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Detection and quantification of blastocystis by specific real-time quantitative PCR | A real-time quantitative PCR assay with a specific probe for | PMC10636941 | ||
Subtyping of blastocystis by massively parallel amplicon sequencing | Samples positive for | PMC10636941 | ||
Parasitome survey using massively parallel amplicon profiling of the 18S rDNA gene | The parasitome survey was performed using massively parallel sequencing with five different PCR amplicons of the 18S rDNA gene, as reported in detail previously [ | PMC10636941 | ||
Quantification of | The single-cell protists with a signal in the parasitome survey ( | PMC10636941 | ||
Bacteriome analysis | The processing, DNA library preparation and sequencing had been done previously by massively parallel amplicon sequencing of the V3-V4 region of the bacterial 16S rRNA gene [ | PMC10636941 | ||
Statistical analysis | The prevalence of single-cell protists was determined by counting any PCR positivity at any level. Their presence and quantity were then modeled using generalized estimating equations (GEE) with the subject as the grouping variable, time point (factor with three levels—0, 3 and 6 months) and a first-order autoregressive covariance structure; the predictors were the study allocation (placebo or probiotics) and whether the sample was taken while on intervention with the live mixture.Bacteriome alpha (within-sample) diversity was assessed from the unfiltered rarefied dataset, agglomerated at the genus level, using the observed counts, Chao1, ACE, Shannon, Simpson, inverse Simpson and Fisher indices. The association of alpha diversity indices with the presence or quantity of For the beta diversity (between samples) analysis, Bray-Curtis distance was calculated on Hellinger-transformed abundance data agglomerated at the taxonomic level of the genus, and ordination was performed using metric multi-dimensional scaling (MDS) and visually inspected. Associations of Using GEE, individual bacterial taxa were tested for associations with the positivity of the two abundant protists (The commented R Markdown code and output of the statistical analysis are shown, along with the session information, as Additional file | PMC10636941 | ||
Results | PMC10636941 | |||
Fecal parasitome analysis | The molecular survey using 18S rDNA parasitome profiling and/or specific quantitative PCR for the single-cell protists revealed positivity in widely varying quantities: in The subject-wise prevalence of these three protists, calculated as at least once positive among the three time points, was highest in Sample- and subject-wise prevalence of the protist among CiPP study participantsQuantity of The protist frequency did not differ between the treatment groups (intervention vs. placebo) at baseline, and no significant effect on protist frequency was noted upon receiving the probiotic intervention (GEE with terms for the allocated treatment group, studied predictor being the ongoing intervention with lactobacilli: | PMC10636941 | ||
Blastocystis subtypes | Blastocystis | Of 26 Blastocystis subtypes. ( | PMC10636941 | |
Protists and the fecal bacteriome | The presence of Alpha diversity of the faecal bacteriome and associations with positivity for Redundancy analysis performed on Hellinger-transformed bacterial abundance data indicated no effect of the intervention (When studying the bacterial taxa associated with positivity for parasites using adjusted GEE (Table Bacterial taxa showing association with protist positivity: (A) with (1) Negative means an inverse correlation (and thus negative coefficient in the gee model) and vice versa(2) (3) Classified as (4) Significance noted also in the fold-change model with data after centered log-ratio transformation (adjusted (5) Significant only at genus level(6) Classified as [Raw | PMC10636941 | ||
Discussion | CDA | This study analyzed the single-cell parasitome in a randomized clinical trial of probiotic strain intervention in CDA and found a relatively stable protist colonization (By targeted molecular testing using quantitative real-time PCR, we first looked at the prevalence of The prevalence of Although The colonization by these protists was stable over time and not influenced by the intervention of lactobacilli strains. The temporal stability in children was well described for The mixture of two lactobacilli strains was found to modulate the immune response [In our study, ST2 was the most often identified subtype among study samples, albeit ST3 is reported as the most frequent worldwide [The fecal bacteriome reaction to the mixture of The probiotics did not influence the bacteriome’s alpha diversity; however, we found evidence of protist positivity increasing the alpha diversity similar to what has previously been described in adults, e.g. [The positivity of The presence of | PMC10636941 | |
Strengths and limitations | celiac disease | CELIAC DISEASE | Our study provides a unique insight into a novel topic in celiac disease research as no study has yet investigated the gut parasitome by molecular techniques. The samples were taken longitudinally, which helps decrease the effects of short-term fluctuations in the abundance of individual microbial taxa [The main limitation is the unavailability of a fresh fecal sample needed for direct morphological assessment by microscopy as only frozen samples were used for DNA extraction. Thus, we do not know what stages of the protist were present and whether morphology relates to the quantity of | PMC10636941 |
Conclusions | The prevalence of | PMC10636941 | ||
Acknowledgements | Zuzana Lhotská from the Institute of Parasitology, Biology Centre, Czech Academy of Sciences, and Zdeněk Verner, from Biotechnology and Biomedicine Center of the Academy of Sciences and Charles University in Vestec (BIOCEV), are sincerely thanked for preparing cultures of | PMC10636941 | ||
Author contributions | RECRUITMENT | JH performed laboratory analyses, analysed some of the data and wrote the manuscript; EO performed some laboratory analyses; AH supervised the laboratory analyses and co-lead the study; KJM and MJ contributed to the preparation of the detection assays, construction of quantitative calibrators and manuscript revision; CA designed and co-lead the study, including the subjects recruitment, metadata gathering and data management; OC designed the laboratory part of this study, analysed the data and revised the manuscript; DA conceived the CiPP study, participated in its organization, subject recruitment and data interpretation and revised the manuscript. | PMC10636941 | |
