Prediction of treatment response to antipsychotic drugs for precision medicine approach to schizophrenia:randomized trials and multiomics analysis

Background:Choosing the appropriate antipsychotic drug(APD)treatment for patients with schizophrenia(SCZ)can be challenging,as the treatment response to APD is highly variable and difficult to predict due to the lack of effective biomarkers.Previous studies have indicated the association between treatment response and genetic and epigenetic factors,but no effective biomarkers have been identified.Hence,further research is imperative to enhance precision medicine in SCZ treatment.Methods:Participants with SCZ were recruited from two randomized trials.The discovery cohort was recruited from the CAPOC trial(n=2307)involved 6 weeks of treatment and equally randomized the participants to the Olanzapine,Risperidone,Quetiapine,Aripiprazole,Ziprasidone,and Haloperidol/Perphenazine(subsequently equally assigned to one or the other)groups.The external validation cohort was recruited from the CAPEC trial(n=1379),which involved 8 weeks of treatment and equally randomized the participants to the Olanzapine,Risperidone,and Aripiprazole groups.Additionally,healthy controls(n=275)from the local community were utilized as a genetic/epigenetic reference.The genetic and epigenetic(DNA methylation)risks of SCZ were assessed using the polygenic risk score(PRS)and polymethylation score,respectively.The study also examined the genetic-epigenetic interactions with treatment response through differential methylation analysis,methylation quantitative trait loci,colocalization,and promoteranchored chromatin interaction.Machine learning was used to develop a prediction model for treatment response,which was evaluated for accuracy and clinical benefit using the area under curve(AUC)for classification,R^(2) for regression,and decision curve analysis.Results:Six risk genes for SCZ(LINC01795,DDHD2,SBNO1,KCNG2,SEMA7A,and RUFY1)involved in cortical morphology were identified as having a genetic-epigenetic interaction associated with treatment response.The developed and externally validated prediction model,which incorporated clinical information,PRS,genetic risk score(GRS),and proxy methylation level(proxyDNAm),demonstrated positive benefits for a wide range of patients receiving different APDs,regardless of sex[discovery cohort:AUC=0.874(95%CI 0.867-0.881),R^(2)=0.478;external validation cohort:AUC=0.851(95%CI 0.841-0.861),R^(2)=0.507].Conclusions:This study presents a promising precision medicine approach to evaluate treatment response,which has the potential to aid clinicians in making informed decisions about APD treatment for patients with SCZ.Trial registration Chinese Clinical Trial Registry(https://www.chictr.org.cn/),18 Aug 2009 retrospectively registered:CAPOC-ChiCTR-RNC-09000521(https://www.chictr.org.cn/showproj.aspx?proj=9014),CAPEC-ChiCTRRNC-09000522(https://www.chictr.org.cn/showproj.aspx?proj=9013).

Social relationship satisfaction and accumulation of chronic conditions and multimorbidity:a national cohort of Australian women

Background Social relationships are associated with mortality and chronic conditions.However,little is known about the effects of social relationship satisfaction on multiple chronic conditions(multimorbidity).Aims To examine whether social relationship satisfaction is associated with the accumulation of multimorbidity.Methods Data from 7694 Australian women who were free from 11 chronic conditions at 45–50 years of age in 1996 were analysed.Five types of social relationship satisfaction(partner,family members,friends,work and social activities)were measured approximately every 3 years and scored from 0(very dissatisfied)to 3(very satisfied).Scores from each relationship type were summed to provide an overall satisfaction score(range:≤5–15).The outcome of interest was the accumulation of multimorbidity in 11 chronic conditions.Results Over a 20-year period,4484(58.3%)women reported multimorbidities.Overall,the level of social relationship satisfaction had a dose–response relationship with the accumulation of multimorbidities.Compared with women reporting the highest satisfaction(score 15),women with the lowest satisfaction(score≤5)had the highest odds of accumulating multimorbidity(odds ratio(OR)=2.35,95%confidence interval(CI):1.94 to 2.83)in the adjusted model.Similar results were observed for each social relationship type.Other risk factors,such as socioeconomic,behavioural and menopausal status,together explained 22.72%of the association.Conclusions Social relationship satisfaction is associated with the accumulation of multimorbidity,and the relationship is only partly explained by socioeconomic,behavioural and reproductive factors.Social connections(eg,satisfaction with social relationships)should be considered a public health priority in chronic disease prevention and intervention.

