Adolescent Developmental Pathways Among Depression, Conduct Problems, and Rejection: Integrative Data Analysis Across Three Samples.

OBJECTIVE: The current study investigated sex differences in longitudinal associations among youth depression, conduct problems, and peer rejection from ages 11 to 16. We hypothesized that girls would follow the irritable depression model, which posits that depression leads to conduct problems, and that peer rejection would mediate this relationship. We hypothesized that boys would follow the cumulative failure model, which suggests that conduct problems predict future depression, mediated by peer rejection. METHOD: We used integrative data analysis to combine three datasets, creating an aggregate sample of 2,322 adolescents, 58.4% of an ethnic minority group, and 51.3% boys. Using random-intercept cross-lagged panel modeling with data from ages 11-16, we conducted a nested model comparison. RESULTS: Results indicated that a model which allowed paths to differ by sex demonstrated better model fit than a constrained model. While depression, conduct problems, and peer rejection were relatively stable over time and had correlated random intercepts, there were few crossover paths between these domains for either sex. When the strengths of individual crossover pathways were compared based on sex, only the path from conduct problems at age 13 to depression at age 14 was significantly different, with this path being stronger for girls. CONCLUSIONS: These results suggest that stable, between-person effects largely drive relationships between depression, conduct problems, and peer rejection during adolescence, whereas there are few transactional, within-person pathways between these domains. This pattern of findings demonstrates the utility of random intercept cross-lagged panel modeling for disentangling between- and within-person effects.

Interferon-Gamma-Inducible Protein-10 (IP-10) and Tumor Necrosis Factor-α (TNF-α) as Serological Predictors of Active Disease Status in Localized Scleroderma.

We investigated the ability of a panel of immune-related cytokines and chemokines to predict the disease activity state in localized scleroderma (LS) subjects followed longitudinally. A total of 194 sera samples were obtained from 45 LS subjects with diverse types of LS (40% linear, 20% mixed, 16% craniofacial, 13% generalized, and 11% circumscribed) in our cohort. Cytokines/chemokines that were significantly elevated at the baseline active disease visit compared to the inactive disease state at follow-up were Interferon-Gamma-Inducible Protein (IP)-10 (p < 0.021) and Tumor Necrosis Factor (TNF)-α (p < 0.033). Mixed effect logit modeling identified IP-10 (Odds Ratio (OR) [95% confidence interval] = 2.1 [1.4, 3.2], p < 0.001), TNF-α (OR = 1.8 [1.1, 3.0], p = 0.016), and Monocyte Chemoattractant Protein (MCP)-1 (OR = 2.0 [1.1, 3.9], p = 0.034) as significant predictors of active disease status. These findings support earlier correlations between IP-10 and TNF-α with disease activity parameters in a cross-sectional Luminex™ serological study and may enhance clinical decision-making when disease activity is challenging to assess by clinical examination alone.

The association between preconception loss of control over eating and depressive symptom trajectories from childhood through first pregnancy.

OBJECTIVE: Loss of control over eating (LOC) during pregnancy impacts prenatal health and often co-occurs with depressive symptoms. However, the role of depression history as a risk factor for LOC prior to pregnancy is unclear; information that is essential for effective prenatal health promotion. We examined the association between trajectories of depressive symptoms from childhood to first pregnancy and preconception LOC. METHOD: Participants (N = 1031) were predominantly Black, first-time mothers enrolled in the population-based Pittsburgh Girls Study. LOC and depressive symptoms were measured annually. Pre-pregnancy height and weight, and gestational weight gain data were abstracted from medical records. RESULTS: There was a significant difference in age of first conception for Black and White individuals (t = 8.73, df = 976, p < .001). Latent class analysis revealed four and three classes of depressive symptom trajectories for Black and White individuals, respectively. In the entire sample, the high-changing and moderate-decreasing classes of depressive symptoms were each associated with lifetime, in preconception year and not in preconception year, LOC (X2 = 56.7, p < .001). DISCUSSION: High levels of lifetime depressive symptoms may increase vulnerability to future LOC prior to first pregnancy, suggesting potential targets for interventions to improve maternal health. PUBLIC SIGNIFICANCE: Both depression history and disordered eating behaviors are known to influence prenatal health. The present study revealed associations between high levels of depressive symptoms from childhood through first pregnancy and loss of control over eating that included the year prior to conception. Results highlight potential targets for preconception interventions with relevance for future prenatal health.

