Professor Benjamin Becker, together with his team in the “Neurotherapy, social cognition and affective neuroscience (neuSCAN) lab” recently published a new study in Biological Psychiatry (impact factor 11.5) demonstrating that the drug losartan has significant effects in improving fear extinction learning in humans via augmenting activity in the ventromedial prefrontal cortex of the brain and its functional connectivity with the amygdala, which plays a key role in fear processing and threat discrimination. This landmark paper entitled “Human extinction learning is accelerated by an angiotensin antagonist via ventromedial prefrontal cortex and its connections with basolateral amygdala” is the 17th paper published by neuSCAN with an impact factor greater than 10 or in PNAS since the lab was established in 2011.
Anxiety-related disorders are one of the most common disorders in both children and adults and which can severely affect people’s social, emotional, work and family functioning. While exposure-based interventions are routinely applied in clinical practice to reduce excessive fear in patients with anxiety-related disorders, a significant number do not adequately respond to the therapy. Based on this background, the neuSCAN team conducted a randomized placebo-controlled pharmacological functional MRI experiment to determine the clinical potential of losartan, an angiotensin = 2 \* ROMAN II type 1 receptor antagonist, in enhancing the effects of extinction learning.
In detail, 70 healthy male subjects underwent Pavlovian threat conditioning and received single-dose losartan (50mg) or placebo administration before extinction learning. Psychophysiological threat reactivity and neural activity during extinction served as primary outcomes. Psychophysiological interaction, voxel-based mediation and novel multivariate pattern classification analyses were employed to determine the underlying neural mechanism. Results show that losartan significantly accelerated the decline of the psychophysiological threat response during the extinction learning and enhanced ventromedial prefrontal cortex activation and its functional connectivity with the basolateral amygdala. The findings, as the first author Zhou Feng speculates, document a pivotal role of angiotensin regulation of extinction learning in humans and suggest that adjunct losartan administration has the potential to facilitate the efficacy of exposure-based interventions in anxiety disorders.
Link to the paper：
Zhou F, Geng Y, Xin F, Li J, Feng P, Liu C, Zhao W, Feng T, Guastella AJ, Ebstein RP, Kendrick KM, Becker B. (2019) Human extinction learning is accelerated by an angiotensin antagonist via ventromedial prefrontal cortex and its connections with basolateral amygdala. Biological Psychiatry (in press) (IF=11.5)
About the journal：