Effects of single- and multiple-dose oxytocin treatment on amygdala low-frequency BOLD fluctuations and BOLD spectral dynamics in autism.

Alaerts K, Bernaerts S, Wenderoth N

Translational psychiatry20 Sept 2022Cited by 9 (Europe PMC)

PMID36127337PMCIDPMC9489696DOI10.1038/s41398-022-02158-8PepBankPUB-36127337

Summary

Prior neuroimaging clinical trials investigating the neural effects of intranasal administration of the neuropeptide oxytocin demonstrated a key role of the amygdala in oxytocin's neuromodulatory effects. These studies mostly demonstrated the acute effects of single-dose administrations, examining task-dependent effects of oxytocin on brain activity elicited during explicit experimental tasks or stimuli presentations. The increased consideration of oxytocin as a potential ameliorating treatment in autism spectrum disorder (ASD) requires a better understanding of how multiple-dose oxytocin administration affects intrinsic, task-free, amygdala function. In this double-blind, randomized, placebo-controlled trial with between-subject design, 38 adult men with ASD underwent resting-state fMRI scanning before and after oxytocin or placebo treatment. Effects were assessed either after a single-dose administration, consisting of 24 international units, or after multiple-dose treatment, consisting of 4 weeks of once-daily nasal spray administrations. Compared to placebo, oxytocin induced a decrease in intrinsic resting-state BOLD signal amplitudes of the bilateral amygdala (fractional amplitudes of low-frequency fluctuations) and modulated cross-frequency interactions between adjacent BOLD frequency components. The right amygdala showed a pattern of reduced cross-frequency harmonicity, while the left amygdala showed a relative increase in harmonic cross-frequency interactions after oxytocin treatment. Notably, the direction and magnitude of BOLD spectral changes induced after a single-dose were qualitatively similar to treatment effects induced after multiple-dose treatment. Furthermore, the identified spectral changes in amygdalar BOLD amplitude and cross-frequency harmonicity were associated with improved feelings of tension, reflecting oxytocin's anxiolytic, stress-reducing neuromodulatory role. The observed effects of oxytocin on amygdalar BOLD spectral characteristics and associated behaviors contribute to a deeper mechanistic understanding of the intrinsic, task-free neuromodulatory dynamics that underlie single- and multiple-dose oxytocin treatment in ASD. European Clinical Trial Registry (Eudract 2014-000586-45).

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study5

5 results from studies that gave the peptide. 5 results from people.

