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Residence in high-crime neighborhoods, especially in childhood, is linked to mental health issues later. Detecting distinct neurobiological processes underlying the effects of this environmental stressor may be critical to identifying prevention and intervention targets. This study examined the relationships of levels of a circulating inflammatory protein with social and monetary reward-related brain function among adolescents who lived in high- versus low-crime neighborhoods during childhood.A total of 70 participants (mean age = 16.3 years; 57% female) completed measures of inflammatory markers, depression history, and health and 2 functional magnetic resonance imaging tasks assessing responsivity to monetary and social rewards. Multivariate linear regression tested whether individuals with higher interleukin 6, an inflammatory cytokine, who also lived in neighborhoods with higher crime had distinct orbitofrontal cortex and nucleus accumbens activation to monetary reward and social acceptance.For adolescents who lived in neighborhoods with more crime, higher interleukin 6 was associated with higher nucleus accumbens responses to social acceptance. We did not detect significant moderating effects of neighborhood crime rates on the associations of interleukin 6 with orbitofrontal cortex responses to social acceptance or orbitofrontal cortex/nucleus accumbens activation during monetary reward anticipation or outcome. These results were obtained before and after adjusting for neighborhood income and other covariates. We did not detect significant moderating effects of neighborhood income.High-threat residence environment and specific demands of the social context in childhood may have shaped the effect of peripheral immune activation on reward-related neural function in adolescence. The prevailing view that inflammation-associated behaviors are characterized by blunted responsiveness to reward may be oversimplistic.

Iron deficiency anemia (IDA) is the leading nutritional disorder in the world. Iron deficiency (ID) occurs commonly in the US, particularly among children and women and in the elderly. Its impact on quality of life includes decreased cognitive ability and increased fatigue. Thus, there is clearly a need for effective and economical approaches to providing adequate dietary iron. We introduce nutritional yeast (S. cerevisiae) technologically modified to express human H-ferritin as a potential source of dietary iron. The efficacy of the yeast ferritin complex (YFC) was tested in established rat and monkey models of ID. In the rat model of ID, YFC improved hemoglobin (Hgb), hematocrit (Hct) levels as well as plasma iron and transferrin saturation and liver and spleen iron concentrations. Moreover, the YFC achieved a larger effect on Hgb and Hct with consumption of less iron compared to ferrous sulfate over a similar period. In the monkeys, YFC supplemented diet significantly improved Hgb levels within one month and increased mean corpuscular volume (MCV) by two months. To demonstrate that the Fe in the YFC was utilized by RBCs, we used a labeled isotope approach and found Fe from the ferritin in the monkeys’ RBCs with 5 days of consumption. This is the first attempt to use H-ferritin homopolymer as a nutritional iron source. Previous data from our laboratory and others have established H-ferritin as a significant iron delivery protein to the brain. Thus, H-ferritin appears to have a novel function as an iron delivery protein independent from its cooperation with L-ferritin to form an iron storage protein.

ObjectivesTo assess the benefits of training in mindfulness-based stress reduction (MBSR) or moderate intensity exercise (EX) for improving sleep quality.DesignRandomized controlled trial.SettingOutpatient, community-based.ParticipantsHealthy adults (n=413) aged 30-69 who did not regularly exercise or practice meditation, and who had no known prior sleep problems.Interventions1) 8-weeks of MBSR training; 2) matched EX training; or 3) wait-list control.MeasurementsThe Pittsburgh Sleep Quality Index (PSQI) was administered at baseline and at 1, 3, 5, and 7-month follow-up visits.AnalysisTotal PSQI scores and three PSQI factors (perceived sleep quality; daily disturbance, sleep efficiency) were assessed using linear mixed effects regression models for longitudinal data.ResultsCompared to controls, PSQI global scores improved significantly for EX (mean change -0.98 points [95% CI -1.56, -0.41] p=0.001) and marginally for MBSR (-0.53 [-1.10, 0.04] p=0.07). The perceived sleep quality factor improved for both EX (-0.18 [-0.30, -0.07] p=0.002) and MBSR (-0.12 [-0.24, -0.01] p=0.035). The daily disturbance factor improved slightly more for MBSR (-0.13 [-0.22, -0.033] p=0.008) than EX (-0.09 [-0.19, 0.004] p=0.06). The sleep efficiency factor did not improve after MBSR (0.08 [-0.045, 0.21] p=0.2) or EX (-0.07 [-0.20, 0.06] p=0.3). Improvements in the sleep quality were sustained over 7 months for both groups.ConclusionsTraining in MBSR and EX produced small but statistically significant and sustained improvements in sleep quality. For EX participants, this improvement was due primarily to improvements in perceived sleep quality. For MBSR, the decrease in daily disturbance was more important.