Developmental Models of Depression, Externalizing Problems, and Self-regulatory Processes: Integrated Data Analysis Across Four Longitudinal Studies of Youth.

Integrative data analysis (IDA) was used to derive developmental models of depression, externalizing problems, and self-regulatory processes in three prevention trials of the Family Check-Up and one longitudinal, community-based study of girls over a 10-year span covering early to late adolescence (N = 4,773; 74.9% female, 41.7% white). We used moderated nonlinear factor analysis to create harmonized scores based on all available items for a given participant in the pooled dataset while accounting for potential differences in both the latent factor and the individual items as a function of observed covariates. We also conducted latent growth model analyses to examine developmental trajectories of risk. Results indicated a bidirectional relationship between depression and externalizing problems, with greater baseline externalizing problems and depression predicting growth in inhibitory control difficulties. Furthermore, initial level of inhibitory control difficulties was associated with growth in depression. We did not, however, find a relationship between early inhibitory control difficulties and growth in externalizing problems. This work illustrates the utility of IDA techniques to harmonize data across multiple studies to identify risk factors for the development of depression and externalizing problems that can be targeted by prevention efforts.

Rumination in Early Adolescent Girls: An EEG Study of Cognitive Control and Emotional Responding in an Emotional Go/NoGo Task.

Although there is a substantial literature on rumination and depression, research examining neurocognitive processes related to rumination is just emerging, and few studies have examined such processes in relation to depression-risk in early adolescence. This study examined the associations between neurocognitive processes and trait-rumination in relation to familial risk for depression in nondepressed girls in early adolescence. Neurocognitive processes were assessed via EEG recording during an emotional Go/NoGo task, and analyses examined two Event-Related Potential components, including the Go and NoGo N2, reflecting attentional engagement and cognitive control processes respectively, and the Go and NoGo P3, reflecting motivated attention and inhibitory motor processes. In higher-risk youth, rumination was associated with specific alterations in both N2 and P3 amplitudes to nonemotional faces when required to enact a response, suggesting disrupted behavioral flexibility in adjusting responses to meet task demands. In lower-risk youth, however, greater rumination was associated with diminished engagement of top-down attention and cognitive control resources (i.e., attenuated N2 amplitudes), and enhanced activation of inhibitory motor control processes (i.e., enhanced P3 amplitudes). Results provide novel information regarding the association between depression-risk, rumination, and emotional processing in early adolescence that may have implications for risk-identification and prevention.

A Carboxyl Ester Lipase (CEL) Mutant Causes Chronic Pancreatitis by Forming Intracellular Aggregates That Activate Apoptosis.

Patients with chronic pancreatitis (CP) frequently have genetic risk factors for disease. Many of the identified genes have been connected to trypsinogen activation or trypsin inactivation. The description of CP in patients with mutations in the variable number of tandem repeat (VNTR) domain of carboxyl ester lipase (CEL) presents an opportunity to study the pathogenesis of CP independently of trypsin pathways. We tested the hypothesis that a deletion and frameshift mutation (C563fsX673) in the CEL VNTR causes CP through proteotoxic gain-of-function activation of maladaptive cell signaling pathways including cell death pathways. HEK293 or AR42J cells were transfected with constructs expressing CEL with 14 repeats in the VNTR (CEL14R) or C563fsX673 CEL (CEL maturity onset diabetes of youth with a deletion mutation in the VNTR (MODY)). In both cell types, CEL MODY formed intracellular aggregates. Secretion of CEL MODY was decreased compared with that of CEL14R. Expression of CEL MODY increased endoplasmic reticulum stress, activated the unfolded protein response, and caused cell death by apoptosis. Our results demonstrate that disorders of protein homeostasis can lead to CP and suggest that novel therapies to decrease the intracellular accumulation of misfolded protein may be successful in some patients with CP.

