EMDR therapy vs. supportive therapy as adjunctive treatment in trauma-exposed bipolar patients: A randomised controlled trial.

INTRODUCTION: Patients with bipolar disorder (BD) are frequently exposed to traumatic events which worsen disease course, but this study is the first multicentre randomised controlled trial to test the efficacy of a trauma-focused adjunctive psychotherapy in reducing BD affective relapse rates. MATERIALS AND METHODS: This multicentre randomised controlled trial included 77 patients with BD and current trauma-related symptoms. Participants were randomised to either 20 sessions of trauma-focused Eye Movement Desensitization and Reprocessing (EMDR) therapy for BD, or 20 sessions of supportive therapy (ST). The primary outcome was relapse rates over 24-months, and secondary outcomes were improvements in affective and trauma symptoms, general functioning, and cognitive impairment, assessed at baseline, post-treatment, and at 12- and 24-month follow-up. The trial was registered prior to starting enrolment in clinical trials (NCT02634372) and carried out in accordance with CONSORT guidelines. RESULTS: There was no significant difference between treatment conditions in terms of relapse rates either with or without hospitalisation. EMDR was significantly superior to ST at the 12-month follow up in terms of reducing depressive symptoms (p=0.0006, d=0.969), manic symptoms (p=0.027, d=0.513), and improving functioning (p=0.038, d=0.486). There was no significant difference in dropout between treatment arms. CONCLUSIONS: Although the primary efficacy criterion was not met in the current study, trauma-focused EMDR was superior to ST in reducing of affective symptoms and improvement of functioning, with benefits maintained at six months following the end of treatment. Both EMDR and ST reduced trauma symptoms as compared to baseline, possibly due to a shared benefit of psychotherapy. Importantly, focusing on traumatic events did not increase relapses or dropouts, suggesting psychological trauma can safely be addressed in a BD population using this protocol.

A meta-analysis of deep brain structural shape and asymmetry abnormalities in 2,833 individuals with schizophrenia compared with 3,929 healthy volunteers via the ENIGMA Consortium.

Schizophrenia is associated with widespread alterations in subcortical brain structure. While analytic methods have enabled more detailed morphometric characterization, findings are often equivocal. In this meta-analysis, we employed the harmonized ENIGMA shape analysis protocols to collaboratively investigate subcortical brain structure shape differences between individuals with schizophrenia and healthy control participants. The study analyzed data from 2,833 individuals with schizophrenia and 3,929 healthy control participants contributed by 21 worldwide research groups participating in the ENIGMA Schizophrenia Working Group. Harmonized shape analysis protocols were applied to each site's data independently for bilateral hippocampus, amygdala, caudate, accumbens, putamen, pallidum, and thalamus obtained from T1-weighted structural MRI scans. Mass univariate meta-analyses revealed more-concave-than-convex shape differences in the hippocampus, amygdala, accumbens, and thalamus in individuals with schizophrenia compared with control participants, more-convex-than-concave shape differences in the putamen and pallidum, and both concave and convex shape differences in the caudate. Patterns of exaggerated asymmetry were observed across the hippocampus, amygdala, and thalamus in individuals with schizophrenia compared to control participants, while diminished asymmetry encompassed ventral striatum and ventral and dorsal thalamus. Our analyses also revealed that higher chlorpromazine dose equivalents and increased positive symptom levels were associated with patterns of contiguous convex shape differences across multiple subcortical structures. Findings from our shape meta-analysis suggest that common neurobiological mechanisms may contribute to gray matter reduction across multiple subcortical regions, thus enhancing our understanding of the nature of network disorganization in schizophrenia.

Treatment of severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and coronavirus disease 2019 (COVID-19): a systematic review of in vitro, in vivo, and clinical trials.

