Eye movement desensitization and reprocessing (EMDR) therapy or supportive counseling prior to exposure therapy in patients with panic disorder: study protocol for a multicenter randomized controlled trial (IMPROVE).

BACKGROUND: Exposure-based therapy is the treatment of choice for anxiety disorders, but many patients do not benefit sufficiently from it. Distressing images of threat related to the future or past may maintain the anxiety symptomatology or impede exposure therapy. An intervention that targets threat-related imagery is eye movement desensitization and reprocessing (EMDR) therapy. The main goal of this multicenter randomized controlled trial is to investigate whether EMDR therapy plus exposure therapy, relative to supportive counseling plus exposure therapy, improves treatment efficacy, tolerability, and adherence in patients with panic disorder. In addition, we will examine potential predictors of optimal treatment allocation, mechanisms of change as well as the long term effects of treatment. Finally, we will assess cost-effectiveness. METHODS: A multicenter randomized controlled trial mixed design will be conducted. Participants will be 50 patients, aged ≥ 18, diagnosed with a panic disorder. They will be randomly assigned to one of two conditions: EMDR therapy (i.e., flashforward strategy) or supportive counseling (each consisting of four weekly sessions of 90 min each) prior to exposure therapy (consisting of eight weekly sessions of 90 min each). Assessments will be made pre-treatment (T1), between-treatments (T2), post-treatment (T3), one month post-treatment (FU1) and six months post-treatment (FU2) by an assessor blind to treatment condition. The primary outcome measure is severity of panic-related symptoms. Secondary outcome measures are: tolerability of exposure therapy (initial avoidance, willingness to start exposure therapy, considered drop-out; no-show and drop-out), related symptomatology (generalized anxiety, depression), and functional impairment. DISCUSSION: The primary goals of this research are to compare the efficacy, tolerability, and adherence of EMDR therapy plus exposure therapy and supportive counseling plus exposure therapy and to identify predictors, moderators, and mediators for treatment success. This multi-center research aims to make a significant contribution to our understanding as to how treatment for patients with anxiety disorders can be optimized, and elucidate who can benefit most from this novel approach. TRIAL REGISTRATION: ISRCTN-ISRCTN29668369: Improving anxiety treatment by modifying emotional memories before real-life exposure. Registered 27 June 2022-retrospectively registered. ISRCTN-ISRCTN29668369.

Forgetting the Future: Emotion Improves Memory for Imagined Future Events in Healthy Individuals but Not Individuals With Anxiety.

Negative thoughts about future events are a central aspect of anxiety disorders. It is important to gain a deeper understanding of how these imagined events are retained over time when considering the impact of negative future thoughts on anxiety. Prior research indicates that emotional intensity fades faster for negative than positive memories in healthy individuals. This so-called fading-affect bias could extend to recall of imagined future events. Furthermore, several studies have suggested that this bias may be reversed in individuals with high levels of anxiety. In the current study, we examined whether individuals with high anxiety (n = 23), relative to individuals with low anxiety (n = 30), showed faster decay for positive than negative future-event simulations. The results show that emotion facilitated cued recall for imagined future events in the low-anxiety group but not in the high-anxiety group. In addition, individuals with high anxiety showed decreased episodic specificity during recall across all emotional conditions.

Individual recovery of health-related quality of life during 18 months post-burn using a retrospective pre-burn measurement: an exploratory study.

