The Landscape of Resource Utilization After Resuscitation of 22-, 23-, and 24-Weeks' Gestation Infants.

OBJECTIVE: To compare estimated healthcare resources needed to care for 22 through 24 weeks' gestation infants. STUDY DESIGN: This multicenter, retrospective cohort study included 1505 live in-born and out-born infants 22 through 24 weeks' gestational age at delivery from 6 pediatric tertiary care hospitals from 2011 through 2020. Median neonatal intensive care unit (NICU) length of stay (LOS) for each gestational age was used as a proxy for hospital resource utilization, and the number of comorbidities and medical technology use for each infant were used as estimates of future medical care needs. Data were analyzed using Kruskal-Wallis with Nemenyi's posthoc test and Fisher's exact test. RESULTS: Of the identified newborns, 22-week infants had shorter median LOS than their 23- and 24-week counterparts due to low survival rates. There was no significant difference in LOS for surviving 22-week infants compared with surviving 23-week infants. Surviving 22-week infants had similar proportions of comorbidities and medical technology use as 23-week infants. CONCLUSIONS: Compared with 23- and 24-week infants, 22-week infants did not use a disproportionate amount of hospital resources. Twenty-two-week infants should not be excluded from resuscitation based on concern for increased hospital care and medical technology requirements. As overall resuscitation efforts and survival rates increase for 22-week infants, future research will be needed to assess the evolution of these results.

Anti-racist interventions to reduce ethnic disparities in healthcare in the UK: an umbrella review and findings from healthcare, education and criminal justice.

OBJECTIVES: To assess the evidence for anti-racist interventions which aim to reduce ethnic disparities in healthcare, with a focus on implementation in the UK healthcare system. DESIGN: Umbrella review. DATA SOURCES: Embase, Medline, Social Policy and Practice, Social Care Online and Web of Science were searched for publications from the year 2000 up to November 2023. ELIGIBILITY CRITERIA: Only systematic and scoping reviews of anti-racist interventions reported in English were included. Reviews were excluded if no interventions were reported, no comparator interventions were reported or the study was primarily descriptive. DATA EXTRACTION AND SYNTHESIS: A narrative synthesis approach was used to integrate and categorise the evidence on anti-racist interventions for healthcare. Quality appraisal (including risk of bias) was assessed using the AMSTAR-2 tool. RESULTS: A total of 29 reviews are included in the final review. 26 are from the healthcare sector and three are from education and criminal justice. The most promising interventions targeting individuals include group-based health education and providing culturally tailored interventions. On a community level, participation in all aspects of care pathway development that empowers ethnic minority communities may provide an effective approach to reducing ethnic health disparities. Interventions to improve quality of care for conditions with disproportionately worse outcomes in ethnic minority communities show promise. At a policy level, structural interventions including minimum wage policies and integrating non-medical interventions such as housing support in clinical care has some evidence for improving outcomes in ethnic minority communities. CONCLUSIONS: Many of the included studies were low or critically low quality due to methodological or reporting limitations. For programme delivery, different types of pathway integration, and providing a more person-centred approach with fewer steps for patients to navigate can contribute to reducing disparities. For organisations, there is an overemphasis on individual behaviour change and recommendations should include a shift in focus and resources to policies and practices that seek to dismantle institutional and systemic racism through a multilevel approach.

Pelvic examination under anesthesia by learners at the time of abortion: Who accepts and who declines?

OBJECTIVES: This study aimed to assess the prevalence of and factors correlated with accepting a pelvic examination under anesthesia (EUA) by learners at the time of surgical abortion. STUDY DESIGN: Retrospective chart review assessing the prevalence of and comparing factors associated with accepting EUA by learners at the time of abortion. RESULTS: Most (88%) of the 274 patients accepted EUA by learners. Declining was associated with prior intimate partner violence. CONCLUSIONS: Most patients accept EUA by learners at the time of abortion. IMPLICATIONS: In adhering to fundamental principles of medical ethics, professional guidelines, and legal mandates, consent prior to pelvic EUA by learners should be obtained universally.

