Impairing memory reconsolidation with propranolol in healthy and clinical samples: a meta-analysis.

BACKGROUND: Reconsolidation impairment using propranolol is a novel intervention for mental disorders with an emotional memory at their core. In this systematic review and meta-analysis, we examined the evidence for this intervention in healthy and clinical adult samples. METHODS: We searched 8 databases for randomized, double-blind studies that involved at least 1 propranolol group and 1 placebo group. We conducted a meta-analysis of 14 studies (n = 478) in healthy adults and 12 studies in clinical samples (n = 446). RESULTS: Compared to placebo, reconsolidation impairment under propranolol resulted in reduced recall of aversive material and cue-elicited conditioned emotional responses in healthy adults, as evidenced by an effect size (Hedges g) of -0.51 (p = 0.002, 2-tailed). Moreover, compared to placebo, reconsolidation impairment under propranolol alleviated psychiatric symptoms and reduced cue-elicited reactivity in clinical samples with posttraumatic stress disorder, addiction or phobia (g = -0.42, p = 0.010). LIMITATIONS: Methodological differences between studies posed an obstacle for identifying sources of heterogeneity. CONCLUSION: Reconsolidation impairment is a robust, well-replicated phenomenon in humans. Its clinical use is promising and deserves further controlled investigation.

PTSD is not the emblematic disorder of the COVID-19 pandemic; adjustment disorder is.

BACKGROUND: Posttraumatic stress disorder (PTSD) has been hailed by some as the emblematic mental disorder of the COVID-19 pandemic, assuming that PTSD's life-threat criterion was met de facto. More plausible outcomes like adjustment disorder (AD) have been overlooked. METHODS: An online cross-sectional survey was launched in the initial stage of the pandemic using a convenience sample of 5 913 adults to compare the prevalence of COVID-related probable PTSD versus probable AD. The abridged Impact of Event Scale - Revised (IES-6) assessed the severity of trauma- and stressor-related symptoms over the previous week. Demographic and pandemic-related data (e.g., receiving a formal diagnosis of COVID-19, job loss, loss of loved one, confinement, material hardship) were collected. A Classification and Regression Tree analysis was conducted to uncover the pandemic experiences leading to clinical 'caseness'. Caseness was defined by a score > 9 on the IES-6 symptom measure and further characterized as PTSD or AD depending on whether the Peritraumatic Distress Inventory's life-threat item was endorsed or not. RESULTS: The participants were predominantly Caucasian (72.8%), women (79.2%), with a university degree (85%), and a mean age of 42.22 (SD = 15.24) years; 3 647 participants (61.7%; 95%CI [60.4, 63.0]) met the threshold for caseness. However, when perceived life-threat was accounted for, only 6.7% (95%CI [6.1, 7.4]) were classified as PTSD cases, and 55% (95%CI [53.7, 56.2]) as AD cases. Among the AD cases, three distinct profiles emerged marked by the following: (i) a worst personal pandemic experience eliciting intense fear, helplessness or horror (in the absence, however, of any life-threat), (ii) a pandemic experience eliciting sadness/grief, and (iii) worrying intensely about the safety of significant others. CONCLUSIONS: Studies considering the life-threat criterion as met de facto during the pandemic are confusing PTSD for AD on most counts. This misconception is obscuring the various AD-related idioms of distress that have emerged during the pandemic and the actual treatment needs.

Media Use During the COVID-19 Pandemic: Cross-sectional Study.

