There is no comprehensive meta-analysis of randomised trials examining the effects of Eye Movement Desensitization and Reprocessing (EMDR) on post-traumatic stress disorder (PTSD) and no systematic ...review at all of the effects of EMDR on other mental health problems. We conducted a systematic review and meta-analysis of 76 trials. Most trials examined the effects on PTSD (62%). The effect size of EMDR compared to control conditions was g = 0.93 (95% CI: 0.67-.18), with high heterogeneity (I
2
= 72%). Only four of 27 studies had low risk of bias, and there were indications for publication bias. EMDR was more effective than other therapies (g = 0.36; 95% CI: 0.14-0.57), but not in studies with low risk of bias. Significant results were also found for EMDR in phobias and test anxiety, but the number of studies was small and risk of bias was high. EMDR was examined in several other mental health problems, but for none of these problems, sufficient studies were available to pool outcomes. EMDR may be effective in the treatment of PTSD in the short term, but the quality of studies is too low to draw definite conclusions. There is not enough evidence to advise it for the use in other mental health problems.
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BFBNIB, DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
In Eye Movement Desensitization and Reprocessing a patient recalls a traumatic memory, while simultaneously performing a dual-task (e.g., making horizontal eye movements, tapping a pattern). Earlier ...lab studies show that increasing the load of a dual-task -and leaving fewer resources for memory recall-results in larger decreases in memory vividness and emotionality compared to control conditions. Therefore, we investigated whether it is necessary to continuously and deliberately recall the memory next to performing high taxing dual-tasks. In two online experiments, participants (N = 172, N = 198) recalled a negative autobiographical memory and were randomly assigned to (1) Memory Recall + Dual-Tasks, (2) Dual-Tasks Only, or (3) No Intervention Control. The dual-tasks were complex pattern tapping and spelling out loud. Before and after the intervention the memory was rated on vividness, emotionality, and accessibility. High taxing dual-tasks, regardless of whether there was continuous memory recall, resulted in the largest reductions in all dependent variables compared to control. Unexpectedly, there was no evidence that the addition of continuous memory recall added to these reductions. These results suggest that continuous memory recall might not, or only minimally needed for the beneficial effects of the dual-task procedure. We discuss the necessity of memory (re)activation, alternative explanations, and implications for practice.
•The necessity of continuous recall in an online dual-task procedure was investigated.•Performing high taxing dual-tasks decreased memory vividness and emotionality.•Adding continuous memory recall to a dual-task did not increase effectiveness.•High taxing dual-task procedures are effective in an online setting.•An exact replication study replicated these results.
IMPORTANCE: Cognitive behavioral therapy is recommended for anxiety-related disorders, but evidence for its long-term outcome is limited. OBJECTIVE: This systematic review and meta-analysis aimed to ...assess the long-term outcomes after cognitive behavioral therapy (compared with care as usual, relaxation, psychoeducation, pill placebo, supportive therapy, or waiting list) for anxiety disorders, posttraumatic stress disorder (PTSD), and obsessive-compulsive disorder (OCD). DATA SOURCES: English-language publications were identified from PubMed, PsycINFO, Embase, Cochrane, OpenGrey (1980 to January 2019), and recent reviews. The search strategy included a combination of terms associated with anxiety disorders (eg, panic or phobi*) and study design (eg, clinical trial or randomized controlled trial). STUDY SELECTION: Randomized clinical trials on posttreatment and at least 1-month follow-up effects of cognitive behavioral therapy compared with control conditions among adults with generalized anxiety disorder, panic disorder with or without agoraphobia, social anxiety disorder, specific phobia, PTSD, or OCD. DATA EXTRACTION AND SYNTHESIS: Researchers independently screened records, extracted statistics, and assessed study quality. Data were pooled using a random-effects model. MAIN OUTCOMES AND MEASURES: Hedges g was calculated for anxiety symptoms immediately after treatment and at 1 to 6 months, 6 to 12 months, and more than 12 months after treatment completion. RESULTS: Of 69 randomized clinical trials (4118 outpatients) that were mainly of low quality, cognitive behavioral therapy compared with control conditions was associated with improved outcomes after treatment completion and at 1 to 6 months and at 6 to 12 months of follow-up for a generalized anxiety disorder (Hedges g, 0.07-0.40), panic disorder with or without agoraphobia (Hedges g, 0.22-0.35), social anxiety disorder (Hedges g, 0.34-0.60), specific phobia (Hedges g, 0.49-0.72), PTSD (Hedges g, 0.59-0.72), and OCD (Hedges g, 0.70-0.85). After 12-month follow-up, these associations were still significant for generalized anxiety disorder (Hedges g, 0.22; number of studies k = 10), social anxiety disorder (Hedges g, 0.42; k = 3), and PTSD (Hedges g, 0.84; k = 5), but not for panic disorder with or without agoraphobia (k = 5) and could not be calculated for specific phobia (k = 1) and OCD (k = 0). Relapse rates after 3 to 12 months were 0% to 14% but were reported in only 6 randomized clinical trials (predominantly for panic disorder with or without agoraphobia). CONCLUSIONS AND RELEVANCE: The findings of this meta-analysis suggest that cognitive behavioral therapy for anxiety-related disorders is associated with improved outcomes compared with control conditions until 12 months after treatment completion. After 12 months, effects were small to medium for generalized anxiety disorder and social anxiety disorder, large for PTSD, and not significant or not available for other disorders. High-quality randomized clinical trials with more than 12 months of follow-up and reported relapse rates are needed.