Rumination-Focused Cognitive Behavioral Therapy Reduces Rumination and Targeted Cross-network Connectivity in Youth With a History of Depression: Replication in a Preregistered Randomized Clinical Trial.

Background: Rumination-focused cognitive behavioral therapy (RF-CBT) is designed to reduce depressive rumination or the habitual tendency to dwell on experiences in a repetitive, negative, passive, and global manner. RF-CBT uses functional analysis, experiential exercises, and repeated practice to identify and change the ruminative habit. This preregistered randomized clinical trial (NCT03859297, R61) is a preregistered replication of initial work. We hypothesized a concurrent reduction of both self-reported rumination and cross-network connectivity between the left posterior cingulate cortex and right inferior frontal and inferior temporal gyri. Methods: Seventy-six youths with a history of depression and elevated rumination were randomized to 10 to 14 sessions of RF-CBT (n = 39; 34 completers) or treatment as usual (n = 37; 28 completers). Intent-to-treat analyses assessed pre-post change in rumination response scale and in functional connectivity assessed using two 5 minute, 12 second runs of resting-state functional magnetic resonance imaging. Results: We replicated previous findings: a significant reduction in rumination response scale and a reduction in left posterior cingulate cortex to right inferior frontal gyrus/inferior temporal gyrus connectivity in participants who received RF-CBT compared with those who received treatment as usual. Reductions were large (z change = 0.84; 0.73, respectively [ps < .05]). Conclusions: This adolescent clinical trial further demonstrates that depressive rumination is a brain-based mechanism that is modifiable via RF-CBT. Here, we replicated that RF-CBT reduces cross-network connectivity, a possible mechanism by which rumination becomes less frequent, intense, and automatic. This National Institute of Mental Health-funded fast-fail study continues to the R33 phase during which treatment-specific effects of RF-CBT will be compared with relaxation therapy.

Rumination Induction Task in fMRI: Test-Retest Reliability in Youth and Potential Mechanisms of Change with Intervention.

Background: Rumination is a transdiagnostic problem that is common in major depressive disorder (MDD). Rumination Focused Cognitive Behavioral Therapy (RF-CBT) explicitly targets the ruminative habit. This study examined changes in brain activation during a rumination induction task in adolescents with remitted MDD following RF-CBT. We also evaluated the reliability of the rumination task among adolescents who received treatment as usual (TAU). Method: Fifty-five adolescents ages 14-17 completed a self-relevant rumination induction fMRI task and were then randomized to either RF-CBT (n = 30) or TAU (n = 25). Participants completed the task a second time either following 10-14 sessions of RF-CBT or the equivalent time delay for the TAU group. We assessed activation change in the RF-CBT group using paired-samples t-tests and reliability by calculating intraclass correlation coefficients (ICCs) of five rumination-related ROIs during each of three blocks for the TAU and RF-CBT groups separately (Rumination Instruction, Rumination Prompt, and Distraction). Results: Following treatment, participants in the RF-CBT group demonstrated an increase in activation of the left precuneus during Rumination Instruction and the left angular and superior temporal gyri during Rumination Prompt ( p < .01). The TAU group demonstrated fair to excellent reliability ( M = .52, range = .27-.86) across most ROIs and task blocks. In contrast, the RF-CBT group demonstrated poor reliability across most ROIs and task blocks ( M = .21, range = -.19-.69). Conclusion: RF-CBT appears to lead to rumination-related brain change. We demonstrated that the rumination induction task has fair to excellent reliability among individuals who do not receive an intervention that explicitly targets the ruminative habit, whereas reliability of this task is largely poor in the context of RF-CBT. This has meaningful implications in longitudinal and intervention studies, particularly when conceptualizing it as an important target for intervention. It also suggests one of many possible mechanisms for why fMRI test-retest reliability can be low that appears unrelated to the methodology itself.