BACKGROUND: Throughout the pandemic, the general population was encouraged to use media to be kept informed about sanitary measures while staying connected with others to obtain social support. However, due to mixed findings in the literature, it is not clear whether media use in such a context would be pathogenic or salutogenic. OBJECTIVE: Therefore, the associations between COVID-19-related stressors and frequency of media use for information-seeking on trauma- and stressor-related (TSR) symptoms were examined while also investigating how social media use for support-seeking and peritraumatic distress interact with those variables. METHODS: A path model was tested in a sample of 5913 adults who completed an online survey. RESULTS: The number of COVID-19-related stressors (ß=.25; P<.001) and extent of information-seeking through media (ß=.24; P=.006) were significantly associated with the severity of TSR symptoms in bivariate comparisons. Associations between levels of peritraumatic distress and both COVID-19-related stressors and information-seeking through media, and social media use for support- and information-seeking through media were found (ßCOVID-19 stressors: Peritraumatic Distress Inventory=.49, P<.001; ßseeking information: Peritraumatic Distress Inventory=.70, P<.001; ßseeking information-seeking support=.04, P<.001). CONCLUSIONS: Results suggest that exposure to COVID-19-related stressors and seeking COVID-19-related information through the media are associated with higher levels of peritraumatic distress that, in turn, lead to higher levels of TSR symptoms. Although exposure to the stress of the COVID-19 pandemic may be unavoidable, the frequency of COVID-19-related information consumption through various media should be approached with caution.

Propranolol's effects on the consolidation and reconsolidation of long-term emotional memory in healthy participants: a meta-analysis.

BACKGROUND: Considering the pivotal role of negative emotional experiences in the development and persistence of mental disorders, interfering with the consolidation/reconsolidation of such experiences would open the door to a novel treatment approach in psychiatry. We conducted a meta-analysis on the experimental evidence regarding the capacity of the ß-blocker propranolol to block the consolidation/reconsolidation of emotional memories in healthy adults. METHODS: Selected studies consisted of randomized, double-blind experiments assessing long-term memory for emotional material in healthy adults and involved at least 1 propranolol and 1 placebo condition. We searched PsycInfo, PubMed, Web of Science, Cochrane Central, PILOTS, Google Scholar and clinicaltrials.org for eligible studies from the period 1995-2012. Ten consolidation (n = 259) and 8 reconsolidation (n = 308) experiments met the inclusion criteria. We calculated effect sizes (Hedges g) using a random effects model. RESULTS: Compared with placebo, propranolol given before memory consolidation reduced subsequent recall for negatively valenced stories, pictures and word lists (Hedges g = 0.44, 95% confidence interval [CI] 0.14-0.74). Propranolol before reconsolidation also reduced subsequent recall for negatively valenced emotional words and the expression of cue-elicited fear responses (Hedges g = 0.56, 95% CI 0.13-1.00). LIMITATIONS: Limitations include the moderate number of studies examining the influence of propranolol on emotional memory consolidation and reconsolidation in healthy adults and the fact that most samples consisted entirely of young adults, which may limit the ecological validity of results. CONCLUSION: Propranolol shows promise in reducing subsequent memory for new or recalled emotional material in healthy adults. However, future studies will need to investigate whether more powerful idiosyncratic emotional memories can also be weakened and whether this weakening can bring about long-lasting symptomatic relief in clinical populations, such as patients with posttraumatic stress or other event-related disorders.

Peritraumatic distress across the lifespan: Clinical implications of age differences during the COVID-19 pandemic.

The Peritraumatic Distress Inventory (PDI) is a well-known self-report questionnaire indexing the distress experienced during and shortly after a most stressful or traumatic event. Although sociodemographic factors contributing to peritraumatic distress have been previously investigated, no research has examined the nature and severity of peritraumatic distress reactions in a non-clinical, community sample as a function of age. An international sample of 5621 adult participants were grouped according the World Health Organization's age stratification protocol. Mean scores and item endorsement on the PDI were compared across groups with respect to their worst experience of the COVID-19 pandemic. A significant between-group difference was found, F(55,615) = 30.74, p < 0.001, n2  = 0.027 whereby participants aged 18-39 years old reported the highest levels of peritraumatic distress. This group also endorsed a higher proportion of items on the PDI's two main factors (emotional distress and physical reactions), and were more likely to endorse feelings of helplessness, than older participants. It appears that severity of peritraumatic distress during the pandemic has affected younger people the most. Results are discussed in light of clinical implications.

