Background: Trait rumination is a habitual response to negative experiences that can emerge during adolescence, increasing risk of depression. Trait rumination is correlated with poor inhibitory control (IC) and altered default mode network (DMN) and cognitive control network (CCN) engagement. Provoking state rumination in high ruminating youth permits investigation of rumination and IC at the neural level, highlighting potential treatment targets. Methods: Fifty-three high-ruminating youth were cued with an unresolved goal that provoked state rumination, then completed a modified Sustained Attention to Response Task (SART) that measures IC (commissions on no-go trials) in a functional MRI study. Thought probes measured state rumination about that unresolved goal and task-focused thoughts during the SART. Results: Greater state rumination during the SART was correlated with more IC failures. CCN engagement increased during rumination (relative to task-focus), including left dorsolateral prefrontal cortex and dorsal-medial prefrontal cortex. Relative to successful response suppression, DMN engagement increased during IC failures amongst individuals with higher state and trait rumination. Exploratory analyzes suggested more bothersome unresolved goals predicted higher left DLPFC activation during rumination. Limitations: The correlational research design did not permit a direct contrast of causal accounts of the relationship between rumination and IC. Conclusions: State rumination was associated with impaired IC and disrupted modulation of DMN and CCN. Increased CCN engagement during rumination suggested effortful suppression of negative thoughts, and this was greater for more bothersome unresolved goals. Relative task disengagement was observed during rumination-related errors. DMN-CCN dysregulation in high-ruminating youth may be an important treatment target.

BACKGROUND:Rumination is implicated in the onset and maintenance of major depressive disorder (MDD). Rumination-Focused Cognitive Behavioral Therapy (RF-CBT) effectively targets rumination and may change resting-state brain connectivity and change in activation during a rumination induction task (RIT) post-intervention predicts depressive symptoms two years later. We examined brain activation changes during an RIT in adolescents with remitted MDD following RF-CBT and evaluated RIT reliability (or stability) during treatment as usual (TAU). METHOD:Fifty-five adolescents ages 14-17 completed an RIT at baseline, were randomized to 10-14 sessions of RF-CBT (n = 30) or treatment as usual (n = 25) and completed an RIT at post-treatment or equivalent time delay. The RIT includes recalling negative memories (Rumination Instruction), dwelling on their meaning/consequences (Rumination Prompt), and imagining unrelated scenes and objects (Distraction). We assessed activation change in the RF-CBT group using paired-samples t-tests. We assessed reliability (or stability) via intraclass correlation coefficients (ICCs) of five rumination-related ROIs for TAU and RF-CBT separately across task blocks. RESULTS:Following treatment, participants receiving RF-CBT demonstrated increased activation of left precuneus during Rumination Instruction and of left angular and superior temporal gyri during Rumination Prompt blocks (p < .01). From baseline to post-treatment, across most ROIs and task blocks, the RF-CBT group demonstrated poor stability (M = 0.21, range = -0.19-0.69), while the TAU group demonstrated fair-to-excellent stability (M = 0.52, range = 0.27-0.86). CONCLUSION:RF-CBT changes activation of rumination-related circuitry during state-induced rumination, offering exciting avenues for future interventions. The RIT has fair-to-excellent stability among individuals not explicitly treated for rumination, and as expected, RIT stability is disrupted by RF-CBT.

IntroductionRumination, 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. MethodWe 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. ResultsLifetime 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. ConclusionDifficulties 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.

To compare body composition and growth in very low birthweight infants according to their source of human milk: maternal expressed breast milk (MEBM) versus donor breast milk (DBM). We hypothesized that infants fed predominately MEBM would exhibit reduced body fat percentage compared to those fed predominately DBM. Premature infants weighing ≤1500 g on an exclusive human milk diet were enrolled in a single-center study between 2017 and 2021. Demographic data and anthropometric measurements were collected. All infants underwent body composition analysis via dual energy x-ray absorptiometry at 36 weeks corrected post menstrual age. A total of 60 infants were enrolled and 48 were included in the primary analysis. No differences were detected in percent body fat (14 vs. 12%, p = 0.7) or fat-free mass (2050 vs. 2130 g, p = 0.7). Both groups displayed similar growth and anthropometric measurements. Caloric and macronutrient intake between groups was similar. In the cohort of patients studied, no differences were observed in percent body fat based on primary human milk type intake in the first 28 postnatal days. Further investigation is required in a larger population of exclusive human milk fed preterm infants to determine if body composition differences exist based on an infant’s primary human milk source.