Funding | Celiac Disease | CELIAC DISEASE | Open access funding provided by Lund University. This project has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement No 874864 HEDIMED. This publication reflects only the authors' views, and the European Commission is not responsible for any use that may be made of the information it contains. The CiPP Study was funded by Stiftelsen Samariten, FoU Region Skåne, SUS fonder, Swedish Celiac Disease Foundation, Swedish Research Council, Grant/Award No.: 2018-02553, Crafoords stiftelse, Dr Per Håkanssons stiftelse, and Probi AB. JH's stay at Lund University was supported by CZ.02.2.69/0.0/0.0/18_053/0016976: International mobility of research, technical and administrative staff at Charles University; O.C. and J.H. are financed by the project | PMC10636941 |
Availability of data and materials | Data are available upon reasonable request. | PMC10636941 | ||
Declarations | PMC10636941 | |||
Ethics approval and consent to participate | The study was approved by the Ethics Committee of the Medical Faculty, Lund University, on September 8th, 2011 (Dnr 2011/335) and on September 1st, 2021 (Dnr 2021-04470). The study is registered in ClinicalTrials.gov (NCT03176095). | PMC10636941 | ||
Consent for publication | Not applicable. | PMC10636941 | ||
Competing interests | MINOR | DA is an inventor in a patent application based on the results of the clinical trial but has signed over all legal rights to the patent to Probi AB. Probi AB has developed and supplied the study material (active and placebo products) for the trial as well as financially supported the trial with minor costs for analyzing material. None of the authors are employed by Probi AB and no salaries, consultancy fees, etc., have been paid by Probi AB to the authors in connection with the trial. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. | PMC10636941 | |
References | PMC10636941 | |||
Purpose: | P. | K. Fanucci and M.J. Pilat contributed as co-first authors and A. Omuro and P. LoRusso as co-last authors to this article.Prior presentation: This study was presented at ASCO 2022 Abstract #367158.Isocitrate dehydrogenase ( | PMC10035510 | |
Methods: | Patients with recurrent, contrast-enhancing | PMC10035510 | ||
Results: | astrocytoma | ASTROCYTOMA | A total of 15 evaluable patients were enrolled. Histology was astrocytoma ( | PMC10035510 |
Conclusion: | tumors, SD | TUMORS | The study did not meet the prespecified response-based activity threshold for moving to step 2. However, prolonged SD was observed in patients with grades 2 and 3 histologies, suggesting olaparib monotherapy could be of clinical benefit in select populations. Grade 4 tumors per 2021 World Health Organization classification defined by histology or | PMC10035510 |
Significance: | A single-arm phase II trial of olaparib in | PMC10035510 | ||
Introduction | heterogenous, Gliomas, tumor, primary brain tumors, gliomas | GLIOMAS, TUMOR, PRIMARY BRAIN TUMORS, DISEASES, GLIOMAS | Gliomas represent a heterogenous group of diseases that account for most primary brain tumors (In general, first-line treatment for gliomas includes maximal safe resection which is often limited by tumor extent and location, adjuvant radiation, and alkylator-based chemotherapy. Chemotherapy options include temozolomide or combination of procarbazine, lomustine, and vincristine (In addition to its prognostic significance, Preclinically, | PMC10035510 |
Materials and Methods | PMC10035510 | |||
Patient Selection | glioma | GLIOMA | Eligible patients had recurrent or transformed glioma that progressed despite standard therapy or for which no effective standard therapy existed with evidence of an | PMC10035510 |
Study Treatment and Design | Toxicities | ADVERSE EVENT | The primary objective of this trial was to estimate the overall response rate (ORR) of olaparib in patients with Treatment cycles were 28 days. Patients were administered olaparib in tablet form orally 300 mg twice daily continually, irrespective of food intake. No premedications were required. Toxicities were graded using the NCI Common Terminology Criteria for Adverse Events version 5.0. Retreatment criteria can be found in Written informed consent was obtained from enrolled patients. Institutional Review Board approvals of the protocol and consent forms were obtained from all sites. Protocol design and conduct complied with all applicable regulations, guidance, and local policies. The study was conducted in accordance with the Declaration of Helsinki. The trial was conducted under an NCI-sponsored Investigational New Drug application ( | PMC10035510 |
Statistical Methods | PD | DISEASE, SECONDARY | The power analysis and sample size estimation were completed using the Bayesian adaptive trial design method. We modeled the probability of ORR using Beta distributions. The prior distribution is Beta(0.1, 0.9), which is fairly pessimistic; the expected value is 0.1, reflecting the response rate based on previous experiences. We estimated the ORR using the posterior distribution and reported its median and 90% credible interval (see protocol for details). It was predetermined that the trial would be terminated if there was a lack of response, that is, the probability of the ORR being greater than 0.1 was 50% or less. Because the ORR in the trial was zero, the trial was terminated. The SD rate and the progressive disease (PD) rate were reported, and the 90% credible intervals were estimated using the posterior distribution. SD was defined as lack of progression at first restaging after two cycles.For secondary objectives, the median PFS and OS were estimated using Kaplan–Meier estimate with 95% confidence intervals (CI). The CIs were based on Greenwood formula for variance. Possible risk factors for PFS and OS of WHO grade and | PMC10035510 |
Data Availability | The data generated in this study are available upon request from the corresponding author. | PMC10035510 | ||
Results | PMC10035510 | |||
Patient Demographics | toxicity, tumor, CNL | TUMOR | Sixteen patients were enrolled. Fifteen patients were evaluable for response and toxicity. One patient was found to be ineligible after signing consent (Consort diagram.Demographics and baseline characteristics (Summary of patients’ diagnosis and tumor characteristicsAbbreviations: CNL, copy-number loss; LOF, loss of function; MS, microsatellite stability; N = No; ND, no genetic alteration detected; NR, not reported; TMB, tumor mutational burden; VUS, variant of unknown significance; Y, Yes. | PMC10035510 |
Toxicity | toxicities, nausea, fatigue | ADVERSE EVENTS | There were no unexpected toxicities reported and most toxicities were grade 1 or 2. The most common toxicities were nausea (67%) and fatigue (47%; Most common (>10%) treatment-related and grade 1–3 treatment-related adverse events (maximum grade, all cycles; | PMC10035510 |
Efficacy | PD, death, tumor | DISEASE, TUMOR | All 15 patients were evaluable for response (Patients’ response to olaparibNOTE: PFS defined as the duration of time from start of treatment to time of progression or death, whichever occurs first. OS calculated from initiation of treatment to date of death or last known date of contact. + = alive or lost to follow-up.