Negative association between non-suicidal self-injury in adolescents and default mode network activation during the distraction blocks of a rumination task.

INTRODUCTION: Rumination, or repetitive and habitual negative thinking, is associated with psychopathology and related behaviors in adolescents, including non-suicidal self-injury (NSSI). Despite the link between self-reported rumination and NSSI, there is limited understanding of how rumination is represented at the neurobiological level among youth with NSSI. METHOD: We collected neuroimaging and rumination data from 39 adolescents with current or past NSSI and remitted major depression. Participants completed a rumination induction fMRI task, consisting of both rumination and distraction blocks. We examined brain activation associated with total lifetime NSSI in the context of the rumination versus distraction contrast. RESULTS: Lifetime NSSI was associated with a greater discrepancy in activation during rumination relative to distraction conditions in clusters including the precuneus, posterior cingulate, superior, and middle frontal gyrus, and cerebellum. CONCLUSION: Difficulties associated with rumination in adolescents with NSSI may be related to requiring greater cognitive effort to distract from ruminative content in addition to increased attention in the context of ruminative content. Increasing knowledge of neurobiological circuits and nodes associated with rumination and their relationship with NSSI may enable us to better tailor interventions that can facilitate lasting well-being and neurobiological change.

Dynamics of mother-infant parasympathetic regulation during face-to-face interaction: The role of maternal emotion dysregulation.

The dynamics of parent-infant physiology are essential for understanding how biological substrates of emotion regulation are organized during infancy. Although parent-infant physiological processes are dyadic in nature, research is limited in understanding how one person's physiological responses predict one's own and as well as the other person's responses in the subsequent moment. In this study, we examined mother-infant respiratory sinus arrhythmia (RSA) dynamics during the Still-Face Paradigm (SFP) among 106 mothers (Mage  = 29.54) and their 7-month-old infants (55 males). Given mothers' role in shaping dyadic interactions with their infant, we also tested how mothers' self-reported emotion dysregulation (measured via the Difficulties in Emotion Regulation Scale) associated with these dynamics. Results showed that both mothers' and infants' RSA tended to return to their respective homeostatic points (i.e., exhibited return strength) during each SFP episode, indicating stability in RSA for mother-infant dyads. Significant shifts in mother and infant RSA return strength were observed across SFP episodes, highlighting the role of contextual demands on each individual's physiological dynamics. Mother-infant RSA dynamics varied as a function of maternal self-reported emotion dysregulation. Specifically, RSA levels of infants with more dysregulated mothers had a weaker tendency to return to homeostasis during the Reunion episode and were less affected by their mothers' RSA during the Still-Face and Reunion episodes of the SFP, suggesting a less effective coregulatory influence. Our findings have implications for the intergenerational transmission of emotion dysregulation via mother-infant physiological dynamics.

Early Emergence of Rumination has no Association with Performance on a Non-affective Inhibitory Control Task.

Rumination is a vulnerability for depression and potentially linked to inhibitory control weaknesses. We aimed to replicate the association observed in adults between inhibitory control and rumination in adolescents, and to examine putative moderating roles of childhood maltreatment and perceived family cohesion in an adolescent sample at risk for depression due to familial/personal history. Ninety adolescents aged 11-17 (M = 14.6, SD = 1.8) completed self-report scales of rumination, maltreatment, and family cohesion, and performed a task assessing inhibitory control. Hierarchical regression models showed no significant relation between inhibitory control and moderator variables on rumination. However, adolescents who reported higher levels of maltreatment and who perceived lower family cohesion tended to indicate higher levels of rumination (BChilhood Maltreatment = 27.52, 95% CIs [5.63, 49.41], BFamily Cohesion = -0.40, 95% CIs [-0.65, -0.15]). These findings demonstrate an alternative understanding of factors that increase depression onset risk and recurrence in adolescents.

Relations of gray matter volume to dimensional measures of cognition and affect in mood disorders.