Early adverse care has long-term impacts on physical and mental health. The influence of rearing conditions on the infant's gut microbiota and its relationship with developmental health has become more evident. The microbiome is essential for normal growth and metabolism, and the signaling from the gut to the brain may underlie individual differences in resilience later in life. Microbial diversity and composition were determined using 16S rRNA gene amplicon sequencing in fecal samples from 17 adolescents adopted internationally from orphanages into the United States and 18 adolescents reared in birth families who had similar educational and income levels. Analyses focused on diversity of the microbial community structure and differences in the abundance of specific bacterial taxa. Blood samples were used to immunophenotype the numbers of several T-cell subsets and cytomegalovirus (CMV) seropositivity. Negative binomial regression analysis revealed several operational taxonomic units that were significantly different based on early rearing conditions and CMV seropositivity. There were significant associations between the relative abundance of certain taxa, the percentages of T-cell subsets in circulation, and CMV seropositivity. These findings demonstrate a possible link between the gut microbiota and associations with immune alterations initiated by early life adversity.

Prior research has demonstrated that the daily experience of negative affect is associated with increased levels of proinflammatory activity as evidenced by higher interleukin-6 among Americans but not among Japanese. This cultural difference may be driven by culturally divergent beliefs about negative affect as a source of threat to self-image versus as natural and integral to life. Here, we examined whether culture may moderate the relationship between negative affect and biological stress responses, with a focus on the hypothalamic-pituitary-adrenal (HPA) axis activity. By using culturally matched surveys of Americans (N = 761) and Japanese (N = 328), we found that negative affect was associated with a flattening of the diurnal cortisol slope among Americans after controlling for demographic variables, personality traits, sleep patterns, and health behaviors. In contrast, the association between negative affect and the HPA axis activity was negligible among Japanese. Moreover, we assessed biological health risk with biomarkers of both inflammation (interleukin-6 and C-reactive protein levels) and cardiovascular function (higher systolic blood pressure and total-to-HDL cholesterol ratio) and found that the relationship between negative affect and increased biological health risk, which was observed only among Americans, was mediated by the flattening of the diurnal cortisol rhythm. These findings suggest that cultural differences in how emotions are construed may make the experience of negative affect more or less stressful and differentially consequential for health. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

This study investigated whether longitudinal changes in inflammatory physiology moderated the relationship between recent stressful life events and subsequent depressive symptoms in adolescence. A diverse sample of adolescents representative of an urban community (N = 129; Age at baseline = 12.5 years; 48.8% female; 55.0% African American) completed measures of stressful life events, depressive symptoms, and two annual blood draws (BD1 and BD2). Controlling for inflammatory activity at BD1, depression at BD1, demographics and the time between assessments, increases in interleukin-6 (IL-6; b = 0.878, p = .007) and C-reactive protein (CRP; b = 0.252, p = .024) from BD1 to BD2 interacted with recent stressful life events before BD1 to predict severity of depressive symptoms at BD2. Similar associations were evident for IL-6 (b = 2.074, p = .040) and CRP (b = 0.919, p = .050) when considering acute stressful life events that had occurred within the two weeks before the first blood collection. More frequent stressful life events before BD1 predicted significantly more severe depressive symptoms at BD2, but only for adolescents with moderate (50th percentile) and high (84th percentile) levels of IL-6 and CRP at BD2. In conclusion, adolescents who experienced both recent stressful life events and larger increases in inflammatory activity following these stressors were at increased risk for more severe depressive symptoms after approximately one year. The findings indicate that the interaction of stress and larger changes in inflammatory activity following these stressors are prognostic risk factors for depression severity in adolescents.