In the whole study population, the median PFS was 3.63 months (95% CI, 1.87–5.53; Kaplan–Meier survival curves. We compared PFS and OS of patients with WHO grade 2 or 3 lesions based on archived tissue from diagnosis, to those with grade 4 by histology or CDKN2A alteration. The median PFS of patients with grade 2 and/or 3 was 5.23 months (95% CI, 3.63–9.2) while those with grade 4 was 1.8 months (95% CI, 1.77–NR; log-rank test Reevaluation of imaging of all patients by a blinded NCI-designated neuroradiologist was performed. Two discordant results were identified: one patient's tumor had progressed after six cycles of treatment but was kept on for four additional cycles by the enrolling site. The corrected months of progression-free disease was reported in the above data. The second patient with discordant results had been taken off treatment due to PD after five cycles by their treating physician. However, reassessment of their scans demonstrated SD. | PMC10035510 |
Discussion | tumor, tumors, infiltrative disease | GLIOBLASTOMA, TUMOR, TUMORS | Olaparib monotherapy was well tolerated in patients with recurrent or progressive contrast-enhancing PARP is important in the repair of single-strand breaks (Recently, preliminary results of the OLAGLI trial investigating olaparib in 35 patients with recurrent An important concern in the development of novel therapies for CNS tumors is the ability of novel agents to penetrate through areas of intact blood–brain barrier to address infiltrative disease. CNS penetration of olaparib in humans has been shown in a phase I study combining temozolomide with olaparib in patients with relapsed glioblastoma; olaparib, given prior to surgery, was detected in 71 of 71 tumor core specimens from 27 patients (Identifying mutations that further define distinct subgroups within In addition to PARPi, a significant focus of research in There are numerous future study directions in this population. Trials investigating timing of | PMC10035510 |
Supplementary Material | Tumor | PROGRESSION, TUMOR | Definition of Progression, Tumor Classification, and Eligibility Criteria, retreatment criteriaClick here for additional data file.Representativeness of Study ParticipantsClick here for additional data file. | PMC10035510 |
Acknowledgments | P. | The authors would like to thank CTEP, The Catherine Ivy Foundation, and The Rising Tide Foundation for their support of this project through grants to P. LoRusso.
| PMC10035510 | |
Authors’ Disclosures | Durecki, P. | EMD | Y. Shyr reports grants from NIH/NCI during the conduct of the study; grants from NIH outside the submitted work. S. Boerner reports grants from NCI-CTEP and Rising Tide Foundation during the conduct of the study. D. Durecki reports grants from NIH/NCI UM1CA186689 during the conduct of the study. J. Drappatz reports other from Pfizer, GSK, Gilead, and Vertex outside the submitted work. V. Puduvalli reports personal fees and other from Servier and Novocure, other from Karyopharm, and personal fees from Orbus therapeutics during the conduct of the study; other from Amarin and Gilead outside the submitted work. F.S. Lieberman reports grants from ABTC during the conduct of the study; grants from Novocure, Chimerix, Blue Diamond Therapeutics, and Abbvie outside the submitted work. J. Gonzalez reports other from AstraZeneca outside the submitted work. P. Giglio reports grants from NCI during the conduct of the study; other from Vanguard Funds; grants from BioMimetix, Denovo Biopharma, Institut de Recherches Internationales Servier, Novocure, and Prelude Therapeutics outside the submitted work. R.S. Bindra reports a patent to 62/344,678 pending. A. Omuro reports grants from Arcus Biosciences; personal fees from Pyramid, Merck, Kiyatec, and Ono outside the submitted work. P. LoRusso reports other from AbbVie, Agios, Five Prime, GenMab, Halozyme, Roche-Genetech, Genentech, CytomX, Takeda, Sotio, Cybrexa, Agenus, Tyme, IQVIA, TRIGR, Pfizer, ImmunoMet, Black Diamond, Glaxo-Smith Kline, QED Therapeutics, AstraZeneca, EMD Serono, Shattuck, Astellas, Salarius, Silverback, MacroGenics, Kyowa Kirin Pharmaceutical, Kineta, Zentalis, Molecular Templates, ABL Bio, SK Life Science, STCube Pharmaceuticals, Bayer, I-Mab, Seagen, imCheck, Relay Therapeutics, Stemline, Compass BADX, Mekanist, Mersana Therapeutics, BAKX Therapeutics, Scenic Biotech, Qualigen, Roivant, and NeuroTrials outside the submitted work. No disclosures were reported by the other authors. | PMC10035510 |
Authors’ Contributions | PMC10035510 | |||
References | PMC10035510 | |||
Key Points | PMC10346121 | |||
Question | nonsuicidal self-injury | What are the efficacy and mechanisms of change of a therapist-guided, internet-delivered emotion regulation therapy for nonsuicidal self-injury among adolescents? | PMC10346121 | |
Findings | assessor-rated nonsuicidal self-injury, nonsuicidal self-injury | In this randomized clinical trial that included 166 adolescents, internet-delivered emotion regulation individual therapy delivered adjunctive to treatment as usual resulted in an 82% reduction in masked assessor-rated nonsuicidal self-injury frequency (vs a 47% reduction in treatment as usual only), a statistically significant difference. Improvements in emotion regulation mediated improvements in nonsuicidal self-injury. | PMC10346121 | |
Meaning | nonsuicidal self-injury | A therapist-guided emotion regulation treatment delivered online may overcome common treatment barriers and increase availability of evidence-based psychological treatments for adolescents with nonsuicidal self-injury.This randomized clinical trial examines the effectiveness of internet-delivered emotion regulation individual therapy in addition to usual care for reducing nonsuicidal self-injury among adolescents in Sweden. | PMC10346121 | |
Importance | Nonsuicidal self-injury | Nonsuicidal self-injury is prevalent in adolescence and associated with adverse clinical outcomes. Effective interventions that are brief, transportable, and scalable are lacking. | PMC10346121 | |
Objective | nonsuicidal self-injury | To test the hypotheses that an internet-delivered emotion regulation individual therapy for adolescents delivered adjunctive to treatment as usual is superior to treatment as usual only in reducing nonsuicidal self-injury and that improvements in emotion regulation mediate these treatment effects. | PMC10346121 | |
Design, Setting, and Participants | nonsuicidal self-injury disorder | This 3-site, single-masked, randomized superiority trial enrolled participants from November 20, 2017, to April 9, 2020. Eligible participants were aged between 13 and 17 years and met diagnostic criteria for nonsuicidal self-injury disorder; they were enrolled as a mixed cohort of consecutive patients and volunteers. Parents participated in parallel to their children. The primary end point was at 1 month after treatment. Participants were followed up at 3 months posttreatment. Data collection ended in January 2021. | PMC10346121 | |
Interventions | Twelve weeks of therapist-guided, internet-delivered emotion regulation individual therapy delivered adjunctive to treatment as usual vs treatment as usual only. | PMC10346121 | ||
Main Outcomes and Measures | Primary outcome was the youth version of the Deliberate Self-harm Inventory, both self-reported by participants prior to treatment, once every week during treatment, and for 4 weeks posttreatment, and clinician-rated by masked assessors prior to treatment and at 1 and 3 months posttreatment. | PMC10346121 | ||
