Oxytocin: opening a window to the neural substrate of social behaviour

publicinfo_Oxytocin_molecule_graphSocial interaction is a feature of every aspect of human life. Deficits causing impairment in social function can have a debilitating effect in someone’s life and are prominent in many neuropsychiatric disorders, such as autism and schizophrenia. This has provided a strong impetus to understand the neural substrate of social behaviour with a view to developing effective treatments. This task has been hindered by the complexity of human social interactions. Nonetheless, animal research since the 1970s has identified a class of molecules that play a key role in the development and regulation of social behaviour and its neural substrate. These are known as nonapeptides because they are composed of nine amino-acids; oxytocin is probably the best-researched member of this class. Studies with humans, particularly over the last decade, have confirmed the importance of oxytocin for human social behaviour as well.

Oxytocin and its homologs in non-mammalian vertebrates date back at least 700 million years (1). Given the quintessential nature of sociality in mammalian life, it is not surprising that such an evolutionarily old molecule plays a key role in its development and regulation. Oxytocin, and the structurally similar arginine vasopressin, initially regulated basic physiological and non-social functions, as well as reproductive behaviour, before evolving to regulate reproductive and social behavior. Functional conservation is accompanied by evolutionary diversification as variation in the oxytocin system (e.g. density and location of its receptors in the brain) underpins species-specific diversity in social behaviour.

The oxytocin system shows remarkable plasticity. This confers the system the required flexibility to regulate social behaviour in a context-dependent manner and contribute to intra- and inter-individual differences. Multiple factors contribute to such plasticity, such as the epigenetic modulation of gene expression in response to social experience, the dynamic interaction with sex-steroid hormones or the complexity of its pattern of release by hypothalamic neurons in response to social cues. Oxytocin can be independently and dynamically released into the blood stream as a hormone, to act at peripheral receptors, locally at synapses in the brain acting as a neuromodulator, or in bulk from the bodies and processes of hypothalamic oxytocin neurons, acting at distant sites that it reaches through volume transmission.

Animal studies have demonstrated the importance of oxytocin signalling in regulating multiple and dissociable dimensions of social behaviour, such as parental care, pair bonding, huddling, as well as sexual and reproductive behavior (2). Using intranasal sprays to increase oxytocin levels in the brain, or designs investigating the effects of polymorphisms in the oxytocin receptor gene, human studies have produced consistent results. They demonstrate the role of the oxytocin system in modulating social cognition, affiliative, co-operative or moral behaviour, anxiety and reactivity to stressors, as well as seeking of social support (3). Importantly, the effects of oxytocin cannot be unitarily described as prosocial, but are flexibly and dynamically shaped, in interaction with sex steroid hormones and other neurotransmitter systems, and depending on the perception of social context (4).

A better understanding of the oxytocin system can provide a window to the mechanistic substrate of human social behaviour. Exciting new studies demonstrate the even wider role that oxytocin plays in cortical development, consistent with the notion that we needed to evolve a large and sophisticated cortex to deal with the complexity of social behaviour (3). Accumulating evidence suggests that the integrity of signalling of oxytocin may affect the development of the nervous system early in life in interaction with early social experiences. For example, a recent study showed that oxytocin mediates the beneficial effects of early sensory stimulation on cross-modal primary sensory cortical development in rodents (5).

These findings have kindled an extensive investigative effort into the therapeutic value of oxytocin for neurodevelopmental and neuropsychiatric disorders characterized by social impairment, such as autism, schizophrenia or anorexia. An increasing number of clinical trials are being conducted to evaluate its potential efficacy, with some promising initial results. However, given the powerful and broad nature of oxytocin’s effects in brain function and cortical development, caution is required when considering interventions altering oxytocin levels, especially early in life. Such interventions may hold great promise, but we currently also lack sufficient evidence to evaluate the extent of potential risks (3).

REFERENCES

  1. Donaldson ZR & Young LJ (2008) Oxytocin, vasopressin, and the neurogenetics of sociality. Science 322(5903):900-904.
  2. Goodson J (2008) Nonapeptides and the evolutionary patterning of sociality. 170:3-15.
  3. Carter CS (2014) Oxytocin pathways and the evolution of human behavior. Annual review of psychology 65:17-39.
  4. Riem MM, Voorthuis A, Bakermans-Kranenburg MJ, & van Ijzendoorn MH (2014) Pity or peanuts? Oxytocin induces different neural responses to the same infant crying labeled as sick or bored. Developmental science 17(2):248-256.
  5. Zheng JJ, et al. (2014) Oxytocin mediates early experience-dependent cross-modal plasticity in the sensory cortices. Nature neuroscience 17(3):391-399.

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