Understanding the relationship between brain measurements and behavioral performance is an important step in developing approaches for early identification of any psychiatric difficulties and interventions to modify these challenges. Conventional methods to identify associations between regional brain volume and behavioral measures are not optimized, either in scale, scope, or specificity. To find meaningful associations between brain and behavior with greater sensitivity and precision, we applied data-driven factor analytic models to identify and extract individual differences in latent cognitive functions embedded across several computerized cognitive tasks. Furthermore, we simultaneously utilized a keyword-based neuroimaging meta-analytic tool (i.e., NeuroSynth), restricted atlas-parcel matching, and factor-analytic models to narrow down the scope of search and to further aggregate gray matter volume (GMV) data into empirical clusters. We recruited an early adult community cross-sectional sample (Total n = 177, age 18-30) that consisted of individuals with no history of any mood disorder (healthy controls, n = 44), those with remitted major depressive disorder (rMDD, n = 104), and those with a diagnosis of bipolar disorder currently in euthymic state (eBP, n = 29). Study participants underwent structural magnetic resonance imaging (MRI) scans and separately completed behavioral testing using computerized measures. Factor-analyzing five computerized tasks used to assess aspects of cognitive and affective processing resulted in seven latent dimensions: (a) Emotional Memory, (b) Interference Resolution, (c) Reward Sensitivity, (d) Complex Inhibitory Control, (e) Facial Emotion Sensitivity, (f) Sustained attention, and (g)Simple Impulsivity/Response Style. These seven dimensions were then labeled with specific keywords which were used to create neuroanatomical maps using NeuroSynth. These masks were further subdivided into GMV clusters. Using regression, we identified GMV clusters that were predictive of individual differences across each of the aforementioned seven cognitive dimensions. We demonstrate that a dimensional approach consistent with core principles of RDoC can be utilized to identify structural variability predictive of critical dimensions of human behavior.

Increased sensitivity of insula to supraliminal faces in adults with histories of mood disorders and self-injury.

BACKGROUND: Mood disorders are associated with neurobiological disruptions in subliminal and supraliminal emotion processing. There may be additional variation based on sex and the presence of self-injurious thoughts and behaviors (SITBs). Examining individuals in remission allows us to understand trait-like emotion processing characteristics that persist in the absence of symptoms. This study investigates neural processing in response to supraliminal and subliminal emotional stimuli based upon mood disorder diagnosis, sex, and SITBs. METHODS: Seventy-five participants with a history of any mood disorder (AMD; 52 female) and 27 healthy controls (HC; 14 female) completed a fMRI task presenting subliminal and supraliminal facial stimuli. Within the AMD group, 20 had no history of SITBs, 26 had histories of suicidal ideation only, and 27 had histories of both SI and self-injurious behavior. We examined activation of salience network regions of interest including the amygdala, insula, and subgenual anterior cingulate cortex (sgACC) during the task. RESULTS: AMD showed greater insula activation in response to happy faces relative to sad faces, which was not seen in the HC group. Males exhibited lower insula activation in response to sad faces relative happy faces, a pattern not seen in females. Individuals with SITBs demonstrated a lack of sgACC blunting during supraliminal versus subliminal trials. CONCLUSIONS: We found different patterns of neural responses related to mood disorder status, sex, and SITBs. Findings highlight the importance of considering heterogeneity within diagnoses and examining neurobiological features in the context of remission.

Developmental foundations of physiological dynamics among mother-infant dyads: The role of newborn neurobehavior.

This study tested whether newborn attention and arousal provide a foundation for the dynamics of respiratory sinus arrhythmia (RSA) in mother-infant dyads. Participants were 106 mothers (Mage  = 29.54) and their 7-month-old infants (55 males and 58 White and non-Hispanic). Newborn attention and arousal were measured shortly after birth using the NICU Network Neurobehavioral Scale. Higher newborn arousal predicted a slower return of infant RSA to baseline. Additionally, greater newborn attention predicted mothers' slower return to baseline RSA following the still-face paradigm, and this effect only held for mothers whose infants had lower newborn arousal. These findings suggest that newborn neurobehavior, measured within days of birth, may contribute to later mother-infant physiological processes while recovering from stress.

