The neuropeptides oxytocin (OXT) and arginine vasopressin (AVP) have had key roles throughout mammalian evolution in the regulation of complex social cognition and behaviours, such as attachment, social exploration, recognition and aggression, as well as anxiety, fear conditioning and fear extinction.
The goal of this Review is to assess the OXT and AVP systems in the human brain from a translational viewpoint with regard to social behaviour, genetics, neuroimaging, neuroendocrinology and clinical studies.
Neuropeptides can be non-invasively delivered to the human brain using intranasal administration, with clear behavioural- and neural systems-level consequences.
Following intranasal administration, OXT improves emotion recognition, enhances gaze to the eye region, promotes trust and prosocial behaviour, and reduces behavioural and endocrine responses to social stress.
In initial studies, intranasal administration of AVP seems to influence social communication and increase reactivity to social stress.
Common genetic risk variants in the genes that encode the brain receptors for OXT and AVP have been associated with autism and social behavioural phenotypes in humans.
Imaging genetics studies show that genetic risk variants in the brain receptors for OXT and AVP affect the structure and function of key regions for social behaviour, including the amygdala, anterior cingulate cortex and hypothalamus.
Functional neuroimaging studies using intranasal application of neuropeptides support the view that the effects of OXT and AVP on social processing are mediated by limbic circuitry with the amygdala as a core structure.
Recent studies have begun to provide evidence for impaired functioning of OXT and AVP in mental disorders that are characterized by early attachment disruption or social interaction pathology — for example, autism, social anxiety disorder, borderline personality disorder and schizophrenia — thereby providing new translational dimensions for novel pharmacological interventions in the neuropeptide system.
We suggest that the key route to translational success is a synergistic combination of OXT administration (including selective and longer-acting OXT receptor agonists) with psychotherapy; a 'propsychotherapeutic' neuropharmacological approach that could be referred to as 'psychobiological therapy'.
The neuropeptides oxytocin (OXT) and arginine vasopressin (AVP) are evolutionarily highly conserved mediators in the regulation of complex social cognition and behaviour. Recent studies have investigated the effects of OXT and AVP on human social interaction, the genetic mechanisms of inter-individual variation in social neuropeptide signalling and the actions of OXT and AVP in the human brain as revealed by neuroimaging. These data have advanced our understanding of the mechanisms by which these neuropeptides contribute to human social behaviour. OXT and AVP are emerging as targets for novel treatment approaches — particularly in synergistic combination with psychotherapy — for mental disorders characterized by social dysfunction, such as autism, social anxiety disorder, borderline personality disorder and schizophrenia.
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A.M.-L. gratefully acknowledges grant support from the Deutsche Forschungsgemeinschaft (DFG; SFB 636), Bundesministerium für Bildung und Forschung (BMBF; NGFN-MooDs, Bernstein-Programme), European Union (NEWMEDS, OPTIMIZE and EU-GEI) and National Alliance for Research on Schizophrenia and Depression (NARSAD; Distinguished Investigator Award) during the preparation of this manuscript. M.H. gratefully acknowledges grant support from the Swiss National Science Foundation (SNSF) and DFG. G.D. gratefully acknowledges grant support from the DFG (Do1312/2-1). The work of P.K. on this manuscript was partly supported by a grant from the DFG (KI576/10-1). The authors thank F. S. Chen and M. Sibold for editorial assistance.
The authors declare no competing financial interests.
- Event-related brain potentials
Electrical potentials that are generated in the brain as a consequence of the synchronized activation of neuronal networks by external stimuli. These evoked potentials are recorded at the scalp and consist of precisely timed sequences of waves or 'components'.
- Trier Social Stress test
(TSST). A standardized psychosocial laboratory stressor that includes public speaking and mental arithmetic.
- Reading the Mind in the Eyes test
Participants are presented with 36 pictures of the eye region of faces and are asked to decide which of four words best describes what the person in the picture is thinking or feeling.
A technique for identifying candidate chromosomal regions that underlie a particular trait based on the extent to which that trait is co-inherited with certain genetic markers.
A combination of alleles at different loci in the genome that tend to be inherited together because they show high linkage disequilibrium (often because they are physically close).
- Reward dependence
A personality measure that quantifies sociability and the interest in, as well as reliance on, social approval.
- Dictator Game
An economic exchange game in which a player (the 'dictator') splits up an asset, such as money, between him- or herself and another player. The amount of money or asset given to the other player is a measure of altruism.
- Linkage disequilibrium
The non-random association (that is, correlation) of alleles at two or more loci, so that certain combinations of alleles occur together more frequently than would be expected by chance. This means that a true causative locus might in fact be one that is in linkage disequilibrium with the one that is under investigation in a genetic association study.
- Prepulse inhibition of the startle response
Electrophysiological paradigm in which a relatively weak sensory event (the prepulse) is presented 30–500 ms before a strong stimulus, which induces startle. The reduction of the magnitude of the startle response following the prepulse is measured.
- Evaluative social stress
A form of social stress that is induced by one's performance being observed and criticized by others.
- Emotional face-matching task
An experimental paradigm that is used to evoke emotional responses implicitly by presenting the participants with a task in which they have to match one of two emotional faces to a target face.
- Social recognition matching task
An experimental paradigm that is used to evoke social information processing implicitly by presenting the participants with a task in which they have to match one of two socially relevant pictures (faces or scenes) to a target picture.
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Meyer-Lindenberg, A., Domes, G., Kirsch, P. et al. Oxytocin and vasopressin in the human brain: social neuropeptides for translational medicine. Nat Rev Neurosci 12, 524–538 (2011). https://doi.org/10.1038/nrn3044
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