Neuroimaging oxytocin modulation of social reward learning in schizophrenia
Open accessAbstract
BACKGROUND: Conventional pharmacological approaches have limited effectiveness for schizophrenia. There is interest in the application of oxytocin, which is involved in social cognition. Clinical trials have yielded mixed results, with a gap in understanding neural mechanisms. AIMS: To evaluate the behavioural impact of oxytocin administration on a social learning task in individuals with schizophrenia, and elucidate any differential neural activity produced. METHOD: We recruited 20 clinically stable right-handed men diagnosed with schizophrenia or schizoaffective disorder. In a double-blind cross-over randomised controlled study, 40 IU of oxytocin or placebo were administered before functional magnetic resonance imaging of participants playing a multi-round economic exchange game of trust. Participants had the role of investors (investment trials) receiving repayment on their investments (repayment trials), playing one session against a computer and a second against a player believed to be human. RESULTS: During investment trials, oxytocin increased neural signalling in the right lateral parietal cortex for both human and computer player trials, and attenuated signalling in the right insula for human player trials. For repayment trials, oxytocin elicited signal increases in left insula and left ventral caudate, and a signal decrease in right amygdala during the human player trials; conversely it resulted in right dorsal caudate activation during the computer player trials. We did not find a significant change in behavioural performance associated with oxytocin administration, or any associations with symptoms. CONCLUSIONS: During a social learning task oxytocin modulates cortical and limbic substrates of the reward-processing network. These perturbations can be putatively linked to the pathoaetiology of schizophrenia.
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In schizophrenia patients, there was a noteworthy trend towards a significant increase in social trust in a cooperative task following intranasal OXT, although the study did not find a statistically significant impact of OXT.
“Although the study did not find a statistically significant impact of OXT, there was a noteworthy trend towards a significant in crease in social trust in a cooperative task (Mouchlianitis et al., 2022).”
From Convergence of oxytocin and dopamine signalling in neuronal circuits: Insights into the neurobiology of social interactions across species (2024) · cites this paper as Mouchlianitis et al., 2022
The Results (Behavioural results; page unavailable) report a trend-level drug-by-player interaction for mean investments (P = 0.06), not a significant behavioural effect. The Discussion (Implications and limitations; page unavailable) says the trend was driven by reduced investment in the oxytocin computer-player condition, rather than a meaningful increase in social trust with the human player. The paper also reports significant neural effects of oxytocin, so the absence of a significant impact applies to the behavioural result, not the study as a whole. (LLM, conf=0.88)
Experimental — accuracy not yet measuredSchizophrenia patients treated with OXT exhibited heightened trust when they believed they were interacting with a human player as opposed to a computer player.
“Specifically, schizophrenia patients treated with OXT exhibited height ened trust when they believed they were interacting with a human player as opposed to a computer player”
From Convergence of oxytocin and dopamine signalling in neuronal circuits: Insights into the neurobiology of social interactions across species (2024) · cites this paper as Mouchlianitis et al., 2022
The Behavioural results report higher mean investment under oxytocin when participants believed the player was human rather than a computer, but the Drug × Player interaction only approached significance (P = 0.06); initial investments showed no significant effects. The Discussion says the trend was driven by reduced investment in the computer-player condition, so the unqualified claim of heightened trust overstates the finding. (LLM, conf=0.88)
Experimental — accuracy not yet measuredThis behavioural change was accompanied by a significant increase in activation in the right lateral parietal cortex and the right anterior insula when interacting with human players.
“This behavioural change was accompanied by a significant increase in activation in the right lateral parietal cortex and the right anterior insula when interacting with human players.”
From Convergence of oxytocin and dopamine signalling in neuronal circuits: Insights into the neurobiology of social interactions across species (2024) · cites this paper as Mouchlianitis et al., 2022
The Results (Structural mask analysis) report increased right lateral parietal activation during investment trials with both human and computer players. The Results (Insula ROI analysis) report reduced right anterior insula activation during investment with a human player, although right insula activation increased during repayment. The Behavioural results do not establish a significant behavioural change accompanying these neural findings. (LLM, conf=0.88)
Experimental — accuracy not yet measuredOXT led to a significant decrease in AMY activity when interacting with human players.
“Additionally, OXT led to a significant decrease in AMY activity when interacting with human players.”
From Convergence of oxytocin and dopamine signalling in neuronal circuits: Insights into the neurobiology of social interactions across species (2024) · cites this paper as Mouchlianitis et al., 2022
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- Authors
- Mouchlianitis, E. D., Tracy, D. K., Wigton, R., Vanes, L. D., Fett, A.-K., & Shergill, S. S.
- Affiliations
- University of East London (GB)
- King's College London (GB)
- Beth Israel Deaconess Medical Center (US)
- City, University of London (GB)
- Corresponding author
- Mouchlianitis, Elias D.
- Venue
- BJPsych Open
- Publisher
- Royal College of Psychiatrists
- Published
- 2022-09
- Volume
- 8
- Issue
- 5
- Pages
- e175-e175
- ISSN
- 2056-4724 (ISSN-L)
- PMC
- PMC9534925
- OpenAlex
- W4297193110
- Cited by
- 8
- References
- 37
- Citations by year
- 2026: 4 · 2025: 2 · 2024: 2
- FWCI
- 0.94
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- BJPsych Open (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Kent Academic Repository (University of Kent) (acceptedVersion)
- City Research Online (City University London) (acceptedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Research Portal (King's College London) (submittedVersion, cc-by)
- Funders
- South London and Maudsley NHS Foundation Trust
- King's College London
- NIHR Maudsley Biomedical Research Centre
- Topics
- Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- oxytocin, schizophrenia, social cognition, trust game, insula, amygdala, caudate nucleus, parietal cortex, reward processing, social learning, schizoaffective disorder
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