Rumination is a process contributing to risk for, worsening of, and poor treatment prognosis in depression. We targeted rumination, a habit related to passive, repetitive, negative thought, using rumination focused cognitive behavioral therapy (RFCBT) in adolescents with a history of depression. This registered clinical trial (NCT03859297) is an R61 grant to evaluate changes in the ruminative habit and resting state connectivity after 10 weeks of RFCBT.

Abstract 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.

Clinical trials registrationNCT01905267, https://clinicaltrials.gov/ct2/show/NCT01905267.

Rumination involves a repetitive, passive focus on one's thoughts and feelings and has been hypothesized as a mechanism contributing to multiple psychopathologies. The current investigation explores secondary outcomes from a pilot study to examine whether rumination-focused cognitive behavior therapy (RFCBT) alleviates symptoms of anxiety, increases behavioral activation, or increases global functioning among adolescents with a history of Major Depressive Disorder (MDD). Thirty-three adolescents were randomized to receive either RFCBT (n = 17) or assessment only (AO; n = 16) over the course of eight weeks. Mixed effects regression models were used to conduct intent-to-treat (ITT) analyses. The quadratic interaction for group-by-time-by-time was significant for anxiety. Adolescents in the RFCBT group experienced a significant decrease in anxiety across the first six weeks of intervention (F = 7.01, df = 108.49, p = 0.009). The group-by-time interaction was significant for the behavioral activation outcome (F = 4.28, df = 25.60, p = 0.049) with youth randomized to RFCBT demonstrating increasing activation compared to AO. Global functioning did not significantly differ between groups (F = 0.40, df = 1, p > 0.05). Preliminary evidence suggests that RFCBT may hold promise as an intervention that alleviates both depressive and anxiety symptoms when comorbid.

Introduction: The use of donor human milk for preterm infants is increasing; however, its effects on body composition (BC) are unknown. Extrauterine growth restriction is a problem, and it is difficult to study BC in critically ill preterm infants. Purpose: The purpose of this study is twofold: to compare the BC of very low birth weight (VLBW) preterm infants predominantly feeding maternal expressed breast milk (MEBM) vs. donor human expressed breast milk (DEBM) and to assess the utility of serial bedside ultrasound to predict VLBW infant BC. Methods: Singleton infants …

This study compared the effect of container material type on macronutrient changes in human breast milk (HBM) during frozen storage. HBM was collected from breastfeeding mothers and baseline macronutrients were analyzed and recorded. The HBM was aliquoted into milk storage containers of five commonly used materials (low-density polyethylene (LDPE), polypropylene (PP), glass, stainless steel, and silicone). The samples were frozen in a standard freezer (-20°F) for 30, 60, and 180 days prior to thawing and retesting macronutrient values. In the 155 samples analyzed, macronutrient changes among different types of storage materials were insignificant at 30 and 60 days of frozen storage. When comparing macronutrients at baseline to 180 days, there was a significant decrease in protein value over time in LDPE containers as compared to silicone containers (p=0.001). Likewise, there was a significant decrease in total calories from baseline to 180 days in both PP and LDPE containers compared to silicone (p=0.046 and 0.013, respectively). While not significant for short-term storage, HBM has losses of macronutrients (protein) with long-term storage in LDPE and PP plastics. These differences could have major nutritional impact on growth, particularly to infants born prematurely.