Attachment Injury Severity, Injury-related Stress, Forgiveness, and Sexual Satisfaction in Injured Adult Partners.

An attachment injury can occur when one partner violates the assumption that they will provide comfort and caring during a moment of increased need. For injured partners, unresolved attachment injuries can underlie an enduring stress reaction and lower relationship satisfaction. However, no research has examined the associations between the perceived severity of the injury and sexual satisfaction, a central component of relationship well-being. In this cross-sectional study, we examined the direct and indirect associations between the perceived severity of the attachment injury and sexual satisfaction via injury-related stress symptoms and levels of forgiveness, in injured partners. A total of 145 adults who reported having experienced an attachment injury in their current relationship completed self-report questionnaires measuring injury severity, event-related stress, forgiveness, and sexual satisfaction. An indirect association between the perceived severity of the attachment injury and sexual satisfaction through higher injury-related stress and lower forgiveness was found via a path analysis. Results suggest that fostering forgiveness and attending to injury-related stress may be key toward sexual satisfaction in couples where a partner reports an attachment injury. Clinical implications of these results are discussed in light of theory and potential treatment strategies for addressing an attachment injury in couple's therapy.

Treatment of adjustment disorder stemming from romantic betrayal using memory reactivation under propranolol: A open-label interrupted time series trial.

OBJECTIVES: In a sustained relationship, romantic betrayal is a catastrophic event that can precipitate an adjustment disorder (AD). Surprisingly, there exists no empirically validated treatment for AD, despite its high prevalence in clinical practice. Considering the promise of memory reactivation under propranolol (i.e., reconsolidation interference) for treating posttraumatic stress disorder, we sought to extend this finding to AD, given that in both disorders, symptoms stem from an identified stressor. METHOD: A single-blind interrupted time series design was used to examine the efficacy of memory reactivation under propranolol to alleviate symptoms of AD. After being placed on a 4-week waitlist, sixty-one participants received 5 weekly 25-min treatments during which they recalled the betrayal event, 1 h after having orally ingested the beta-blocker propranolol. RESULTS: Segmented regression analyses on the intent-to-treat sample revealed that AD symptoms significantly decreased during the treatment phase (pre/post Cohen's d = 1.44), compared to the waitlist phase (d = 0.01). Significant pre/post reductions in anxio-depressive symptomatology were also found. Improvement was maintained at the 4-month follow-up on all outcomes. CONCLUSION: Memory reactivation under propranolol shows promise in reducing symptoms of AD. This study provides the theoretical framework and necessary effect sizes to inform larger, double-blind, placebo-controlled clinical trials.

Is romantic partner betrayal a form of traumatic experience? A qualitative study.

According to a growing body of research, betrayal by a romantic partner is increasingly considered as a form of interpersonal trauma. Between 30% and 60% of betrayed individuals experience symptoms of post-traumatic stress disorder (PTSD), depression and anxiety to clinically meaningful levels. From a clinical perspective, this constellation of symptoms can be conceptualized as a stressor-related adjustment disorder. Yet, no qualitative research has examined the association between romantic betrayal and traumatic stress from the perspective of betrayed individuals. Face-to-face semi-structured interviews were conducted with 13 participants who had completed a clinical trial for a new treatment for adjustment disorder stemming from betrayal. Data were analysed using thematic content analysis. Although betrayal was experienced as a shocking and destabilizing event, and participants used trauma or 'feeling traumatized' as a metaphor to describe their experience, few had constructed their reaction as traumatic stress. In fact, participants reported experiencing difficulties understanding the intensity of their experience. However, when exposed to external sources (e.g., books and interviews by psychologists and researchers) that used a trauma and PTSD framework to explain the effects of betrayal, participants reported feeling clarity, validation and relief. Findings are discussed in the light of theoretical and clinical implications.

Reversed polarized delivery of an aquaporin-2 mutant causes dominant nephrogenic diabetes insipidus.