Fragile X Messenger Ribonucleoprotein 1(FMR1), a novel inhibitor of osteoblast/osteocyte differentiation, regulates bone formation, mass, and strength in young and aged male and female mice

Fragile X Messenger Ribonucleoprotein 1(FMR1)gene mutations lead to fragile X syndrome,cognitive disorders,and,in some individuals,scoliosis and craniofacial abnormalities.Four-month-old(mo)male mice with deletion of the FMR1 gene exhibit a mild increase in cortical and cancellous femoral bone mass.However,consequences of absence of FMR1 in bone of young/aged male/female mice and the cellular basis of the skeletal phenotype remain unknown.We found that absence of FMR1 results in improved bone properties with higher bone mineral density in both sexes and in 2-and 9-mo mice.The cancellous bone mass is higher only in females,whereas,cortical bone mass is higher in 2-and 9-mo males,but higher in 2-and lower in 9-mo female FMR1-knockout mice.Furthermore,male bones show higher biomechanical properties at 2mo,and females at both ages.Absence of FMR1 increases osteoblast/mineralization/bone formation and osteocyte dendricity/gene expression in vivo/ex vivo/in vitro,without affecting osteoclasts in vivo/ex vivo.Thus,FMR1 is a novel osteoblast/osteocyte differentiation inhibitor,and its absence leads to age-,site-and sex-dependent higher bone mass/strength.

Use of an immunocapture device to detect cytokine release in discrete brain regions

Production of proinflammatory cytokines in the central nervous system is a key process in the neuroinflammatory response to trauma,infection,and neurodegenerative diseases(Kumar,2019).These intercellular signaling molecules play multiple roles in the immune response in the central nervous system including the orchestration of the sickness response to innate immune perturbations in the brain(Dantzer et al.,2008).

Sleep-based neuronal oscillations as a physiological biomarker for Alzheimer's disease:is night time the right time?

Dementia is a devastating syndrome characterized by memory problems,confusion,and behavior changes that prevent people from performing everyday activities.It is the leading cause of dependency and disability amongst older people,resulting in a global economic cost of ~$1.3 trillion.Around 58 million people are currently afflicted by dementia worldwide,with Alzheimer s disease(AD) causing most(60-70%) of these cases.

Insight into endoplasmic reticulum-mitochondria contacts in human amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis(ALS) is a fastprogressing fatal neurodegenerative disease and the most common form of motor neuron disease.There is currently no cure and approximately 90% of cases are sporadic.ALS shares genetic causes,clinical and neuropathological features with frontotemporal dementia,the second most common form of presenile dementia.ALS and frontotemporal dementia are therefore considered a disease spectrum(Abramzon et al.,2020).

Assessing the quality of studies in meta-analyses: Advantages and limitations of the Newcastle Ottawa Scale

One of the most important points in the meta-analyses is certainly represented by the assessment of the quality of the studies included in such research. The meta-analyses are considered the highest level of evidence in science. Also for this reason, the quality of the studies included should be accurately evaluated by standardized tools. The overall results of the metaanalysis depend indeed also on a rigorous evaluation of the studies quality. Among all the possible tools for this complex evaluation, the Newcastle Ottawa Scale(NOS) is one of the most used worldwide, above all for observational studies. In this review, we will discuss the strengths and limitation of the NOS, also on the basis of the branch of science in which it has been applied.