Inflammation is gaining support as a biological mediator between stress and many negative outcomes that have heightened risk during adolescence (e.g., mood disorders). Thus, an important line of inquiry is evaluating whether risk factors for mood psychopathology also are associated with heightened inflammatory responses to stress during this developmental period. Two prominent risk factors that interact to predict mood psychopathology are reward sensitivity and perseverative cognitive response styles, which also have been associated with heightened inflammatory proteins. These factors could influence inflammation by synergistically amplifying stress reactivity. Ninety-four late adolescents (Mage = 18.3 years, range = 15.6 – 21.9 years) completed measures of reward sensitivity, cognitive response style, and blood draws before and 90-minutes after a modified Trier Social Stress Task to determine levels of inflammation. Higher reward drive interacted with more perseverative response style ratios (rumination relative to distraction + problem-solving) to predict larger increases in interleukin-6 (a proinflammatory protein). Follow-up analyses found that reward drive interacted with all three components of the ratio to predict change in interleukin-6. Thus, these results suggest that high reward drive and perseverative cognitive response styles are associated with increased inflammatory response to social stress in adolescents, a potential physiological mechanism linking these risk factors to mood psychopathology during this developmental period.

AIM: To compare the prevalence of poor glycemic control in probability samples of Japanese and American adults, and to determine the association with their somatic phenotypes. MATERIAL AND METHODS: Blood samples and anthropometric measures were obtained from 382 Japanese, 32–79 years of age, randomly selected to reflect the 23 wards of Tokyo. HA1c values were compared to 1215 Americans, 35–86 years of age, from a national study across the 48 continental states, along with an over-sampling of African-Americans from one city (www.midus.wisc.edu). Body Mass Index (BMI) and Waist-hip ratio (WHR) were also assessed. RESULTS: Many Japanese now have high HA1c approaching Caucasian-American levels, although elevated HA1c (>6.5%, 48 mmol/mol) is not nearly as prevalent as among African-Americans. Significant age-related trends were evident in both countries, with poor glycemic control occurring at younger ages in males and rarely found until old age in Japanese women. Japanese had higher HA1c levels at BMIs of 23–25, in contrast to Americans with Type 2 diabetes who more typically had a BMI over 30. Central adiposity predicted HA1c levels better than BMI, a relationship also apparent at a smaller WHR in Japan. CONCLUSION: The prevalence of high HA1c in Tokyo almost rivals white Americans, but those statistics are dwarfed by the 37% of Afr-Amer adults identified with Type 2 diabetes. Elevated HA1c was more common in men, reflecting central adiposity, but poor glycemic control was also widespread among overweight Afr-Amer women. Type 2 diabetes was higher among older Japanese, when more women succumb. Overall, the findings highlight the societal and clinical challenges posed by demographic trends in both countries.

This research was supported by National Institute of Mental Health Grants MH079369 and MH101168 awarded to Lauren Alloy, National Institute of Mental Health Grant MH096478 awarded to Lauren Ellman and National Research Service Awards F31MH118808 to Naoise Mac Giollabhui.

