BDNF genotype Val66Met interacts with acute plasma BDNF levels to predict fear extinction and recall.

Brain-derived neurotropic factor (BDNF) is a potent regulator of memory processes and is believed to influence the consolidation of fear extinction memories. No previous human study has tested the effect of unstimulated BDNF on fear extinction recall, and no study has tested the association between plasma BDNF levels and psychophysiological responding during an extinction paradigm. We tested the association between fear responses during a 2-day differential conditioning, extinction and extinction recall paradigm and Val66Met genotype in a group of healthy participants (N = 191). There were no group differences during habituation or acquisition. Met allele carriers compared to Val homozygotes displayed higher responses to the CS + compared to the CS- during extinction learning and had higher responding to both the CS+ and CS- during extinction recall. Plasma levels of BDNF protein that were collected in a sub-sample of the group (n = 56) moderated the effect of Met allele presence, such that lower BDNF level was associated with higher skin conductance response in the Met but not Val group to the CS+ during extinction learning and to both the CS+ and CS- during extinction recall. The current results extend previous observations of a Val66Met effect during fear extinction learning to extinction recall and show for the first time that these effects are moderated by plasma BDNF level.

Inconsistent analytic strategies reduce robustness in fear extinction via skin conductance response.

Robustness of fear conditioning and extinction paradigms has become increasingly important for many researchers interested in improving the study of anxiety and trauma disorders. We recently illustrated the wide variability in data analysis techniques in this paradigm, which we argued may result in a lack of robustness. In the current study, we resampled data from six of our own fear acquisition and extinction data sets, with skin conductance as the outcome. In the resampled and original data sets, we found that effect sizes that were calculated using discrepant statistical strategies, sourced from a non-exhaustive search of high-impact articles, were often poorly correlated. The main contributors to poor correlations were the selection of trials from different stages of each experimental phase and the use of average compared to trial-by-trial analysis. These findings reinforce the importance of focusing on robustness in the psychophysiological measurement of fear acquisition and extinction in the laboratory and may guide prospective researchers in which decisions may most impact the robustness of their results.

An alternative theory for hormone effects on sex differences in PTSD: The role of heightened sex hormones during trauma.

Women are at least twice as susceptible to developing post-traumatic stress disorder (PTSD) compared to men. Although most research seeking to explain this discrepancy has focussed on the role of oestradiol during fear extinction learning, the role of progesterone has been overlooked, despite relatively consistent findings being reported concerning the role of progesterone during consolidation of emotional and intrusive memories. In this review article, we outline literature supporting the role of progesterone on memory formation, with particular emphasis on potential memory-enhancing properties of progesterone when subjects are placed under stress. It is possible that progesterone directly and indirectly exerts memory-enhancing effects at the time of trauma, which is an effect that may not be necessarily captured during non-stressful paradigms. We propose a model whereby progesterone's steroidogenic relationship to cortisol and brain-derived neurotrophic factor in combination with elevated oestradiol may enhance emotional memory consolidation during trauma and therefore present a specific vulnerability to PTSD formation in women, particularly during the mid-luteal phase of the menstrual cycle.

Modulation of the endocannabinoid system by sex hormones: Implications for posttraumatic stress disorder.

The endocannabinoid system is an increasingly recognised pharmacological target for treating stress and anxiety disorders, including post-traumatic stress disorder (PTSD). Recent preclinical developments have implicated the endocannabinoid system in stress responses, emotional memories and fear extinction, all critical to PTSD aetiology. However, preclinical research in endocannabinoid biology has neglected the influential role of sex hormone differences on PTSD symptomology, which is particularly important given that PTSD is twice as common in women as in men. In this review, we compile and consider the evidence that the endocannabinoid system is influenced by ovarian hormones, with application to stress disorders such as PTSD. It is clear that therapeutic modulation of the endocannabinoid system needs to be approached with awareness of ovarian hormonal influences, and knowledge of these influences may enhance treatment outcomes for female PTSD populations.