PURPOSE: This study explored the individual trajectories of health-related quality of life (HRQL) compared to recalled pre-burn level of HRQL and investigated whether burn severity and post-traumatic stress disorder (PTSD) symptoms increase the risk of not returning to pre-burn level of HRQL. METHODS: Data were obtained from 309 adult patients with burns in a multicenter study. Patients completed the EQ-5D-3L questionnaire with a Cognition bolt-on shortly after hospital admission, which included a recalled pre-injury measure, and, again, at 3, 6, 12 and 18 months post-burn. Burn severity was indicated by the number of surgeries, and PTSD symptoms were assessed with the IES-R at three months post-burn. Pre- and post-injury HRQL were compared to norm populations. RESULTS: Recalled pre-injury HRQL was higher than population norms and HRQL at 18 months post-burn was comparable to population norms. Compared to the pre-injury level of functioning, four HRQL patterns of change over time were established: Stable, Recovery, Deterioration, and Growth. In each HRQL domain, a subset of patients did not return to their recalled pre-injury levels, especially with regard to Pain, Anxiety/Depression, and Cognition. Patients with more severe burns or PTSD symptoms were less likely to return to pre-injury level of functioning within 18 months post-burn. CONCLUSION: This study identified four patterns of individual change. Patients with more severe injuries and PTSD symptoms were more at risk of not returning to their recalled pre-injury HRQL. This study supports the face validity of using a recalled pre-burn HRQL score as a reference point to monitor HRQL after burns.

Reduction of conditioned avoidance via contingency reversal.

There is an increased interest in how excessive avoidance can diminish. Avoidance reduction is typically tested by using Extinction with Response Prevention (ExRP) protocols, where feared stimuli are presented without any aversive outcome while avoidance is prevented. These effects, however, often do not persist. Here, we tested whether pairing an avoidance response with the presence of an aversive event would reduce avoidance more than ExRP. Participants (N = 58) first saw a picture of a square (A) being paired with a shock whereas another picture of a square (B) not being paired with a shock. Then, they learned to press a button during the presentation of A to avoid the shock. Afterwards, the ExRP group saw unreinforced presentations of A and B without being able to press the avoidance button, whereas the Contingency Reversal group (ConR) received a shock whenever they pressed the button in presence of A. In the test phase, participants saw unreinforced presentations of A and B. Results showed that after successful acquisition of fear and avoidance, in the test phase the ConR group avoided A less often than did the ExRP group. Research on contingency reversal could prove helpful for developing avoidance reduction protocols.

Changing emotional visual and auditory memories: are modality-matched dual-tasks more effective?

Clinical and laboratory studies have demonstrated that executing a demanding dual-task while recollecting emotional memories weakens the emotional intensity and vividness of these memories. While this approach is generally effective, there is room for improvement. According to multi-component working memory theories, the effectiveness of dual-tasks may be improved by loading specifically the same sensory modality of the emotional memories. So far, however, the evidence for this idea is mixed. In the current report, this idea was tested in a pilot study (N = 36) and a pre-registered experiment (N = 60) by exposing participants to pictures of the International Affective Picture System database and to sounds of the International Affective Digital Sounds database, thus creating single-modality emotional memories. Using a within-subjects design, participants had to recollect their memories of the sounds and pictures while executing a visually-demanding task (i.e. identifying visual letters), an auditory-demanding task (i.e. identifying auditory letters), or no task. Across both studies, we only found limited evidence for modality-specific effects of dual-tasks on single-modality emotional memories. We discuss the relevance of our findings for working memory theories of memory change and therapeutic practices.

Changing negative autobiographical memories in the lab: a comparison of three eye-movement tasks.

There is strong evidence that executing eye-movement (EM) tasks that load working memory (WM) while thinking of an emotional memory reduces the emotionality and vividness of this memory. According to WM theory, EM tasks that load WM more should be more effective to devalue emotional memories. In this study, we compared three EM tasks: dot tracking, letter identification, and a combination of dot tracking and letter identification. First, participants completed a reaction time (RT) task to assess the WM load of the three EM tasks relative to a control task (viewing a black screen). Then, participants were asked to think of a negative autobiographical memory while executing one of these EM tasks and asked to recall another negative memory while executing the control task. Before and after each task, participants rated emotionality and vividness of the memory. All EM tasks slowed down RTs relative to the control task, and the letter identification task induced the largest RTs. Reductions of vividness relative to the control task, however, were comparable across the EM tasks, and there were no reliable reductions of emotionality. We discuss these findings in light of the WM theory and alternative theories for the effects of dual-task interventions.

Targeting avoidance via compound extinction.