Chronic alcohol misuse can result in chronically elevated interleukin (IL)-6, a pro-inflammatory cytokine, in the bloodstream. Given that Mindfulness-Based Relapse Prevention (MBRP) has been shown to reduce alcohol misuse, MBRP might also be effective in reducing IL-6 concentrations. Past research has found, however, that IL-6 does not respond consistently to mindfulness-based interventions. Building on prior studies, we examined whether between-person variability in engagement with mindfulness training (i.e., formal mindfulness practice time) is associated with between-person variability in changes in serum IL-6, using data from a randomized controlled trial evaluating MBRP for Alcohol Dependence (MBRP-A). Participants were 72 alcohol dependent adults (mean age = 43.4 years, 63.9% male, 93.1% White) who received a minimum dose (i.e., at least four sessions) of MBRP-A either at the start of the trial (n = 46) or after a 26-week delay (n = 26). IL-6 concentrations did not significantly change from pre- to post-intervention for the full sample. Nevertheless, greater mindfulness practice time was significantly associated with reduced IL-6 levels (r = −0.27). The association between practice time and IL-6 changes remained significant when controlling for intervention timing (i.e., immediate or after the 26-week delay), demographic characteristics, and changes in mindful awareness, obsessive-compulsive drinking, and depressive symptoms. The association between practice time and IL-6 changes was not significant when omitting the minimum treatment dose requirement. Overall, results suggest that the level of engagement in mindfulness training may predict changes in the inflammatory pathophysiology in adults with alcohol dependence.

A better understanding of the maturational correlates of inflammatory activity during adolescence is needed to more appropriately study both normal and abnormal development. Inflammation is the immune system’s first response to infection, injury, or psychological stress, and it has been shown to be elevated in individuals with both physical and psychological conditions. This study examined unique associations between (1) pubertal status and inflammatory biomarkers, and (2) age and inflammatory biomarkers, and whether these relationships differed by sex in a diverse sample of 155 adolescents (54.2% female, 45.8% male; M(age) = 16.22) from a northeastern city in the US. A more advanced pubertal status was uniquely associated with lower levels of tumor necrosis factor alpha (TNF-α) and interleukin-8 (IL-8). Chronological age was uniquely associated with lower IL-8 levels. The association between pubertal status and C-reactive protein (CRP) levels differed by sex: more mature females had higher CRP, whereas pubertal status and CRP were not significantly associated in males. These findings highlight an important relation between pubertal development and inflammatory activity during adolescence.

Past studies have documented links between mindfulness practice and stress-related outcomes, but these links have typically been found over the course of treatment and at the between-person level of analysis. Building on past work, the present study aimed to evaluate practice-stress associations after treatment and at the within-person and between-person levels. We drew extant data collected from 138 community-recruited adults who had received a standard, 8-week mindfulness-based stress reduction (MBSR) course and were asked to record formal and informal mindfulness practice time daily and complete a self-report measure of stress every 2 months over a 6-month follow-up period. Latent curve modeling was used to test the within-person and between-person components of the relation between practice and stress over the follow-up period. Results indicated that, at the within-person level, formal practice time from 2 to 4 months after treatment significantly predicted stress levels 4 months after treatment, and formal and informal practice time from 4 to 6 months after treatment significantly predicted stress levels 6 month after treatment. At the between-person level, formal and informal practice times were not significantly related to stress levels over the follow-up period. Overall, the present findings highlight the potential importance of post-intervention practice and suggest that higher practice engagement 2 to 6 months after MBSR training predicts lower levels of subsequent stress. Results are discussed in the context of mindfulness theory and MBSR training curriculum.