Voxel-based magnetic resonance imaging investigation of poor and preserved clinical insight in people with schizophrenia

AIM To define regional grey-matter abnormalities in schizophrenia patients with poor insight(Insight-),relative to patients with preserved clinical insight(Insight+),and healthy controls.METHODS Forty stable schizophrenia outpatients(20 Insight-and 20 Insight+) and 20 healthy controls underwent whole brain magnetic resonance imaging(MRI).Insight in all patients was assessed using the Birchwood Insight Scale(BIS;a self-report measure).The two patient groups were preselected to match on most clinical and demographic parameters but,by design,they had markedly distinct BIS scores.Voxel-based morphometry employed in SPM8 was used to examine group differences in grey matter volumes across the whole brain.RESULTS The three participant groups were comparable in age [F(2,57) = 0.34,P = 0.71] and the patient groups did not differ in age at illness onset [t(38) = 0.87,P = 0.39].Insight-and Insight+ patient groups also did not differ in symptoms on the Positive and Negative Syndromes scale(PANSS):Positive symptoms [t(38) = 0.58,P = 0.57],negative symptoms [t(38) = 0.61,P = 0.55],general psychopathology [t(38) = 1.30,P = 0.20] and total PANSS scores [t(38) = 0.21,P = 0.84].The two patient groups,as expected,varied significantly in the level of BIS-assessed insight [t(38) = 12.11,P < 0.001].MRI results revealed lower fronto-temporal,parahippocampal,occipital and cerebellar grey matter volumes in Insightpatients,relative to Insight+ patients and healthy controls(for all clusters,family-wise error corrected P < 0.05).Insight+ patient and healthy controls did not differ significantly(P > 0.20) from each other.CONCLUSION Our findings demonstrate a clear association between poor clinical insight and smaller fronto-temporal,occipital and cerebellar grey matter volumes in stable long-term schizophrenia patients.

Reasoning and Rehabilitation cognitive skills programme for mentally disordered offenders: Predictors of outcome

AIM To investigate factors predicting treatment completion and treatment outcome of the Reasoning and Rehabilitation Mental Health Programme(R&R2MHP) cognitive skills programme for mentally disordered offenders. METHODS Secondary analysis of data previously obtained from 97 male patients who were sectioned and detained under the United Kingdom Mental Health Act in low, medium and high security hospitals and who had completed R&R2MHP. Predictors of treatment completion included background variables and five outcome measures: Four self-reported measures of violent attitudes, social problem-solving skills, reactive anger and locus of control and an objective measure of behaviour on theward that was completed by staff. Completion of the 16 session programme, which was delivered on a weekly basis, was classified as ≥ 12 sessions.RESULTS It was found that the R&R2MHP is appropriate for delivery to participants of different ages, ethnic background, and at different levels of security without the completion rate or treatment effectiveness being compromised. Participants taking oral typical psychotropic medication were over seven times more likely to complete the programme than other participants. Behavioural disturbance on the ward prior to commencing the programme predicted non-completion(medium effect size). As far as treatment completion was concerned, none of the background factors predicted treatment effectiveness(age, ethnic background, level of security, number of previous convictions and number of previous hospital admissions). The best predictor of treatment effectiveness was attitude towards violence suggesting that this should be the primary outcome measure in future research evaluating outcomes of the R&R2MHP cognitive skills program. CONCLUSION The findings suggest that a stable mental state is a key factor that predicts treatment completion.

