**4.1. OXT and male human affiliation**

The investigations of OXT and affiliation in humans do not necessarily examine affiliation directly. For instance, intranasal OXT promotes trust and prosocial behaviors which are critical to human bonding and it is also associated with trustworthiness [72, 73]. Intranasal OXT increases cooperation following unreciprocated cooperation in a social experiment and this behavioral effect was associated with increased fMRI activity in OXT regions associated with affiliation [74]. Studies investigating affiliation and/or sexual behavior conclude that the effects of OXT are often mediated by direct physical contact as increased plasma OXT has been recorded in men during social contact with a partner [75], and during orgasm [76-78].

Impaired affiliation has been associated with decreased plasma OXT in autistic patients [79]. Normal affiliative expression is especially impaired in autistic males, and some autistic males have deficits in OXT receptor expression [80, 81]. Several cases were associated with hypermethylation of the OXT receptor gene and a decrease in OXT receptor mRNA. Furthermore, clinical studies have reported enhanced social interactions (eye contact, social memory) in autistic patients following intranasal OXT [82]. Several labs have investigated the use of OXT for the treatment of social behavior deficits in autism [82-84] and social anxiety disorder [85], and research in this area is ongoing.