There is substantial variability across studies of default mode network (DMN) connectivity in major depressive disorder, and reliability and time-invariance are not reported. This study evaluates whether DMN dysconnectivity in remitted depression (rMDD) is reliable over time and symptom-independent, and explores convergent relationships with cognitive features of depression. A longitudinal study was conducted with 82 young adults free of psychotropic medications (47 rMDD, 35 healthy controls) who completed clinical structured interviews, neuropsychological assessments, and 2 resting-state fMRI scans across 2 study sites. Functional connectivity analyses from bilateral posterior cingulate and anterior hippocampal formation seeds in DMN were conducted at both time points within a repeated-measures analysis of variance to compare groups and evaluate reliability of group-level connectivity findings. Eleven hyper- (from posterior cingulate) and 6 hypo- (from hippocampal formation) connectivity clusters in rMDD were obtained with moderate to adequate reliability in all but one cluster (ICC's range = 0.50 to 0.76 for 16 of 17). The significant clusters were reduced with a principle component analysis (5 components obtained) to explore these connectivity components, and were then correlated with cognitive features (rumination, cognitive control, learning and memory, and explicit emotion identification). At the exploratory level, for convergent validity, components consisting of posterior cingulate with cognitive control network hyperconnectivity in rMDD were related to cognitive control (inverse) and rumination (positive). Components consisting of anterior hippocampal formation with social emotional network and DMN hypoconnectivity were related to memory (inverse) and happy emotion identification (positive). Thus, time-invariant DMN connectivity differences exist early in the lifespan course of depression and are reliable. The nuanced results suggest a ventral within-network hypoconnectivity associated with poor memory and a dorsal cross-network hyperconnectivity linked to poorer cognitive control and elevated rumination. Study of early course remitted depression with attention to reliability and symptom independence could lead to more readily translatable clinical assessment tools for biomarkers.

Background: Major Depressive Disorder (MDD) is a prevalent, disruptive illness. A majority of those with MDD are at high risk for recurrence and increased risk for morbidity and mortality. This study examined whether multimodal baseline (and retest) Cognitive Control performance and neuroimaging markers (task activation and neural connectivity between key brain nodes) could differentiate between those with and without future recurrence of a major depressive (MD) episode within one year. We hypothesized that performance and neuroimaging measures of Cognitive Control would identify markers that differ between these two groups. Methods: A prospective cohort study of young adults (ages 18-23) with history (h) of early-onset MDD (N = 60), now remitted, and healthy young adults (N = 49). Baseline Cognitive Control measures of performance, task fMRI and resting state connectivity (and reliability retest 4-12 weeks later) were used to compare those with future recurrence of MDD (N = 21) relative to those without future recurrence of MDD (N = 34 with resilience). The measures tested were (1) Parametric Go/No-Go (PGNG) performance, and task activation for (2) PGNG Correct Rejections, (3) PGNG Commission errors, and (4 & 5), resting state connectivity analyses of Cognitive Control Network to and from subgenual anterior cingulate. Results: Relative to other groups at baseline, the group with MDD Recurrence had less bilateral middle frontal gyrus activation during commission errors. MDD Recurrence exhibited greater connectivity of right middle frontal gyrus to subgenual anterior cingulate (SGAC). SGAC connectivity was also elevated in this group to numerous regions in the Cognitive Control Network. Moderate to strong ICCs were present from test to retest, and highest for rs-fMRI markers. There were modest, significant correlations between task, connectivity and behavioral markers that distinguished between groups. Conclusion: Markers of Cognitive Control function could identify those with early course MD who are at risk for depression recurrence. Those at high risk for recurrence would benefit from maintenance or preventative treatments. Future studies could test and validate these markers as potential predictors, accounting for sample selection and bias in feature detection.

Objective: Rumination levels and depression are associated with disrupted connectivity within the default mode network (DMN) and between the DMN and cognitive control network (CCN). This study aims to test these associations of long-distance connectivity of these networks in both healthy and remitted-depressed adolescents and young adults (ages 12 – 28), during peak development.

