Using unconditioned responses to predict fear acquisition, fear extinction learning, and extinction retention patterns: Sex hormone status matters.

Following a traumatic event, fear dysregulation can increase the likelihood of developing post-traumatic stress disorder (PTSD). This psychopathology is twice as prevalent in women than in men. High physiological reactivity following trauma may be an early risk indicator for the development of PTSD. Elevated physiological reactivity and low estradiol levels have individually been associated with higher fear acquisition and/or lower extinction retention. Thus, sex hormone status may also modulate fear regulation abilities. However, it is unknown whether these two vulnerability factors interact to modulate fear learning and regulation. Using a fear conditioning and extinction protocol, we examined whether physiological reactivity to the aversive stimulus during fear acquisition training predicted fear responses during fear learning, extinction learning, and extinction retention. We verified whether these associations differed according to sex hormone status. Seventy-seven non-clinical participants were recruited including oral contraceptive users (n = 18), early follicular women (n = 20, [low estradiol]), mid-cycle women (n = 20, [high estradiol]), and men (n = 19). Participants underwent a three-day fear conditioning and extinction protocol (day 1: fear acquisition training; day 2: extinction training; day 3: retention test). Skin conductance responses were recorded. In early follicular women, physiological reactivity predicted conditioned and extinguished stimulus fear responses during all phases. For the remaining women, this effect was only present during fear learning and extinction learning. These findings highlight the importance of considering physiological reactivity and sex hormone status following a traumatic event. This knowledge could aid in the early identification of those at higher risk of developing PTSD.

Impact of Stress and Exercise on Fear Extinction.

This chapter reviews the literature on the impact of stress and exercise on fear extinction. Given that key brain regions of the fear circuitry (e.g., hippocampus, amygdala and frontal cortex) can be modulated by stress hormones, it is important to investigate how stress influences this process. Laboratory-based studies performed in healthy adults have yielded mixed results, which are most likely attributable to various methodological factors. Among these factors, inter-individual differences modulating the stress response and timing of stressor administration with respect to the task may contribute to this heterogeneity. Given that fear is a core manifestation of various psychopathologies and that exposure-based therapy relies on fear extinction principles, several studies have attempted to assess the role of stress hormones on exposure-based therapy in patients suffering from post-traumatic stress disorder or anxiety disorders. These studies tend to suggest a beneficial impact of stress hormones (through either natural endogenous variations or synthetic administration) on exposure-based therapy as assessed mostly by subjective fear measures. Similar to stress, exercise can have an impact on many physiological and biological systems in humans. Of note, exercise modulates biomarkers such as brain-derived neurotrophic factor (BDNF) and anandamide (EAE) that act on brain regions implicated in the fear circuitry, supporting the importance of studying the impact of exercise on fear extinction. Overall, the results converge and indicate that fear extinction (tested in the laboratory or via exposure-based therapy in clinical populations) can be enhanced with exercise. Further research is needed to understand the mechanisms by which stress and exercise modulate fear learning and extinction processes, as well as to maximize the applicability to clinical contexts.

Pre-pandemic socio-emotional vulnerability, internalizing and externalizing symptoms predict changes in hair cortisol concentrations in reaction to the COVID-19 pandemic in children.

The COVID-19 pandemic led to increased distress in many children, particularly in girls. Socio-emotional vulnerability, as well as psychiatric symptomatology prior to or during the initial stages of the pandemic, have been identified as important predictors of this distress. Still, it is unclear whether the pandemic also had physiological repercussions in children. If so, it remains to be determined whether these same predictors could provide insight into inter-individual variability. This longitudinal study aimed to investigate the effects of socio-emotional vulnerability, as well as pre-pandemic internalizing and externalizing symptoms, on hair cortisol concentrations (HCC) in response to the COVID-19 pandemic in healthy youth. In June 2020 (T1), 69 healthy children (M = 11.57 y/o) who visited the laboratory between 2017 and 2019 (T0) provided a 6 cm hair sample. This technique allowed us to quantify cortisol secretion during the three months preceding the COVID-19 pandemic (Segment A) and during the first three months of the first wave of the pandemic in Quebec, Canada (Segment B). At T0, participants completed the Dominic Interactive to assess pre-pandemic internalizing and externalizing symptoms. A socio-emotional composite score (SECS) was derived using a weighted z-score with the following constructs: anxiety sensitivity (Childhood Anxiety Sensitivity Index) measured at T0, trait anxiety (Trait subscale of the State-Trait Anxiety Inventory for Children (STAI-C)), intolerance of uncertainty (Intolerance of Uncertainty Scale for Children), and trait rumination (Children's Response Style Scale) measured at T1. A linear regression was conducted using the percent change in HCC across Segment A and B as the dependent variable, where SECS, pre-pandemic internalizing and externalizing symptoms, and sex were used as predictors. We found a main effect of sex, with girls presenting increased HCC reactivity compared to boys. We also found that SECS and internalizing symptoms negatively predicted HCC, whereas the opposite relationship was found between externalizing symptoms and HCC reactivity. For healthy children, our results suggest that previous psychiatric symptoms and socio-emotional vulnerability may be risk factors for the presentation of diverging cortisol response patterns in response to an adverse life event (such as the COVID-19 pandemic).