Rationale: Coronavirus disease 2019 (COVID-19) has spread worldwide and poses a threat to humanity. However, no specific therapy has been established for this disease yet. We conducted a systematic review to highlight therapeutic agents that might be effective in treating COVID-19. Methods: We searched Medline, Medrxiv.org, and reference lists of relevant publications to identify articles of in vitro, in vivo, and clinical studies on treatments for severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and COVID-19 published in English until the last update on October 11, 2020. Results: We included 36 studies on SARS, 30 studies on MERS, and 10 meta-analyses on SARS and MERS in this study. Through 12,200 title and 830 full-text screenings for COVID-19, eight in vitro studies, 46 randomized controlled trials (RCTs) on 6,886 patients, and 29 meta-analyses were obtained and investigated. There was no therapeutic agent that consistently resulted in positive outcomes across SARS, MERS, and COVID-19. Remdesivir showed a therapeutic effect for COVID-19 in two RCTs involving the largest number of total participants (n = 1,461). Other therapies that showed an effect in at least two RCTs for COVID-19 were sofosbuvir/daclatasvir (n = 114), colchicine (n = 140), IFN-ß1b (n = 193), and convalescent plasma therapy (n = 126). Conclusions: This review provides information to help establish treatment and research directions for COVID-19 based on currently available evidence. Further RCTs are required.

Consumption of Fish and ω-3 Fatty Acids and Cancer Risk: An Umbrella Review of Meta-Analyses of Observational Studies.

Multiple studies have suggested that ω-3 fatty acid intake may have a protective effect on cancer risk; however, its true association with cancer risk remains controversial. We performed an umbrella review of meta-analyses to summarize and evaluate the evidence for the association between ω-3 fatty acid intake and cancer outcomes. We searched PubMed, Embase, and the Cochrane Database of Systematic Reviews from inception to December 1, 2018. We included meta-analyses of observational studies that examined associations between intake of fish or ω-3 fatty acid and cancer risk (gastrointestinal, liver, breast, gynecologic, prostate, brain, lung, and skin) and determined the level of evidence of associations. In addition, we appraised the quality of the evidence of significant meta-analyses by using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. We initially screened 598 articles, and 15 articles, including 57 meta-analyses, were eligible. Among 57 meta-analyses, 15 reported statistically significant results. We found that 12 meta-analyses showed weak evidence of an association between ω-3 fatty acid intake and risk of the following types of cancer: liver cancer (n = 4 of 6), breast cancer (n = 3 of 14), prostate cancer (n = 3 of 11), and brain tumor (n = 2 of 2). In the other 3 meta-analyses, studies of endometrial cancer and skin cancer, there were no assessable data for determining the evidence levels. No meta-analysis showed convincing, highly suggestive, or suggestive evidence of an association. In the sensitivity analysis of meta-analyses by study design, we found weak associations between ω-3 fatty acid intake and breast cancer risk in cohort studies, but no statistically significant association in case-control studies. However, the opposite results were found in case of brain tumor risk. Although ω-3 fatty acids have been studied in several meta-analyses with regard to a wide range of cancer outcomes, only weak associations were identified in some cancer types, with several limitations. Considering the nonsignificant or weak evidence level, clinicians and researchers should cautiously interpret reported associations between ω-3 fatty acid consumption and cancer risks.

Comparative meta-analyses of brain structural and functional abnormalities during cognitive control in attention-deficit/hyperactivity disorder and autism spectrum disorder.

BACKGROUND: People with attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) have abnormalities in frontal, temporal, parietal and striato-thalamic networks. It is unclear to what extent these abnormalities are distinctive or shared. This comparative meta-analysis aimed to identify the most consistent disorder-differentiating and shared structural and functional abnormalities. METHODS: Systematic literature search was conducted for whole-brain voxel-based morphometry (VBM) and functional magnetic resonance imaging (fMRI) studies of cognitive control comparing people with ASD or ADHD with typically developing controls. Regional gray matter volume (GMV) and fMRI abnormalities during cognitive control were compared in the overall sample and in age-, sex- and IQ-matched subgroups with seed-based d mapping meta-analytic methods. RESULTS: Eighty-six independent VBM (1533 ADHD and 1295 controls; 1445 ASD and 1477 controls) and 60 fMRI datasets (1001 ADHD and 1004 controls; 335 ASD and 353 controls) were identified. The VBM meta-analyses revealed ADHD-differentiating decreased ventromedial orbitofrontal (z = 2.22, p < 0.0001) but ASD-differentiating increased bilateral temporal and right dorsolateral prefrontal GMV (zs ⩾ 1.64, ps ⩽ 0.002). The fMRI meta-analyses of cognitive control revealed ASD-differentiating medial prefrontal underactivation but overactivation in bilateral ventrolateral prefrontal cortices and precuneus (zs ⩾ 1.04, ps ⩽ 0.003). During motor response inhibition specifically, ADHD relative to ASD showed right inferior fronto-striatal underactivation (zs ⩾ 1.14, ps ⩽ 0.003) but shared right anterior insula underactivation. CONCLUSIONS: People with ADHD and ASD have mostly distinct structural abnormalities, with enlarged fronto-temporal GMV in ASD and reduced orbitofrontal GMV in ADHD; and mostly distinct functional abnormalities, which were more pronounced in ASD.