Results | self-injury, nonsuicidal self-injury | A total of 166 adolescents (mean [SD] age, 15.0 [1.2] years; 154 [92.8%] female) were randomized to internet-delivered emotion regulation therapy plus treatment as usual (84 participants) or treatment as usual only (82 participants). The experimental intervention was superior to the control condition in reducing clinician-rated nonsuicidal self-injury (82% vs 47% reduction; incidence rate ratio, 0.34; 95% CI, 0.20-0.57) from pretreatment to 1-month posttreatment. These results were maintained at 3-month posttreatment. Improvements in emotion dysregulation mediated improvements in self-injury during treatment. | PMC10346121 | |
Conclusions and Relevance | self-injury, nonsuicidal self-injury | In this randomized clinical trial, a 12-week, therapist-guided, internet-delivered emotion regulation therapy delivered adjunctive to treatment as usual was efficacious in reducing self-injury, and mediation analysis supported the theorized role of emotion regulation as the mechanism of change in this treatment. This treatment may increase availability of evidence-based psychological treatments for adolescents with nonsuicidal self-injury. | PMC10346121 | |
Trial Registration | ClinicalTrials.gov Identifier: | PMC10346121 | ||
Introduction | NSSI, Nonsuicidal self-injury, psychiatric, assessor-rated NSSI, impulsive self-destructive behaviors | SECONDARY | Nonsuicidal self-injury (NSSI), the deliberate destruction of one’s body tissue without suicidal intent,There are very few empirically supported treatments for NSSI in adolescence.One way to treat NSSI more effectively is to target key mechanisms underlying NSSI.This study presents the results from what is to our knowledge the first randomized clinical trial of internet-delivered treatment for adolescents with NSSID. The first aim was to investigate the efficacy of therapist-guided IERITA delivered adjunctive to treatment as usual (TAU) compared with TAU only. The second aim was to examine emotion regulation as a mechanism of change in IERITA. We expected that IERITA plus TAU, relative to TAU only, would lead to both larger reductions in self-reported and assessor-rated NSSI frequency and greater improvements in the secondary outcomes of emotion dysregulation, global functioning, impulsive self-destructive behaviors, and psychiatric symptoms. Finally, we expected that improvements in emotion regulation would mediate improvements in NSSI during treatment. | PMC10346121 |
Methods | PMC10346121 | |||
Design | RECRUITMENT | This was a 3-site, single-masked, randomized superiority trial comparing a 12-week, therapist-guided IERITA delivered adjunctive to TAU with TAU only for adolescents with NSSID and their parents. The trial was conducted within the Child and Adolescent Mental Health Services (CAMHS) in Stockholm, Västra Götaland, and Skåne in Sweden. Recruitment took place from November 20, 2017, to April 9, 2020. The primary end point was 1 month after treatment. Participants were followed up 3 months after treatment (ended January 2021). Participants randomized to TAU only were offered IERITA after the 3-month follow-up. We followed the Consolidated Standards of Reporting Trials ( | PMC10346121 | |
Participants | NSSI, anorexia nervosa, psychotic or bipolar I disorder, primary psychiatric disorder | DISORDER | Referrals from health care professionals and self-referrals from families living in Sweden were accepted. The trial was advertised in CAMHS, schools, and newspapers and on social media.Inclusion criteria for the adolescents were: ages 13 to 17 years, meeting diagnostic criteria for NSSID, experiencing 1 or more NSSI episode during the past month, and having 1 guardian (hereafter referred to as parent) who could participate in the parent program. Exclusion criteria for the adolescents included: immediate suicide risk (ie, history of suicide attempt[s] [if triggers and/or life circumstances had not changed significantly since the attempt] or current suicide plans); diagnosis of psychotic or bipolar I disorder or ongoing (defined as past month) substance use disorder; other primary psychiatric disorder requiring immediate treatment (eg, severe anorexia nervosa); insufficient understanding of the Swedish language; life circumstances that could prevent treatment participation or that required immediate intervention; and a clinician-assessed global functioning level corresponding to a Children’s Global Assessment Scale (CGAS) | PMC10346121 |
Procedures | psychiatric disorders | Procedures for being admitted into the trial included an initial telephone screening, consecutive self-reported baseline assessments every 7 days for 4 weeks, and a face-to-face assessment at the clinic. During the face-to-face assessment, a psychologist or psychotherapist administered semi-structured interviews to assess for NSSID and other co-occurring psychiatric disorders (eMethods in Eligible participants were randomly allocated without stratification to IERITA plus TAU or TAU only. The random allocation sequence was based on a true random number service (Random.org) and conducted by an independent researcher in blocks of 4 or 6 per treatment clinic and placed in opaque sealed envelopes. Outcome measures included masked clinician-rated interviews (via telephone) and self-reported measures (via online platform). Psychologists and psychotherapists masked to treatment allocation and independent from the scientific team conducted the clinician-rated follow-up assessments. Details on masking and participant reimbursement are available in eMethods in | PMC10346121 | |
Outcomes | NSSI | The primary outcome was self-reported and clinician-rated NSSI frequency as measured by the youth version of the Deliberate Self Harm Inventory (DSHI-Y). | PMC10346121 | |
Interventions | The therapist-guided IERITA used in this study had been optimized based on feasibility studies,The comparison condition TAU was chosen to control for some nonspecific aspects of treatment (eg, time, monitoring) and ensure patient safety. The TAU was delivered in both conditions within regular CAMHS care by community clinicians (external to the research group) and typically involved supportive therapy sessions every 2 weeks. Thus, participants in IERITA plus TAU typically had contact with 2 clinicians (face-to-face contact with a community clinician and online contact with the IERITA therapist). TAU was enhanced by weekly self-rated assessments and as needed follow-ups from the research team (when deterioration in mental health was detected) (eMethods in | PMC10346121 | ||
Statistical Analysis | DERS-16, NSSI, self-destructive behaviors, assessor-rated NSSI | REGRESSION | See eMethods in Treatment effects were evaluated according to the intention-to-treat principle. The primary outcome analysis of self-reported NSSI included treatment condition and weekly self-reports of NSSI frequency (using the DSHI-Y). A zero-inflated negative binomial generalized linear-mixed effects regression model was used to estimate the trend over time for self-reported NSSI counts measured every week by including an interaction term between treatment condition and time while allowing for a random intercept and slope per individual. Treatment condition and study site were included as categorical variables and time (weeks zero to 16) was treated as a continuous variable. Exploratory analyses investigated whether certain relevant TAU or client characteristics moderated treatment effects (eMethods in For pretreatment and 1-month and 3-month posttreatment analyses, each assessment point was included as a dummy variable in separate mixed effects regression models including a random intercept, and an interaction term between treatment condition and the categorized time variable (pretreatment, 1-month posttreatment, 3-month posttreatment). Treatment condition and study site were included as categorical variables. For assessor-rated NSSI frequency (DSHI-Y), a zero-inflated negative binomial regression model was fitted to the NSSI counts. For counts on other self-destructive behaviors (BSL-Supplement), zero-inflated Poisson regression models were used. Model comparisons are available in eTable 10 in To determine whether change in week-to-week emotion dysregulation (DERS-16) during treatment mediated the overall effect of IERITA on week-to-week change in the self-reported NSSI frequency, we employed a parallel process latent growth curve modeling approach for mediation. | PMC10346121 |