01HumanRandomized controlled trialMechanism
In adult men with ASD, oxytocin decreased intrinsic resting-state BOLD signal amplitudes of the bilateral amygdala compared with placebo.
In plain wordsIn men with autism, oxytocin lowered resting brain-signal strength in the amygdala compared with placebo.
Peptide
Oxytocin
Outcome
DecreaseBilateral amygdala resting-state BOLD signal amplitude (fALFF)
Study
n = 38
Comparator
Placebo
Outcome group
Brain and neuronal activity · Nervous system and cognition
Studied dose
24 international units (single dose); multiple-dose amount not stated · nasal spray · single dose or 4 weeksAs given in this study (human).
Source sentences
Summary
Compared to placebo, oxytocin induced a decrease in intrinsic resting-state BOLD signal amplitudes of the bilateral amygdala (fractional amplitudes of low-frequency fluctuations)
1 context sentence(design, population, supporting numbers)
Summary · context
In this double-blind, randomized, placebo-controlled trial with between-subject design, 38 adult men with ASD underwent resting-state fMRI scanning before and after oxytocin or placebo treatment.
Show in the study text Report a problemFND-3612733701
02HumanRandomized controlled trialMechanism
In adult men with ASD, the right amygdala showed reduced cross-frequency harmonicity after oxytocin treatment.
In plain wordsIn men with autism, a measure of signal interaction in the right amygdala was lower after oxytocin.
Peptide
Oxytocin
Outcome
DecreaseRight amygdala cross-frequency harmonicity
Study
n = 38
Comparator
Placebo
Outcome group
Brain and neuronal activity · Nervous system and cognition
Studied dose
24 international units (single dose); multiple-dose amount not stated · nasal spray · single dose or 4 weeksAs given in this study (human).
Source sentences
Summary
The right amygdala showed a pattern of reduced cross-frequency harmonicity
1 context sentence(design, population, supporting numbers)
Summary · context
In this double-blind, randomized, placebo-controlled trial with between-subject design, 38 adult men with ASD underwent resting-state fMRI scanning before and after oxytocin or placebo treatment.
Show in the study text Report a problemFND-3612733702
03HumanRandomized controlled trialMechanism
In adult men with ASD, the left amygdala showed a relative increase in harmonic cross-frequency interactions after oxytocin treatment.
In plain wordsIn men with autism, a measure of signal interaction in the left amygdala was higher after oxytocin.
Peptide
Oxytocin
Outcome
IncreaseLeft amygdala cross-frequency harmonicity
Study
n = 38
Comparator
Placebo
Outcome group
Brain and neuronal activity · Nervous system and cognition
Studied dose
24 international units (single dose); multiple-dose amount not stated · nasal spray · single dose or 4 weeksAs given in this study (human).
Source sentences
Summary
while the left amygdala showed a relative increase in harmonic cross-frequency interactions after oxytocin treatment.
1 context sentence(design, population, supporting numbers)
Summary · context
In this double-blind, randomized, placebo-controlled trial with between-subject design, 38 adult men with ASD underwent resting-state fMRI scanning before and after oxytocin or placebo treatment.
Show in the study text Report a problemFND-3612733703
04HumanRandomized controlled trialMechanism
In adult men with ASD, the oxytocin-induced spectral changes in amygdalar BOLD amplitude and cross-frequency harmonicity were associated with improved feelings of tension.
In plain wordsIn men with autism, brain-signal changes after oxytocin were linked to improved feelings of tension.
Peptide
Oxytocin
Outcome
Not applicableAssociation of amygdalar spectral changes with feelings of tension
Study
n = 38
Outcome group
Brain and neuronal activity · Nervous system and cognition
Studied dose
Dose not stated · nasal sprayAs given in this study (human).
Source sentences
Summary
Furthermore, the identified spectral changes in amygdalar BOLD amplitude and cross-frequency harmonicity were associated with improved feelings of tension, reflecting oxytocin's anxiolytic, stress-reducing neuromodulatory role.
1 context sentence(design, population, supporting numbers)
Summary · context
In this double-blind, randomized, placebo-controlled trial with between-subject design, 38 adult men with ASD underwent resting-state fMRI scanning before and after oxytocin or placebo treatment.
Show in the study text Report a problemFND-3612733705
05HumanRandomized controlled trialMechanism
In adult men with ASD, the direction and magnitude of BOLD spectral changes after a single dose were qualitatively similar to those after multiple-dose treatment.
In plain wordsIn men with autism, brain-signal changes after one dose of oxytocin looked similar to changes after four weeks of daily doses.
Peptide
Oxytocin
Outcome
No significant changeSingle-dose versus multiple-dose effects on BOLD spectral changes
Study
n: not reported in source
Comparator
Multiple-dose oxytocin (4 weeks)
Outcome group
Brain and neuronal activity · Nervous system and cognition
Studied dose
24 international units (single dose) · nasal spray · single doseAs given in this study (human).
Source sentences
Summary
Notably, the direction and magnitude of BOLD spectral changes induced after a single-dose were qualitatively similar to treatment effects induced after multiple-dose treatment.
1 context sentence(design, population, supporting numbers)
Summary · context
In this double-blind, randomized, placebo-controlled trial with between-subject design, 38 adult men with ASD underwent resting-state fMRI scanning before and after oxytocin or placebo treatment.
Show in the study text Report a problemFND-3612733704

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

Version 2Current
11 Oct 2026, 00:50 UTC
Study results updated
Version 1
9 Oct 2026, 02:48 UTC
First added · source update from Europe PMC

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