The hypothalamic peptide oxytocin modulates a wide range of social and cognitive functions in humans and nonhuman primates. As a result, much effort is currently being devoted to developing oxytocin into an adjunct treatment for mental illness, with a particular focus on anxiety, autism, and schizophrenia spectrum disorders.

In the field of imaging neuroscience, one of the most consistent findings with oxytocin is an inhibition of human amygdala responses to fearful facial expressions following exogenous administration of a single nasal dose—an effect recently replicated in macaques (Liu et al, 2015). An oxytocin-induced modulation of neural activity in the amygdala and other regions is in line with observations that intranasal administration yields increased cerebrospinal fluid concentrations of the peptide in humans (Striepens et al, 2013) as well as macaques (Freeman et al, 2016), although much controversy still exists regarding the exact route of brain penetration.

We recently reported that oxytocin may facilitate fear extinction by downregulating the amygdala and concomitantly upregulating medial prefrontal cortex activity in healthy volunteers (Eckstein et al, 2015), implicating the peptide as a potential adjunct treatment during extinction-based psychotherapy to reduce fear renewal. Interestingly, in a follow-up imaging study, oxytocin produced the opposite effect by promoting fear-conditioned responses (Eckstein et al, 2016). Thus, depending on the timing of administration, i.e., prior to versus after conditioning, the peptide can enhance the acquisition or extinction of fear, leading to contrary behavioral outcomes. Another intriguing example in this vein is a social economics experiment, in which volunteers could donate money for a charity project located in the Kongo delta. Subjects treated with placebo devoted more money to saving the rainforest rather than supporting the indigenous population living in that reserve. Under oxytocin treatment, participants showed the opposite behavioral pattern, suggesting that administration of the peptide can transiently alter altruistic attitudes and reward values, thereby shaping decisions towards social priorities (Marsh et al, 2015). These results are in accord with current concepts that the contextual framing of an experimental scenario interacts with oxytocin and determines its effects in a top-down regulatory manner (Quattrocki and Friston, 2014). The latter is substantiated by our observation that oxytocin increased the hedonic pleasure associated with social touch when heterosexual male volunteers were made believe that a female experimenter performed the touch as opposed to a male (Scheele et al, 2014).

Contextual framing not only matters to ‘message makers’ in journalism, advertising, or politics—it is also of crucial relevance to psychotherapy, especially when interventions are trialled with oxytocin. Converging evidence from a series of imaging experiments carried out in our laboratory suggests that nasal oxytocin evokes a shift in the neural activity away from the amygdala to the anterior insula, pregenual anterior cingulate cortex, and precuneus—areas that orchestrate the conscious monitoring of what happens in and around us. Current attempts to translate oxytocin neuroscience to psychotherapy thus face the crucial caveat that therapeutic context should be strictly controlled to avoid the risk of unfavorable outcomes.


RH was supported by a German Research Foundation (DFG) grant (BE 5465/2). The author declares no conflict of interest.