Results | A total of 166 participants (mean [SD] age, 15.0 [1.2] years; 154 [92.8%] female) were recruited and randomly allocated to IERITA plus TAU (84 participants) or TAU only (82 participants) ( | PMC10346121 | ||
Study and Participant Characteristics | Dysmorphic Disorder, borderline personality disorder, nonsuicidal self-injury, attention-deficit hyperactivity disorder, ADHD, BPD, dysmorphic disorder, hyperactive-impulsive, OCD, obsessive-compulsive disorder, Mini-International Neuropsychiatric | ANOREXIA NERVOSA AND BULIMIA | Abbreviations: ADHD, attention-deficit hyperactivity disorder; BDD, body dysmorphic disorder; BPD, borderline personality disorder; CBT, cognitive behavioral therapy; IERITA, internet-delivered emotion regulation individual therapy for adolescents; TAU, enhanced treatment as usual; NSSI, nonsuicidal self-injury; OCD, obsessive-compulsive disorder; PDT, psychodynamic therapy; SSRI, selective serotonin reuptake inhibitors.In case of 2 parents, 1 was assigned and consented to contribute to answer self-reports questions. Multiple answers were allowed.Assessed by the research team using the MINI-KID (Mini-International Neuropsychiatric Interview for Children and Adolescents) version 6 and the Body Dysmorphic Disorder Questionnaire (administered as an interview).Includes both combined, primarily inattentive, and primarily hyperactive-impulsive subtype.Includes anorexia nervosa and bulimia nervosa.Assessed by the research team using the Structured Clinical Interview for In total 8 participants (5%) had missing value on this variable.Classes of psychopharmacological medication were based on World Health Organization anatomic therapeutic chemical categories. See eTable 13 in | PMC10346121 |
Characteristics of Enhanced Treatment as Usual Within Each Condition and Differences Between Conditions | SE, NSSI | Abbreviations: CBT, cognitive behavioral therapy; IERITA, internet-delivered emotion regulation therapy for adolescents; TAU, enhanced treatment as usual; SSRI, serotonin reuptake inhibitors.Description of the level and content of enhanced treatment as usual that both conditions received during the trial.Classes of psychopharmacological medication were based on World Health Organization anatomic therapeutic chemical categories (eTable 13 in Pharmalogical results included 76 participants in the IERITA plus TAU arm.Ratings of treatment credibility, expectancy, and satisfaction with IERITA were moderate to high (eTable 11 in Reduction in self-reported NSSI frequency (DSHI-Y) was larger in IERITA plus TAU vs TAU only from pretreatment to 1-month posttreatment (β [SE], −0.08 [0.02]; | PMC10346121 | |
Results From the Generalized and Linear Mixed Model Analyses and Effect Sizes | SE, assessor-rated NSSI, NSSI | REGRESSION, SECONDARY, ADVERSE EVENTS, POSITIVE | Abbreviations: BSL, Borderline Symptom List; CGAS, Children’s Global Assessment Scale; Of count and continuous outcomes evaluating treatment differences in change from pretreatment to 1-month posttreatment (primary end point) and 3-month posttreatment (secondary end point). Fixed-effects parameter estimates β (SE) represent the time × group interaction with all randomized individuals (166 total). Positive effect sizes IRR and Numbers of participants contributing with data.This outcome was analyzed using a zero-inflated negative binomial regression model.Effect size result is an IRR.This outcome was analyzed using a zero-inflated Poisson regression model.This outcome was analyzed using a linear mixed effects regression model assuming a normal distribution.Effect size result given as Compared with TAU only, adolescents in IERITA plus TAU had larger improvements in self-reported emotion dysregulation (DERS: Masked assessors were not more accurate than chance at guessing participants’ condition at 1-month posttreatment, although they were slightly more accurate than chance at 3-month posttreatment. The number of assessor-rated NSSI episodes at 1-month posttreatment (β [SE] = 0.29 [0.33], The mediation analysis indicated that, relative to TAU only, IERITA plus TAU led to greater decreases in emotion dysregulation, which, in turn, were associated with decreases in NSSI. The estimated indirect (mediated) effect (Five participants (6%) reported suicide attempts in the IERITA plus TAU condition during the study period, compared with 9 participants (11%) in the TAU only condition. Further information on adverse events is presented in the eResults in | PMC10346121 |
Discussion | anxiety, NSSI, assessor-rated, psychiatric, depression | Findings of this randomized clinical trial support the efficacy of this IERITA delivered adjunctive to TAU (vs TAU only). IERITA resulted in greater improvements in NSSI frequency (both self-reported and assessor-rated) and emotion dysregulation from pretreatment to 1-month posttreatment than TAU only. Results also revealed superior effects of IERITA plus TAU (vs TAU only) on global functioning and other self-destructive behaviors, with between-group effect sizes in the moderate range. Notably, treatment effects were maintained at 3-month posttreatment, suggesting durability of effects. Finally, week-to-week improvements in emotion dysregulation mediated week-to-week reductions in NSSI frequency in IERITA, providing further support for the theoretical framework underlying this treatment.The conditions did not differ significantly in psychiatric symptoms at 1 or 3 months following treatment, suggesting that IERITA results in improvements in emotion dysregulation and global functioning despite comparable levels of depression and anxiety (relative to TAU). These findings are consistent with the emphasis in IERITA on the acceptance of internal experiences and control of behaviors in the context of emotional distress (vs the control or downregulation of emotions themselves), and suggest that targeting emotion regulation may not be sufficient for the treatment of anxiety and depression among adolescents. | PMC10346121 | |