BACKGROUND:Three well-established intrinsic connectivity networks (ICNs) involved in cognitive-affective processing include the cognitive control network (CCN), default mode network (DMN), and salience and emotional network (SEN). Despite recent advances in understanding developmental changes in these ICNs, the majority of research has focused on single seeds or networks in isolation with limited age ranges. Additionally, although internalizing psychopathologies (IPs), such as anxiety and depression, are often characterized by maladaptive cognitive-affective processing styles, it is not clear how IP history influences age-related changes in brain networks. METHOD:The current study aimed to characterize the normative development of the CCN, DMN, and SEN across a large age-span (7-29 year olds) of typically developing (TD) individuals (n = 97). We also explore how age may impact differences in network connectivity between TD individuals and patients with IPs (n = 136). RESULTS:Among TD individuals, DMN and CCN connectivity strengthened with age, whereas connectivity between the SEN and ventromedial prefrontal cortex weakened across development. When exploring group (IP vs. TD) differences, the IP group was characterized by greater connectivity between the CCN and cerebellum and between the SEN and caudate from childhood to early adulthood, relative to TD individuals. In addition, patients with IPs, versus TD individuals, exhibited reduced connectivity between the SEN and medial frontal gyrus from adolescence to adulthood. CONCLUSIONS:The current findings shed light on differential age-related changes in brain network patterns among psychiatrically free, TD individuals and those with internalizing disorders, and may provide plausible targets for novel mechanism-based treatments that differ based on developmental stage.

Many individuals with major depressive disorder (MDD) experience cognitive dysfunction including impaired cognitive control and negative cognitive styles. Functional connectivity magnetic resonance imaging studies of individuals with current MDD have documented altered resting‐state connectivity within the default‐mode network and across networks. However, no studies to date have evaluated the extent to which impaired connectivity within the cognitive control network (CCN) may be present in remitted MDD (rMDD), nor have studies examined the temporal stability of such attenuation over time. This represents a major gap in understanding stable, trait‐like depression risk phenotypes. In this study, resting‐state functional connectivity data were collected from 52 unmedicated young adults with rMDD and 47 demographically matched healthy controls, using three bilateral seeds in the CCN (dorsolateral prefrontal cortex, inferior parietal lobule, and dorsal anterior cingulate cortex). Mean connectivity within the entire CCN was attenuated among individuals with rMDD, was stable and reliable over time, and was most pronounced with the right dorsolateral prefrontal cortex and right inferior parietal lobule, results that were corroborated by supplemental independent component analysis. Attenuated connectivity in rMDD appeared to be specific to the CCN as opposed to representing attenuated within‐network coherence in other networks (e.g., default‐mode, salience). In addition, attenuated connectivity within the CCN mediated relationships between rMDD status and cognitive risk factors for depression, including ruminative brooding, pessimistic attributional style, and negative automatic thoughts. Given that these cognitive markers are known predictors of relapse, these results suggest that attenuated connectivity within the CCN could represent a biomarker for trait phenotypes of depression risk. Hum Brain Mapp 38:2939–2954, 2017. © 2017 Wiley Periodicals, Inc.

Understanding abnormal resting-state functional connectivity of distributed brain networks may aid in probing and targeting mechanisms involved in major depressive disorder (MDD). To date, few studies have used resting state functional magnetic resonance imaging (rs-fMRI) to attempt to discriminate individuals with MDD from individuals without MDD, and to our knowledge no investigations have examined a remitted (r) population. In this study, we examined the efficiency of support vector machine (SVM) classifier to successfully discriminate rMDD individuals from healthy controls (HCs) in a narrow early-adult age range. We empirically evaluated four feature selection methods including multivariate Least Absolute Shrinkage and Selection Operator (LASSO) and Elastic Net feature selection algorithms. Our results showed that SVM classification with Elastic Net feature selection achieved the highest classification accuracy of 76.1% (sensitivity of 81.5% and specificity of 68.9%) by leave-one-out cross-validation across subjects from a dataset consisting of 38 rMDD individuals and 29 healthy controls. The highest discriminating functional connections were between the left amygdala, left posterior cingulate cortex, bilateral dorso-lateral prefrontal cortex, and right ventral striatum. These appear to be key nodes in the etiopathophysiology of MDD, within and between default mode, salience and cognitive control networks. This technique demonstrates early promise for using rs-fMRI connectivity as a putative neurobiological marker capable of distinguishing between individuals with and without rMDD. These methods may be extended to periods of risk prior to illness onset, thereby allowing for earlier diagnosis, prevention, and intervention.