TNF-α,IL-6 and hs CRP in patients with melancholic,atypical and anxious depression:an antibodyyarrayanalysis related to somatic symptoms

Background The association between inflammation and major depressive disorder(MDD)remains poorly understood,given the heterogeneity of patients with MDD.Aims We investigated inflammatory markers,such as interleukin(IL)-6,high-sensitivity C reactive protein(hsCRP)and tumour necrosis factor-α.(TNF-α)in melancholic,atypical and anxious depression and explored whether baseline inflammatory protein levels could indicate prognosis.Methods The sample consisted of participants(aged 18-55 years)from a previously reported multicentre randomised controlled trial with a parallel-group design registered with ClinicalTrials.gov,including melancholic(n=44),atypical(n=37)and anxious(n=44)patients with depression and healthy controls(HCs)(n=33).Subtypes of MDD were classified according to the 30-item Inventory of Depressive Symptomatology,Self-Rated Version and the.17-item Hamilton Depression Rating Scale.Blood levels.of TNF-α,IL-6 and hsCRP were assessed using antibody array analysis.Results Patients with MDD,classified according to melancholic,atypical and anxious depression subtypes,and HCs did not differ significantly in baseline TNF-α,IL-6 and hsCRP levels after adjustment.In patients with anxious depression,hsCRP levels increased significantly if they experienced no pain(adjusted(adj.)p=0.010)or mild to moderate pain(adj.p=0.038)compared with those with severe pain.However,the patients with anxious depression and severe pain showed a lower trend in hsCRP levels than patients with atypical depression who experienced severe pain(p=0.022;adj.p=0.155).Baseline TNF-α(adj.p=0.038)and IL-6(adj.p=0.006)levels in patients in remission were significantly lower than those in patients with no remission among the participants with the atypical depression subtype at the eighth-week follow-up.Conclusions This study provides evidence of differences in inflammatory proteins in patients with varied symptoms among melancholic,atypical and anxious depression subtypes.Further studies on the immunoinflammatory mechanism underlying different subtypes of depression are expected for improved individualised therapy.

Effects of Religious vs. Conventional Cognitive-Behavioral Therapy on Inflammatory Markers and Stress Hormones in Major Depression and Chronic Medical Illness: A Randomized Clinical Trial

Background: Depressive disorder is often accompanied by physiological changes that may adversely affect the course of medical illness, including an increase in pro-inflammatory cytokines. Methods: We examine the effects of religious cognitive behavioral therapy (RCBT) vs. conventional CBT (CCBT) on pro-/anti-inflammatory indicators and stress hormones in 132 individuals with major depressive disorder (MDD) and chronic medical illness who were recruited into a multi-site randomized clinical trial. Biomarkers (C-reactive protein and pro-inflammatory cytokines TNF-α, IL-1β, IFN-γ, IL-6, IL-12-p70), anti-inflammatory cytokines (IL1ra, IL-4, IL-10), and stress hormones (urinary cortisol, epinephrine, norepinephrine) were assessed at baseline, 12 weeks, and 24 weeks. Differential effects of baseline religiosity on treatment response were also examined, along with effects of religiosity on changes in biomarkers over time independent of treatment group. Biomarker levels were log transformed where possible to normalize distributions. Mixed models were used to examine trajectories of change. Results: CRP increased and IL-4, IL-10, and epinephrine decreased over time, mostly in the opposite direction expected (except epinephrine). No significant difference between RCBT and CCBT was found on average trajectory of change in any biomarkers. Religiosity interacted with treatment group in effects on IL-6, such that CCBT was more effective than RCBT in lowering lL-6 in those with low religiosity whereas RCBT appeared to be more effective than CCBT in those with high religiosity. Higher baseline religiosity also tended to predict an increase in pro-inflammatory cytokines INF-γ and IL-12 (p70) and urinary cortisol over time. Conclusions: RCBT and CCBT had similar effects on stress biomarkers. CCBT was more effective in reducing IL-6 levels in those with low religiosity, whereas RCBT tended to be more effective in those with high religiosity. Unexpectedly, higher baseline religiosity was associated with an increase in several stress biomarkers.