Strengths and Limitations | NSSI | This study had several strengths. These include the use of TAU as the control condition, the use of weekly measures of NSSI, inclusion of both self-reported and clinician-administered assessments, integrity of the masked assessments, and the sexual orientation diversity of the sample.The study also has limitations. IERITA was delivered adjunctive to TAU and compared with TAU only. Although this type of augmentation design holds value in the early stages of treatment development, the lack of equipoise between conditions precludes any conclusions regarding the specific effects of IERITA or mechanistic claims of the intervention. Also, not receiving IERITA could constitute a nocebo condition. Furthermore, although our mediation analysis included a sensitivity analysis to assess the impact of unobserved pretreatment confounders, potential posttreatment confounding (including reverse causality) was not addressed. Future studies should include an active internet-delivered control condition matched on level of activity and attention from therapist and include additional mediators (eg, self-compassion, self-acceptance, other measures of emotion regulation, therapeutic alliance) and analysis (eg, cross-lagged models) to test whether the mediator temporally precedes the outcome. Additionally, data cannot speak to whether participants’ ongoing psychopharmacological treatment was appropriately targeted and dosed. However, given that the onset, type, and frequency of counselling and psychopharmacological treatment were equivalent across conditions, it is unlikely that the observed treatment effects were the result of differences in these additional treatment contacts alone. Furthermore, although 39% of participants were self-referred and may have been particularly motivated to engage in an internet-delivered intervention, most participants were clinician-referred and many of the self-referred patients had previous or ongoing contact with CAMHS, suggesting that the sample is clinically representative. Moreover, the lack of data on interrater reliability of the clinician-administered assessments across clinicians and time is an important limitation and precludes determination of the quality of the clinician-rated outcomes (including measures of NSSI and global functioning), thereby threatening the validity of the findings. Nonetheless, replication of findings across self-reported and clinician-assessed NSSI frequency suggests that findings pertaining to the primary outcome of NSSI were not driven solely by rater differences.Likewise, the predominantly female sample and focus on adolescents with NSSID limit the generalizability of our findings. Future studies should examine the efficacy of this treatment among self-injuring adolescents without NSSID and with greater gender diversity. Future studies of IERITA should also include longer follow-up periods of at least 1 year. Moreover, at some weeks, the proportion of missing self-reported weekly data was moderate and the wide variety of observed missing data patterns precluded formal sensitivity analysis (treating data as not missing at random). However, intermittent missing observations are common in clinical trials employing weekly measures, and it is often reasonable to assume that these data points are randomly missing. | PMC10346121 | |
Conclusions | NSSI | Results of this trial suggest that a 12-week, therapist-guided, IERITA delivered adjunctive to TAU is efficacious in the treatment of NSSI and related factors compared with TAU only. Findings that week-to-week improvements in emotion dysregulation were associated with week-to-week reductions in NSSI frequency during IERITA provide preliminary support for the proposed mechanism of change in IERITA. | PMC10346121 | |
Introduction | psychomotor disturbances, OGM, non-dysphoric, pain, mindfulness-based stress reduction, dysphoric, depression, Depression | EVENT | Depression is characterised by somatic symptoms such as poor sleep, low energy, and psychomotor disturbances [A key mechanism that is linked to OGM is rumination [Remoteness of memories (the age of the memory’s event) has been suggested to influence several characteristics of AM and therefore an important question is whether remoteness would impact AM retrieval in remitted depression following a self-discrepancy induction. Falco et al. (2015) required dysphoric and non-dysphoric individuals to complete a variant of the AMT and date the memory after retrieval [Memory valence has been found to be associated with remoteness of specific memories [Remote memories are also associated with memories being recalled from an observer perspective (third-person perspective), in comparison to a field perspective (first-person perspective). Field memories often contain the emotions the individual experienced during the original event [Moreover, emotional valence of the memory has been found to be associated with vantage perspective. While healthy controls tend to use a field perspective for the recall of positive AM [Given activated self-discrepancies might affect features of AM retrieval, such as specificity, remoteness, valence, and vantage perspective, it is prudent to examine methods to reduce self-discrepant thinking. For instance, loving-kindness meditation (LKM) might reduce self-discrepant thinking by augmenting self-compassion. Three main attributes of self-compassion have been identified: self-kindness, common humanity, and mindfulness, an awareness of present moment suffering without the use of avoidance [A further focus of LKM is on extending compassion towards others. This aspect of the meditation might improve a sense of common humanity which might help one to feel less alone in their pain and shift their focus away from self-discrepant thinking that focuses solely on the self. For example, one study compared the effects of a compassion training programme (Compassion Cultivation Training) with mindfulness-based stress reduction where participants engaged in 2.5-hours of face-to-face sessions per week and 30–45 minutes of daily practices [ | PMC10306223 |
Outline of proposed mechanisms by which features of AM retrieval come to be compromised. | depression, depressed, OGM | POSITIVE | Rumination about self-relevant, semantically related information, and self-discrepant thinking are proposed to compromise the search for a specific memory and influence the remoteness, valence, and vantage perspective of the memory. Difficulty recalling specific memories, biases for retrieving more remote memories, using the observer perspective, and recalling negative memories then leads to emotion dysregulation, for example. LKM is proposed to reduce state rumination, self-discrepant thinking, and emotion dysregulation, thereby influencing features of AM retrieval.Kindness based practices, such as LKM, have further been shown to enhance emotion regulation and higher-level perspective-taking [LKM might also impact OGM through its impact on neurobiological mechanisms underpinning OGM. For example, low tryptophan (an essential amino acid required for the production of serotonin) has been identified as a possible neurobiological mechanism underlying OGM as low-dose tryptophan depletion reduced output of specific AM when remitted depressed women were asked to retrieve specific AM to negative cue words [Tryptophan’s primary catabolic route has been identified to be the kynurenine system [We therefore used two groups with remitted depression to explore whether a brief LKM could influence AM specificity, remoteness, valence, and vantage perspective by reducing self-discrepancies. LKM is broadly accessible in that individuals do not need to leave their home to practice, and the meditation can be completed within ten minutes. An active control colouring group was also used to control for the possibility that effects of LKM might be due to distraction. Distraction has been shown to effectively reduce sad mood in both current and remitted depressed samples [In a remitted depressed sample, we used positive cue words in the AMT with an aim to examine the effects of LKM on four features of AM retrieval: specificity, remoteness, valence, and vantage perspective. We aimed to increase retrieval of specific, positive, and field memories in remitted depression after a four-week LKM intervention. Positive cue words were used with an intention to elicit a greater magnitude of impact of self-discrepancies and because vantage perspective research has indicated a greater influence on positive memories [It was hypothesised that in comparison to the colouring group, the LKM group would show an increase in AM specificity across both time conditions (free-recall and remote conditions). Moreover, an interaction was expected where specificity would increase more in remote memories in the LKM group. Literature has demonstrated that remote memories tend to be more overgeneral than recent memories [ | PMC10306223 |
