significance.7”
§ Intranasal Oxytocin in Children and Adolescents with Autism Spectrum Disorder > Abstract > CONCLUSIONS
What the sources say
- Not checked — no full text of the sourcecites [7] LoParo D, Waldman ID. The oxytocin receptor gene (OXTR) is associated with autism spectrum disorder: a meta-analysis. Mol Psychiatry 2015; 20: 640– 6. 25092245 source
Strength:hedged· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In contrast, the total daily doses of oxytocin in our trial ranged from 8 to 80 IU, depending on adverse effects in the participants rather than on participant age or weight.”
§ Intranasal Oxytocin in Children and Adolescents with Autism Spectrum Disorder > DISCUSSION
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“The concentration of the Novartis product is 4 IU of oxytocin per 0.1 ml of solution; a dose of 24 IU requires that 0.6 ml of solution be delivered at one time, which may influence absorption.”
§ Intranasal Oxytocin in Children and Adolescents with Autism Spectrum Disorder > DISCUSSION
Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“A minimum score on this scale was not required for enrollment, which potentially limited our ability to detect improvements in children who had low ABC-mSW scores at baseline.”
§ Intranasal Oxytocin in Children and Adolescents with Autism Spectrum Disorder > DISCUSSION
Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
The paper relies on this without support.
The modified ABC Social Withdrawal subscale (ABC-mSW) is a valid measure of social interaction in children and adolescents with autism spectrum disorder for the purpose of this trial.
“The ABC-mSW that was used to determine the primary outcome was a modification of the ABC Lethargy–Social Withdrawal subscale that omitted three questions (3, 32, and 53) pertaining to reduced physical movement in order to increase specificity for social function.”
“our primary outcome was based on the use of the ABC-mSW, which has not been validated.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“the randomized, double-blind, parallel-group, placebo-controlled study by Sikich et al. was rigorous, robust, and thorough in both design and execution1”
From Refining oxytocin therapy for autism: context is key (2022) · cites this paper as [1]
In the citing paper
“A recent clinical trial found no effect of chronic intranasal oxytocin on social behaviour in children with autism spectrum disorders.”
From Refining oxytocin therapy for autism: context is key (2022) · cites this paper as [1]
In the citing paper
“now we have compelling evidence that chronic administration of oxytocin is not beneficial”
From Refining oxytocin therapy for autism: context is key (2022) · cites this paper as [1]
In the citing paper
“a sample size more than adequate to detect an effect of clinically meaningful size”
From Refining oxytocin therapy for autism: context is key (2022) · cites this paper as [1]
In the citing paper
“Data were collected from 277 of the 290 participants enrolled across seven academic sites”
From Refining oxytocin therapy for autism: context is key (2022) · cites this paper as [1]
In the citing paper
“Given the context-dependent nature of oxytocin’s effects, the fact that Sikich et al.1 found no effect of context-independent oxytocin administration is unsurprising.”
From Refining oxytocin therapy for autism: context is key (2022) · cites this paper as [1]
In the citing paper
“the data presented by Sikich et al.1 clearly demonstrate that chronic intranasal oxytocin administration independent of context is not beneficial for children with ASD”
From Refining oxytocin therapy for autism: context is key (2022) · cites this paper as [1]
In the citing paper
“A recent randomized controlled trial (RCT) however did not show any significant effects between the OXT and placebo group in aberrant behavior, social communication, or cognition [86].”
From An Update on Psychopharmacological Treatment of Autism Spectrum Disorder (2022) · cites this paper as [86]
In the citing paper
“Results of OXT studies in children have overall been more equivocal with mixed results.”
From An Update on Psychopharmacological Treatment of Autism Spectrum Disorder (2022) · cites this paper as [86]
Citations
Cites
Oxytocin increases trust in humans
Kosfeld, M., Heinrichs, M., Zak, P. J., Fischbacher, U., & Fehr, E. (2005) · Nature · doi:10.1038/nature03701 · Cited by 3,690
Risperidone in Children with Autism and Serious Behavioral Problems
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Self-citationOxytocin improves “mind-reading” in humans
Domes, G., Heinrichs, M., Michel, A., Berger, C., & Herpertz, S. C. (2007) · Biological Psychiatry · doi:10.1016/j.biopsych.2006.07.015 · Cited by 1,298
The Neuropeptide Oxytocin Regulates Parochial Altruism in Intergroup Conflict Among Humans
De Dreu, C. K. W., Greer, L. L., Handgraaf, M. J. J., Shalvi, S., Van Kleef, G. A., Baas, M., Ten Velden, F. S., Van Dijk, E., & Feith, S. W. W. (2010) · Science · doi:10.1126/science.1189047 · Cited by 1,148
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Intranasal oxytocin improves emotion recognition for youth with autism spectrum disorders.
Guastella, A. J., Einfeld, S. L., Gray, K. M., Rinehart, N. J., Tonge, B. J., Lambert, T. J., & Hickie, I. B. (2010) · Biological Psychiatry · doi:10.1016/j.biopsych.2009.09.020 · Cited by 962
Promoting social behavior with oxytocin in high-functioning autism spectrum disorders.