Patients with post-traumatic stress disorder frequently and involuntarily experience intrusions, which are strongly linked to the trauma hotspot. Voluntary memory characteristics (i.e., vividness and ...unpleasantness) of this hotspot can be reduced by performing a dual-task, such as making horizontal eye movements, which is frequently used in Eye Movement Desensitization and Reprocessing. We tested whether such dual-task interventions would also reduce involuntary memory (i.e., intrusions). Moreover, we examined if changes in hotspot vividness and unpleasantness predicted intrusion frequency. Additionally, we examined whether the effects were dependent on dual-task modality. We tested this in three experiments. Participants watched a trauma film and performed one of the interventions 10-min post-film (1) Recall + Eye movements, (2) Recall + Counting, or (3) No-Task Control. Before and after the intervention, participants rated the hotspot vividness and unpleasantness. They recorded intrusive memories about the film in a diary for a week. Unexpectedly, we found that hotspot vividness and unpleasantness ratings were not affected by the intervention. However, the prolonged (experiment 2), but not standard (experiment 1), dual-task interventions resulted in a lower number of intrusions, regardless of modality. However, this effect was not replicated in experiment 3. We discuss potential explanations and present suggestions for future research.
•Dual-tasks did not reduce vividness/unpleasantness of voluntary memories.•Prolonged dual-tasks, regardless of modality, reduced involuntary intrusions.•This effect on involuntary intrusions was not replicated in experiment 3.•Vividness/unpleasantness of voluntary memories was not related to intrusions.
For large segments of the population in the US--people covered by the marketplaces created by the Affordable Care Act (2010) and those covered by private plans in Medicare and Medicaid--mental health ...care is financed through private health insurance markets. Integration of mental health care within private health insurance has never been entirely comfortable. A universal challenge is to prevent skimping on quality of care and mitigate incentives for insurers not to enroll and serve persons with mental illness. Here, McGuire et al summarizes the evolving policies applied in The Netherlands to counteract such incentives and draws possible lessons for insurer payment policies in the US with respect to mental health care.
The nuclear receptor subfamily 1 group H member 4 (NR1H4, also called FXR) is a ligand-activated transcription factor that, upon binding of bile acids, regulates the expression of genes involved in ...bile acid, fat, sugar, and amino acid metabolism. Transcript variants encode the FXR isoforms alpha 1, alpha 2, alpha 3, and alpha 4, which activate different genes that regulate metabolism. Little is known about the mechanisms by which the different isoforms regulate specific genes or how the expression of these genes affects the outcomes of patients given drugs that target FXR.
We determined genome-wide binding of FXR isoforms in mouse liver organoids that express individual FXR isoforms using chromatin immunoprecipitation, followed by sequencing analysis and DNA motif discovery. We validated regulatory DNA sequences by mobility shift assays and with luciferase reporters using mouse and human FXR isoforms. We analyzed mouse liver organoids and HepG2 cells that expressed the FXR isoforms using chromatin immunoprecipitation, quantitative polymerase chain reaction, and immunoblot assays. Organoids were analyzed for mitochondrial respiration, lipid droplet content, and triglyceride excretion. We used the FXR ligand obeticholic acid to induce FXR activity in organoids, cell lines, and mice. We collected data on the binding of FXR in mouse liver and the expression levels of FXR isoforms and gene targets in human liver tissue and primary human hepatocytes from the Gene Expression Omnibus.
In mouse liver cells, 89% of sites that bound FXR were bound by only FXRα2 or FXRα4, via direct interactions with the DNA sequence motif ER-2. Via DNA binding, these isoforms regulated metabolic functions in liver cells, including carbon metabolism and lipogenesis. Incubation with obeticholic acid increased mitochondrial pyruvate transport and reduced insulin-induced lipogenesis in organoids that expressed FXRα2 but not FXRα1. In human liver tissues, levels of FXRα2 varied significantly and correlated with expression of genes predicted to be regulated via an ER-2 motif.
Most metabolic effects regulated by FXR in mouse and human liver cells are regulated by the FXRα2 isoform via specific binding to ER-2 motifs. The expression level of FXRα2 in liver might be used to predict responses of patients to treatment with FXR agonists.