Self-Injury in Adolescence Is Associated with Greater Behavioral Risk Avoidance, Not Risk-Taking.

Strategies to link impulsivity and self-injurious behaviors (SIBs) show highly variable results, and may differ depending on the impulsivity measure used. To better understand this lack of consistency, we investigated correlations between self-report and behavioral impulsivity, inhibitory control, SIBs, and rumination. We included participants aged 13-17 years with either current or remitted psychopathology who have (n = 31) and who do not have (n = 14) a history of SIBs. Participants completed self-report measures of impulsivity, the Rumination Responsiveness Scale (RRS), and two behavioral measures of impulsivity: the Balloon Analogue Risk Task (BART) and Parametric Go/No-Go (PGNG). Lifetime SIBs were positively associated with self-reported impulsivity, specifically positive and negative urgency. However, individuals with greater lifetime SIBs demonstrated greater risk aversion (lower impulsivity) as measured by the BART, whereas there was no relation between lifetime SIBs and PGNG performance. There was no relation between rumination and behavioral impulsivity, although greater rumination was associated with higher negative urgency. Future research examining the role of SIBs in the context of active versus remitted psychopathology is warranted. Because most adolescents were remitted from major depressive disorder at the time of study, follow-up studies can determine if lower risk-taking may aid individuals with more prior SIBs to achieve and maintain a remitted state.

Sudden Death in High School Athletes: A Case Series Examining the Influence of Sickle Cell Trait.

ABSTRACT: Athletes with sickle cell trait (SCT) have up to a 37-fold increased risk of exercise-related death. Exertional collapse associated with sickle cell trait (ECAST) is uncommon but can lead to exercise-related death due to exertional sickling. We present a case series of fatal ECAST in high school athletes aged 14 to 16 years. All 3 athletes experienced collapse during practice sessions with muscle pain or weakness. Upon evaluation at the hospital, the athletes had a significant metabolic acidosis that did not respond as expected to fluid resuscitation. Admitting diagnoses for the athletes included exertional heat stroke or dehydration. All 3 athletes had profound rhabdomyolysis leading to acute renal failure, worsening metabolic acidosis, and hyperkalemia. They rapidly progressed to disseminated intravascular coagulation, multiorgan system failure, and death. The autopsies of all 3 athletes showed extensive sickle cell vaso-occlusion involving the spleen liver, and muscles. Final clinical and pathologic diagnosis supported ECAST with fatal exertional rhabdomyolysis. Exertional collapse associated with sickle cell trait is an uncommon but potentially deadly condition that is often underrecognized or misdiagnosed as exertional heat stroke. The development of ECAST is thought to be multifactorial with exercise intensity, recent illness, and exercising conditions (ie, heat and altitude). Prevention should be the primary goal for athletes with SCT through exercise modification, education of precipitation factors, and cessation of exercise with recent illness. Athletes with suspected ECAST should undergo aggressive resuscitation with a low threshold for early transfer to a tertiary care facility for further management and potential hemodialysis.

Using Network Parcels and Resting-State Networks to Estimate Correlates of Mood Disorder and Related Research Domain Criteria Constructs of Reward Responsiveness and Inhibitory Control.

