Oxytocin & well-being as promoters of affect regulation and homeostasis : a neuroscientific review

Recebido em: 4 abr. 2018. Aprovado em: 26 set. 2019. Publicado em: 4 set. 2020. Abstract: Context: The term “Well-being” [WB] has many different meanings in scientific literature. Objectives: To search specific situations and related semantics for feelings of well-being [WB] associated to oxytocin [OT] release. Data sources: A systematic review using PRISMA guidelines in PubMed, BVS Virtual (Medline, Lilacs) and SIBI-USP Portal de Busca Integrada (1970-1999 & 2014-2018). Study selection: Reviews and clinical trials (PICOS) on OT, & WB and similar concepts in humans. Data extraction: Independent selection of articles by two reviewers; selection of articles by one reviewer, using predefined criteria. Data synthesis: 46 articles were selected out of 339, with 26 additional articles. Main data referred to social situations, sensorial stimuli, trust and psychiatric and health studies. Conclusions: The identified variables involved brain-body-mind interactions, and health/disease; translational neuroscience seems to be the best theoretical reference to investigate it.

How to articulate the release of OT with feelings of WB? What would be the specific characteristics of this type of WB? What semantics are used to refer to it? Answering these questions should be of great interest to the health scientist and has led to this review.
Around the 1980s, neuroscientific research started to acknowledge that neuropeptide OT was implicated in the generation of positive moods.
The uncovering of neuroendocrine mechanisms revealed that this neuroendocrine primary-process system is typically aroused in the mother during the last months of pregnancy and delivery; and, after birth, both in the mother and the baby, generating pleasurable feelings of WB during their interaction (Panksepp, 1998). The baby usually relaxes upon receiving care, as OT promotes the release of endogenous opioids (Nelson & Panksepp, 1998). This state of pleasantness and relaxation counteracts many states of painful excitatory arousal, helping the baby to reach an affective, followed by a physiological, regulatory, state (and not the contrary). Mothers are also regulated through interaction with the baby (Schore, 2015).
The articulation of a neuroendocrine mechanism, a correspondent affective mood and a specific behavior results in a "whole" brain-mind-body phenomenon (Panksepp & Biven, 2012). Accordingly, the authors of this review propose that OT & WB be considered as a brain-body-mind phenomenon that translates into a healthy, homeostatic balance; as such, a translational neuroscientific approach is suggested to investigate it.
Objectives: to identify in reviews and clinical trials (PICOS, phenomenological and neurobiological characteristics, as well as semantic equivalents, of WB linked to OT, as promoters of affect regulation and homeostasis, following PRISMA Guidelines (Liberati et al, 2009

Example of electronic search
In BVS Virtual (Lilacs & Medline), an initial search was performed for "OT" AND "WB", yielding 333 results. Eligibility assessment and data collection process were performed by Eliana Nogueira-Vale.
Reviews and clinical trials (PICOS), were screened in early  and current periods of OT history (2014-2018), in a search for WB situations and equivalent semantics. Additional data were included for more comprehensive information.
Data were organized by categories.
Since this was a qualitative investigation, statistical measures were not applicable.

Press published Jaak Panksepp's work on Affective
Neuroscience: the foundations of animal and human emotions, which extensively mapped discrete neural circuits in mammals, corresponding to basic affects (Panksepp, 1998 should be considered that one stimulus may activate more than one sense at a time. As a social hormone, OT has been associated to WB in many social, sexual, affiliative and care contexts (Carter, 2014;Shalvi &, De Dreu, 2014); and also in nonsocial situations stimuli, such as psychosomatic manifestations of chills and tearing (crying) in music-listening (Mori & Iwanaga, (2017). In this search, the following categories associated to OT & WB were identified: • Semantic categories (see Table 2) • Skin stimuli (see Table 3) Emotion of warmth-liking: this category of emotion was identified as a system of opioidergic modulation activated during interpersonal and close relationships, creating a state of "physiological quiescence, less negative feelings and psychophysiological resilience" (Burgdorf, Rinn & Stemmler, 2016, p.1712. OT release has been frequently associated to µ opioids in similar situations (Nelson & Panksepp, 1998;Nummenmaa et al, 2016), but in that study, it was not cited. One of the authors argued that "more research on OT [concerning the subject] was needed" (e-correspondence between Nogueira-Vale and Stemmler, October, 29 th , 2017).
Touch: considered one of the most powerful social stimuli, touch is fundamental for child development, attachment and the formation of human bonds (Carter, 2014), producing concomitant feelings of comfort, and behaviors of eye closure and cessation of stress vocalization in mammals; a role for OT release in human intimacy was anticipated in early literature (Panksepp, 1998). In attachment contexts, insistent physical closeness and contact with the mother is sought by young mammals, in a search for feelings of soothing and calmness (Carter, 1998;Uvnas-Moberg, 1998). In 1990, a special type of lowthreshold, unmyelinated, mechanosensitive, tactile C-afferent fiber [CT-afferent] was identified (Vallbo, Olausson, & Wessberg 1990), innervating hairy, but not glabrous, human skin, and associated to social touch (Gentsch, Panagiotopoulou, & Fotopoulou, 2015). Some authors even consider that CT-afferent fibers constitute a specific neurobiological substrate for affect in affiliative behaviors and psychological WB (Walker & McGlone, 2013), in opposition to the discriminative Skin-to-skin contact: skin-to-skin contact with the mother is usually the first one in a newborn's life, and has a primal, ontological role (Nelson & Panksepp, 1998;Carter, in: Uvnas-Moberg & Carter, 1998;Porges, 2011 constitutes one of the first and most important kinds of social contacts between baby and mother, coinciding with an increase in OT release (Carter, Lederhendler, & Kirkpatrick, 1997); intranasal OT was also reported to enhance eye-contact in autistic, as well as in normal people (Quattrocki & Friston, 2014).
Pleasant mental images: the reminiscence of positive memories is associated to OT release, and seems to attenuate acute stress responses, contributing to emotion regulation (Speer & Delgado, 2017); this elicit positive affect more than positive pictures; OT release, on the other side, can enhance retrieval of positive social memories, attenuating stress feelings (Wudarczyk, Earp, Guastella, & Savulescu, 2013;Kirsch, 2015).
Face memory/recognition: the human brain was programmed during evolution to preferentially identify and recognize human faces among other visual stimuli (Porges, 2011). OT release improves emotion recognition in faces, the encoding of positive social memories in humans, and recognition of familiar faces identity (Guastella, Mitchell, & Mathews, 2008).