A Multicenter Phase II Rater-Blinded Randomized Controlled Trial to Compare the Effectiveness of Eye Movement Desensitization Reprocessing Therapy vs. Treatment as Usual in Patients With Substance Use Disorder and History of Psychological Trauma: A Study Design and Protocol.

Background: Psychological trauma has a strong negative impact on the onset, course and prognosis of substance use disorders (SUD). Few trauma-oriented treatment approaches have been trialed, but preliminary evidence exists of the efficacy of Eye Movement Desensitization and Reprocessing (EMDR) therapy in improving clinical symptoms in SUD patients. Objective: To assess if EMDR therapy leads to: (1) reduced substance consumption; (2) an improvement in psychopathological and in trauma-related symptoms; and (3) an improvement in overall functioning. Our hypothesis is that the EMDR group will improve in all variables when compared to the treatment as usual (TAU) group at 6 and 12-months visits. Method: In this multicenter phase II rater-blinded randomized controlled trial, 142 SUD patients with a history of psychological trauma will be randomly assigned to EMDR (n = 71) or to TAU (n = 71). Patients in the EMDR group will receive 20 psychotherapeutic sessions of 60 min over 6 months. Substance use will be measured using the Timeline Followback Questionnaire, the Dependence Severity Scale and the Visual Analog Scale. Traumatic events will be measured by The Holmes-Rahe Life Stress Inventory, the Childhood Trauma Questionnaire Scale, the Global Assessment of Posttraumatic Stress Questionnaire, the Impact of Event Scale-Revised and the Dissociative Experiences Scale. Clinical symptomatology will be evaluated using the Hamilton Depression Rating Scale, the Young Mania Rating Scale and the Brief Psychiatric Rating Scale. Functionality will be assessed with the Functioning Assessment Short Test. All variables will be measured at baseline, post-treatment and 12 months as follow-up. Primary outcome: to test the efficacy of EMDR therapy in reducing the severity of substance use. The secondary outcomes: to test the efficacy in reducing trauma-related psychological symptoms and psychopathological symptoms and in improving overall functioning in patients with comorbid SUD and a history of psychological trauma. Conclusion: This study will provide evidence of whether EMDR therapy is effective in reducing addiction-related, trauma and clinical symptoms and in improving functionality in patients with SUD and a history of trauma. Clinical Trial Registration: The trial is registered at ClinicalTrials.gov, identifier: NCT03517592.

A Multicenter Phase II RCT to Compare the Effectiveness of EMDR Versus TAU in Patients With a First-Episode Psychosis and Psychological Trauma: A Protocol Design.

Background: Patients with a first episode psychosis (FEP) who are admitted for the first time to a psychiatric hospital frequently have experienced prior psychological trauma. Additionally, 40-80% develop posttraumatic stress symptoms, which are summarized as a post-psychotic post-traumatic syndrome (PPS). Eye Movement Desensitization and reprocessing (EMDR) therapy could be an effective psychotherapy to treat a PPS and prior psychological traumas in this population. Objectives: To assess if EMDR therapy leads to: 1) a reduction of relapses after intervention, 2) an improvement of trauma-related, psychotic and affective symptoms, 3) an improvement of overall functioning, and 4) an improvement in quality of life. Methods: This is a multicenter phase II rater-blinded randomized controlled trial in which 80 FEP patients with a history of psychological trauma will be randomly assigned to EMDR (n = 40) or to TAU (n = 40). Traumatic events will be measured by the Global Assessment of Posttraumatic Stress Questionnaire, the Cumulative Trauma Screening, the Impact of Event Scale-Revised, the Dissociative Experiences Scale, the Childhood Trauma Scale, the Holmes-Rahe Life Stress Inventory, and the Dissociative Experiences Questionnaire. Clinical symptomatology will be evaluated using the Suicide and Drug Consumption module of the International Neuropsychiatric Interview, Structured Clinical Interview for Positive and Negative Syndrome Scale, Young's Scale for Mania Evaluation, and Beck Depression II Questionnaire. Functionality will be assessed with the Global Assessment of Functioning and the Quality of Life with the Standardized Instrument developed by the EuroQol Group. The cognitive insight and adherence to the treatment will be assessed with the Beck Cognitive Insight Scale and the Drug Attitude Inventory. All variables will be measured at baseline, post-treatment and at 12-month follow-up. Conclusion: This study will provide evidence of whether EMDR therapy is effective in reducing trauma and clinical symptoms, reducing relapses and in improving functionality and quality of life in patients with FEP and a history of trauma. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT03991377.

