A growing literature associates the neuropeptides oxytocin (OT) and arginine vasopressin (AVP) with affiliative and cognitive outcomes. The majority of this work in humans, however, considers these neuropeptides separately. Also, despite evidence that OT and AVP interact with gonadal hormones, still warranted is an examination of sex and age variations in endogenous neuropeptide levels, their interrelations, and their functional relationships with attachment and cognition in humans. This study measured endogenous plasma OT and AVP levels in generally healthy young (18-31 years) and older (63-81 years) men and women to (i) determine levels of and interrelations between OT and AVP; (ii) explore functional relationships with self-reported attachment (attachment anxiety and avoidance) and performance-based cognition (processing speed, verbal memory); and (iii) identify variations in these effects by sex and age. We observed sex- and age-differential patterns of results: Women had higher plasma OT levels than men and older adults had higher plasma AVP levels than young adults. The two neuropeptides were highly negatively intercorrelated across all groups. Functionally, higher AVP levels were associated with greater attachment anxiety and higher OT and lower AVP levels were associated with faster sensorimotor processing speed, with sex and age moderating these effects. This integrated approach identifies variations in endogenous peripheral neuropeptide levels in humans, supporting their sex- and age-specific role as "difference makers" in attachment and cognition.

Introduction

Human and nonhuman animal research suggests that greater oxytocin (OT) activity is protective against harmful substance use. Most research on this topic is preclinical, with few studies evaluating the association between substance use and individual differences in the human OT system. The present study sought to fill this gap by evaluating the relationship between alcohol use and multiple biological measures of OT activity in an overall low to moderate-drinking sample.

Method

As part of a larger study, generally healthy young (n = 51) and older (n = 53) adults self-reported whether they regularly used alcohol and how much alcohol they consumed per week. Participants also provided blood samples from which peripheral OT, and in an age-heterogeneous subset of participants (n = 56) variation in the oxytocin receptor gene (the OXTR rs53576 polymorphism) and OXTR DNA methylation levels (at cytosine-guanine dinucleotide sites -860, -924, -934), were obtained.

Results

A-allele carriers of the OXTR rs53579 polymorphism were less likely to regularly consume alcohol. Among regular alcohol consumers, number of alcoholic drinks per week was positively associated with peripheral OT in regression models excluding observations of high influence (postdiagnostic models). Number of alcoholic drinks per week was consistently negatively associated with OXTR DNA methylation at site -860; and with OXTR DNA methylation at site -924 in postdiagnostic models.

Conclusions

The significant associations between alcohol use and individual differences in OT activity support the involvement of the OT system in alcohol use, which most likely reflect the role of OT when alcohol use is under control of its rewarding properties and/or the acute impacts of alcohol on the OT system. Additional research with markers of OT activity and alcohol use, particularly longitudinal, is needed to clarify the bidirectional effects of OT and alcohol use in moderate to harmful drinking and dependence.