Andari, E., Duhamel, J.-R., Zalla, T., Herbrecht, E., Leboyer, M., & Sirigu, A. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0910249107 · Cited by 941
Aripiprazole in the Treatment of Irritability in Children and Adolescents With Autistic Disorder
Owen, R., Sikich, L., Marcus, R. N., Corey-Lisle, P., Manos, G., McQuade, R. D., Carson, W. H., & Findling, R. L. (2009) · Pediatrics · doi:10.1542/peds.2008-3782 · Cited by 613
Self-citationGenomic and epigenetic evidence for oxytocin receptor deficiency in autism
Gregory, S. G., Connelly, J. J., Towers, A. J., Johnson, J., Biscocho, D., Markunas, C. A., Lintas, C., Abramson, R. K., Wright, H. H., Ellis, P., et al. (2009) · BMC Medicine · doi:10.1186/1741-7015-7-62 · Cited by 576
Self-citationShea, S. E., Turgay, A., Carroll, A. M., Schulz, M., Orlik, H., Smith, I. M., & Dunbar, F. (2004) · PEDIATRICS · doi:10.1542/peds.2003-0264-f · Cited by 576
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Cited by
Sorted by citations
Autism Spectrum Disorder: A Review
Hirota, T., & King, B. H. (2023) · JAMA · doi:10.1001/jama.2022.23661 · Cited by 957
Self-citationSignalling pathways in autism spectrum disorder: mechanisms and therapeutic implications
Jiang, C.-C., Lin, L., Long, S., Ke, X., Fukunaga, K., Lu, Y., & Han, F. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-01081-0 · Cited by 295
An Update on Psychopharmacological Treatment of Autism Spectrum Disorder
Aishworiya, R., Valica, T., Hagerman, R., & Restrepo, B. (2022) · Neurotherapeutics · doi:10.1007/s13311-022-01183-1 · Cited by 233
“A recent randomized controlled trial (RCT) however did not show any significant effects between the OXT and placebo group in aberrant behavior, social communication, or cognition [86].”
BackgroundEvaluation of Recent Intranasal Drug Delivery Systems to the Central Nervous System
Crowe, T. P., & Hsu, W. H. (2022) · Pharmaceutics · doi:10.3390/pharmaceutics14030629 · Cited by 208
“to replicate the eff cts in humans [9].”
BackgroundSiafis, S., Çıray, O., Wu, H., Schneider‐Thoma, J., Bighelli, I., Krause, M., Rodolico, A., Ceraso, A., Deste, G., Huhn, M., et al. (2022) · Molecular Autism · doi:10.1186/s13229-022-00488-4 · Cited by 148
Oxytocin receptor is not required for social attachment in prairie voles
Berendzen, K. M., Sharma, R., Alvarado, M., Wei, Y., Rogers, F. D., Simmons, T. C., Seelke, A. M. H., Bond, J. M., Larios, R., Goodwin, N. L., et al. (2023) · Neuron · doi:10.1016/j.neuron.2022.12.011 · Cited by 120
Mazzone, L., Dooling, S. W., Volpe, E., Uljarević, M., Waters, J. L., Sabatini, A., Arturi, L., Abate, R., Riccioni, A., Siracusano, M., et al. (2023) · Cell Host & Microbe · doi:10.1016/j.chom.2023.11.021 · Cited by 113
Autism spectrum disorder: pathogenesis, biomarker, and intervention therapy
Zhuang, H., Liang, Z., Ma, G., Qureshi, A., Ran, X., Feng, C., Liu, X., Yan, X., & Shen, L. (2024) · MedComm · doi:10.1002/mco2.497 · Cited by 111
The neurobiological effects of childhood maltreatment on brain structure, function, and attachment
Tomoda, A., Nishitani, S., Takiguchi, S., Fujisawa, T. X., Sugiyama, T., & Teicher, M. H. (2024) · European Archives of Psychiatry and Clinical Neuroscience · doi:10.1007/s00406-024-01779-y · Cited by 115
Refining oxytocin therapy for autism: context is key
Ford, C. L., & Young, L. J. (2022) · Nature Reviews Neurology · doi:10.1038/s41582-021-00602-9 · Cited by 73
Guastella, A. J., Boulton, K., Whitehouse, A., Song, Y. J. C., Thapa, R., Gregory, S. G., Pokorski, I., Granich, J., DeMayo, M. M., Ambarchi, Z., et al. (2022) · Molecular Psychiatry · doi:10.1038/s41380-022-01845-8 · Cited by 77
“Most recently, a large study across 277 participants aged 3–16 showed no benefit of oxytocin relative to placebo [16].”
BackgroundMethodSelf-citationThe modulation of emotional and social behaviors by oxytocin signaling in limbic network
Triana-Del Rio, R., Ranade, S., Guardado, J., LeDoux, J., Klann, E., & Shrestha, P. (2022) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2022.1002846 · Cited by 58
“, 2021), while others report no effects on social deficits (Yamasue et al., 2020; Sikich et al., 2021).”
BackgroundResultOxytocin alleviates liver fibrosis via hepatic macrophages
Zhai, X., Zhang, H., Xia, Z., Liu, M., Du, G., Jiang, Z., Zhou, H., Luo, D., Dou, D., Li, J., et al. (2024) · JHEP Reports · doi:10.1016/j.jhepr.2024.101032 · Cited by 59
Daniëls, N., Moerkerke, M., Steyaert, J. G., Bamps, A., Debbaut, E., Prinsen, J., Tang, T., der Donck, S. V., Boets, B., & Alaerts, K. (2023) · Molecular Autism · doi:10.1186/s13229-023-00546-5 · Cited by 57
“Similarly, in a recent large-scale trial administering OT over a 24-week period, it was noted that the long duration might have attenuated initial early responses to OT [19].”