Vasopressin regulates body water conservation by redistributing aquaporin-2 (AQP2) water channels from intracellular vesicles to the apical surface of renal collecting ducts, resulting in water reabsorption from urine. Mutations in AQP2 cause autosomal nephrogenic diabetes insipidus (NDI), a disease characterized by the inability to concentrate urine. Here, we report a frame-shift mutation in AQP2 causing dominant NDI. This AQP2 mutant is a functional water channel when expressed in Xenopus oocytes. However, expressed in polarized renal cells, it is misrouted to the basolateral instead of apical plasma membrane. Additionally, this mutant forms heterotetramers with wild-type AQP2 and redirects this complex to the basolateral surface. The frame shift induces a change in the COOH terminus of AQP2, creating both a leucine- and a tyrosine-based motif, which cause the reversed sorting of AQP2. Our data reveal a novel cellular phenotype in dominant NDI and show that dominance of basolateral sorting motifs in a mutant subunit can be the molecular basis for disease.

Assessing trauma and posttraumatic stress disorder: Single, open-ended question versus list-based inventory.

Trauma exposure is a precursor to a diagnosis of posttraumatic stress disorder (PTSD). A dearth of empirical evidence exists on the impact of different measurement practices on estimates of trauma exposure and PTSD within representative epidemiological samples. In the present study, we examined differences in reported trauma exposure and rates of PTSD using single, open-ended question versus list-based trauma assessments in a general community sample. Using data from the third wave of the Montreal epidemiological catchment area study (N = 1029), participants were interviewed in person by a lay interviewer about lifetime history of trauma exposure and PTSD. Prevalence rates of trauma exposure and PTSD diagnosis using single, open-ended question and list-based assessment were compared using a within-subject design. A single, open-ended question versus list-based trauma assessment yielded trauma-exposure rates of 61%, 95% CI [57.8, 63.8] and 78%, 95% CI [75.2, 80.3], respectively. Conditional rates of lifetime PTSD decreased from 6.7%, 95% CI [5.8, 9.4] to 6%, 95% CI [4.4, 7.7], respectively. Increases in trauma exposure were more pronounced in women (33.7%) than men (21.5%), as well as in the younger stratum of study participants (15-24 years old; 36.1%). Underestimation of PTSD using a single, open-ended question assessment was minimal, although all missing cases were women. Our results lend support to the importance of using comprehensive assessments of exposure to potentially traumatic events when conducting epidemiological research, especially when reporting conditional rates of PTSD. Previous research may have underestimated the prevalence of trauma exposure, particularly among young women. (PsycINFO Database Record

Reactivating addiction-related memories under propranolol to reduce craving: A pilot randomized controlled trial.

BACKGROUND: The reconsolidation blocker propranolol abolishes alcohol and drug-seeking behavior in rodents and attenuates conditioned emotional responses to drug-cues in humans in experimental settings. This suggests a role for its use in the treatment of substance dependence. In this translational pilot study, we explored the feasibility and efficacy of this procedure as an adjunct treatment for addiction. We hypothesized that guided addiction-related memory reactivation under propranolol would significantly attenuate tonic craving, a central element in relapse following addiction treatment. METHODS: Seventeen treatment-seeking adults diagnosed with substance dependence were randomized to receive double-blind propranolol (n = 9) or placebo (n = 8) on six occasions prior to reading a personalized script detailing a drug-using experience. The primary outcome measure was self-reported craving intensity. RESULTS: After controlling for baseline craving scores, intent-to-treat analysis revealed a time by group interaction, F(1, 14) = 5.68, p = .03, η(2) = 0.29; craving was reduced in the propranolol-treated group (Cohen's d = 1.40, p < .05) but not in the placebo group (d = 0.06, n.s.). LIMITATIONS: The usual limitations related to small sample size and the lack of a follow-up apply here. CONCLUSION: Drug-related memory reactivation under propranolol can subsequently reduce craving among substance-dependent individuals. Considering the relapse rate among individuals treated for substance dependence, our study highlights the feasibility of, and need for, more comprehensive trials of this treatment approach.