Neural Correlates of Success and Failure Signals During Neurofeedback Learning.

Feedback-driven learning, observed across phylogeny and of clear adaptive value, is frequently operationalized in simple operant conditioning paradigms, but it can be much more complex, driven by abstract representations of success and failure. This study investigates the neural processes involved in processing success and failure during feedback learning, which are not well understood. Data analyzed were acquired during a multisession neurofeedback experiment in which ten participants were presented with, and instructed to modulate, the activity of their orbitofrontal cortex with the aim of decreasing their anxiety. We assessed the regional blood-oxygenation-level-dependent response to the individualized neurofeedback signals of success and failure across twelve functional runs acquired in two different magnetic resonance sessions in each of ten individuals. Neurofeedback signals of failure correlated early during learning with deactivation in the precuneus/posterior cingulate and neurofeedback signals of success correlated later during learning with deactivation in the medial prefrontal/anterior cingulate cortex. The intensity of the latter deactivations predicted the efficacy of the neurofeedback intervention in the reduction of anxiety. These findings indicate a role for regulation of the default mode network during feedback learning, and suggest a higher sensitivity to signals of failure during the early feedback learning and to signals of success subsequently.

Efficacy of Eye Movement Desensitization and Reprocessing in Children and Adolescent with Post-traumatic Stress Disorder: A Meta-Analysis of Randomized Controlled Trials.

Background: Post-traumatic stress disorder (PTSD) can occur in both adults and children/adolescents. Untreated PTSD can lead to negative long-term mental health conditions such as depression, anxiety, low self-concept, disruptive behaviors, and/or substance use disorders. To prevent these adverse effects, treatment of PTSD is essential, especially in young population due to their greater vulnerability. The principal aim of this meta-analysis was to examine the efficacy of eye movement desensitization and reprocessing (EMDR) therapy for PTSD symptoms in children and adolescents. Secondary objectives were to assess whether EMDR therapy was effective to improve depressive or anxious comorbid symptoms. Methods: We conducted a thorough systematic search of studies published until January 2017, using PubMed, Medline, Scopus, and ScienceDirect as databases. All randomized controlled trials with an EMDR group condition compared to a control group, such as treatment as usual or another psychological treatment, were included. Meta-analysis was conducted with MetaNSUE to avoid biases related to missing information. Results: Eight studies (n = 295) met our inclusion criteria. EMDR therapy was superior to waitlist/placebo conditions and showed comparable efficacy to cognitive behavior therapy (CBT) in reducing post-traumatic and anxiety symptoms. A similar but non-statistically significant trend was observed for depressive symptoms. Exploratory subgroup analyses showed that effects might be smaller in studies that included more males and in more recent studies. Conclusion: Despite the small number of publications, the obtained results suggest that EMDR therapy could be a promising psychotherapeutic approach for the treatment of PTSD and comorbid symptoms in young individuals. However, further research with larger samples is needed to confirm these preliminary results as well as to analyze differences in the efficacy of EMDR therapy versus CBT.

Eye movement desensitization and reprocessing therapy versus supportive therapy in affective relapse prevention in bipolar patients with a history of trauma: study protocol for a randomized controlled trial.

