Placebo induced expectations of mood enhancement generate a positivity effect in emotional processing

Abstract

A perceptual bias towards negative emotions is a consistent finding in mood disorders and a major target of therapeutic interventions. Placebo responses in antidepressant treatment are substantial, but it is unclear whether and how underlying expectancy effects can modulate response biases to emotional inputs. In a first attempt to approach this question, we investigated how placebo induced expectation can shape the perception of specific emotional stimuli in healthy individuals. In a controlled cross-over design, positive treatment expectations were induced by verbal instructions and a hidden training manipulation combined with an alleged oxytocin nasal spray before participants performed an emotion classification task on happy and fearful facial expressions with varying intensity. Analyses of response criterion and discrimination ability as derived from emotion-specific psychometric functions demonstrate that expectation specifically lowered participants’ threshold for identifying happy emotions in general, while they became less sensitive to subtle differences in emotional expressions. These indications of a positivity bias were directly correlated with participants’ treatment expectations as well as subjective experiences of treatment effects and went along with a significant mood enhancement. Our findings show that expectations can induce a perceptual positivity effect in healthy individuals which is probably modulated by top-down emotion regulation and which may be able to improve mood state. Clinical implications of these promising results now need to be explored in studies of expectation manipulation in patients with mood disorders.

Placebo treatment entails resource-dependent downregulation of negative inputs

“…This aligns with prior research using this paradigm, showing a positivity bias in older adults confined to the high attention condition (37). In contrast to a previous study on positive expectation effects in emotion detection (19) we did not observe a positivity bias in terms of increased distraction by happy faces under placebo. This could be attributed to divergent task instructions, specifically the distinction between emotional detection and interference.…”

“…One could also have expected a placebo-related increased distraction by happy faces consistent with the instruction that oxytocin enhances positive stimulus perception. Indeed, we found an induced positivity bias in face perception in a previous study on positive expectation effects in emotion detection (Baker et al, 2022). The fact that we did not see such a clear effect in the present study might be due to the different nature of the task.…”

“…For instance, positive expectations can reduce experimentally induced sadness (Anna et al, 2019;Haas et al, 2020;Schaefer et al, 2023), anxiety or fear (Meyer et al, 2015(Meyer et al, , 2019Petrovic et al, 2005;Shafir et al, 2023;Zhang et al, 2011) and social stress (Abrams et al, 2001;Balodis et al, 2011). Moreover, placebo manipulations can positively influence baseline mood states (Baker et al, 2022;Zhang et al, 2011). Interestingly, such effects are still observable when the placebo manipulation is not deceptive as in open-label placebo studies (Hahn et al, 2022;Schienle et al, 2022;Sezer et al, 2022).…”

“…A promising approach to illuminate the role of cognitive control for expectation effects is to directly combine the manipulation of cognitive resources and expectations with functional neuroimaging of prefrontal networks during emotional processing. In the present study, 49 healthy volunteers, characterized in their general cognitive control ability, participated in a randomized, cross-over fMRI study that was combined with a controlled induction of positive expectations (Baker et al, 2022). During fMRI, participants performed a spatial cueing paradigm that manipulated attentional load on emotional face distractors and thus attentional resources to process emotional stimuli in a goal directed manner (Brassen et al, 2010(Brassen et al, , 2011.…”

“…For instance, positive expectations can reduce experimentally induced sadness (9)(10)(11), anxiety or fear (12)(13)(14)(15)(16) and social stress (17,18). Moreover, placebo manipulations can enhance baseline mood states (16,19). Interestingly, effects persist in open-label placebo studies (20)(21)(22).…”