BackgroundOxytocin—a social peptide? Deconstructing the evidence
Leng, G., Leng, R., & Ludwig, M. (2022) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2021.0055 · Cited by 51
Bennett (2023) · doi:10.1097/yco.0000000000000775 · Cited by 51
Schmitt, L., Smith, E. G., Pedapati, E. V., Horn, P. S., Will, M., Lamy, M., Barber, L., Trebley, J., Meyer, K., Heiman, M. L., et al. (2023) · Scientific Reports · doi:10.1038/s41598-023-30909-0 · Cited by 58
Ke, X., Song, W. D., Yang, M., Li, J., & Liu, W. (2022) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2022.905113 · Cited by 74
“A placebo-controlled trial of intranasal oxytocin therapy in children and adolescents with ASD showed no significant between-group differences in the least-squares mean change from baseline on social functioning measures of over 24 weeks (14).”
BackgroundThe Synaptic and Circuit Functions of Vitamin D in Neurodevelopment Disorders
Ye, X., Zhou, Q., Ren, P., Xiang, W., & Xiao, L. (2023) · Neuropsychiatric Disease and Treatment · doi:10.2147/ndt.s407731 · Cited by 58
“n = 277) who received intranasal oxytocin once a day for 24 weeks did not show any significant improvement in social or cognitive assessments when compared to the control group.(150) The discrepancy in the therapeutic effects reported by these”
ResultIffland, M., Livingstone, N., Jorgensen, M. L., Hazell, P., & Gillies, D. M. (2023) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd011769.pub2 · Cited by 58
Nakama, N., Usui, N., Doi, M., & Shimada, S. (2023) · Progress in Neuro-psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2023.110783 · Cited by 43
Zhao, F., Zhang, H., Wang, P., Cui, W., Xu, K., Chen, D., Hu, M., Li, Z., Geng, X., & Wei, S. (2022) · Frontiers in Neuroscience · doi:10.3389/fnins.2022.919890 · Cited by 44
“In a study of 355 children and adolescents with ASD who were given intranasal oxytocin continuously, there was no significant difference in cognitive behavior between the treatment group and the placebo group within 24 weeks (Geschwind, 2021; Sikich et al., 2021).”
BackgroundChronic oxytocin administration stimulates the oxytocinergic system in children with autism
Moerkerke, M., Daniëls, N., Tibermont, L., Tang, T., Evenepoel, M., der Donck, S. V., Debbaut, E., Prinsen, J., Chubar, V., Claes, S. J., et al. (2024) · Nature Communications · doi:10.1038/s41467-023-44334-4 · Cited by 46
“Less is more”: A dose-response account of intranasal oxytocin pharmacodynamics in the human brain
Martins, D., Brodmann, K., Veronese, M., Dipasquale, O., Mazibuko, N., Schuschnig, U., Zelaya, F. O., Fotopoulou, A., & Paloyelis, Y. (2022) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2022.102239 · Cited by 43
Sniffing oxytocin: Nose to brain or nose to blood?
Yao, S., Chen, Y., Zhuang, Q., Zhang, Y., Lan, C., Zhu, S., Becker, B., & Kendrick, K. M. (2023) · Molecular Psychiatry · doi:10.1038/s41380-023-02075-2 · Cited by 41
“For VC pre-treatment, individuals in all three treatment groups received both a pretreatment (either VC or PLC) followed 10 min later by a main treatment (either OXT or PLC).”
MethodAudunsdottir, K., Sartorius, A. M., Kang, H., Glaser, B. D., Bøen, R., Nærland, T., Alaerts, K., Kildal, E. S.-M., Westlye, L. T., Andreassen, O. A., et al. (2024) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2024.107067 · Cited by 43
“However, some of these early reports of oxytocin ’ s effects on social cognition and behavior have failed to replicate (Alvares et al., 2017; Mierop et al., 2020; Sikich et al., 2021).”
Oxytocin neurons mediate stress-induced social memory impairment
Zhan, S., Qi, Z., Cai, F., Gao, Z., Xie, J., & Hu, J. (2023) · Current Biology · doi:10.1016/j.cub.2023.11.037 · Cited by 44
McCormack, S. E., Wang, Z., Wade, K., Dedio, A., Cilenti, N., Crowley, J., Plessow, F., Bamba, V., Roizen, J. D., Jiang, Y., et al. (2023) · Journal of the Endocrine Society · doi:10.1210/jendso/bvad037 · Cited by 37
“Also, as a recent negative study of OXT in autism illustrates, selection of the most appropriate participants and OXT-sensitive outcomes is essential [70].”
BackgroundUnderstanding autism: Causes, diagnosis, and advancing therapies
Wang, M., Zhang, X., Zhong, L., Zeng, L., Li, L., & Yao, P. (2025) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2025.111411 · Cited by 67
“However, a large-scale RCT published in 2021, involving 290 ASD patients aged 3 – 17 years, showed that 24 weeks of nasal oxytocin therapy did not improve social or cognitive functions in participants (Sikich et al., 2021).”