Cryogel scaffolds: soft and easy to use tools for neural tissue culture

The mammalian central nervous system(CNS)is highly complex,with a vast array of processes and interactions occurring in a dynamic and often transient manner.How these processes are combined to regulate our behavior remains poorly understood.This has in turn led to a lack of understanding of how these processes have gone awry in the many disorders of the nervous system.In order to address this,researchers need a controlled way to manipulate the nervous system in in vitro and ex vivo cultures,in both a specific area and for a specific period of time to start to pick apart these interactions.To date,this has been technically challenging,especially when modeling focal injury to the CNS or when working with human brain tissue.

How the Brain Process Stimulus-Response Conflict? New Insights from Lateralized Readiness Potentials Scalp Topography and Reaction Times

Stimulus-Response Compatibility (SRC) refers to the fact that some tasks are performed easier and better than others because of the way stimuli and responses are paired with each other. To assess the brain responses to stimulus-response conflicts, we investigated the behavioral (accuracy and Reaction Times: RTs) as well as the physiological response (Lateralized Readiness Potentials: LRP) modulations in a positional blocked and a conditional mixed design in twelve university students. Results revealed that the performance was less accurate and the RTs, as well as the LRP onset, were delayed under the mixed conditional design. A greater compatibility effect was also noted on accuracy, RTs and LRP onset latency in the mixed design. Consistent with these findings, smaller peak activation at fronto-central areas suggests that more selective inhibition is needed in a mixed design context. Despite a smaller activation, the topographical distribution is similar in both designs. These results indicate that the translation time between stimulus- and response codes are greater under the mixed instruction, while the similar LRP topography suggests that common neural structures underlie LRPs in response to both type of designs.

Quetiapine augmentation of prolonged exposure therapy in veterans with PTSD and a history of mild traumatic brain injury: design and methodology of a pilot study

Background: Selective serotonergic reuptake inhibitors(SSRIs) are first-line pharmacologic treatments for patients with posttraumatic stress disorder(PTSD), but must be given over extended period of time before the onset of action. The use of SSRIs in PTSD patients with mild traumatic brain injury(m TBI) is problematic since SSRIs could exacerbate post-concussion syndrome(PCS) symptoms. VA/DOD guidelines identify trauma-focused psychotherapy as the best evidence-based treatment for PTSD, but overall effectiveness is limited by reduced levels of patient engagement and retention. A previous study from this research group suggested that quetiapine monotherapy, but not risperidone or valproate, could increase engagement in trauma-focused psychotherapy.Methods: We report the study protocol of a pilot study funded under the South-Central Mental Illness Research, Education, and Clinical Center pilot study program from the U.S. Department of Veterans Affairs. This randomized, open-label study was designed to evaluate the feasibility of completing a randomized trial of quetiapine vs. treatment as usual to promote patient engagement in PTSD patients with a history of m TBI.Discussion: We expect that the success of this ongoing study should provide us with the preliminary data necessary to design a full-scale randomized trial. Positive efficacy results in a full-scale trial should inform new VA guidelines for clinical practice by showing that quetiapine-related improvements in patient engagement and retention may be the most effective approach to assure that VA resources achieve the best possible outcome for veterans.Trial registration: NCT04280965.

Self-compassion and resilience mediate the relationship between childhood exposure to domestic violence and posttraumatic growth/stress disorder during COVID-19 pandemic