A longitudinal investigation of psychological distress in children during COVID-19: the role of socio-emotional vulnerability.

Background: Although the COVID-19 pandemic has increased the incidence of distress in youth, some children show increased resilience, emphasizing the need to better understand the predictors of distress in youth. Objective: This longitudinal study aimed to assess the combined impact of known socio-emotional predictors of stress-related psychopathology, namely anxiety sensitivity, anxiety trait, intolerance to uncertainty, and rumination, on COVID-related distress in healthy youth. Method: A total of 92 parent-child dyads that previously participated in a laboratory-based experiment assessing observational fear learning in families between 2017 and 2019 (T0) were recontacted. Of them, 84 children aged between 9 and 14 agreed to participate. They completed online questionnaires in June 2020 (T1), September 2020 (T2), December 2020 (T3), and March 2021 (T4). Participants were free of mental illness at T0 and T1. To create a socio-emotional composite score (SECS), we measured anxiety sensitivity (Childhood Anxiety Sensitivity Index) at T0, trait anxiety (Trait subscale of the State-Trait Anxiety Inventory for Children (STAI-C)), intolerance to uncertainty (Intolerance of Uncertainty Scale for Children), and trait rumination (Children's Response Style Scale) at T1 and created a weighted z-score. To assess symptoms of anxiety, post-traumatic stress (PTS), and depression in reaction to COVID-19, participants completed the State subscale of the STAI-C, the Children's Revised Impact of Event Scale, and the Children's Depression Inventory at T1-T4. Three general linear models were run with sex, age group (9-11 and 12+ years old), and SECS as predictors. Results: Analyses revealed a SECS*Time interaction, with higher SECS predicting elevated anxiety symptoms at T1 and T4, and elevated PTS symptoms at T1 and T2. Conclusion: These results suggest that healthy youth endorsing high levels of socio-emotional vulnerability to psychopathology have a higher risk of suffering from anxiety and PTS, but not depressive symptoms, in the year following a major stressor.

Antecedentes: Aunque la pandemia de COVID-19 ha aumentado la incidencia de angustia en jóvenes, algunos niños muestran una mayor resiliencia, relevando la necesidad de comprender mejor los predictores de la angustia en los jóvenes.Objetivo: Este estudio longitudinal tuvo como objetivo evaluar el impacto combinado de los predictores socioemocionales conocidos de la psicopatología relacionada con el estrés, como son la sensibilidad a la ansiedad, rasgos ansiosos, intolerancia a la incertidumbre y rumiación, en la angustia relacionada con COVID en jóvenes sanos.Método: 92 díadas de padres e hijos que participaron previamente en un experimento de laboratorio que evaluó el aprendizaje del miedo observacional en familias entre 2017 y 2019 (T0) fueron contactados nuevamente. Participaron 84 niños de entre 9 y 14 años. Completaron cuestionarios en línea en junio de 2020 (T1), septiembre de 2020 (T2), diciembre de 2020 (T3) y marzo de 2021 (T4). Los participantes estaban libres de enfermedad mental en T0 y T1. Para crear una puntuación socioemocional compuesta (SECS), medimos la sensibilidad a la ansiedad (Índice de sensibilidad a la ansiedad infantil) en T0, rasgo de ansiedad (subescala de rasgo del Inventario de ansiedad estado-rasgo para niños (STAI-C)), intolerancia a la incertidumbre (escala de intolerancia a la incertidumbre para niños) y rasgo de rumiación (Escala de estilo de respuesta en niños) en T1 y se creó una puntuación z ponderada. Para evaluar los síntomas de ansiedad, estrés postraumático (PTS) y depresión en reacción al COVID-19, los participantes completaron la subescala de estado de STAI-C, la escala de impacto de eventos para niños revisada, y el inventario de depresión infantil en T1­T4. Se ejecutaron tres modelos lineales generales con sexo, grupo de edad (9­11 y 12+ años) y SECS como predictores.Resultados: Los análisis revelaron una interacción entre el tiempo y la puntuación socioemocional compuesta (SECS), donde un SECS más alto predice síntomas de ansiedad elevados en T1 y T4, y síntomas elevados de PTS (Estrés post traumático) en T1 y T2.Conclusión: Estos resultados sugieren que la juventud sana que presenten altos niveles de vulnerabilidad socioemocional a la psicopatología, tiene un mayor riesgo desufrir de ansiedad y síndrome de estrés postraumático, pero no síntomas depresivos, en el año siguiente a un evento estresante mayor.