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Oxytocin treatment induces long-lasting neurobiological adaptations in autism

Presented by
Dr Kaat Alaerts, KU Leuven, Belgium
ECNP 2022
Daily treatment with oxytocin for 4 weeks induced long-term behavioural changes and long-term adaptations in the connectivity between the amygdala and orbital frontal cortex, studies in both adults and children with autism show.

Oxytocin is an important neuromodulator that has a role in affiliative behaviour, including inter-personal bonding, social attachment, and trust. Intranasal administration of oxytocin is increasingly considered as a potential treatment option for elevating the socio-communicative problems that are at the core of autism spectrum disorders.

Dr Kaat Alaerts (KU Leuven, Belgium) first reviewed the results of several randomised-controlled trials of oxytocin in autism [1]. Although most studies reported a positive outcome on social behaviour, the largest trial (n=277) did not [2]. These contradictory outcomes are likely due to differences in populations, symptom severity, as well as variations in trial design, suggested Dr Alaerts.

Secondly, Dr Alaerts discussed the long-term neurobiological effects of repeated oxytocin doses, which are hardly studied. The results from 2 recent, randomised-controlled trials give some clues on this matter. In the first trial (NCT02940574), 40 adult men with autism were treated with a daily nasal dose of oxytocin 24 IU for 4 weeks, with a follow-up of 1 year. Oxytocin proved to attenuate amygdala activity, which lasted throughout the follow-up [3,4]. In addition, connectivity from the amygdala to the orbital frontal cortex was attenuated throughout the follow-up. This was interpreted as a decreased need for prefrontal cognitive control over amygdala reactivity after oxytocin treatment. Concerning behavioural effects, a reduction of ‘feelings of avoidance’ was observed after oxytocin treatment. At an individual level, improvement in behaviour correlated with attenuation of amygdala activity. Oxytocin treatment also –temporarily– increased endogenous oxytocin production [5]. This might suggest a positive spiral of oxytocin release.

A similar designed randomised-controlled trial in children (with follow-up from only 4 weeks after the last oxytocin dose) showed comparable changes in the connectivity between the amygdala and the orbital frontal cortex. In addition, in this cohort, a positive correlation was found between baseline oxytocin receptor expression and change in the amygdala-orbital frontal cortex connectivity. This suggests that at least some level of oxytocin receptor expression is needed to react to the oxytocin treatment, Dr Alaerts explained. Also in line with the findings in the adult cohort, improvement in behaviour correlated with attenuation of amygdala activity.

  1. Alaerts K, et al. Oxytocin pharmacotherapy for autism – an overview of the state-of-the-art and future directions to take. Abstract S17.03, ECNP Congress 2022, 15–18 October, Vienna, Austria.
  2. Sikich L, et al. N Eng J Med. 2021;14;385.
  3. Bernaerts S, et al. Transl Psychiatry. 2020;10:383.
  4. Bernaerts S, et al. Mol Autism. 2020;11:6.
  5. Alaerts K, et al. Eur Neuropsychopharmacol. 2021;43:147–152.


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