BACKGROUND Studies have indicated that childhood exposure to domestic violence is a common factor in posttraumatic growth(PTG)and posttraumatic stress disorder(PTSD),but it is unclear whether PTG and PTSD share a common/different underlying mechanism.AIM To explore the common/different underlying mechanism of PTG and PTSD.METHODS Between February 12 and 17,2020,a nationwide cross-sectional online survey was conducted in China among 2038 university students,and a self-administered questionnaire was used for the data collection.The data included demographic characteristics,such as age,gender,and subjective social economic status,and childhood exposure to domestic violence scale that was selected from the Chinese version of revised Adverse Childhood Experiences Question,Self-compassion Scale,Connor–Davidson Resilience Scale,Posttraumatic Growth Inventory,and the Abbreviated PTSD Checklist-Civilian version.A structural equation model was used to test the hypotheses.RESULTS Exposure to domestic violence was significantly associated with PTG and PTSD via a 1-step indirect path of self-compassion(PTG:β=-0.023,95%CI:-0.44 to-0.007;PTSD:β=0.008,95%CI:0.002,0.014)and via a 2-step indirect path from self-compassion to resilience(PTG:β=-0.008,95%CI:-0.018 to-0.002;PTSD:β=0.013,95%CI:0.004-0.024).However,resilience did not mediate the relationship between exposure to domestic violence and PTG and PTSD.CONCLUSION PTG and PTSD are common results of childhood exposure to domestic violence,which may be influenced by self-compassion and resilience.

Cognitive Functioning and Insulin Regulation in Obese Youth

Background: There are data that suggest adiposity is associated with diminished cognitive functioning in adults and youth, independent of related co-morbidities. Little is known about the pathophysiological mechanisms associated with cognitive function in obese youth. The objective of the present study was to assess the associations among cognitive functioning and insulin regulation in a sample of obese youth. Methods: The sample consisted of 30 obese, non-diabetic youth (BMI > 95th percentile) ages 6-16 years (mean age = 12.60 years) referred to an outpatient pediatric endocrinology clinic. Youth were administered the Wechsler Abbreviated Scale of Intelligence (WASI) and Wide Range Assessment of Memory and Learning (WRAML-2). Results: Verbal memory, attention/concentration, and intelligence scores were similar across obese youth with elevated insulin levels and normal insulin levels. Obese youth with elevated insulin levels had lower scores in visual memory, with a medium effect (effect size = 0.51). Fasting insulin levels were not associated with any of the four cognitive domains in the multiple linear regression analysis (P > 0.05). Conclusions: These data provide preliminary evidence that visual memory may be impacted in obese youth with insulin resistance. Longitudinal studies examining insulin regulation, cognitive functioning, and weight status over time are needed.

Hypnosis for burn-related pain:Case studies and a review of the literature

Burn injuries create severe pain and psychological distress that are highly variable between patients. Distinct types of pain during various stages of injury and recovery make treatment complex. Standard pharmacological treatment of pain can have adverse effects and is not effective in treating anxiety and other psychological issues. Researchers have proposed that integrating clinical hypnosis as a complementary therapy can be highly beneficial to burn patients and their healthcare providers. The existing literature is reviewed and specific hypnosis techniques are discussed. Evidence exists indicating that adjunctive hypnosis is effective at reducing pain and procedural anxiety. Implementing a multidisciplinary burn care team that includes clinical hypnosis and focuses on the patients' psychological health as well as pain reduction is likely to result in faster healing and reduced distress for patients and caregivers alike.

Association between Active School Travel and Depressive Symptoms among 51,702 Adolescents in 26 Low- and Middle-Income Countries

Little is known about the role of active school travel(AST)on mental health among adolescents.Thus,this study aimed to explore the AST-depression association among adolescents aged 12–15 years from 26 low-and middle-income countries(LMICs).Data from the Global School-based Student Health Survey were analyzed in 51,702 adolescents[mean(SD)age 13.8(1.0)years;49.3%boys).Both depressive symptoms and AST were assessed by a single question self-reported measure,respectively.Participants who reported having 5 days or above were considered as AST.Multivariable logistic regression analysis(accounting for sampling weights)was performed while controlling for gender,age,physical activity,sedentary behavior,and food insecurity,and a countrywide meta-analysis was undertaken.The prevalence of depressive symptoms and AST were 30.1%and 37.0%,respectively.Compared with those not having AST,adolescents with AST were less likely to have self-reported depressive symptoms(OR=0.88,95%CI:0.85-0.93)regardless of gender.Countrywide meta-analysis demonstrated that having AST versus not having AST was associated with 12%lower odds for depressive symptoms(OR=0.88;95%CI:0.82-0.94)but with a moderate between-country heterogeneity(I^(2)=59.0%).Based on large samples of adolescents from LMICs,it would be expected that AST may play a critical role in preventing adolescent depression worldwide.However,it is necessary to consider more country-specific factors when implementing AST-related mental health interventions.Future studies should adopt the solid study design to confirm or negate our researchfindings.

