Unlocking the Potential of Estradiol in Posttraumatic Stress Disorder Symptom Reduction: Is Habituation the Key?

The risk for developing a trauma-related psychopathology such as posttraumatic stress disorder (PTSD) is multidetermined but depends in part on biological sex. Women develop PTSD at approximately twice the rate of men while also experiencing greater symptom severity and longer symptom duration (1). However, the mechanisms underlying women’s disproportionate PTSD risk remain grossly understudied. Because these sex disparities cannot be fully accounted for by environmental factors, such as degree of exposure to particular types of trauma, more research is needed to understand biological factors that contribute to differential PTSD risk between sexes. Importantly, we need a better understanding of dysregulated neurocircuitries in traumatized women with and without PTSD to guide better treatments that target sex-specific neurobiological features of the disorder

Using a Contrast Illusion to Teach Principles of Neural Processing

Neuroscience is a rapidly growing, multidisciplinary field that is advancing our understanding of the human condition. Therefore, studying key principles in neuroscience is critical for a well-rounded education across a wide range of disciplines. However, neuroscience concepts can be intimidating and challenging for undergraduate students to learn, especially when they lack active learning opportunities. To address this problem, we developed an interactive laboratory exercise to challenge students to use observational measurements of a visual contrast illusion to study neural activity. The goal of this study was to understand the effectiveness of this active learning exercise in increasing students\u27 fundamental understanding of how perception is shaped by neural circuits in the retina. Students conducted simple psychophysical experiments to measure thresholds for detecting illusory spots under various conditions and described their results in a laboratory assignment. Assessment of students\u27 confidence and practical understanding of neural processing, before and after engagement with the laboratory exercise, was used to improve curriculum and instruction

Estrogen and Extinction of Fear Memories: Implications for Posttraumatic Stress Disorder Treatment

Posttraumatic stress disorder (PTSD) is a psychiatric illness whose prevalence in women is more than twice the rate as men. Despite a burgeoning literature characterizing sexdifferences in PTSD incidence and its disproportionate burden on society, there is a dearth of literature describing biological mechanisms underlying these disparities. However, the recent identification of biomarkers of PTSD by translational neuroscientists offers a promising opportunity to explore sex interactions in PTSD phenotypes. A notable observation is that individuals with PTSD show deficits in their ability to inhibit conditioned fear responding after extinction training. Given that extinction procedures, via exposure-based cognitive behavioral therapy, make up one of the predominant modes of treatment in PTSD, there is a critical need for more research on sex interactions in this form of fear regulation. An emerging hypothesis is that fluctuatinggonadal hormones, especially estrogen, in the menstrual cycle may play a critical role in fear extinction and, hence, PTSD vulnerability and symptom severity in women. The current review discusses how the study of putative activational effects of estrogen on fear extinction may be harnessed to advance the search for better treatments for PTSD in women. We conclude that estrogen treatment may be a putative pharmacologic adjunct in extinction-based therapies and should be tracked in the menstrual cycle during the course of PTSD treatment

Differing effects of systemically administered rapamycin on consolidation and reconsolidation of context vs. cued fear memories

Rapamycin, an inhibitor of the mammalian target of rapamycin (mTOR) kinase, has attracted interest as a possible prophylactic for post-traumatic stress disorder (PTSD)-associated fear memories. We report here that although rapamycin (40 mg/kg, i.p.) disrupted the consolidation and reconsolidation of fear-potentiated startle paradigm to a shock-paired context, it did not disrupt startle increases to a 4-sec odor cue, even though post-training increases in amygdala mTOR activity were prevented by rapamycin (also 40 mg/kg, i.p.). Thus, while rapamycin may prove useful in retarding the development of some PTSD-associated memories, its relative ineffectiveness against cued fear memories may limit its clinical usefulness

Fear Load: The Psychophysiological Over-Expression of Fear as an Intermediate Phenotype Associated with Trauma Reactions

Psychophysiological measures of fear expression provide observable intermediate phenotypes of fear-related symptoms. Research Domain Criteria (RDoC) advocate using neurobiological intermediate phenotypes that provide dimensional correlates of psychopathology. Negative Valence Systems in the RDoC matrix include the construct of acute threat, which can be measured on a physiological level using potentiation of the acoustic startle reflex assessed via electromyography recordings of the orbicularis oculi muscle. Impairments in extinction of fear-potentiated startle due to high levels of fear (termed fear load) during the early phases of extinction have been observed in posttraumatic stress disorder (PTSD). The goals of the current work were to examine dimensional associations between fear-related symptoms of PTSD and fear load variables to test their validity as an intermediate phenotype. We examined extinction of fear-potentiated startle in a cohort (n = 269) of individuals with a broad range of civilian trauma exposure (range 0–13 traumatic events per person, mean = 3.5). Based on previously reported findings, we hypothesized that fear load would be significantly associated with intrusion and fear memories of an index traumatic event. The results indicated that early extinction was correlated with intrusive thoughts(p = 0.0007) and intense physiological reactions to trauma reminders (p = 0.036). Degree of adult or childhood trauma exposure, and depression severity were not associated with fear load. After controlling for age, sex, race, income, level of prior trauma, and level of fear conditioning, fear load during extinction was still significantly predictive of intrusive thoughts (p = 0.004). The significance of these findings is that they support dimensional associations with symptom severity rather than diagnostic category and, as such, fear load may emerge as a transdiagnostic intermediate phenotype expressed across fear-related disorders (e.g., specific phobia, social phobia)