Althammer, F., Muscatelli, F., Grinevich, V., & Schaaf, C. P. (2022) · Translational Psychiatry · doi:10.1038/s41398-022-02054-1 · Cited by 35
“Given that both SYS and PWS patients display ASDrelated symptoms [48], and the recent negative result of a Phase III trial assessing the efficacy of intranasal OT for the treatment of autism [105], it will be important to also consider the role of context, timing, and behavioral therapy.”
BackgroundXiao, L., Huo, X., Wang, Y., Li, W., Li, M., Wang, C., Wang, F., & Sun, T. (2023) · BMC Psychiatry · doi:10.1186/s12888-023-04666-3 · Cited by 39
SCGN deficiency is a risk factor for autism spectrum disorder
Liu, Z., Tan, S., Zhou, L., Chen, L., Liu, M., Wang, W., Tang, Y., Yang, Q., Chi, S., Jiang, P., et al. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-01225-2 · Cited by 34
“Several studies have shown that intranasal oxytocin can improve impaired social behavior in autistic children;(62,63) a recent study, however, found that oxytocin did not confer any significant benefit.(64) Possible reasons for these inconsistencies might include the lack of differentiation in the original serum oxyto…”
BackgroundOxytocin and microglia in the development of social behaviour
Gonzalez, A. M., & Hammock, E. A. D. (2022) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2021.0059 · Cited by 32
Ye, C., Wang, S., Niu, L., Yang, F., Wang, G., Wang, S., Xie, J., Chen, Y., Qi, J., Shen, H., et al. (2024) · Theranostics · doi:10.7150/thno.98587 · Cited by 28
“Intranasal oxytocin (OT) administration is a clinically approved and effective means for assisting women with labor and lactation and has shown promising results in improving social disorders such as autism [16].”
BackgroundParent-Reported Assessment Scores Reflect the ASD Severity Level in 2- to 7-Year-Old Children
Jagadeesan, P., Kabbani, A., & Vyshedskiy, A. (2022) · Children · doi:10.3390/children9050701 · Cited by 30
Annamneedi, A., Gora, C., Dudas, A., Leray, X., Bozon, V., Crépieux, P., & Pellissier, L. P. (2023) · British Journal of Pharmacology · doi:10.1111/bph.16216 · Cited by 29
“Unexpectedly, administration of OT failed to improve social abilities over placebo in phase 2 clinical trials and induced frequent side effects in several studies (Leppanen et al., 2018; Sikich et al., 2021; Witte et al., 2022).”
BackgroundA bibliometrics analysis and visualization of autism spectrum disorder
Rong, P., Fu, Q., Zhang, X., Liu, H., Zhao, S., Song, X., Gao, P., & Ma, R. (2022) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2022.884600 · Cited by 30
Lin, P., Zhang, Q., Sun, J., Li, Q., Li, D., Zhu, M., Fu, X., Zhao, L., Wang, M., Lou, X., et al. (2024) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2023.1318637 · Cited by 32
Role of Oxytocin in Different Neuropsychiatric, Neurodegenerative, and Neurodevelopmental Disorders
Ghazy, A. A., Soliman, O., Elbahnasi, A. I., Alawy, A. Y., Mansour, A. M., & Gowayed, M. A. (2022) · Reviews of physiology, biochemistry and pharmacology · doi:10.1007/112_2022_72 · Cited by 27
Oxytocin for Autism Spectrum Disorder — Down, but Not Out
Geschwind, D. H. (2021) · New England Journal of Medicine · doi:10.1056/nejme2110158 · Cited by 25
The Oxytocin System and Implications for Oxytocin Deficiency in Hypothalamic-Pituitary Disease
Aulinas, A., & Lawson, E. A. (2025) · Endocrine Reviews · doi:10.1210/endrev/bnaf008 · Cited by 31
Oral Administration of Oxytocin, Like Intranasal Administration, Decreases Top-Down Social Attention
Zhuang, Q., Zheng, X., Yao, S., Zhao, W., Becker, B., Xu, X., & Kendrick, K. M. (2022) · The International Journal of Neuropsychopharmacology · doi:10.1093/ijnp/pyac059 · Cited by 26
The Role of Oxytocin in Early-Life-Stress-Related Neuropsychiatric Disorders
Jin, Y., Song, D. F., Yan, Y., Quan, Z., & Qing, H. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241310430 · Cited by 30
“However, a 2022 study with ASD model mice demonstrated that oxytocin modulates the vomeronasal nucleus and alters social behavior [153,180].”
BackgroundOxytocin receptor is not required for social attachment in prairie volesPreprint
Berendzen, K. M., Sharma, R., Mandujano, M. A., et al. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.07.22.501192 · Cited by 26
“Based on observations in prairie voles and other mammals, including humans, clinical trials have used exogenous oxytocin or small molecule ligands to OxtR to ameliorate the deficits in social attachment and cognition seen in multiple psychiatric conditions; these studies however have yielded mixed results (Di Simplici…”
BackgroundDigital interventions for autism spectrum disorders: A systematic review and meta‐analysis
Wang, T., Ma, Y., Du, X., Li, C., Peng, Z., Wang, Y., & Zhou, H. (2024) · Pediatric Investigation · doi:10.1002/ped4.12417 · Cited by 37
“7,8 However, the specialized therapist, specific settings, and fixed time of traditional therapies contribute to the heavy burden on individuals with ASD, their families, and society.”