BACKGROUND: Resting-state graph-based network edges can be powerful tools for identification of mood disorders. We address whether these edges can be integrated with Research Domain Criteria (RDoC) constructs for accurate identification of mood disorder-related markers, while minimizing active symptoms of disease. METHODS: We compared 132 individuals with currently remitted or euthymic mood disorder with 65 healthy comparison participants, ages 18-30 years. Subsets of smaller brain parcels, combined into three prominent networks and one network of parcels overlapping across these networks, were used to compare edge differences between groups. Consistent with the RDoC framework, we evaluated individual differences with performance measure regressors of inhibitory control and reward responsivity. Within an omnibus regression model, we predicted edges related to diagnostic group membership, performance within both RDoC domains, and relevant interactions. RESULTS: There were several edges of mood disorder group, predominantly of greater connectivity across networks, different than those related to individual differences in inhibitory control and reward responsivity. Edges related to diagnosis and inhibitory control did not align well with prior literature, whereas edges in relation to reward responsivity constructs showed greater alignment with prior literature. Those edges in interaction between RDoC constructs and diagnosis showed a divergence for inhibitory control (negative interactions in default mode) relative to reward (positive interactions with salience and emotion network). CONCLUSIONS: In conclusion, there is evidence that prior simple network models of mood disorders are currently of insufficient biological or diagnostic clarity or that parcel-based edges may be insufficiently sensitive for these purposes.

Comparing Intratympanic Gentamicin with Methylprednisolone in Meniere's Disease with Non-Serviceable Hearing.

Abstract: To compare the effectiveness of high dose fixed alternate day intratympanic gentamicin with methylprednisolone in the treatment of patients with unilateral, intractable Meniere's disease with poor hearing. Randomized single blind prospective parallel group trial in a tertiary referral centre. Twenty-two patients with definite unilateral Meniere's disease with average pure tone thresholds worse than 50 dB in the affected ear were enrolled. Eleven patients were treated with intratympanic buffered gentamicin and the other eleven were administered intratympanic methylprednisolone (both 4 injections, 40 mg/ml, on alternate days). Patients were assessed pre-intervention, 3 months post intervention and subsequently followed up for 2-4 years. Both groups of patients had significant control of vertigo, DHI scores and THI scores after treatment while the functional scores in the methylprednisolone group was not better than the pre- treatment scores in the long-term follow-up. 9 of 11(82%) patients in gentamicin group and 3 of 11(27%) patients in the methylprednisolone group achieved Class A vertigo control. The gentamicin group had better post intervention DHI scores (p = 0.016, 3 months and p = 0.046, long term) and Functional score (p = 0.014, 3 months and p = 0.05, long term). The hearing in both groups and THI scores, post intervention was similar between both groups. In patients with unilateral intractable MD with non-serviceable hearing, high fixed doses of both intratympanic gentamicin and methylprednisolone are effective in alleviating disease symptoms in long term follow-up. However, intratympanic gentamicin resulted in better control of vertigo, total DHI score and functional level scores than intratympanic methylprednisolone with no significant difference in hearing levels. Trail Registration Number: Clinical Trials Registry of India (CTRI- REF/2016/10/012363).

Glycogen Synthase Kinase 3 Regulates the Genesis of Displaced Retinal Ganglion Cells3.

Glycogen synthase kinase 3 (GSK3) proteins (GSK3α and GSK3ß) are key mediators of signaling pathways, with crucial roles in coordinating fundamental biological processes during neural development. Here we show that the complete loss of GSK3 signaling in mouse retinal progenitors leads to microphthalmia with broad morphologic defects. A single wild-type allele of either Gsk3α or Gsk3ß is able to rescue this phenotype. In this genetic context, all cell types are present in a functional retina. However, we unexpectedly detected a large number of cells in the inner nuclear layer expressing retinal ganglion cell (RGC)-specific markers (called displaced RGCs, dRGCs) when at least one allele of Gsk3α is expressed. The excess of dRGCs leads to an increased number of axons projecting into the ipsilateral medial terminal nucleus, an area of the brain belonging to the non-image-forming visual circuit and poorly targeted by RGCs in wild-type retina. Transcriptome analysis and optomotor response assay suggest that at least a subset of dRGCs in Gsk3 mutant mice are direction-selective RGCs. Our study thus uncovers a unique role of GSK3 in controlling the production of ganglion cells in the inner nuclear layer, which correspond to dRGCs, a rare and poorly characterized retinal cell type.

