The Effect of Self-Reported REM Behavior Disorder Symptomology on Intrusive Memories in Post-Traumatic Stress Disorder

Background: PTSD is characterised by severe sleep disturbances, which is increasingly recognised to in many cases consist of similar symptomology to sleep disorders such as REM Behaviour Disorder (RBD). The present study aimed to investigate whether different aspects of sleep quality influence intrusive memory development and whether PTSD status moderates this relationship.Participants and Methods: 34 PTSD, 52 trauma-exposed (TE) and 42 non-trauma exposed (NTE) participants completed an emotional memory task, where they viewed 60 images (20 positive, 20 negative and 20 neutral) and, two days later, reported how many intrusive memories they had of each valence category. Participants also completed three measures of sleep quality: the Pittsburgh Sleep Quality Index, the REM Behaviour Disorder Screening Questionnaire and total hours slept before each session.Results: The PTSD group reported poorer sleep quality than both TE and NTE groups on all three measures, and significantly more negative intrusive memories than the NTE group. Mediation analyses revealed that self-reported RBD symptomology before the second session mediated the relationship between PTSD status and intrusive memories. Follow-up moderation analyses revealed that self-reported RBD symptomology before the second session was only a significant predictor of intrusion in the PTSD group, though with a small effect size.Conclusions: These findings suggest that RBD symptomology is an indicator of consolidation of intrusive memories in PTSD but not trauma-exposed or healthy participants, which supports the relevance of characterising RBD in PTSD

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 lack of robustness. In the current study, we resampled data from six of our own fear acquisition and extinction datasets, with skin conductance as the outcome. In the resampled and original datasets, 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 selection of trials from different stages of each experimental phase and use of averaged compared to trial-by-trial analysis. These findings reinforce the importance of focusing on robustness in 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

Sex differences in schizophrenia, bipolar disorder and PTSD: Are gonadal hormones the link?

In this review, we describe the sex differences in prevalence, onset, symptom profiles and disease outcome that are evident in schizophrenia, bipolar disorder and post-traumatic stress disorder. Women with schizophrenia tend to exhibit less disease impairment than men; by contrast, women with post-traumatic stress disorder are more affected than men. The most likely candidates to explain these sex differences are gonadal hormones. This review details the clinical evidence that estradiol and progesterone are dysregulated in these psychiatric disorders. Notably, existing data on estradiol, and to a lesser extent, progesterone, suggest that low levels of these hormones may increase the risk of disease development and worsen symptom severity. We argue that future studies require a more inclusive, considered analysis of gonadal steroid hormones and the intricacies of the interactions between them, with methodological rigour applied, to enhance our understanding of the roles of steroid hormones in psychiatric disorders

Reaction time as an outcome measure during online fear conditioning: Effects of number of trials, age, and levels of processing

Recent studies have shown that fear conditioning experiments can be successfully conducted online. However, there is limited evidence that measures other than subjective ratings of threat expectancy can be collected, which means that online research may not be able to adequately replace laboratory experiments. In the current study, we conducted an online fear conditioning experiment consisting of habituation, acquisition, extinction and 48 h delayed extinction recall using ratings of threat expectancy and conditional stimulus pleasantness, and probe reaction time as outcome measures. The conditional stimuli were categories of words and a levels of processing manipulation explored whether words that were processed at a deeper level during extinction evoked smaller differential threat responses during extinction recall. Although the levels of processing manipulation did not produce a significant outcome, we found that extinction recall was successfully operationalised in our study. Reaction time indicated differential responding during both acquisition and extinction recall, and age of participants was correlated in one of two experiments with differential threat expectancy and reaction time, such that older participants showed better safety learning. The outcomes of this experiment provide multiple novel tools for researchers to explore fear conditioning, especially in an online environment.</p

Fear conditioning depends on the nature of the unconditional stimulus and may be related to hair levels of endocannabinoids

The replicability of fear conditioning research has come under recent scrutiny, with increasing acknowledgment that the use of differing materials and methods may lead to incongruent results. Direct comparisons between the main two unconditional stimuli used in fear conditioning – an electric shock or a loud scream—are scarce, and yet these stimuli are usually used interchangeably. In the present study, we tested whether a scream, a shock, or an unpredictable combination of the two affected fear acquisition, extinction, and return of fear amongst healthy participants (N = 109, 81 female). We also collected hair samples and tested the relationship between fear conditioning and hair endocannabinoid levels. Our findings suggest that, although subjective ratings of pleasantness, arousal, and anxiety were similar regardless of the unconditional stimuli used, skin conductance responses were significantly lower for stimuli paired with the scream compared to a shock alone. Further, reducing the predictability of the unconditional stimulus reduced habituation of skin conductance responses during acquisition and reacquisition, but did not produce stronger conditioning compared to shock alone. Exploratory analyses suggested that hair endocannabinoids were associated with overall physiological arousal during fear conditioning, as well as higher return of fear to the threat cue, but not to the safety cue. These findings have multiple implications for the design and replicability of fear conditioning research and provide the first evidence for an association between hair levels of endocannabinoids and human fear conditioning.</p

The endocannabinoid system and posttraumatic stress disorder (PTSD): A new narrative

