‘Oxytocin’ for the outwardly oriented: Evidence for interactive effects in placebo responding
Introduction
There is now considerable evidence demonstrating that placebo treatments can exert meaningful effects on health outcomes [1], [2]. With primary care burdened by symptomatic individuals and psychologically-influenced conditions [3], [4], [5], [6], placebos may become an essential part of future treatment repertoires. However, not everyone responds to placebo treatments [7] and one of the challenges preventing this phenomenon from being harnessed for clinical benefit is understanding which individuals might benefit from taking a placebo.
Recently, a new conceptualisation of placebo responsiveness was offered, the two-faceted Transactional Model of Placebo Responding (TMPR) [8]. This approach suggests responding to placebos arises from a transaction between an individual's dispositional style and cues in their environment. In alignment with Gray's bio-behavioural, stimulus–response model of personality [9], [10], [11], [12], the TMPR suggests there are two facets of responsiveness – inward orientation and outward orientation – that are governed by different neurological systems and which generate different responses to environmental stimuli. Inwardly oriented individuals are characterised by an ‘avoidant’ style, being sensitive to anxiety-relevant cues, and more oriented to their internal environment or experience. Conversely, outwardly oriented individuals are predisposed to an ‘approach’ style which generates a desire to interact with the external environment and move towards goals and possible rewards [8].
A review of the placebo personality literature [8] reveals more evidence for the outwardly oriented responder with traits such as ego resiliency [13], extraversion [14], fun, novelty-seeking, and behavioural drive [15], openness to experience [16], optimism [17], and a dopamine-related genotype [18] related to placebo responses; however, this work has almost exclusively been conducted within pain paradigms. Given the possibility of a transaction between dispositional style and environmental cues, pain paradigms may be offering particular cues to which outwardly oriented individuals are differentially responsive. For example, it may be that the offer of relief from painful stimulus represents a goal or reward that tends to elicit responses from the outwardly oriented individual.
Conversely, research in other settings has linked placebo responding to traits included within the inward orientation facet [8]. In multiple sclerosis patients, higher absorption was related to greater responsiveness [19]; in the context of pulmonary function in asthmatics, suggestibility was linked to responding to the placebo suggestion [20]; a serotonin-related genotype was related to greater placebo responses in the context of social anxiety [21]; and in psychosocial stress recovery, behavioural drive and optimism were inversely linked to placebo responses [22]. Thus, there is some evidence to support the notion that placebo responsiveness is not best characterised by one personality type and that different cues in the environment may contribute to different patterns of responding for different types of person.
The possible importance of an interaction between disposition and environment in eliciting placebo responses has already been noted in placebo discourse [23], [24], [25]; however, studies directly investigating this possibility are scarce. One study found an interaction between personality and practitioner's therapeutic style, with extraversion predicting placebo responses only in the augmented session in which the practitioner was empathic and caring [14]. Another research group have suggested an interactionist approach to placebo responding based on evidence that optimists respond to positively valenced cues [23] and pessimists respond to negative cues [26]. Beyond the valence of the expectancy manipulation and the practitioner style, the way in which a placebo treatment is described is also a contextual cue that could be manipulated to test for interactions between dispositional style and environmental cues in eliciting responses.
The current study aimed to test the TMPR by manipulating contextual cues in the form of treatment descriptors, to “match” the two possible facets of responsiveness described above. In the context of general psychological distress arising from the challenges of life (stress, anxiety and depressive symptoms), participants were randomised to receive one of two different placebo treatments: an ‘oxytocin’ compound designed to be aligned with an outwardly oriented disposition; or a ‘serotonin’ compound designed to correspond to inward orientation. The BIS/BAS scale [11], which assesses ‘avoid’ versus ‘approach’ behavioural styles [12], was used as a proxy for inward and outward orientations (respectively). It was hypothesised that those higher in BAS would have a greater placebo response to the ‘oxytocin’ placebo and those high in BIS would have a greater response to the ‘serotonin’ placebo.
Section snippets
Method
This was a randomised, controlled, non-laboratory study. All participants were randomised into one of three groups: (1) wait-list control group; (2) Treatment S (‘serotonin’); or (3) Treatment O (‘oxytocin’). Those in the treatment groups were instructed to self-administer an intranasal treatment spray for three days in between pre- (Day 1) and post-treatment (Day 5) measures. Both sprays were placebos containing sterile saline (5%), but were described differently (see Participants and procedure
Sample characteristics
Participants were aged from 19 to 50 years of age (M = 24, SD = 5.92) and predominantly female (70%). New Zealand Europeans (Caucasians) made up the largest ethnic group (53%) with Asian (including Indian, Sri Lankan, and Pakistani participants) the next largest group (40%) and the remainder describing themselves as ‘other’ (7%). The perceived stress levels of this sample were similar to those reported in prior research with stressed student samples [35], [36]. The dichotomized BIS and BAS scales
Discussion
This study was designed to extend understanding of the personality factors associated with placebo responding. In particular, it tested the two-faceted Transactional Model of Placebo Responding (TMPR) by manipulating treatment descriptors to match the two hypothesised facets of responsiveness. Using the BIS/BAS scale to represent the inward and outward facets set out in the model, it was hypothesised that high BAS types would have greater placebo responses when taking an outwardly oriented
Acknowledgements
None. No funding outside the basic funding from the university was received. The authors have no competing interests to report.
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All authors affiliated with the Faculty of Medical and Health Sciences at the University of Auckland, New Zealand.