Quintana, D. S. (2021) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2021.105642 · Cited by 22
Moerkerke, M., Daniëls, N., der Donck, S. V., Tibermont, L., Tang, T., Debbaut, E., Bamps, A., Prinsen, J., Steyaert, J. G., Alaerts, K., et al. (2023) · Journal of Child Psychology and Psychiatry · doi:10.1111/jcpp.13850 · Cited by 23
The dopamine hypothesis of autism spectrum disorder: A comprehensive analysis of the evidence
Pavăl, D. (2023) · International review of neurobiology · doi:10.1016/bs.irn.2023.08.009 · Cited by 25
The distribution of neuroligin4, an autism-related postsynaptic molecule, in the human brain
Toya, A., Fukada, M., Aoki, E., Matsuki, T., Ueda, M., Eda, S., Hashizume, Y., Iio, A., Masaki, S., & Nakayama, A. (2023) · Molecular Brain · doi:10.1186/s13041-023-00999-y · Cited by 22
A class of secreted mammalian peptides with potential to expand cell-cell communication
Wiggenhorn, A. L., Abuzaid, H. Z., Voilquin, L., Li, V. L., Tanzo, J. T., Wei, W., Lyu, X., Svensson, K. J., & Long, J. Z. (2023) · Nature Communications · doi:10.1038/s41467-023-43857-0 · Cited by 27
“As a referenceandcomparisonset,weonceagainusedUniprottomanually curate a set of known mouse peptide hormones and neuropeptides (see Methods and Supplementary Data 3).”
InfluentialArnold, M., Netson, R. A., & Vyshedskiy, A. (2022) · Journal of Autism and Developmental Disorders · doi:10.1007/s10803-022-05769-8 · Cited by 22
“Longitudinal intervention studies commonly use parent-reported assessments of child development as an outcome measure (Ebert, 2017; Sikich et al., 2021).”
Wang, T., Zhao, T., Liu, L., Teng, H., Fan, T., Li, Y., Wang, Y., Li, J., Xia, K., & Sun, Z. S. (2022) · EBioMedicine · doi:10.1016/j.ebiom.2022.104091 · Cited by 19
“26,27,34,35 Given that these clinical trials employed different experimental designs, inclusion and exclusion criteria for recruiting participants, intervention methods, and approaches for evaluating intervention efficiencies, inconsistencies in the outcomes are inevitable.”
Zhao, W., Le, J., Liu, Q., Zhu, S., Lan, C., Zhang, Q., Zhang, Y., Li, Q., Kou, J., Yang, W., et al. (2024) · Translational Psychiatry · doi:10.1038/s41398-024-03025-4 · Cited by 20
Korisky, A., Gordon, I., & Goldstein, A. (2022) · Molecular Autism · doi:10.1186/s13229-022-00513-6 · Cited by 19
“While former studies show that some individuals with ASD can benefit from the administration of OT, in their comprehensive meta-analysis Sikich and colleagues [81] suggest that over time the effects of OT on common social behaviors are not significant.”
Liang, Z.-K., Xiong, W. G., Wang, C., Chen, L., Zou, X. G., Mai, J.-W., Dong, B., Guo, C., Xin, W., Luo, D., et al. (2024) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2024.03.040 · Cited by 20
Borie, A. M., Young, L. J., & Liu, R. C. (2022) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2021.0057 · Cited by 17
Genomic and proteomic biomarker landscape in clinical trials
Piñero, J., Fraga, P. S. R., Valls-Margarit, J., Ronzano, F., Accuosto, P., Jane, R. L., Sanz, F., & Furlong, L. I. (2023) · Computational and Structural Biotechnology Journal · doi:10.1016/j.csbj.2023.03.014 · Cited by 19
“This hormone has been tested as a possible treatment for this condition [22].”
BackgroundNetson, R. A., Fucks, A. S., Santos, A. S. S., Poloni, L. E. P., Nacano, N. N., Fucks, E., Radi, K., Strong, W. E., Carnaval, A. A., Russo, M., et al. (2024) · Pediatric Reports · doi:10.3390/pediatric16010016 · Cited by 18
“Not surprisingly, longitudinal studies often employ parent-reported assessments of child development as an outcome measure [12,48–51].”
BackgroundWang, Y., Xu, H., Chen, S., Chen, J., Zheng, Q., Ma, Y., Zhao, X., Shi, Y., & Xiao, L. (2024) · Advanced Science · doi:10.1002/advs.202310244 · Cited by 18
Alaerts, K., Daniëls, N., Moerkerke, M., Evenepoel, M., Tang, T., der Donck, S. V., Chubar, V., Claes, S. J., Steyaert, J. G., Boets, B., et al. (2023) · Psychotherapy and Psychosomatics · doi:10.1159/000534114 · Cited by 21
Coleman, K. K. L., Berry, S. M., Cummings, J. L., Hsiung, G. R., Laforce, R. J., Huey, E. D., Ducharme, S., Tartaglia, M. C., Mendez, M. F., Onyike, C. U., et al. (2025) · The Lancet Neurology · doi:10.1016/s1474-4422(24)00456-3 · Cited by 21
Oztan, O., Zyga, O., Stafford, D. E. J., & Parker, K. J. (2022) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2022.104870 · Cited by 18
Peripartum effects of synthetic oxytocin: The good, the bad, and the unknown
Rashidi, M., Maier, E., Dekel, S., Sütterlin, M., Wolf, R. C., Ditzen, B., Grinevich, V., & Herpertz, S. C. (2022) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2022.104859 · Cited by 18
Beversdorf, D. Q., Anagnostou, E. A., Hardan, A. Y., Wang, P. P., Erickson, C. A., Frazier, T. W., & Veenstra-VanderWeele, J. M. (2023) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2022.1079006 · Cited by 19
“As one of the few examples of the potential utility of biomarkers to dissect heterogeneity within ASD treatment studies, low baseline plasma oxytocin level predicted response to intranasal oxytocin for social responsivity; although this did not replicate in a larger study (50).”
