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.

/pdf/oxytocin-and-vasopressin-in-the-human-brain-social-1itms1rz5b.pdf

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

Oxytocin: the Great Facilitator of Life

The membrane proteins CD38 and CD157 belong to an evolutionarily conserved family of enzymes that play crucial roles in human physiology. Expressed in distinct patterns in most tissues, CD38 (and C...

Evolution and Function of the ADP Ribosyl Cyclase/CD38 Gene Family in Physiology and Pathology

http://www.wisebrain.org/media/Papers/OxytocinSocCog.pdf

Oxytocin and the Neural Mechanisms Regulating Social Cognition and Affiliative Behavior

In addition to various reproductive stimuli, the neuropeptide oxytocin (OXT) is released both from the neurohypophysial terminal into the blood stream and within distinct brain regions in response to stressful or social stimuli. Brain OXT receptor-mediated actions were shown to be significantly involved in the regulation of a variety of behaviours. Here, complementary methodological approaches are discussed which were utilised to reveal, for example, anxiolytic and anti-stress effects of OXT, both in females and in males, effects that were localised within the central amygdala and the hypothalamic paraventricular nucleus. Also, in male rats, activation of the brain OXT system is essential for the regulation of sexual behaviour, and increased OXT system activity during mating is directly linked to an attenuated anxiety-related behaviour. Moreover, in late pregnancy and during lactation, central OXT is involved in the establishment and fine-tuned maintenance of maternal care and maternal aggression. In monogamous prairie voles, brain OXT is important for mating-induced pair bonding, especially in females. Another example of behavioural actions of intracerebral OXT is the promotion of social memory processes and recognition of con-specifics, as revealed in rats, mice, sheep and voles. Experimental evidence suggests that, in humans, brain OXT exerts similar behavioural effects. Thus, the brain OXT system seems to be a potential target for the development of therapeutics to treat anxiety- and depression-related diseases or abnormal social behaviours including autism.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1365-2826.2008.01726.x

Brain Oxytocin: A Key Regulator of Emotional and Social Behaviours in Both Females and Males

CD38, a transmembrane glycoprotein with ADP-ribosyl cyclase activity, catalyses the formation of Ca2+ signalling molecules, but its role in the neuroendocrine system is unknown. Here we show that adult CD38 knockout (CD38-/-) female and male mice show marked defects in maternal nurturing and social behaviour, respectively, with higher locomotor activity. Consistently, the plasma level of oxytocin (OT), but not vasopressin, was strongly decreased in CD38-/- mice. Replacement of OT by subcutaneous injection or lentiviral-vector-mediated delivery of human CD38 in the hypothalamus rescued social memory and maternal care in CD38-/- mice. Depolarization-induced OT secretion and Ca2+ elevation in oxytocinergic neurohypophysial axon terminals were disrupted in CD38-/- mice; this was mimicked by CD38 metabolite antagonists in CD38+/+ mice. These results reveal that CD38 has a key role in neuropeptide release, thereby critically regulating maternal and social behaviours, and may be an element in neurodevelopmental disorders.

CD38 is critical for social behaviour by regulating oxytocin secretion

Two genetic variants of CD38 in subjects with autism spectrum disorder and controls.

Autism spectrum disorder (ASD) or pervasive developmental disorder (PDD) is a neurodevelopmental disease, beginning in childhood but extending through to adulthood. ASD is characterised by impairments in reciprocal social interaction and communication, and by restricted or stereotyped patterns of interests and activities. This disorder has received much scientific and social attention1,2. ASD is more common than previously supposed with a frequency of 0.6-3 out of 100 births2-6 and occurs either sporadically or in a familial pattern, and far more commonly in males7-9. The etiology remains largely unknown10. Previously we demonstrated that CD38 acts as a ‘niceness’ protein for mouse social behavior, by regulating release of oxytocin (OT)11, which seems to be essential for mutual recognition and trust12,13. Therefore, here, we describe our results on single nucleotide polymorphisms (SNPs) of CD38 in ASD patients and control subjects14. In addition, we report our experience of treatment of one ASD patient with a CD38 SNP by nasal OT administration.

/pdf/a-missense-mutation-in-cd38-associated-with-autism-spectrum-1c09jxwabj.pdf

Akihiro Matsushima

Papers

CD38 is critical for social behaviour by regulating oxytocin secretion

Two genetic variants of CD38 in subjects with autism spectrum disorder and controls.

A Missense Mutation in CD38 Associated with Autism Spectrum Disorder in Three Pedigrees