Methods | PMC10306223 | |||
Group demographic, diagnostic, and intervention compliance data. | depression, Depression | Diagnoses were assessed via the MINI-Plus [Participants aged 18–45 were recruited via university communications where individuals with a previous experience of depression were invited to participate in a study that involved either a meditation or colouring practice for four weeks. Participants were included in the study if they met criteria for past episodes of Major Depression but not a current episode as assessed via the MINI-Plus [ | PMC10306223 | |
Measures | At baseline, the first six participants completed all questionnaires in writing, while the AMT was administered via Microsoft Excel [ | PMC10306223 | ||
MINI-Plus structured interview | The MINI-Plus [ | PMC10306223 | ||
Depression, Anxiety, Stress Scales (DASS) | The DASS [ | PMC10306223 | ||
Rumination Response Scale (RRS) | The RRS [ | PMC10306223 | ||
Self-Compassion Scale (SCS) | The SCS [ | PMC10306223 | ||
Self-discrepancy induction | The self-discrepancy induction is a 50-item self-report questionnaire designed to induce a focus on self-discrepancies and elicit state-rumination [ | PMC10306223 | ||
Visual Analogue Scales (VAS) | Three visual analogue scales were used: mood, experienced discrepancy, and focused discrepancy in line with previous research [ | PMC10306223 | ||
Visual analogue mood scale | Participants were asked to rate their current level of sadness (0 – | PMC10306223 | ||
Visual analogue experienced self-discrepancy scale | Participants were asked to rate the extent to which they currently experience a discrepancy between their actual and ideal self (0 – | PMC10306223 | ||
Visual analogue self-discrepancy focus scale | Participants were asked to rate the extent to which their current thoughts were about wondering how large the difference is between their actual and ideal self (0 – | PMC10306223 | ||
Autobiographical Memory Test (AMT): Extended version | EVENT | The AMT [Participants were instructed to retrieve a specific, personal memory in response to the cue word by typing it into the available text box via Qualtrics within 60 seconds. In Excel, the text box was an enlarged cell. A specific memory was defined as a memory of an event which lasted less than a day and occurred at a particular time and place. Examples of correct and incorrect responses were provided, and two practice trials were given at baseline before the task commenced. Participants proceeded to the test phase once they successfully completed the practice trials. In the test phase, participants were requested not to repeat memories. Additionally, participants were instructed to recall a memory from any time (free recall condition) for half of the cues, whereas memories were requested to be from more than one year ago (remote condition) for the other half. Remoteness condition was randomised in presentation order. Further, cue words were randomised between remoteness conditions and in presentation.After 60 seconds, the recall page automatically progressed in Qualtrics, whereas if completed via Excel, the researcher’s timer sounded to manually continue to the next sheet. On the subsequent page, participants were instructed to select answers to the following questions: i) Was the memory: positive, negative, neutral, or other? ii) From what perspective did you recall the memory: first-person, observer, blended, or no image? The blended option was described to include at least two of the perspective options. iii) When did the event occur? Participants were asked to provide a date of the memory’s event. Unlimited time was allowed to answer these questions.Following previous studies [ | PMC10306223 | |
Experimental and control treatment interventions | anxiety | Groups were standardized in procedure and adherence was uncontrolled but monitored. Participants of both groups were encouraged to continue with any current medication or other treatment phase as they would have done otherwise. Both groups completed their respective daily practices at home, individually, for four weeks.Upon completion of baseline measurements, participants in the LKM group were taught the meditation by a certified instructor via Microsoft Teams. LKM participants then independently practiced the meditation every day from either an upright, seated, or lying down position [In the control colouring group, participants were asked to (digitally) colour one mandala image of their choice per day. Digital colouring has shown a similar decrease in anxiety symptoms in comparison to pen-and-paper colouring [ | PMC10306223 | |
Procedure | The study was administered online via Microsoft Teams and Qualtrics (Provo, UT). Participants attended an initial session during which they provided informed, written consent, demographic information, and were interviewed using the MINI-Plus for screening and diagnostic purposes. The first session lasted an average of 45 minutes. Eligible participants were invited to a second session (within one week) during which they completed baseline questionnaires and the AMT extended version. Measurements were completed in the following order: i) DASS, ii) RRS, iii) SCS, iv) VAS, v) self-discrepancy induction, vi) VAS, vii) AMT extended version. Following completion of baseline measures, participants were randomly allocated by the lead researcher, using Simple Randomisation, to either the LKM or colouring group and were introduced to the treatment. A distraction task was subsequently administered that asked participants to spend three minutes thinking about neutral situations from a list of thirty (e.g. think about the colour of clouds). This second session lasted an average of 45 minutes. Within one week of treatment completion, participants were reassessed on all baseline measures and were then debriefed on the nature of the study. Participants in the colouring group were subsequently invited to learn the meditation and access the Moodle recordings. The final session lasted an average of 40 minutes. | PMC10306223 | ||
Statistical analysis | MDD | JASP (0.13.1) was used for statistical analyses and an alpha level of 0.05 was used for all statistical tests. The study’s design was between-subjects (LKM, colouring). The participant characteristics (e.g. age, number of previous MDD episodes, etc.) and baseline scores on the mood measures (e.g. DASS, RRS, etc.) were analysed using Bayesian independent samples t-tests. Bonferroni post hoc analyses were performed where appropriate for ANOVAs. | PMC10306223 | |
Results | PMC10306223 | |||
Participants at baseline | The mean pre- and post-intervention scores for each group can be seen on | PMC10306223 | ||
Means and standard deviations for relevant variables at pre- and post-intervention. | depressed | Specific, positive (Pos-), and field memories include data regarding total mean numbers (across both remoteness conditions) while recent and remote specific include mean numbers from the free-recall condition. Mean proportions (prop) for specific, positive, and field data represent the mean number retrieved out of 20. Mean proportions for recent and remote specific data represent the mean number retrieved out of 10. Omissions were included in the denominator in line with previous research demonstrating that when formerly depressed participants made an omission, non-specific content was often retrieved [ | PMC10306223 | |