Exercise and meditation improve health and well-being, potentially through decreasing systemic inflammation. In this study, healthy adults (N = 413) were randomized to 8 weeks of training in aerobic exercise, matched mindfulness-based stress reduction, or wait-list control. Three inflammation-related biomarkers (C-reactive protein, interleukin-6, and interferon-gamma-inducible protein-10) were assessed preintervention, directly postintervention, and 17 weeks later. Within-group analyses found that exercise participants had decreased serum interferon-gamma-inducible protein-10 postintervention and 17 weeks later, whereas C-reactive protein was lower in mindfulness-based stress-reduction participants 17 weeks postintervention only. Self-reported physical activity or amount of meditation practice did not predict biomarker changes. This study suggests that (a) training in aerobic exercise can lower interferon-gamma-inducible protein-10, a chemokine associated with interferon activity and illness, and (b) training in mindfulness meditation may have a delayed effect on C-reactive protein, an important inflammatory biomarker. The findings highlight the likelihood of multiple, distinct pathways underlying the health-promoting effects of these lifestyle interventions.

BackgroundThere is substantial evidence that many depressed individuals experience impaired executive functioning. Understanding the causes of executive dysfunction in depression is clinically important because cognitive impairment is a substantial contributor to functional impairment. This study investigated whether elevated levels of an inflammatory cytokine [interleukin-6 (IL-6)] and/or higher body mass index (BMI) concurrently and/or prospectively accounted for the relationship between depressive symptoms and impaired executive functioning in adolescents.MethodsA diverse, community sample of adolescents (N = 288; mean age = 16.33; 51.4% female; 59.0% African-American) completed assessments of height and weight, IL-6, depressive symptoms, and self-report/behavioral measures of executive functioning (selective attention, switching attention) and future orientation annually over 3 years. Adolescents experiencing acute illness or medical conditions that affect inflammation were excluded from analyses. Path analysis within a structural equation modeling framework simultaneously examined the concurrent and prospective relationships between BMI, IL-6, depressive symptoms, and the measures of cognitive functioning across three timepoints.ResultsAcross all timepoints, higher BMI was prospectively associated with higher levels of IL-6 and depressive symptoms, while higher levels of IL-6 were associated with worse performance on three behavioral and self-report measures of cognitive functioning. Higher depressive symptoms also were prospectively associated with elevated IL-6 and both higher depressive symptoms and a higher BMI predicted worse future executive functioning via increased IL-6.ConclusionsMore severe depressive symptoms and increased BMI may disrupt executive functioning via elevated IL-6.

Much inflammation research examines individual proteins; however, some studies have used summed score composites of all available inflammatory markers without first investigating dimensionality. Using three different samples (MIDUS-2: N = 1,255 adults, MIDUS-R: N =863 adults, and ACE: N = 315 adolescents), this study investigates the dimensionality of eight inflammatory proteins (C-reactive protein (CRP), interleukin (IL)-6, IL-8, IL-10, tumor necrosis factor- (TNF-), fibrinogen, E-selectin, and intercellular adhesion molecule (ICAM)-1) and compares the resulting factor structure to a) an "a priori" factor structure in which all inflammatory proteins equally load onto a single dimension (a technique that has been used previously) and b) proteins modeled individually (i.e., no latent variable) in terms of model fit, replicability, reliability, temporal stability, and their associations with medical history and depression symptoms. A hierarchical factor structure with two first-order factors (Factor 1A: CRP, IL-6, fibrinogen; Factor 2A: TNF-, IL-8, IL-10, ICAM-1, IL-6) and a second-order general inflammation factor was identified in MIDUS-2 and replicated in MIDUS-R and partially replicated in ACE (which unfortunately only had CRP, IL-6, IL-8, IL-10, and TNF- but, unlike the other two, has longitudinal data). Both the empirically-identified structure and modeling proteins individually fit the data better compared to the one-dimensional "a priori" structure. Results did not clearly indicate whether the empirically-identified factor structure or the individual proteins modeled without a latent variable had superior model fit. Modeling the empirically-identified factors and individual proteins (without a latent factor) as outcomes of medical diagnoses resulted in comparable conclusions, but modeling empirically-identified factors resulted in fewer results "lost" to correction for multiple comparisons. Importantly, when the factor scores were recreated in a longitudinal dataset, none of the individual proteins, the "a priori" factor, or the empirically-identified general inflammation factor significantly predicted concurrent depression symptoms in multilevel models. However, both empirically-identified first-order factors were significantly associated with depression, in opposite directions. Measurement properties are reported for the different aggregates and individual proteins as appropriate, which can be used in the design and interpretation of future studies. These results indicate that modeling inflammation as a unidimensional construct equally associated with all available proteins does not fit the data well. Instead, empirically-supported aggregates of inflammation, or individual inflammatory markers, should be used in accordance with theory. Further, the aggregation of shared variance achieved by constructing empirically-supported aggregates might increase predictive validity compared to other modeling choices, maximizing statistical power.