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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.
•VR exposure reduced public speaking fear one week later.•Positive mood induction before exposure did not change CS valence after exposure.•Positive mood led to more CS negative valence one week later than negative mood.•CS valence after exposure did not predict return of fear.
A recent, large randomized controlled trial employing different forms of eye (non-)movements in eye movement desensitization and reprocessing (EMDR) showed that fixating the eyes either on a ...therapist's moving or non-moving hand led to equal reductions in symptoms of post-traumatic stress disorder (PTSD). However, numerous EMDR lab analogue studies found that eye movements produce larger memory effects than eyes stationary. These beneficial effects are typically explained by differences in working memory (WM) taxation. We tested the degree of WM taxation of several eye (non-)movement conditions used in the clinical trial.
All participants (N = 40) performed: (1) eyes moving by following the experimenter's moving finger, (2) eyes fixed on the experimenter's stationary finger, (3) eyes closed, or (4) looking unfocused into the room. Simultaneously they performed a simple reaction time task. Reaction times are an objective index of the extent to which different dual attention tasks tax WM.
Eyes moving is more taxing than eyes fixed, while eyes fixed did not differ from eyes unfocused. All conditions were more taxing than eyes closed.
We studied WM taxation in a laboratory setting; no clinical interventions were applied.
In line with previous lab studies, making eye movements was more taxing than eyes fixed. We discuss why this effect was not observed for reductions in PTSD symptoms in the clinical trial (e.g., differences in dependent variables, sample population, and intervention duration). For more comprehensive future insights, we recommend integration of mechanistically focused lab analogue studies and patient-oriented clinical studies.
•Eye (non-)movement conditions differentially tax working memory (WM)•EMDR clinical and lab studies show conflicting evidence about these conditions•This study shows that eyes moving is more taxing than eyes fixed•Keeping the eyes fixed or unfocused does not result in differences in WM taxation•The current results are in line with EMDR lab analogue studies
The Farnesoid X receptor (FXR) is a nuclear receptor which is activated by bile acids. Bile acids function in solubilization of dietary fats and vitamins in the intestine. In addition, bile acids ...have been increasingly recognized to act as signaling molecules involved in energy metabolism pathways, amongst others
activating FXR. Upon activation by bile acids, FXR controls the expression of many genes involved in bile acid, lipid, glucose and amino acid metabolism. An inability to properly use and store energy substrates may predispose to metabolic disorders, such as obesity, diabetes, cholestasis and non-alcoholic fatty liver disease. These diseases arise through a complex interplay between genetics, environment and nutrition. Due to its function in metabolism, FXR is an attractive treatment target for these disorders. The regulation of FXR expression and activity occurs both at the transcriptional and at the post-transcriptional level. It has been shown that FXR can be phosphorylated, SUMOylated and acetylated, amongst other modifications, and that these modifications have functional consequences for DNA and ligand binding, heterodimerization and subcellular localization of FXR. In addition, these post-translational modifications may selectively increase or decrease transcription of certain target genes. In this review, we provide an overview of the posttranslational modifications of FXR and discuss their potential involvement in cholestatic and metabolic disorders.
A plethora of eye movement desensitization and reprocessing (EMDR) analogue studies has shown that, in the short term, making eye movements (EM) during brief imaginal exposure (“recall + EM”) blurs ...memories more than just imaginal exposure (“recall only”). Yet, results of the few studies that included a follow-up test are inconsistent. We improved this paradigm's ecological validity by including an extended intervention phase and multiple assessments per phase. We hypothesized that recall + EM results in larger immediate and 24 h reductions in memory vividness, negative valence, and distress than recall alone. We explored the persistence of the effects, as well as the predictive value of memory characteristics and individual differences.
Students (N = 100) selected a negative autobiographical memory and were randomized to recall + EM or recall alone; both interventions lasted 32 intervals of 24s. During the interventions they rated the memory after every four intervals.
After 4 × 24s intervention, recall + EM resulted in memory deflation, while recall only caused memory inflation. After the full intervention (i.e., 32 × 24s), both conditions resulted in immediate and 24 h reductions on all outcome measures. Crucially, memory effects in the recall + EM condition partially relapsed 24 h later, while the effects in the recall only condition persisted. Change patterns were hardly explained by predictive variables.
We used a non-clinical sample; replication in clinical samples is warranted.
Making EM during imaginal exposure leads to short-lived effects compared to imaginal exposure alone. However, EM may offer a response aid for those who avoid imaginal exposure.
•At intervention start, making EM during imaginal exposure prevents memory inflation.•Imaginal exposure with or without EM causes immediate and 24 h memory deflation.•Imaginal exposure + EM leads to short-lived effects compared to imaginal exposure.•Change patterns were hardly explained by predictive variables.
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