Avoidance towards innocuous cues is a key diagnostic criterion across anxiety-related disorders. Importantly, the most effective intervention for anxiety-related disorders, exposure therapy with response prevention, sometimes does not prevent the relapse of anxiety's symptomatology. We tested whether extinction effects, the experimental proxy of exposure, are enhanced by increasing the discrepancy between the prediction of an unpleasant event happening (shock presentation), and the actual event (shock omission). Forty-eight individuals first saw pictures of three stimuli. Two pictures (CSA, CSB) were followed by a shock (US) and one (CS-) was not. Next, participants learned to avoid the US by pressing a computer key. An extinction and response prevention procedure followed. In the first part of it, participants saw unreinforced presentations of all CSs. In the second part, the single group saw unreinforced presentations of the CSA and CS-. The compound group encountered compound unreinforced presentations of the CSA and CSB, and separate presentations of the CS-. Return of avoidance and fear was tested after unsignalled presentations of the US. Compound extinction resulted in comparable reduction of fear and avoidance compared to standard extinction. We discuss how future research could enhance extinction effects by adding costs to the avoidance behaviour.

Intervention strength does not differentially affect memory reconsolidation of strong memories.

Recently, it has become clear that retrieval (i.e., reactivation) of consolidated memories may return these memories into a labile state before they are restored into long-term memory ('reconsolidation'). Using behavioral manipulations, reactivated memories can be disrupted via the mechanism of novel learning. In the present study, we investigated whether changing a strong memory during reconsolidation depends on the strength of novel learning. To test this, participants (N=144) in six groups acquired a relatively strong memory on Day 1 by viewing and recalling a series of pictures three times. On Day 8, these pictures were reactivated in three groups, and they were not reactivated in the other three groups. Then, participants viewed and recalled new pictures once (weak new learning) or three times (strong new learning), or they did not learn any new pictures. On Day 9, participants performed a recognition test in which their memory for Day 1 pictures was assessed. Two main results are noted. First, the groups that reactivated pictures from Day 1 and received weak or strong new learning did not differ in memory performance. Second, these two groups consistently performed similar to groups that controlled for new learning without reactivation. Because these results contradict what was expected based on the reconsolidation hypothesis, we discuss possible explanations and implications.

Local Geographical Distribution of Acute Involuntary Psychiatric Admissions in Subdistricts In and Around Utrecht, the Netherlands.

BACKGROUND: Acute involuntary psychiatric admissions (AIPA) tend to be applied more often in urban areas. OBJECTIVE: The current study aims to describe AIPA prevalence differences between the subdistricts in an urban area, and to identify which district characteristics are associated with a higher AIPA district density. METHODS: Information was collected on consecutive AIPAs over a 64-month period (2005-2010) in 49 subdistricts in and around the city of Utrecht, the Netherlands, including 1098 AIPAs. District characteristics included several demographic and economical factors and health care characteristics such as number of sheltered living facilities. RESULTS: The AIPA density (mean 4.4/10,000 inhabitants/y) was four to five times higher in the most urbanized subdistrict (around 12) compared to the suburban subdistricts (2.5-3). On the district level, the main correlates with AIPA density per district were unemployment rate and small household size. Other correlates were percentage of non-Western immigrants and number of facilities of sheltered living. CONCLUSIONS: The considerable AIPA density variation between subdistricts in this urban environment reflects that people who are prone to psychiatric admissions live in economically less prosperous environments. Impaired social networks and economic concerns may also contribute to an environment representing social defeat, increased demoralization, or social fragmentation.

Somatic Care with a Psychotic Disorder. Lower Somatic Health Care Utilization of Patients with a Psychotic Disorder Compared to Other Patient Groups and to Controls Without a Psychiatric Diagnosis.

Patients with non-affective psychotic disorders (NAPD) face higher risk of somatic problems and early natural death compared to the general population. Therefore, treatment guidelines for schizophrenia and psychosis stress the importance of monitoring somatic risk factors. This study examined somatic Health Care utilization (HCu) of patients with NAPD compared to non-psychiatric controls and patients with depression, anxiety or bipolar disorders using a large Health Insurance database. Results show lower specialist somatic HCu of patients with NAPD compared to matched controls and also lower percentages for prescribed somatic medication and general practitioner consultations for patients aged ≥60 years and after longer illness duration.