Mindfulness in Pregnancy and Postpartum: Protocol of a Pilot Randomized Trial of Virtually Delivered Mindfulness-Based Cognitive Therapy to Promote Well-Being during the Perinatal Period.

BACKGROUND: During the period from pregnancy through the first year postpartum, vulnerable individuals are at elevated risk for the onset or worsening of psychological distress, and accessible (e.g., virtually delivered) mental health interventions are needed. Research suggests that Mindfulness-Based Cognitive Therapy (MBCT) can effectively mitigate psychological distress, although few studies have evaluated MBCT in the perinatal period, and samples have been clinically homogenous. Thus, we have designed and are conducting a pilot trial of virtually delivered MBCT with pregnant individuals experiencing a range of psychological symptoms to assess its feasibility and preliminarily explore its effectiveness. Here, we present the study protocol. METHODS: Eligible participants (target N = 70) are ≥18 years with pregnancies between 12 and 30 weeks of gestation. Participants complete a diagnostic interview, self-report symptom ratings, and a computerized cognitive battery assessing self-regulation at the baseline. Participants are then randomized to either MBCT or care as usual. The MBCT intervention involves eight weekly group sessions delivered virtually, with each session focusing on a mindfulness practice followed by group discussion and skill development. Participants in the intervention group are also encouraged to practice mindfulness skills between sessions. Participants in the control condition are provided with information about mindfulness and treatment resources. Baseline measures are repeated following the eight-week intervention period and at three months postpartum. CONCLUSIONS: This pilot study is designed to evaluate the feasibility of virtually delivered MBCT and explore group differences in psychological symptoms during the perinatal period, and will lay the foundation for a larger clinical trial focused on optimizing this intervention to improve psychological functioning among diverse pregnant individuals.

Reproducibility between preschool and school-age Social Responsiveness Scale forms in the Environmental influences on Child Health Outcomes program.

Evidence suggests core autism trait consistency in older children, but development of these traits is variable in early childhood. The Social Responsiveness Scale (SRS) measures autism-related traits and broader autism phenotype, with two age-dependent forms in childhood (preschool, 2.5-4.5 years; school age, 4-18 years). Score consistency has been observed within forms, though reliability across forms has not been evaluated. Using data from the Environmental Influences on Child Health Outcomes (ECHO) program (n = 853), preschool, and school-age SRS scores were collected via maternal report when children were an average of 3.0 and 5.8 years, respectively. We compared reproducibility of SRS total scores (T-scores) and agreement above a clinically meaningful cutoff (T-scores ≥ 60) and examined predictors of discordance in cutoff scores across forms. Participant scores across forms were similar (mean difference: 3.3 points; standard deviation: 7), though preschool scores were on average lower than school-age scores. Most children (88%) were classified below the cutoff on both forms, and overall concordance was high (92%). However, discordance was higher in cohorts following younger siblings of autistic children (16%). Proportions of children with an autism diagnoses were also higher among those with discordant scores (27%) than among those with concordant scores (4%). Our findings indicate SRS scores are broadly reproducible across preschool and school-age forms, particularly for capturing broader, nonclinical traits, but also suggest that greater variability of autism-related traits in preschool-age children may reduce reliability with later school-age scores for those in the clinical range.

The Arg92Cys colipase polymorphism impairs function and secretion by increasing protein misfolding.

