Oxytocin and vasopressin in the human brain: social neuropeptides for translational medicine

• Published in: Nature reviews. Neuroscience Vol. 12; no. 9; pp. 524 - 538
• Main Authors: Meyer-Lindenberg, Andreas, Heinrichs, Markus, Domes, Gregor, Kirsch, Peter
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01-09-2011; Nature Publishing Group
• Subjects: 631/378/2645; 631/92/609; 692/698/1688/1366/64; Adult and adolescent clinical studies; Animal Genetics and Genomics; Animals; Anxiety; Autism; Behavioral Sciences; Biological and medical sciences; Biological Techniques; Biomedical and Life Sciences; Biomedicine; Brain; Cognition & reasoning; Fundamental and applied biological sciences. Psychology; General aspects. Models. Methods; Hormones; Humans; Interpersonal Relations; Medical sciences; Mental disorders; Neural Pathways - metabolism; Neurobiology; Neuropeptides; Neuropeptides - metabolism; Neurosciences; Oxytocin; Oxytocin - metabolism; Peptides; Physiological aspects; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Psychoses; review-article; Schizophrenia; Social aspects; Social Behavior; Social support; Stress; Translational Medical Research - methods; Translational Medical Research - trends; Vasopressin; Vasopressins - metabolism; Vertebrates: nervous system and sense organs; Germany; Human; Borderline; Oxytocin; Social phobia; Interaction; Central nervous system; Anxiety disorder; Psychotherapy; Schizophrenia; Developmental disorder; Cognition; Neuropeptide; Personality disorder; Vasopressin; Encephalon; Psychosis; Autism; Treatment; Neurohypophyseal hormone; Mental disorder; Social behavior disorder
• ISSN: 1471-003X; 1471-0048; 1469-3178
• DOI: 10.1038/nrn3044

Key Points
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'.
Animal studies have shown that oxytocin (OXT) and arginine vasopressin (AVP) are crucial regulators of social behaviour. In this Review, Meyer-Lindenberg and colleagues consider behavioural, genetic and neuroimaging studies that show that these peptides also influence social behaviour and cognition in humans, and suggest that the OXT and AVP systems could be targets for the treatment of mental disorders characterized by social dysfunction.
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.