BACKGROUND: Up to 60% of patients with bipolar disorder (BD) have a history of traumatic events, which is associated with greater episode severity, higher risk of comorbidity and higher relapse rates. Trauma-focused treatment strategies for BD are thus necessary but studies are currently scarce. The aim of this study is to examine whether Eye Movement Desensitization and Reprocessing (EMDR) therapy focusing on adherence, insight, de-idealisation of manic symptoms, prodromal symptoms and mood stabilization can reduce episode severity and relapse rates and increase cognitive performance and functioning in patients with BD. METHODS/DESIGN: This is a single-blind, randomized controlled, multicentre trial in which 82 patients with BD and a history of traumatic events will be recruited and randomly allocated to one of two treatment arms: EMDR therapy or supportive therapy. Patients in both groups will receive 20 psychotherapeutic sessions, 60 min each, during 6 months. The primary outcome is a reduction of affective episodes after 12 and 24 months in favour of the EMDR group. As secondary outcome we postulate a greater reduction in affective symptoms in the EMDR group (as measured by the Bipolar Depression Rating Scale, the Young Mania Rating Scale and the Clinical Global Impression Scale modified for BD), and a better performance in cognitive state, social cognition and functioning (as measured by the Screen for Cognitive Impairment in Psychiatry, The Mayer-Salovey-Caruso Emotional Intelligence Test and the Functioning Assessment Short Test, respectively). Traumatic events will be evaluated by The Holmes-Rahe Life Stress Inventory, the Clinician-administered PTSD Scale and the Impact of Event Scale. DISCUSSION: The results of this study will provide evidence whether a specific EMDR protocol for patients with BD is effective in reducing affective episodes, affective symptoms and functional, cognitive and trauma symptoms. TRIAL REGISTRATION: The trial is registered at ClinicalTrials.gov, identifier: NCT02634372 . Registered on 3 December 2015.

Midline Brain Abnormalities Across Psychotic and Mood Disorders.

Patients with schizophrenia are known to have increased prevalence of abnormalities in midline brain structures, such as a failure of the septum pellucidum to fuse (cavum septum pellucidum) and the absence of the adhesio interthalamica. This is the first study to investigate the prevalence of these abnormalities across a large multidiagnostic sample. Presence of cavum septum pellucidum and absence of the adhesio interthalamica was assessed in 639 patients with chronic schizophrenia, delusional disorder, schizoaffective disorder, bipolar disorder, major depressive disorder, or a first episode of psychosis, mania or unipolar depression. This was compared with 223 healthy controls using logistic-regression-derived odds ratios (OR). Patients with psychotic or mood disorders showed an increased prevalence of both abnormalities (OR of cavum septum pellucidum = 2.1, OR of absence of the adhesio interthalamica = 2.6, OR of both cavum septum pellucidum and absence of the adhesio interthalamica = 3.8, all P < .001). This increased prevalence was separately observed in nearly all disorders as well as after controlling for potential confounding factors. This study supports a general increased prevalence of midline brain abnormalities across mood and psychotic disorders. This nonspecificity may suggest that these disorders share a common neurodevelopmental etiology.

Eye movement desensitization and reprocessing therapy in subsyndromal bipolar patients with a history of traumatic events: a randomized, controlled pilot-study.

Traumatic events are frequent in bipolar patients and can worsen the course of the disease. Psychotherapeutic interventions for these events have not been studied so far. Twenty DSM-IV bipolar I and II patients with subsyndromal mood symptoms and a history of traumatic events were randomly assigned to Eye Movement Desensitization and Reprocessing therapy (n=10) or treatment as usual (n=10). The treatment group received between 14 and 18 Eye Movement Desensitization and Reprocessing sessions during 12 weeks. Evaluations of affective symptoms, symptoms of trauma and trauma impact were carried out by a blind rater at baseline, 2 weeks, 5 weeks, 8 weeks, 12 weeks and at 24 weeks follow-up. Patients in the treatment group showed a statistically significant improvement in depressive and hypomanic symptoms, symptoms of trauma and trauma impact compared to the treatment as usual group after intervention. This effect was only partly maintained in trauma impact at the 24 weeks follow-up visit. One patient dropped from Eye Movement Desensitization and Reprocessing group whereas four from the treatment as usual group. This pilot study suggests that Eye Movement Desensitization and Reprocessing therapy may be an effective and safe intervention to treat subsyndromal mood and trauma symptoms in traumatized bipolar patients.