Over the last decade, multiple studies have highlighted the essential role of gut microbiota in normal infant development. However, the sensitive periods during which gut bacteria are established and become associated with physical growth and maturation of the brain are still poorly defined. This study tracked the assembly of the intestinal microbiota during the initial nursing period, and changes in community structure after transitioning to solid food in infant rhesus monkeys (Macaca mulatta). Anthropometric measures and rectal swabs were obtained at 2-month intervals across the first year of life and bacterial taxa identified by 16S rRNA gene sequencing. At 12 months of age, total brain and cortical regions volumes were quantified through structural magnetic resonance imaging. The bacterial community structure was dynamic and characterized by discrete maturational phases, reflecting an early influence of breast milk and the later transition to solid foods. Commensal microbial taxa varied with diet similar to findings in other animals and human infants; however, monkeys differ in the relative abundances of Lactobacilli and Bifidobacteria, two taxa predominant in breastfed human infants. Higher abundances of taxa in the phylum Proteobacteria during nursing were predictive of slower growth trajectories and smaller brain volumes at one year of age. Our findings define discrete phases of microbial succession in infant monkeys and suggest there may be a critical period during nursing when endogenous differences in certain taxa can shift the community structure and influence the pace of physical growth and the maturational trajectory of the brain.

A high percent of oxidative energy metabolism is needed to support brain growth during infancy. Unhealthy diets and limited nutrition, as well as other environmental insults, can compromise these essential developmental processes. In particular, iron deficiency anemia (IDA) has been found to undermine both normal brain growth and neurobehavioral development. Even moderate ID may affect neural maturation because when iron is limited, it is prioritized first to red blood cells over the brain. A primate model was used to investigate the neural effects of a transient ID and if deficits would persist after iron treatment. The large size and postnatal growth of the monkey brain makes the findings relevant to the metabolic and iron needs of human infants, and initiating treatment upon diagnosis of anemia reflects clinical practice. Specifically, this analysis determined whether brain maturation would still be compromised at 1 year of age if an anemic infant was treated promptly once diagnosed. The hematology and iron status of 41 infant rhesus monkeys was screened at 2-month intervals. Fifteen became ID; 12 met clinical criteria for anemia and were administered iron dextran and B vitamins for 1–2 months. MRI scans were acquired at 1 year. The volumetric and diffusion tensor imaging (DTI) measures from the ID infants were compared with monkeys who remained continuously iron sufficient (IS). A prior history of ID was associated with smaller total brain volumes, driven primarily by significantly less total gray matter (GM) and smaller GM volumes in several cortical regions. At the macrostructual level, the effect on white matter volumes (WM) was not as overt. However, DTI analyses of WM microstructure indicated two later-maturating anterior tracts were negatively affected. The findings reaffirm the importance of iron for normal brain development. Given that brain differences were still evident even after iron treatment and following recovery of iron-dependent hematological indices, the results highlight the importance of early detection and preemptive supplementation to limit the neural consequences of ID.