Digital Phenotyping of Emotion Dysregulation Across Lifespan Transitions to Better Understand Psychopathology Risk.

Ethical and consensual digital phenotyping through smartphone activity (i. e., passive behavior monitoring) permits measurement of temporal risk trajectories unlike ever before. This data collection modality may be particularly well-suited for capturing emotion dysregulation, a transdiagnostic risk factor for psychopathology, across lifespan transitions. Adolescence, emerging adulthood, and perinatal transitions are particularly sensitive developmental periods, often marked by increased distress. These participant groups are typically assessed with laboratory-based methods that can be costly and burdensome. Passive monitoring presents a relatively cost-effective and unobtrusive way to gather rich and objective information about emotion dysregulation and risk behaviors. We first discuss key theoretically-driven concepts pertaining to emotion dysregulation and passive monitoring. We then identify variables that can be measured passively and hold promise for better understanding emotion dysregulation. For example, two strong markers of emotion dysregulation are sleep disturbance and problematic use of Internet/social media (i.e., use that prompts negative emotions/outcomes). Variables related to mobility are also potentially useful markers, though these variables should be tailored to fit unique features of each developmental stage. Finally, we offer our perspective on candidate digital variables that may prove useful for each developmental transition. Smartphone-based passive monitoring is a rigorous method that can elucidate psychopathology risk across human development. Nonetheless, its use requires researchers to weigh unique ethical considerations, examine relevant theory, and consider developmentally-specific lifespan features that may affect implementation.

Mechanisms of rumination change in adolescent depression (RuMeChange): study protocol for a randomised controlled trial of rumination-focused cognitive behavioural therapy to reduce ruminative habit and risk of depressive relapse in high-ruminating adolescents.

BACKGROUND: Adolescent-onset depression often results in a chronic and recurrent course, and is associated with worse outcomes relative to adult-onset depression. Targeting habitual depressive rumination, a specific known risk factor for relapse, may improve clinical outcomes for adolescents who have experienced a depressive episode. Randomized controlled trials (RCTs) thus far have demonstrated that rumination-focused cognitive behavioral therapy (RFCBT) reduces depressive symptoms and relapse rates in patients with residual depression and adolescents and young adults with elevated rumination. This was also observed in a pilot RCT of adolescents at risk for depressive relapse. Rumination can be measured at the self-report, behavioral, and neural levels- using patterns of connectivity between the Default Mode Network (DMN) and Cognitive Control Network (CCN). Disrupted connectivity is a putative important mechanism for understanding reduced rumination via RFCBT. A feasibility trial in adolescents found that reductions in connectivity between DMN and CCN regions following RFCBT were correlated with change in rumination and depressive symptoms. METHOD: This is a phase III two-arm, two-stage, RCT of depression prevention. The trial tests whether RFCBT reduces identified risk factors for depressive relapse (rumination, patterns of neural connectivity, and depressive symptoms) in adolescents with partially or fully remitted depression and elevated rumination. In the first stage, RFCBT is compared to treatment as usual within the community. In the second stage, the comparator condition is relaxation therapy. Primary outcomes will be (a) reductions in depressive rumination, assessed using the Rumination Response Scale, and (b) reductions in resting state functional magnetic resonance imaging connectivity of DMN (posterior cingulate cortex) to CCN (inferior frontal gyrus), at 16 weeks post-randomization. Secondary outcomes include change in symptoms of depression following treatment, recurrence of depression over 12 months post-intervention period, and whether engagement with therapy homework (as a dose measure) is related to changes in the primary outcomes. DISCUSSION: RFCBT will be evaluated as a putative preventive therapy to reduce the risk of depressive relapse in adolescents, and influence the identified self-report, behavioral, and neural mechanisms of change. Understanding mechanisms that underlie change in rumination is necessary to improve and further disseminate preventive interventions. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03859297 , registered 01 March 2019.