ResultSelf-citationOxytocin in neurodevelopmental disorders: Autism spectrum disorder and Prader-Willi syndrome
Josselsohn, A., Zhao, Y., Espinoza, D., & Hollander, E. (2024) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2024.108734 · Cited by 16
Microbes, oxytocin and stress: Converging players regulating eating behavior
Cuesta‐Marti, C., Uhlig, F., Muguerza, B., Hyland, N. P., Clarke, G. A., & Schellekens, H. (2023) · Journal of Neuroendocrinology · doi:10.1111/jne.13243 · Cited by 17
“125 At the level of the brain, Oxt administration enhances functional connectivity between the ventral PFC and striatum, 126 which suggests that the mesocorticolimbic system is potentially involved in this Oxt-mediated effects on ASD.”
Anhedonia and Hyperhedonia in Autism and Related Neurodevelopmental Disorders
Dichter, G. S., & Rodríguez-Romaguera, J. (2022) · Current topics in behavioral neurosciences · doi:10.1007/7854_2022_312 · Cited by 16
Complexity of the Hypothalamic Oxytocin System and its Involvement in Brain Functions and Diseases
Cui, X., & Xiao, L. (2025) · Neuroscience Bulletin · doi:10.1007/s12264-025-01424-1 · Cited by 17
“However, the efficiency and feasibility of using oxytocin to treat these disorders/diseases remain controversial [141, 142].”
Olfactory Drug Aerosol Delivery with Acoustic Radiation
Jamalabadi, M. Y. A., & Xi, J. (2022) · Biomedicines · doi:10.3390/biomedicines10061347 · Cited by 15
The Causal Role of Temporoparietal Junction in Mediating Self–Other Mergence during Mentalizing
Sun, F., Yang, T., Liu, N., & Wan, X. (2023) · Journal of Neuroscience · doi:10.1523/jneurosci.1026-23.2023 · Cited by 16
Beke, E., Gondran, C., Chovelon, B., Peyrin, É., Holzinger, M., & Ravelet, C. (2025) · Biosensors and Bioelectronics · doi:10.1016/j.bios.2025.117306 · Cited by 16
Siecinski, S. K., Giamberardino, S. N., Spanos, M., Hauser, A. C., Gibson, J., Chandrasekhar, T., Trelles, M. D. P., Rockhill, C., Palumbo, M. L., Cundiff, A. W., et al. (2023) · Autism Research · doi:10.1002/aur.2884 · Cited by 15
Self-citationPutnam, P. T., & Chang, S. W. C. (2022) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2021.0047 · Cited by 13
“However, a robustly effective approach has not yet been identified [48,76,77].”
BackgroundHu, L., Du, X., Jiang, Z., Song, C., & Liu, D. (2023) · European Journal of Clinical Pharmacology · doi:10.1007/s00228-023-03545-w · Cited by 14
Cannabinoid treatment for the symptoms of autism spectrum disorder
Aran, A. A., & Cayam-Rand, D. (2024) · Expert Opinion on Emerging Drugs · doi:10.1080/14728214.2024.2306290 · Cited by 19
“…studies assessing nasal oxytocin, efficacy was identified through post-hoc analyses of subpopulations: younger children, specifically those aged 3–5 years in a 12-week treatment study [24] and children who received psychosocial training in conjunction with oxytocin in a 4-week duration study [25].”
BackgroundMethodXu, D., Li, Q., Zhuang, Q., Zhang, Y., Yao, S., Zhao, W., & Kendrick, K. M. (2022) · Frontiers in Neuroscience · doi:10.3389/fnins.2022.1022101 · Cited by 15
“, 2017) a large-scale (n = 277) study across a wider agerange (3–17 years) and using an escalating dose strategy of up to 80IU per day did not (Sikich et al., 2021).”
BackgroundAlaerts, K., Bernaerts, S., & Wenderoth, N. (2022) · Translational Psychiatry · doi:10.1038/s41398-022-02158-8 · Cited by 12
The use of intranasal oxytocin in the treatment of eating disorders
Malewska-Kasprzak, M., Jowik, K., & Tyszkiewicz‐Nwafor, M. (2023) · Neuropeptides · doi:10.1016/j.npep.2023.102387 · Cited by 13
“Although the number of studies is increasing, many practical aspects of hormone use remain unclear (Sikich et al., 2021), such as optimization of dose, sequence, and duration of treat-ment, as well as a reliable tool to objectively assess changes in ASD symptoms (Yamasue et al., 2022; Guastella et…”
Intranasal oxytocin in a genetic animal model of autism
Szabó, J., Mlynár, M., Feješ, A., Renczés, E., Borbélyová, V., Ostatníková, D., & Celec, P. (2023) · Molecular Psychiatry · doi:10.1038/s41380-023-02330-6 · Cited by 16
Capps, M. E., Moyer, A. J., Conklin, C. L., Martina, V., Torija-Olson, E. G., Klein, M. C., Gannaway, W. C., Calhoun, C. C., Vivian, M. D., & Thyme, S. B. (2025) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2402557122 · Cited by 23
McKernan, E. P., Kumar, M., Martino, A. D., Shulman, L., Kolevzon, A. L., Lord, C., Narayanan, S. S., & Kim, S. H. (2022) · Scientific Reports · doi:10.1038/s41598-022-07299-w · Cited by 12
“) and the Secret Agent Society (SAS) 27 as well as a clinical trial testing the use of intranasal oxytocin for the treatment of autism symptoms 28 .”