The endocannabinoid system has been proposed as a promising candidate for treating posttraumatic stress disorder (PTSD). Despite a proliferation of preclinical and healthy human research, there is currently sparse endocannabinoid and cannabinoid research involving individuals with PTSD. Current evidence suggests discrepancies in the relationship between endocannabinoids and PTSD between basic (preclinical, healthy human) and clinical research. Specifically, more research is needed to understand how extreme stress and trauma exposure influence circulating concentrations of endocannabinoids acutely, as well what occurs to endocannabinoid tone and reactivity in the aftermath of trauma (e.g., 6 months following trauma). More information is also needed to understand how genotypes identified in basic research correlate with PTSD symptomology and fear-conditioning performance, as well as how treatment with cannabinoid compounds affects PTSD treatment outcomes. The current review discusses each of these issues in a comprehensive review of available evidence and suggests critical areas of future research

Renewal in human fear conditioning: A systematic review and meta-analysis

Renewal is a ‘return of fear’ manipulation in human fear conditioning to investigate learning processes underlying anxiety and trauma. Even though renewal paradigms are widely used, no study has compared the strength of different renewal paradigms. We conduct a systematic review (N = 80) and meta-analysis (N = 23) of human fear conditioning studies assessing renewal. Our analysis shows that the classic ABA design is the most effective paradigm, compared to ABC and ABBA designs. We present evidence that conducting extinction in multiple contexts and increasing the similarity between acquisition and extinction contexts reduce renewal. Furthermore, we show that additional cues can be used as safety and ‘protection from extinction’ cues. The review shows that alcohol weakens the extinction process and that older adults appear less sensitive to context changes and thus show less renewal. The large variability in approaches to study renewal in humans suggests that standardisation of fear conditioning procedures across laboratories would be of great benefit to the field.</p

Intolerance of uncertainty affects electrodermal responses during fear acquisition : Evidence from electrodermal responses to unconditional stimulus omission

Past research has shown that Intolerance of Uncertainty (IU) affects Pavlovian fear conditioning processes. In particular, extinction of learned fear is delayed in those reporting high IU. Reports of differences during acquisition are less consistent with most of the studies reporting no evidence for effects of IU. This may be due to past studies' focus on first interval electrodermal responses or fear potentiated startle, rather than on indices that may better capture uncertainty – like the response to the absence of a probabilistic unconditional stimulus. The current analysis combined data across three experiments that employed a 50 % reinforcement schedule and assessed electrodermal responses and (in two experiments) ratings of conditional stimulus pleasantness. Participants scoring high on IU showed overall larger electrodermal first interval responses during habituation and acquisition but did not differ from those scoring low on IU in differential conditioning (the difference between CS+ and CS-), as indicated by electrodermal first or second interval responses or ratings of CS pleasantness. However, participants high in IU showed larger differential third interval electrodermal responses to the omission of the electro-tactile unconditional stimulus during acquisition. Some evidence for this difference emerged in each experiment, supporting the reliability of the result. The current results suggest that effects of IU emerge in conditions of high uncertainty in Pavlovian fear learning tasks, such as during the omission of probabilistic unconditional stimuli.</p

Gonadal steroid hormones and emotional memory consolidation: A systematic review and meta-analysis

Anxiety and stress-related disorders are more prevalent in women and associated with negative emotional memory consolidation as well as impaired fear extinction recall. Recent research has identified a role of gonadal steroid hormones in influencing emotional memories and fear extinction, however most individual studies have small samples and employed various protocols. A systematic review and meta-analysis were conducted on studies that examined sex hormones (estrogen, progesterone, testosterone, allopregnanolone, dehydroepiandrosterone) on four aspects of memory, namely, intentional recall (k = 13), recognition memory (k = 7), intrusive memories (k = 9), and extinction recall (k = 11). The meta-analysis on natural cycling women revealed that progesterone level was positively associated with negative recall and negative intrusive memories, and this effect on intentional recall was enhanced under stress induction. Estradiol level was positively associated with extinction recall. This study reveals an important role of progesterone and estradiol in influencing emotional memory consolidation. It highlights the need to control for these hormonal effects and examine progesterone and estradiol concurrently across all menstrual phases in future emotional memory paradigms

Conditional stimulus choices affect fear learning : Comparing fear conditioning with neutral faces and shapes or angry faces

Past fear conditioning studies have used different types of conditional stimuli (CSs). Whether this choice affects learning outcomes in particular when neutral stimuli (e.g., neutral faces vs. shapes) are used is unclear. Data were aggregated across nine studies using an electric shock unconditional stimulus to test for differences in acquisition and extinction of electrodermal responses and self-reported CS pleasantness when CSs were neutral faces or shapes (Experiment 1, N = 594) and when CSs were angry or neutral faces (Experiment 2, N = 157). Reliable electrodermal conditioning was observed in all stimulus conditions. We found stronger differential conditioning in electrodermal second interval responses and CS pleasantness and more pronounced extinction in CS pleasantness for neutral shape than neutral face CSs, but no differences in electrodermal first interval responses, the most frequently reported index of fear conditioning. For angry and neutral face CSs, there were no differences during acquisition, but the extinction of first and second interval electrodermal conditioning to angry faces was retarded relative to neutral faces. Acquisition of differential CS pleasantness, which was reliably observed for neutral face CSs, was absent for angry face CSs. The current results suggest that fear conditioning with a neutral face and shape CSs yields broadly similar results with differences limited to second interval electrodermal responses and CS pleasantness ratings. Using angry face CSs resulted in impaired extinction of electrodermal indices and no differential CS pleasantness ratings and should only be considered in studies designed to address questions about these specific CS materials.</p