Pregnenolone Reduces Stress-Induced Craving, Anxiety, and Autonomic Arousal in Individuals with Cocaine Use Disorder.

Chronic cocaine use leads to adaptations in stress biology and in neuroactive steroid system. These adaptations are associated with high cocaine craving and increased relapse risk. This study tested whether potentiation of the neuroactive steroid system with the precursor pregnenolone (PREG) affects stress- and cue-induced cocaine craving, anxiety and autonomic response in individuals with cocaine use disorder (CUD). Thirty treatment-seeking individuals (21 Male, 9 Female) with CUD were randomized to placebo (PBO) or supraphysiologic PREG doses of 300 mg or 500 mg per day for 8 weeks. After 2 weeks of treatment, participants were exposed to 5-min personalized guided imagery provocation of stress, cocaine, or neutral/relaxing cues in a 3-day experiment, one condition per day on separate days, in a random, counterbalanced order. Repeated assessment of cocaine craving, anxiety, heart rate (HR), systolic (SBP) and diastolic blood pressure (DBP) were assessed on each day. PREG significantly increased pregnenolone levels compared to PBO. Both PREG doses decreased stress- and cocaine cue-induced craving and reduced both stress- and cue-induced anxiety only in the 500 mg/day group. The 500 mg/day PREG group also displayed decreased stress-induced HR, SBP and DBP. Findings indicate that pregnenolone decreases stress- and cocaine cue-provoked craving and anxiety and reduces stress-induced autonomic arousal in individuals with CUD.

A model of negative emotional contagion between male-female rat dyads: Effects of voluntary exercise on stress-induced behavior and BDNF-TrkB signaling.

Emotional contagion refers to the sharing of emotional states between individuals and can cause depressive behaviors in healthy persons who live with depressed individuals. Negative emotional contagion has been observed in animal models, but the vast majority of studies are short-term and bear little resemblance to long-term human relationships. Thus, the first aim of this study was to establish an animal model of stress-induced negative emotional contagion that develops across time and between pairs. To accomplish this, we tested the hypothesis that sedentary male rats that cohabitate for five weeks with a stress-exposed female will exhibit a depression-like phenotype that is observable on behavioral and physiological measures. In addition, drawing from a comprehensive literature that describes the beneficial effects of prior exercise on stress-related behavior, we tested our second hypothesis that in males that were paired with a stressed female, prior voluntary exercise will diminish the impact of negative emotional contagion. We found that pair housing a healthy male with a stressed female led to emotional contagion; males gained less body weight, were anhedonic, demonstrated heightened anxiety-like behavior, had lower serum brain-derived neurotrophic factor (BDNF) levels, had decreased hippocampal BDNF-stimulated tyrosine receptor kinase B (TrkB) signaling and had increased pro-inflammatory cytokine expression in the hippocampus. For the most part, the five-week exercise window that occurred prior to pair housing had few effects in non-stress paired rats, but had partial, yet substantial protective effects in rats that were pair-housed with a stressed female. Specifically, stress-paired, exercised rats showed less depressive-like behavior, had partially preserved hippocampal BDNF-stimulated TrkB signaling, had normalized serum BDNF concentration, and had hippocampal cytokine and immediate early gene levels that were equivalent to controls. These preclinical findings introduce a new model of negative emotional contagion between dyads of male-female rats and support the view that inclusion of exercise programs would be beneficial for persons that may, in the future, be susceptible to negative emotional contagion.

A cross-national study of factors associated with women's perinatal mental health and wellbeing during the COVID-19 pandemic.

Pregnant and postpartum women face unique challenges during the COVID-19 pandemic that may put them at elevated risk of mental health problems. However, few large-scale and no cross-national studies have been conducted to date that investigate modifiable pandemic-related behavioral or cognitive factors that may influence mental health in this vulnerable group. This international study sought to identify and measure the associations between pandemic-related information seeking, worries, and prevention behaviors on perinatal mental health during the COVID-19 pandemic. An anonymous, online, cross-sectional survey of pregnant and postpartum women was conducted in 64 countries between May 26, 2020 and June 13, 2020. The survey, available in twelve languages, was hosted on the Pregistry platform for COVID-19 studies (https://corona.pregistry.com) and advertised in social media channels and online parenting forums. Participants completed measures on demographics, COVID-19 exposure and worries, information seeking, COVID-19 prevention behaviors, and mental health symptoms including posttraumatic stress via the IES-6, anxiety/depression via the PHQ-4, and loneliness via the UCLA-3. Of the 6,894 participants, substantial proportions of women scored at or above the cut-offs for elevated posttraumatic stress (2,979 [43%]), anxiety/depression (2,138 [31%], and loneliness (3,691 [53%]). Information seeking from any source (e.g., social media, news, talking to others) five or more times per day was associated with more than twice the odds of elevated posttraumatic stress and anxiety/depression, in adjusted models. A majority of women (86%) reported being somewhat or very worried about COVID-19. The most commonly reported worries were related to pregnancy and delivery, including family being unable to visit after delivery (59%), the baby contracting COVID-19 (59%), lack of a support person during delivery (55%), and COVID-19 causing changes to the delivery plan (41%). Greater worries related to children (i.e., inadequate childcare, their infection risk) and missing medical appointments were associated with significantly higher odds of posttraumatic stress, anxiety/depression and loneliness. Engaging in hygiene-related COVID-19 prevention behaviors (face mask-wearing, washing hands, disinfecting surfaces) were not related to mental health symptoms or loneliness. Elevated posttraumatic stress, anxiety/depression, and loneliness are highly prevalent in pregnant and postpartum women across 64 countries during the COVID-19 pandemic. Excessive information seeking and worries related to children and medical care are associated with elevated symptoms, whereas engaging in hygiene-related preventive measures were not. In addition to screening and monitoring mental health symptoms, addressing excessive information seeking and women's worries about access to medical care and their children's well-being, and developing strategies to target loneliness (e.g., online support groups) should be part of intervention efforts for perinatal women. Public health campaigns and medical care systems need to explicitly address the impact of COVID-19 related stressors on mental health in perinatal women, as prevention of viral exposure itself does not mitigate the pandemic's mental health impact.