Updated meta-analysis of classical fear conditioning in the anxiety disorders.

The aim of the current study was twofold: (1) to systematically examine differences in fear conditioning between anxiety patients and healthy controls using meta-analytic methods, and (2) to examine the extent to which study characteristics may account for the variability in findings across studies. Forty-four studies (published between 1920 and 2013) with data on 963 anxiety disordered patients and 1,222 control subjects were obtained through PubMed and PsycINFO, as well as from a previous meta-analysis on fear conditioning (Lissek et al.). Results demonstrated robustly increased fear responses to conditioned safety cues (CS-) in anxiety patients compared to controls during acquisition. This effect may represent an impaired ability to inhibit fear in the presence of safety cues (CS-) and/or may signify an increased tendency in anxiety disordered patients to generalize fear responses to safe stimuli resembling the conditioned danger cue (CS+). In contrast, during extinction, patients show stronger fear responses to the CS+ and a trend toward increased discrimination learning (differentiation between the CS+ and CS-) compared to controls, indicating delayed and/or reduced extinction of fear in anxiety patients. Finally, none of the included study characteristics, such as the type of fear measure (subjective vs. psychophysiological index of fear), could account significantly for the variance in effect sizes across studies. Further research is needed to investigate the predictive value of fear extinction on treatment outcome, as extinction processes are thought to underlie the beneficial effects of exposure treatment in anxiety disorders.

Metacognitive appraisal of memory inconsistency for traumatic events in Dutch veterans.

Although memories of traumatic events are often remembered vividly, these memories are subject to change over time. In our previous study, we found that Dutch infantry veterans who had served in Iraq often reported stressful events at a second assessment point that they had not reported during a prior assessment point and vice versa. In the present exploratory study, we recontacted subjects from this previous study and asked how they explained the discrepancy in their memory reports between post-deployment assessment points 1 and 2. Common explanations were: interpreting the item differently, having forgotten the incident initially, repression and having accidentally incorporated someone else's experience into their own memory. Although such reports are not necessarily revelatory of the mechanisms driving discrepancies in memory reports over time, our study illuminates the metacognitive variables involved.

Anger: cause or consequence of posttraumatic stress? A prospective study of Dutch soldiers.

Many studies have shown that individuals with posttraumatic stress disorder (PTSD) experience more anger over time and across situations (i.e., trait anger) than trauma-exposed individuals without PTSD. There is a lack of prospective research, however, that considers anger levels before trauma exposure. The aim of this study was to prospectively assess the relationship between trait anger and PTSD symptoms, with several known risk factors, including baseline symptoms, neuroticism, and stressor severity in the model. Participants were 249 Dutch soldiers tested approximately 2 months before and approximately 2 months and 9 months after their deployment to Afghanistan. Trait anger and PTSD symptom severity were measured at all assessments. Structural equation modeling including cross-lagged effects showed that higher trait anger before deployment predicted higher PTSD symptoms 2 months after deployment (ß = .36), with stressor severity and baseline symptoms in the model, but not with neuroticism in the model. Trait anger at 2 months postdeployment did not predict PTSD symptom severity at 9 months, and PTSD symptom severity 2 months postdeployment did not predict subsequent trait anger scores. Findings suggest that trait anger may be a pretrauma vulnerability factor for PTSD symptoms, but does not add variance beyond the effect of neuroticism.

Blurring of emotional and non-emotional memories by taxing working memory during recall.