BackgroundSelf-citationHiguchi, Y., Tachigori, S.-I., & Arakawa, H. (2022) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2022.106004 · Cited by 13
Involvement of oxytocin receptor deficiency in psychiatric disorders and behavioral abnormalities
Wei, J., Zheng, H., Li, G., Chen, Z., Fang, G., & Yan, J. (2023) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2023.1164796 · Cited by 13
“Additionally, a recent study published in the N Engl J Med journal found that intranasal OXT in children and adolescents with ASD showed no significant difference in the improvements of social or cognitive functions compared with the placebo group (Sikich et al., 2021).”
BackgroundTsingotjidou, A. (2022) · Biomolecules · doi:10.3390/biom12111603 · Cited by 18
“1Mus-deficient mice [104] Magel1-deficient mice [105] Magel2-deficient mice [106] Magel2-deficient mice [107] VPA rats and FRX mice [108] BALB/cByJ and C58/J mice [110,111] Oprm1−/− Mouse [112] HPC-1/Syntaxin1A Knockout Mice [113] Shank3-Deficient Rat [114] Intranasal OXT in adolescent boys [87] Intranasal OXT treatme…”
BackgroundMethodLan, C., Chen, Y., Zhang, Y., Kou, J., Huang, L., Xu, T., Yang, X., Xu, D., Yang, W., Kendrick, K. M., et al. (2023) · Neuroendocrinology · doi:10.1159/000531064 · Cited by 12
Gao, Y. Z., Duo, L., Zhe, X., Hao, L., Song, W., Gao, L., Cai, J., & Liu, D. (2023) · Animals · doi:10.3390/ani13193076 · Cited by 11
An Update on Psychopharmacological Treatment of Autism Spectrum Disorder
Aishworiya, R., Valica, T., Hagerman, R. J., & Restrepo, B. (2024) · FOCUS The Journal of Lifelong Learning in Psychiatry · doi:10.1176/appi.focus.24022006 · Cited by 16
Talbot, C. F., Oztan, O., Simmons, S. M. V., Trainor, C., Ceniceros, L. C., Nguyen, D. K. K., Rosso, L. A. D., Garner, J. P., Capitanio, J. P., & Parker, K. J. (2024) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2418635121 · Cited by 12
“Third, we did not evaluate the effects of an AVPR1A antagonist or nebulized OXT here, largely because recent multisite clinical trials have shown that neither balovaptan [an AVPR1A antagonist ( 49 )], nor OXT ( 50 ), improve core behavioral symptoms in people with ASD.”
Takiguchi, S., Makita, K., Fujisawa, T. X., Nishitani, S., & Tomoda, A. (2023) · Frontiers in Child and Adolescent Psychiatry · doi:10.3389/frcha.2022.1056115 · Cited by 9
“However, a recent placebo-controlled trial of intranasal OT therapy that included 290 children with ASD revealed no signi fi cant improvement in measures of social or cognitive functioning over 24 weeks (81).”
Highly Specific Detection of Oxytocin in Saliva
Rana, M., Yildirim, N., Ward, N. E., Vega, S. P., Heffernan, M. J., & Argun, A. A. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24054832 · Cited by 14
“Exogenous administration of oxytocin has improved various outcomes associated with social responsiveness, including eye contact, emotion recognition, social cognition, and neural circuitry associated with social awareness [17,18,22].”
BackgroundSocial rank-dependent effects of testosterone on huddling strategies in mice
Zhao, Y., Yin, X., Yu, Y., Huang, S., Feng, H., Wang, S., Cai, Y., Zhao, R., Gao, S., Liu, Y., et al. (2023) · iScience · doi:10.1016/j.isci.2023.106516 · Cited by 13
“Non-aggressive male schizophrenic patients with lower T levels have more severe negative symptoms.(31) These studies mean that an appropriate amount of T administration may have a potential therapeutic effect on the social withdrawal symptoms of patients with autism, depression, post-traumatic stress syndrome and schi…”
BackgroundLindenmaier, Z., Ellegood, J., Stuive, M., Easson, K., Yee, Y., Fernandes, D., Foster, J. A., Anagnostou, E. A., & Lerch, J. P. (2022) · NeuroImage · doi:10.1016/j.neuroimage.2022.119243 · Cited by 12
Coccurello, R., Marrone, M. C., & Maccarrone, M. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.869606 · Cited by 12
“, 2014) or to fail in eliciting significant differences between oxytocin-treated subjects and placebo group (Sikich et al., 2021).”
