Humans are obliged to face a paradox which is fundamental to the survival of the species: they are attracted to, courted by and breed with genetically unrelated individuals whom they would otherwise instinctively avoid. Romantic attachment is the psychological strategy which enables us to overcome neophobia and to mate with and create a strong, often life-long bond with a complete stranger, so that we may produce healthier offspring. On the same time, we are rewarded by a deep sense of pleasure and satisfaction through the intervention of specific neural substrates which have become the topic of recent investigations 1. Besides neural networks, within the last decade, various sets of data have highlighted the possible role of oxytocin and vasopressin, two small neuropeptides composed by 9 aminoacids and synthesized in the paraventricular and in the supraoptic nuclei of the hypothalamus 2, in linking social signals with cognition, behaviours and reward 3. Oxytocin and vasopressin, in fact, have been shown to be involved in the creation of pair-bonding in monogamous rodents, such as prairie voles 4, in maternal behaviour in rats 567, in the postpartum acceptance of offspring in sheep 89, and the relief of distress vocalization in rat pups 10.

The relevance of these intriguing findings for humans has not been clarified as yet 1112. Oxytocin receptors in the human brain are mainly distributed in the substantia nigra, globus pallidus, anterior cingulate and medial insula, areas which have been shown to be activated in adults while looking at pictures of their partners, or in mothers while looking at their children 11314 and belong to the recently-hypothesized circuits of the "social brain" 151617. It is interesting to note that oxytocin seems to be released during sexual intercourse and orgasm 18 and during the application of different relaxation techniques 1920, so that it is thought to be one of the promoters of attachment and/or mediators in the decrease of the stress responses which are related to positive social bonding 212223.

Although the measurement of oxytocin plasma levels represents the easiest and relatively noninvasive way of evaluating its presence in humans, it is still unclear whether plasma levels reliably reflect concentrations in the brain, since it would seem that central and peripheral oxytocin derive from different hypothalamus cell populations 49. However, different convergent observations on parallel changes in oxytocin levels in plasma and in the brain 202425 would suggest a cooperative process of regulation and, thus, support the use of the peripheral marker as a mirror of the central one 826. Therefore, given the lack of direct data in humans, in the present study we explored the possible relationships between plasma oxytocin levels and a typical social bonding of our species, that is, romantic attachment, selected from amongst the different types of attachment, because it was considered particularly relevant for adults that constituted our subject population 27. In addition, to achieve this goal, we had to set up a sensitive assay to measure oxytocin in plasma of healthy subjects, since the available kits did not permit this assessment; the hypothesis was that oxytocin might influence some features or styles of romantic attachment.

The oxytocin plasma levels, representing the mean+SD of three evaluations performed within one hour, ranged between 0.13 ± 0.02 and 4.59 ± 0.01 pg/ml (mean ± SD: 1.53 ± 1.18), and the frequency distribution of maximum oxytocin levels was skewed to the right. No difference was detected between women and men, or between subjects with and without a romantic relationship.

Plasma oxytocin levels were unrelated with age, gender, marital status, or length of the relationship, while, as shown in figure 1, a significant and positive correlation was observed between the anxiety scale of the ECR and oxytocin levels (r = 0.30, p = 0.04); on the contrary, no relationship with the avoidance scale was detected.

The distribution of attachment styles was typical of healthy control subjects. Twenty-six (57.8 %) subjects showed a secure attachment, 12 (26.7 %) a preoccupied, 5 (11.1) a fearful/avoidant and 2 (4.4 %) a dismissing style. A trend towards higher peptide concentrations was detected in those subjects with the preoccupied style of attachment, although it did not reach the statistical significance.

The major finding of the present study was the detection of a statistically significant and positive correlation between oxytocin plasma levels and the anxiety scale of the ECR, a self-report questionnaire measuring adult romantic attachment, which showed that the higher the oxytocin levels, the higher the score on the anxiety scale of the ECR.

Some caution is, however, warranted in the interpretation of these results, given the controversies which exist regarding the reliability of plasma oxytocin levels as a peripheral mirror of central concentrations. In any case, it is worth noting that various physiological conditions, in particular labour, lactation and sexual activity, have been shown to provoke a parallel release of central and peripheral oxytocin 89, that emotional states may sometimes modify plasma oxytocin 202532, and that even the peripheral administration of different peptides, including cholecystokinin and interleukin 6, may trigger their central release 26.

In addition, oxytocin shows a pulsatile secretion, so that, in order to overcome this possible bias, all subjects included in our study underwent three blood samplings within one hour and the analyses were performed by using the means of the different measurements.

Another bias may be related to the subjects include in the study, all belonging to the medical class, so that our sample may not be representative of the general population,

In spite of the above-mentioned limitations, our findings may constitute undoubtedly the first report of a link between oxytocin and that state of anxiety which is associated with romantic attachment in our species. However, it is not possible to conclude from our data whether the oxytocin levels are in fact a consequence or a cause of the anxiety measured by the scale of the ECR, although, in line with the majority of available findings showing in animals anxiolytic-like properties for oxytocin 333435, we would suggest tentatively that the former might be the case, and that oxytocin might serve to help to counteract anxiety – or, at least, that form of anxious stress associated with romantic attachment and deep concern over its continuance 11192136.

Previoulsy, the relationship between oxytocin and human anxiety was sustained only by the indirect evidence that basal oxytocin levels correlate with measures of anxiety, aggression, guilt and suspicion 37, and noise stress provoke the release of the neuropeptide in highly emotional women 38. Also, recent findings have reported that low plasma oxytocin levels would seem to be typical of individuals with low anxiety traits 39.

That oxytocin and anxiety may be linked in some way in the modulation of social bonding is supported also by scattered data showing that a moderate level of stress seems to promote pair bonding in different species, including human beings 40. Pursuing this line of thought, romantic relationships, and perhaps social relationships in general, could be interpreted as amounting to stress conditions, both acute and chronic depending on the phase 41. The role of oxytocin would seem generally to be that of keeping anxiety levels under control to a point where they are no longer harmful (in fact, low oxytocin concentrations have been linked with pain syndromes, such as fibromyalgia 42 or abdominal pain 43, but may nevertheless lead to such strategies and behaviours as are best suited to ensure a partner's continued proximity both during the first stages of the romance and subsequently. Oxytocin might thus be considered an essential element in securing the rewarding effects of a romantic relationship, as a result of its increasing a prospective sexual partner's willingness to accept the risk deriving from social contacts 23, through the modulation of anxiety mechanisms perhaps at the level of amygdala 33.

Of course, with particularly vulnerable individuals, if excessively affected by the relationship itself or by other events, these delicate mechanisms might be maladaptive, in the sense that such subjects might become too anxious and thus cross the line between normal and pathological states, even to the point of developing a full-blown psychiatric disorder 44. Such a hypothesis might be relevant to the onset of anxiety disorders and disturbances of social communications, such as autism.