Memories that are recalled while working memory (WM) is taxed, e.g., by making eye movements (EM), become blurred during the recall + EM and later recall, without EM. This may help to explain the effects of Eye Movement and Desensitisation and Reprocessing (EMDR) in the treatment of post-traumatic stress disorder (PTSD) in which patients make EM during trauma recall. Earlier experimental studies on recall + EM have focused on emotional memories. WM theory suggests that recall + EM is superior to recall only but is silent about effects of memory emotionality. Based on the emotion and memory literature, we examined whether recall + EM has superior effects in blurring emotional memories relative to neutral memories. Healthy volunteers recalled negative or neutral memories, matched for vividness, while visually tracking a dot that moved horizontally ("recall + EM") or remained stationary ("recall only"). Compared to a pre-test, a post-test (without concentrating on the dot) replicated earlier findings: negative memories are rated as less vivid after "recall + EM" but not after "recall only". This was not found for neutral memories. Emotional memories are more taxing than neutral memories, which may explain the findings. Alternatively, transient arousal induced by recall of aversive memories may promote reconsolidation of the blurred memory image that is provoked by EM.

The generalization of threat beliefs to novel safety stimuli induced by safety behaviors.

Safety behaviors are responses that can reduce or even prevent an expected threat. Moreover, empirical studies have shown that using safety behaviors to a learnt safety stimulus can induce threat beliefs to it. No research so far has examined whether threat beliefs induced this way generalize to other novel stimuli related to the safety stimulus. Using a fear and avoidance conditioning model, the current study (n=116) examined whether threat beliefs induced by safety behaviors generalize to other novel generalization stimuli (GSs). Participants first acquired safety behaviors to a threat predicting conditioned stimulus (CSthreat). Safety behaviors could then be performed in response to one safe stimulus (CSsafeShift) but not to another (CSsafe). In a following generalization test, participants showed a significant but small increase in threat expectancies to GSs related to CSsafeShift compared to GSs related to CSsafe. Interestingly, the degree of safety behaviors used to the CSsafeShift predicted the subsequent increase in generalized threat expectancies, and this link was elevated in trait anxious individuals. The findings suggest that threat beliefs induced by unnecessary safety behaviors generalize to other related stimuli. This study provides a potential explanation for the root of threat belief acquisition to a wide range of stimuli or situations.

Mental threat rehearsal increases fear generalization.

BACKGROUND AND OBJECTIVES: Fear generalization to harmless stimuli characterizes anxiety-related disorders, but much remains unknown about its determinants. Based on studies showing that mental imagery of threat can increase conditioned fear responding, we tested whether it also facilitates fear generalization, and whether threat inflation moderates this effect. METHODS: In a fear conditioning study, 120 participants first completed an acquisition phase, in which one of two pictures was followed by an aversive sound (human scream). Then, the sound was presented 11 times at an increasing (threat inflation) or constant volume (no threat inflation). Finally, a generalization stimulus was presented, and some participants were asked to imagine the last sound (threat rehearsal) and others were not (no threat rehearsal). RESULTS: Bayesian informative hypotheses tests indicated that imagery-based threat rehearsal increased generalization of threat expectancy, and, combined with threat inflation, it also resulted in stronger generalized distress. LIMITATIONS: due to the absence of a test phase, it is unclear whether our effects would transfer to other GSs and whether they would persist beyond the manipulation phase. CONCLUSIONS: Mental imagery of threat may put individuals at risk for fear generalization. Future studies should examine whether modulating imagery may prevent clinical anxiety.

The effectiveness of two novel approaches to prevent intrusions: A pilot study comparing Tetris_dualtask and imagery rescripting to control.