Manipulation checks at baseline | No reliable conclusion could be drawn regarding a significant change in sadness following the self-discrepancy induction at baseline, | PMC10306223 | ||
Autobiographical Memory Test | The descriptive statistics for the AMT variables pre- and post-intervention are shown in | PMC10306223 | ||
Correlations between rumination and memory specificity at baseline | After inducing state rumination, a significant, positive correlation (Pearson correlation coefficient) was observed at baseline between trait rumination (RRS) and the number of specific memories, | PMC10306223 | ||
Autobiographical memory remoteness at baseline | To determine whether there was a tendency for more remote memories to be retrieved, we calculated the difference in number of recent-specific memories (up to one year old) versus remote-specific memories (over one year old) retrieved at baseline in the free-recall condition. Retrieval of recent-specific and remote-specific memories did not differ significantly, We further measured the remoteness of specific memories by calculating a distance memory score (DMS) for each participant [ | PMC10306223 | ||
Autobiographical memory valence at baseline | We calculated the difference in number of positive-specific recent memories (up to one year old) versus positive-specific remote memories (over one year old) retrieved at baseline in the free-recall condition. Contrary to expectations, no significant difference was revealed, | PMC10306223 | ||
Changes in negative affect, rumination, self-compassion, and self-discrepancies, from pre- to post-intervention | depression | Bayesian repeated measures ANOVAs were conducted on negative affect, rumination, self-discrepancies, and self-compassion with time (pre-and post-intervention) as a within-subjects factor, group (LKM, colouring) as a between-subjects factor, and intervention compliance as a covariate. An analysis of residuals confirmed the assumptions of linearity. For negative affect (total DASS), results were inconclusive regarding a main effect of time, BF10 = 2.40, and group, BF10 = 0.45, and there was no interaction between time and group, BF10 = 0.32. Results suggested no difference in the reduction of negative affect over time depending upon group. The Bayesian repeated measures ANOVA for depression (DASS depression) revealed inconclusive results regarding a main effect of time, BF10 = 0.94, and group, BF10 = 0.72, and there was no interaction between time and group, BF10 = 0.28, suggesting no difference in the reduction of depression over time depending upon group. Regarding rumination (RRS), there was a main effect of time, BF10 = 9.15, but inconclusive results regarding a main effect of group, BF10 = 1.93, and regarding an interaction between time and group, BF10 = 0.85. Results suggested no reliable conclusion could be drawn regarding a difference in the reduction of rumination over time depending upon group. Further, the Bayesian repeated measures ANOVA for self-compassion revealed inconclusive results regarding a main effect of time, BF10 = 1.00, while there was no main effect of group, BF10 = 0.006. Further, results were inconclusive regarding an interaction between time and group, BF10 = 1.18, suggesting no reliable conclusion could be drawn regarding a change in self-compassion over time depending upon group. There was a main effect of time for experienced self-discrepancies ( | PMC10306223 | |
Changes in memory specificity from pre- to post-intervention | A repeated measures ANOVA was conducted on the total number of specific memories on the AMT (across both remoteness conditions) with time (pre- and post-intervention) as a within-subjects factor, and group (LKM, colouring) as a between-subjects factor. An analysis of residuals confirmed the assumptions of linearity. Results revealed a main effect of time, F(1, 48) = 4.73, A Bayesian repeated measures ANOVA was then performed on the number of specific memories in the free-recall condition using remoteness (recent and remote) and time (pre- and post-intervention) as within-subjects factors, and group (LKM, colouring) as between-subjects factors. An analysis of residuals confirmed the assumptions of linearity. Results revealed no main effect of time, BF10 = 0.17, while results were inconclusive regarding a main effect of remoteness, BF10 = 0.64, and group, BF10 = 0.90. Results were further inconclusive regarding an interaction between time and group, BF10 = 0.99 and remoteness and group, BF10 = 1.75, while there was no interaction between time, remoteness, and group, BF10 = 0.14. Reliable conclusions could not be drawn regarding group differences in a change in specificity over time in the free-recall condition.Moreover, to examine whether specificity increased over time in remote memories in the remote condition, a Bayesian repeated measures ANOVA was performed on the number of specific memories using time (pre- and post-intervention) as a within-subjects factor, and group (LKM, colouring) as a between-subjects factor. There was no main effect of time, BF10 = 0.23, while results were inconclusive regarding group, BF10 = 1.19, and regarding an interaction between time and group, BF10 = 0.84. Results demonstrated that specificity of remote memories (in the remote condition) was not significantly altered over time, while reliable conclusions could not be drawn regarding group differences in a change in retrieval of remote specific memories. | PMC10306223 | ||
Changes in positive memory retrieval from pre- to post-intervention | positive-specific memories | A Bayesian repeated measures ANOVA was conducted on the total number of positive-specific memories (across both remoteness conditions) with time (pre-and post-intervention) as a within-subjects factor, and group (LKM, colouring) as a between-subjects factor. An analysis of residuals confirmed the assumptions of linearity. There was a main effect of time, BF10 = 4.82, while results were inconclusive regarding a main effect of group, BF10 = 0.39, and regarding an interaction between time and group, BF10 = 1.05, contrary to our hypothesis (see | PMC10306223 | |
Means and standard deviations for memory valence and vantage perspective at pre- and post-intervention. | depression, positive-specific memories | Data include total mean numbers of specific memories (across both remoteness conditions).A Bayesian repeated measures ANOVA was then conducted on the number of positive-specific memories in the free-recall condition using remoteness (recent and remote) and time (pre- and post-intervention) as within-subjects factors, and group (LKM, colouring) as a between-subjects factor. There was no main effect of time, BF10 = 0.18, remoteness, BF10 = 0.27, or group, BF10 = 0.24. For the interactions, there was no interaction between time and group, BF10 = 0.25, while results were inconclusive regarding remoteness and group, BF10 = 1.70, time and remoteness, BF10 = 0.51, and time, remoteness, and group, BF10 = 0.42. Results were inconclusive regarding a change in positive-specific memory retrieval over time in the free-recall condition depending upon the age of the memory. To further examine remote positive-specific memories, correlation analyses were conducted (Pearson correlation coefficient) between the number of remote positive-specific memories and DASS depression scores at baseline, | PMC10306223 |
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