Background Microbiome research has expanded to consider contributions of microbial kingdoms beyond bacteria, including fungi (i.e., the mycobiome). However, optimal specimen handling protocols are varied, including uncertainty of how enzymes utilized to facilitate fungal DNA recovery may interfere with bacterial microbiome sequencing from the same samples. Methods With Institutional Animal Care and Use Committee approval, fecal samples were obtained from 20 rhesus macaques (10 males, 10 females; Macaca mulatta). DNA was extracted using commercially available kits, with or without lyticase enzyme treatment. 16S ribosomal RNA (bacterial) and Internal Transcribed Spacer (ITS; fungal) sequencing was performed on the Illumina MiSeq platform. Bioinformatics analysis was performed using Qiime and Calypso. Results Inclusion of lyticase in the sample preparation pipeline significantly increased usable fungal ITS reads, community alpha diversity, and enhanced detection of numerous fungal genera that were otherwise poorly or not detected in primate fecal samples. Bacterial 16S ribosomal RNA amplicons obtained from library preparation were statistically unchanged by the presence of lyticase. Conclusions We demonstrate inclusion of the enzyme lyticase for fungal cell wall digestion markedly enhances mycobiota detection while maintaining fidelity of microbiome identification and community features in non-human primates. In restricted sample volumes, as are common in limited human samples, use of single sample DNA isolation will facilitate increased rigor and controlled approaches in future work.

The calcineurin inhibitors cyclosporine and tacrolimus are used for their immunosuppressive effects. Neurotoxic side effects include tremor, paresthesia, and headache. Rarer neurotoxicities include seizure, posterior reversible encephalopathy syndrome, and encephalopathy. Tacrolimus tends to be more neurotoxic than cyclosporine. Management of toxicities associated with calcineurin inhibitors includes dose reduction, switching between calcineurin inhibitors, or switching to a calcineurin-free regimen. Tumor necrosis factor (TNF) inhibitors are used in autoimmune diseases. Management of demyelinating conditions among patients treated with anti-TNF should follow standard of care and withdrawal of the anti-TNF. This drug class should be avoided in patients with a history of demyelinating conditions.

Background Allogeneic hematopoietic cell transplantation (HCT) is a widely used treatment for hematologic cancers, with survival rates ranging from 25% to 78%. Known risk factors for chronic graft-versus-host disease (cGVHD), a serious and common long-term complication, disease relapse, and mortality following HCT have been identified, but much of the variability in HCT outcomes is unexplained. Biobehavioral symptoms including depression, sleep disruption, and fatigue are some of the most prevalent and distressing for patients; yet research on biobehavioral risk factors for HCT outcomes is limited. This study evaluated patient-reported depression, sleep disruption, and fatigue as risk factors for cGVHD, disease relapse, and mortality. Methods Adults receiving allogeneic HCT for a hematologic malignancy (N = 241) completed self-report measures of depression symptoms, sleep quality, and fatigue (severity, interference) pre-HCT and 100 days post-HCT. Clinical outcomes were monitored for up to 6 years. Results Cox proportional hazard models (2-tailed) adjusting for patient demographic and medical characteristics revealed that high pre-HCT sleep disruption (Pittsburgh Sleep Quality Index >9; hazard ratio [HR] = 2.74, 95% confidence interval [CI] = 1.27 to 5.92) and greater post-HCT fatigue interference (HR = 1.32, 95% CI = 1.05 to 1.66) uniquely predicted increased risk of mortality. Moderate pre-HCT sleep disruption (Pittsburgh Sleep Quality Index 6-9) predicted increased risk of relapse (HR = 1.99, 95% CI = 1.02 to 3.87). Biobehavioral symptoms did not predict cGVHD incidence. Conclusions Biobehavioral symptoms, particularly sleep disruption and fatigue interference, predicted an increased risk for 6-year relapse and mortality after HCT. Because these symptoms are amenable to treatment, they offer specific targets for intervention to improve HCT outcomes.