BACKGROUND AND OBJECTIVES: Post-traumatic stress disorder (PTSD) is a global health problem. Although effective treatments for it exist, early interventions that prevent PTSD from developing are lacking. The aim of this pilot analogue trauma study was to compare the effects of two potential early intervention strategies, namely Tetris_dualtask and imagery rescripting (IR) to a no-intervention control group on intrusion frequency and the vividness and emotionality of aversive film memory. METHODS: Sixty healthy students were subjected to the trauma film paradigm and randomly allocated to either: Tetris_dualtask, IR or no-intervention. Main outcomes were the number of film-related intrusions at one week and vividness and emotionality ratings of the most aversive film memory. Secondary outcomes were PTSD-like symptoms, intrusion intensity, and explicit film memory. RESULTS: The Tetris_dualtask group reported significant fewer intrusions compared to the no-intervention group; whereas the IR group did not. No effect was found on vividness and emotionality ratings, PTSD-like symptoms, intrusion intensity, and explicit memory. LIMITATIONS: The sample size was small, and analogue trauma in healthy individuals was examined, thus generalizability may be limited. Also, to increase comparability between interventions, the duration of Tetris_dualtask and IR was standardized. As a result, the IR intervention was shorter compared to other studies, which might have decreased its efficacy. CONCLUSIONS: The results of this pilot study suggest that playing Tetris during retrieval of traumatic images, might hold potential as an early intervention strategy to reduce intrusions in the early aftermath of trauma and adversity. However, future large-scale replication research is needed.

Positive mood induction does not reduce return of fear: A virtual reality exposure study for public speaking anxiety.

Previous laboratory work has shown that induction of positive mood prior to fear extinction decreases the negative valence of the conditional stimulus (CS) and reduces reinstatement of fear. Before translating these insights to clinical practice, it is important to test this strategy in anxious individuals. Students with a high fear of public speaking (N = 62) were randomized to either a positive mood induction, a negative mood induction, or no induction control group. All participants performed two weekly sessions of virtual reality exposure and a 1-week follow-up test including a spontaneous recovery test and reinstatement test after a social rejection (unconditional stimulus). We used self-reported fear measures and skin conductance responses. We expected that the positive group, compared to the other groups, would evaluate the CS (i.e., speaking in front of an audience) as less negative following exposure and would show less spontaneous recovery and reinstatement of fear following a social rejection. Although mood was successfully manipulated, there were no group differences in CS valence following exposure. In all conditions, VR exposure successfully reduced public speaking fear, and these effects were stable at follow-up. In contrast with expectations, the positive group showed more spontaneous recovery of CS negative valence than the negative group. To conclude, we found no evidence that positive mood induction prior to exposure optimizes exposure effects for anxious individuals.

Ironic effects of compulsive perseveration.

Individuals with obsessive-compulsive disorder (OCD) exhibit perseverative behaviours, like checking, to reduce uncertainty, but perseveration paradoxically enhances uncertainty. It is unclear what mechanism might be responsible. We hypothesised that perseverative OC-like behaviour produces "semantic satiation" and interferes with the accessibility of meaning. Healthy participants repeated 20 types of OC-like checking behaviour nonperseveratively (2 times) or perseveratively (20 times). Afterwards, they decided as quickly as possible whether a picture was semantically related to the checked object. The nonperseverative condition showed spreading of activation: Judgements were faster for related than for unrelated objects and pictures. The effect was blocked in the perseverative condition, where reaction times for related and unrelated items were similar. The results suggest that the ironic effects of compulsive perseveration are due to interference with spreading of activation.

On EMDR: eye movements during retrieval reduce subjective vividness and objective memory accessibility during future recall.

In eye movement desensitization and reprocessing (EMDR), a treatment for post-traumatic stress disorder (PTSD), patients make eye movements (EM) during trauma recall. Earlier experimental studies found that EM during recall reduces memory vividness during future recalls, and this was taken as laboratory support for the underlying mechanism of EMDR. However, reduced vividness was assessed with self-reports that may be affected by demand characteristics. We tested whether recall+EM also reduces memory vividness on a behavioural reaction time (RT) task. Undergraduates (N=32) encoded two pictures, recalled them, and rated their vividness. In the EM group, one of the pictures was recalled again while making EM. In the no-EM group one of the pictures was recalled without EM. Then fragments from both the recalled and non-recalled pictures, and new fragments were presented and participants rated whether these were (or were not) seen before. Both pictures were rated again for vividness. In the EM group, self-rated vividness of the recalled+EM picture decreased, relative to the non-recalled picture. In the no-EM group there was no difference between the recalled versus non-recalled picture. The RT task showed the same pattern. Reduction of memory vividness due to recall+EM is also evident from non-self-report data.