Religious Involvement, Inflammatory Markers and Stress Hormones in Major Depression and Chronic Medical Illness

Background: Religious practices/experiences (RPE) may produce positive physiological changes in patients with major depressive disorder (MDD) and chronic medical illness. Here, we report cross-sectional relationships between depressive symptoms, RPE and stress biomarkers (pro-/anti-inflammatory measures and stress hormones), hypothesizing positive associations between depressive symptoms and stress biomarkers and inverse associations between RPE and stress biomarkers. Methods: We recruited 132 individuals with both MDD and chronic illness into a randomized clinical trial. First, stress biomarkers in the baseline sample were compared to biomarker levels from a community sample. Second, relationships between depressive symptoms and biomarkers were examined, and, finally, relationships between RPE and biomarkers were analyzed, controlling for demographics, depressive symptoms, and physical functioning. Results: As expected, inflammatory markers and stress hormones were higher in our sample with MDD compared to community participants. In the current sample, however, depressive symptoms were largely unrelated to stress biomarkers, and were unexpectedly inversely related to proinflammatory cytokine levels (TNF-α, IL-1β). Likewise, while RPE were largely unrelated to stress biomarkers, they were related to the anti-inflammatory cytokine IL-1RA and the stress hormone norepinephrine in expected directions. Unexpectedly, RPE were also positively related to the proinflammatory cytokine IFN-γ and to IFN-γ/IL-4 and IFN-γ/IL-10 ratios. Conclusions: Little evidence was found for a consistent pattern of relationships between depressive symptoms or religiosity and stress biomarkers. Of the few significant relationships, unexpected findings predominated. Future research is needed to determine whether religious interventions can alter stress biomarkers over time in MDD.

A Mindfulness-Based Cognitive Therapy (MBCT) Intervention to Improve Resilience and Mitigate Symptoms of Burnout Syndrome in Critical Care Nurses: Results of a Randomized Trial

Objective: Critical care nurses work in a challenging intensive care (ICU) environment that results in work-related psychological distress. Our objective was to pilot an in-person or virtual mindfulness-based cognitive therapy (MBCT) program enhanced resilience and a similarly designed attention control group. Methods: We randomized ICU nurses with symptoms of burnout syndrome and decreased resilience to an MBCT program or a similarly formatted book club control. Our primary outcome was change in resilience as measured by the Connor-Davidson Resilience Scale (CD-RISC). Results: One-hundred one nurses completed study-related procedures. Overall, 70% had baseline symptoms of anxiety and 26% had symptoms of depression. For the in-person cohorts, there was no statistical difference between intervention and control groups regarding the total number of sessions attended (3.85 days ± 1.4 versus 3.75 days ± 0.15;p = 0.64). Using the Client/Patient Satisfaction Questionnaire-8 (CSQ-8), satisfaction scores were higher in the intervention group for weeks two through four of the program: p = 0.03, 0.0003, 0.007 respectively. There was no difference in the change in CD-RISC scores between the two groups (mean difference: treatment = 5.0, control = 7.0;p = 0.30). The online intervention cohort had greater improvements in the change of their median emotional exhaustion burnout scores when compared to the in-person intervention cohorts (-5 [-8 to -1.5] vs. 2 [-5 to 8], p = 0.049). Conclusions: We developed a feasible and acceptable in-person and online MBCT-ICU intervention that did not increase resilience scores in ICU nurses when compared to an attention control group. These results could help guide the proper design of larger trials to determine the efficacy of other resilience interventions.