BackgroundOxytocin signaling regulates maternally directed behavior during early life
Zelmanoff, D. D., Bornstein, R., Kaufman, M., Dine, J., Wietek, J., Litvin, A., Abraham, S., Cohen, S., Atzmon, A., Porat, I., et al. (2025) · Science · doi:10.1126/science.ado5609 · Cited by 13
Intranasal oxytocin as a treatment for anxiety and autism: From subclinical to clinical applications
Yin, H., Jiang, M., Han, T., & Xu, X. (2024) · Peptides · doi:10.1016/j.peptides.2024.171211 · Cited by 11
Pantouli, F., Pujol, C., Derieux, C., Fonteneau, M., Pellissier, L. P., MARSOL, C., Karpenko, J., Bonnet, D., Hibert, M., Bailey, A., et al. (2024) · Neuropsychopharmacology · doi:10.1038/s41386-024-01915-1 · Cited by 11
Le, J., Zhang, L., Zhao, W., et al. (2022) · medRxiv · doi:10.1101/2022.01.03.22268708 · Cited by 11
Brain region–specific neural activation by low-dose opioid promotes social behavior
Ohnami, S., Naito, M., Kawase, H., Higuchi, M., Hasebe, S., Takasu, K., Kanemaru, R., Azuma, Y., Yokoyama, R., Kochi, T., et al. (2024) · JCI Insight · doi:10.1172/jci.insight.182060 · Cited by 11
Kong, X., Kang, J., & Liu, K. (2023) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2023.08.006 · Cited by 11
Diencephalic and Neuropeptidergic Dysfunction in Zebrafish with Autism Risk MutationsPreprint
Capps, M. E., Moyer, A. J., Conklin, C. L., et al. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.01.18.576309 · Cited by 10
“For example, intranasal oxytocin has yielded mixed outcomes as a treatment for reduced social abilities in ASD ( 84 , 85 ).”
Background
Metadata
- Authors
- Sikich, L., Kolevzon, A., King, B. H., McDougle, C. J., Sanders, K. B., Kim, S.-J., Spanos, M., Chandrasekhar, T., Trelles, M. D. P., Rockhill, C. M., Palumbo, M. L., Witters Cundiff, A., Montgomery, A., Siper, P., Minjarez, M., Nowinski, L. A., Marler, S., Shuffrey, L. C., Alderman, C., Weissman, J., Zappone, B., Mullett, J. E., Crosson, H., Hong, N., Siecinski, S. K., Giamberardino, S. N., Luo, S., She, L., Bhapkar, M., Dean, R., Scheer, A., Johnson, J. L., Gregory, S. G., & Veenstra-VanderWeele, J.
- Affiliations
- University of North Carolina at Chapel Hill (US)
- From the Department of Psychiatry and Behavioral Sciences (L. Sikich, M.S., T.C., C.A., A.S.), the Duke Clinical Research Institute (L. Sikich, C.A., S.L., L. She, M.B.), the Duke Molecular Physiology Institute (S.K.S., S.N.G., S.G.G.), and the Departments of Biostatistics and Bioinformatics (S.L.) and Neurology (S.G.G.), Duke University, Durham, the Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill (L. Sikich, M.S., T.C., C.A., R.D., A.S., J.L.J.), and SAS Institute, Cary (J.L.J.) — all in North Carolina; the Department of Psychiatry, Icahn School of Medicine at Mount Sinai (A.K., M.D.P.T., P.S., J.W.), the Department of Psychiatry, Columbia University (A.M., L.C.S., N.H., J.V.-V.), and New York State Psychiatric Institute (J.V.-V.), New York, and the Center for Autism and the Developing Brain, Weill Cornell Medicine, White Plains (J.V.-V.) — all in New York; the Department of Psychiatry, University of California San Francisco, San Francisco (B.H.K.); the Department of Psy...
- ORCID
- Sikich, Linmarie
- Kolevzon, Alexander
- King, Bryan H.
- McDougle, Christopher J.
- Sanders, Kevin B.
- Spanos, Marina
- Chandrasekhar, Tara
- Rockhill, Carol M.
- Montgomery, Alicia
- Siper, Paige
- Marler, Sarah
- Shuffrey, Lauren C.
- Weissman, Jordana
- Hong, Natalie
- Siecinski, Stephen K.
- Luo, Sheng
- She, Lilin
- Dean, Russell
- Scheer, Abby
- Johnson, Jacqueline L.
- Gregory, Simon G.
- Veenstra-VanderWeele, Jeremy
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2021-10-14
- Volume
- 385
- Issue
- 16
- Pages
- 1462-1473
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- PMC
- PMC9701092
- OpenAlex
- W3206744275
- Cited by
- 298
- References
- 36
- Citations by year
- 2026: 52 · 2025: 53 · 2024: 52 · 2023: 74 · 2022: 63 · 2021: 4
- FWCI
- 23.92
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Florida International University Digital Commons (Florida International University) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD073984)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Neuroendocrine regulation and behavior
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Keywords
- intranasal oxytocin, autism spectrum disorder, children and adolescents, social withdrawal, social functioning, Aberrant Behavior Checklist, adverse events, cognitive function
- MeSH terms
- Autism Spectrum Disorder, Administration, Intranasal, Adolescent, Child, Child, Preschool, Double-Blind Method, Female, Humans, Male, Oxytocin, Social Behavior, Least-Squares Analysis, Treatment Failure, Social Skills
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
A language model drew the claims from the paper on 2026-10-08, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-08 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Cited sources are checked with a language model’s help (gpt-6-sol).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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