Background The effectiveness and safety of gastroenterologist (GI)-lead treatment of iron deficiency anemia (IDA) in inflammatory bowel disease (IBD) have not been well-studied. Methods A retrospective chart review of patients with IBD, IDA, and evidence of treatment with iron at a tertiary IBD center was conducted. Results In 351 patients, hemoglobin and quality of life scores increased significantly after treatment with iron. Twelve of 341 patients treated with intravenous iron had an adverse effect. Twenty-seven patients required a hematology referral. Conclusion GIs should consider treating patients with IBD and IDA with intravenous iron as it is safe and effective., Lay Summary We reviewed records of patients with anemia and inflammatory bowel disease and found that gastroenterologists can effectively and safely treat anemia in these patients. This improved patients’ quality of life. Most patients did not need to see a separate specialist.

Chronic, systemic inflammation is implicated in physical and mental health; little is known about whether sex and racial differences detected in adulthood are observed during adolescence or about normative changes occurring during adolescence. This longitudinal, United States-based study examined four biomarkers of systemic inflammation [C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and IL-8) in 315 adolescents (51% female; 58% black; baseline age = 16.49 years (SD = 1.56; range: 12.14–21.28)] at three timepoints. Notable results included: general decline in inflammatory biomarkers in older adolescents, lower levels of TNF-α/IL-8 in black adolescents, elevated CRP/IL-6 in females, and especially higher levels of IL-6 in black, female adolescents. Implications are discussed, particularly the potential health implications of elevated IL-6 in black females.

This study examined whether early life adversity (ELA) limited to infancy was associated with an increase in circulating levels of proinflammatory cytokines and cellular cytokine responses to three stimulants [lipopolysaccharide (LPS), phytohemagglutinin (PHA), and phorbol myristate acetate plus ionomycin (PMA/IO)]. Participants were previously institutionalized (PI) youth (N = 45, 56 % female) who had spent their first years in institutional care (e.g., orphanages, baby homes) before being adopted into well-resourced homes (median age at adoption = 13 mos) and non-adopted comparisons (NA; N = 38, 55 % female). Their age range was 13.3–21.2 years (M = 16.3 years). This analysis followed up an earlier report on these youth (Reid et al., 2019a) that identified an increase in terminally differentiated CD8 + CD57 T cells among the PI relative to the NA youth. Cytokine levels in circulation were not highly correlated and thus examined separately. PI youth had higher circulating levels of Tumor Necrosis Factor-alpha (TNFα), but not Interleukin-1β (IL-1β) or Interleukin-6 (IL-6). Cytokine responses to in vitro activation within each stimulant condition were highly correlated and were thus combined to generate an index of the inflammatory reaction to each stimulant. Using Multivariate Analysis of Covariance, there was a highly significant multivariate effect of group, which was carried primarily by the PMA/IO condition, with PI youth exhibiting a larger inflammatory response than NA youth. Tests of mediation showed that both the early rearing effects on circulating TNFα and the composite inflammatory index of PMA/IO responsiveness were mediated in the statistical model by the percentage of CD8 + CD57+ TEMRA cells in circulation, a marker of replicative senescence in T cells. Sex differences were also found in circulating levels of IL-6 and TNFα, with males having higher levels than females.

There are inconsistent findings in the literature about the directionality and magnitude of the association between inflammation and depressive symptoms. This analysis separates predictors into between-persons and within-person components to gain greater clarity about this relationship. Blood samples were collected and depressive symptoms assessed in 140 adolescents (54% female, 59% Black; mean age = 16.1 years) with at least three blood draws and a total of 394 follow-up observations. Multilevel modeling indicated that the within-persons effect of tumor necrosis factor α predicted change in total depressive symptoms, which suggests a potential causal relationship. There were no significant within-persons effects of total depressive symptoms on change in biomarkers. Exploratory analyses examined associations between inflammatory biomarkers and subsets of depressive symptoms. These findings inform modeling decisions that may explain inconsistencies in the extant literature as well as suggest potential causal relationships between certain proteins with significant within-persons effects on depressive symptoms and vice-versa.