Paraprofessional workforces are becoming more common and can serve the otherwise unmet needs of diverse children and families. Compared to other workforces, limited research to date has explored factors such as stress and burnout that influence the sustainability of this workforce. Mindfulness-based interventions have been studied as stress-reduction programs for other workforces, but it is currently unknown whether mindfulness is acceptable to paraprofessionals, particularly those of a diverse ethnicity living in low-income, urban environments. The current investigation is a pilot study examining whether six weeks of mindfulness-based skills training can reduce stress, burnout, and improve sleep quality among a diverse paraprofessional workforce. Twenty six paraprofessionals (ages 24–58, M = 37.04, SD = 9.65) completed measures pre-training, post-training, and at a four week follow-up. Results indicated that this paraprofessional workforce found mindfulness practices acceptable and experienced significant reductions in perceived stress and emotional exhaustion, as well as improved sleep quality (p < .05) Mindfulness-based interventions may be useful in supporting the wellbeing of paraprofessionals from diverse backgrounds working in low-income, urban environments.

ABSTRACTObjectives:The aim of the study was to determine the acute and long‐term outcomes of preterm infants treated with an intravenous fish oil–based lipid emulsion (FishLE) for parenteral nutrition–associated liver disease (PNALD).Methods:Preterm infants 14 days to 24 months of age with anatomic short gut or severe intestinal dysmotility, serum direct bilirubin ≥4 mg/dL, and requiring >60% calories from parenteral nutrition were eligible. Enrolled infants received 1 g · kg–1 · day−1 of FishLE until resolution of direct hyperbilirubinemia or return of enteral nutrition. Acute clinical effects and biochemical markers of liver function were monitored. Growth and developmental scores at 6 and 12 months postmenstrual age (PMA) were assessed and compared with controls matched by gestational age (GA).Results:Thirteen patients with mean GA of 28 ± 4 weeks were treated and compared with 119 GA‐matched controls. Their mean direct bilirubin was 9.8 ± 6.4 mg/dL at enrollment. All infants had resolution of cholestasis after study completion. There were no acute adverse events, deaths, or liver/intestinal transplants. Weight and head circumference were similar between FishLE‐treated patients and controls at 6‐ and 12‐month PMA. Cognitive and motor scores were decreased at 6 and 12 months PMA in FishLE‐treated infants. Logistic regression analysis showed that prolonged hospitalization was detrimental to cognitive and motor development, whereas treatment was not.Conclusions:The use of intravenous FishLEs in premature infants appears to be safe and reverses PNALD despite significant liver disease and intestinal failure. This therapy should be used in preterm infants with PNALD and followed long term to evaluate development.

Maternal rumination is a cognitive-affective trait that could influence offspring's ability to respond flexibly to positive and negative events, depending on the quality of maternal problem-solving behaviors with which rumination co-occurs. As reward circuitry is sensitive to stressors and related to risk for depression, reward circuitry is an appropriate candidate mechanism for how maternal characteristics influence offspring. We evaluated the independent and combined effect of maternal rumination and disengagement on adolescent neural response to reward win and loss. Participants were 122 boys and their mothers from low-income, urban backgrounds followed prospectively in a longitudinal study. The combination of high maternal rumination at child age 6 and high maternal disengagement during problem-solving at child age 10-12 was associated with lower anterior cingulate response to winning reward at age 20, but unrelated to neural response to losing reward. Lower anterior cingulate response to winning reward was associated with fewer anxiety symptoms during late adulthood. Findings suggest that maternal rumination occurring within the context of maternal disengagement during challenging experiences may be related to offspring blunted engagement during positive events. Helping highly ruminative mothers to restructure repetitive negative thoughts and to develop context appropriate problem-solving behaviors may be important for promoting offspring affective development.