How can neurobiology of fear extinction inform treatment?

Anxiety, posttraumatic stress, and depression markedly increased worldwide during the COVID-19 pandemic. People with these conditions experience distressing intrusive thoughts, yet conventional therapies often urge them to avoid suppressing their thoughts because intrusions might rebound in intensity and frequency, worsening the disorders. In contrast, we hypothesized that training thought suppression would improve mental health. One hundred and twenty adults from 16 countries underwent 3 days of online training to suppress either fearful or neutral thoughts. No paradoxical increases in fears occurred. Instead, suppression reduced memory for suppressed fears and rendered them less vivid and anxiety provoking. After training, participants reported less anxiety, negative affect, and depression with the latter benefit persisting at 3 months. Participants high in trait anxiety and pandemic-related posttraumatic stress gained the largest and most durable mental health benefits. These findings challenge century-old wisdom that suppressing thoughts is maladaptive, offering an accessible approach to improving mental health.

Emotional coordination constitutes one of the crucial building blocks for social adaptation. Humans, like other primate species, are able to rapidly and accurately respond to others' non-verbal emotional signals by preparing and executing adaptive motor responses. In this chapter, we present a general overview of how emotional expressions emitted by others promote, in the observer’s brain, fast processing and elaboration of multiple possibilities for action of different levels of complexity, from stimulus-driven reactions to goal-directed actions, via different communicating subcortical and cortical pathways, that compete to flexibly orchestrate our social behavior.

BackgroundEndogenous sex hormones and oral contraceptives (OCs) have been shown to influence key regions implicated in fear processing. While OC use has been found to impact brain morphology, methodological challenges remain to be addressed, such as avoiding selection bias between OC users and non-users, as well as examining potential lasting effects of OC intake.ObjectiveWe investigated the current and lasting effects of OC use, as well as the interplay between the current hormonal milieu and history of hormonal contraception use on structural correlates of the fear circuitry. We also examined the role of endogenous and exogenous sex hormones within this network.MethodsWe recruited healthy adults aged 23-35 who identified as women currently using (n = 62) or having used (n = 37) solely combined OCs, women who never used any hormonal contraceptives (n = 40), or men (n = 41). Salivary endogenous sex hormones and current users’ salivary ethinyl estradiol (EE) were assessed using liquid chromatography – tandem mass spectrometry. Using structural magnetic resonance imaging, we extracted surface-based gray matter volumes (GMVs) and cortical thickness (CT) for regions of interest of the fear circuitry. Exploratory whole-brain analyses were conducted with surface-based and voxel-based morphometry methods.ResultsCompared to men, all three groups of women exhibited a larger GMV of the dorsal anterior cingulate cortex, while only current users showed a thinner ventromedial prefrontal cortex. Irrespective of the menstrual cycle phase, never users exhibited a thicker right anterior insular cortex than past users. While associations with endogenous sex hormones remain unclear, we showed that EE dosage in current users had a greater influence on brain anatomy compared to salivary EE levels and progestin androgenicity, with lower doses being associated with smaller cortical GMVs.DiscussionOur results highlight a sex difference for the dorsal anterior cingulate cortex GMV (a fear-promoting region), as well as a reduced CT of the ventromedial prefrontal cortex (a fear-inhibiting region) specific to current OC use. Precisely, this finding was driven by lower EE doses. These findings may represent structural vulnerabilities to anxiety and stress-related disorders. We showed little evidence of durable anatomical effects, suggesting that OC intake can (reversibly) affect fear-related brain morphology.