Music-listening: Frisson, chills and goosebumps
were observed in situations of music-listening (Colver & El-Alayli, 2015). Would this kind of phenomenon also occur in the appreciation of other aesthetic stimuli? Decreases in blood pressure and heart rate were also observed in coronary male patients, but not in normal men, during music listening; it reduced stress, anxiety and depression, as well as enhanced life satisfaction, optimism, hope and 65meaning in life, more intense in coronary male patients than in healthy man (Gupta & Gupta, 2015). Conversely, unpleasant music seemed to increase anxiety when listened during stress exposure (Jezova et al, 2013).
Music-singing: a recent study relates an improvement in the mood, and a significant immunological increase, but an apparently contradictory finding on decreases in OT and β-endorphin, in cancer patients after music singing. The hypothesis for that unexpected result was that the decrease represented "a generalized down-regulation of stress response, which may have over-ridden any social bonding or happiness-associated increase" (Fancourt et al, 2016, p.9). However, another study found that OT concentrations increased significantly both in singers after a singing lesson (Grape, Sandgren, Hansson, Ericson, & Theorell, 2003).

Sounds of infant distress: Adult humans react to sounds and visual cues of infant vulnerability
and stress by exhibiting brain amygdala activation (Marsh, 2016). This might be due to the survival value of this kind of alert concerning helpless children.

Shade in nature
An original study found that there was an ideal range of tree shade, promoted by the density of tree canopy, in the recovery from an experimental stress situation in men, but not in women. Density of tree cover showed a dose-response curve in the form of an inverted U, assessed by salivary cortisol levels and Trier Social Stress Test. It was also suggested that contact with nature brings WB and health (Jiang, Chang, & Sullivan, 2014).
Other categories frequently associated with OT & WB
OT & WB and variations for age, gender, context and individual profile As with other hormones, OT release in humans seems to decline with age (Elabd et al, 2014). The existence of genetic, neural and sociocognitive processes related to OT release, as well as individual differences in socioemotional processes associated with the OT receptor gene. together with social isolation, may represent a potential risk for depression, social stress, and anxiety in the eldest (Ebner, Maura, Macdonald, Westberg, & Fischer H, 2013;Emeny et al, 2014). Besides variation on the production of OT with age, variations were also found for gender (Behnia et al, 2014); personality profile (Kelly & Goodson, 2014), social context (Schladt et al, 2017) and interindividuality (Ollf et al, 2013) in response to OT administration.

OT & WB and Familiarity
In early OT research, it was demonstrated that OT mediated conditioned place (Liberzon, Trujillo, Akil, & Young, 1997) and smell preference (Kojima & Alberts, 2011) in rats. Familiarity is a condition often linked to OT & WB, as it has an important survival value (De Dreu, Greer, Van Cleef, Shalvi, & Handgraaf, 2011). It should also be considered the fact that OT is mainly a prosocial and affiliative hormone, having a pivotal importance in attachment processes (Swain et al, 2014), and has shown to be adaptive in situations associated to OT & WB such as: partner's touch (Bennia et al, 2014), face-memory and prosocial cooperation (Kirsch, 2015), altruism among family, but not other people (Marsh, 2016), caring for ageing people (Ebner et al, 2013), and even promoting dishonesty in behalf of one's group (Shalvi & De Dreu, 2014). The neurobiological common ground for these different situations of familiarity is probably linked to vagal activation, which occurs in situations of proximity without fear, inhibiting visceral activation (Porges, 2011), and contributing to affective regulation (Schore, 2015).

Synthesis of results
The main variables associated to OT & WB found in this review refer to social situations, sensorial stimuli, and trust. Variations according to gender, age, familiarity, individual profile and context were found for the studied variables.   Psico, Porto Alegre, v. 51, n. 2, p. 1-12, abr.-jun. 2020 | e-30291   Skin-to-skin contact Calmness and WB; affective-emotional pleasantness