Colipase is essential for efficient fat digestion. An arginine-to-cysteine polymorphism at position 92 of colipase (Arg92Cys) associates with an increased risk for developing type-2 diabetes through an undefined mechanism. To test our hypothesis that the extra cysteine increases colipase misfolding, thereby altering its intracellular trafficking and function, we expressed Cys92 colipase in HEK293T cells. Less Cys92 colipase is secreted and more is retained intracellularly in an insoluble form compared with Arg92 colipase. Nonreducing gel electrophoresis suggests the folding of secreted Cys92 colipase differs from Arg92 colipase. Cys92 colipase misfolding does not trigger the unfolded protein response (UPR) or endoplasmic reticulum (ER) stress. The ability of secreted Cys92 colipase to stimulate pancreatic triglyceride lipase (PTL) is reduced with all substrates tested, particularly long-chain triglycerides. The reaction of Cys92 colipase with triolein and Intralipid has a much longer lag time, reflecting decreased ability to anchor PTL on those substrates. Our data predicts that humans with the Arg92Cys substitution will secrete less functional colipase into the duodenum and have less efficient fat digestion. Whether inefficient fat digestion or another property of colipase contributes to the risk for developing diabetes remains to be clarified.

Effects of binge drinking and depression on cognitive-control processes during an emotional Go/No-Go task in emerging adults.

INTRODUCTION: The goal of the current study was to examine differences in neurocognitive processes across groups marked by binge drinking and depression to identify patterns of cognitive and affective processing impairments. METHODS: Undergraduate students (N = 104; 64% female) were recruited based on self-reported symptoms of depression and alcohol use. They completed an emotional Go/No-Go task while undergoing EEG. Mean amplitudes for N2 and P3 components were examined with 2 (Depressed/Non-depressed) X 2 (Binge/Non-binge drinkers) X 4 (Happy/Sad/Angry/Calm) X 3 (Left/Middle/Right) X 2 (Go/No-Go) repeated measures ANOVAs. RESULTS: There were significant Trial Type X Valence X Depression X Binge Drinking interactions for N2 (F(3, 80) = 6.62, p < .01) and P3 (F(3, 80) = 4.65, p < .01) components. There was a significant Valence X Depression X Binge Drinking interaction for response bias (F(3, 65) = 3.11, p < .05). LIMITATIONS: The source of our sample may be a limitation, as all participants were university students, potentially making the results less generalizable. Further, we cannot be certain that social desirability did not interfere with honest reporting of alcohol use in this population. CONCLUSIONS: Differences in early inhibitory control were observed across emotions based on trial type among depressed non-binge drinkers, and these differences were attenuated in the presence of binge drinking. Further, the effects of depression on later inhibitory control were specific to non-binge drinkers. Results help to clarify the nature of underlying patterns of neurocognitive and affective risk processes that could be targeted by prevention and intervention programs.

Disordered eating during pregnancy among individuals participating in the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC).

BACKGROUND: Food insecurity is associated with adverse psychosocial and health consequences in pregnancy. In non-pregnant populations, evidence suggests that food insecurity is linked to eating pathology, independent of depression or anxiety. Food assistance programs intended to reduce food insecurity, such as the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC), may unintentionally contribute to eating pathology through a "feast-or-famine" cycle (i.e., cyclical periods of food deprivation and food access over the benefit month). Thus, the present study examined associations between WIC participation and disordered eating in pregnancy, covarying for depressive symptoms. METHODS: The present study is a secondary analysis of the Pittsburgh Girls Study (PGS), a 21-year prospective longitudinal study that over-sampled households in low resourced neighborhoods. The present analysis included a subset of pregnant PGS participants (N = 210; 13-25 years of age) who reported on WIC participation, and disordered eating and depressive symptoms on validated measures. RESULTS: Negative binomial regression models covarying for participant's age at conception and gestational age at assessment found that WIC participation was associated with higher scores on overall eating pathology as well as dieting and oral control subscales, but not bulimic or food preoccupation subscales, or a binge-eating item. Patterns of findings did not change when depressive symptom severity was included in models. DISCUSSION: WIC participation was associated with eating pathology during pregnancy. Future research should clarify directional relationships among food insecurity, food assistance, and eating behavior in pregnancy to promote health equity.

The role of substance use coping in linking depression and alcohol use from late adolescence through early adulthood.

Although theoretical models highlight the role of coping motivations in promoting co-development of depression and alcohol use, few longitudinal studies have examined such processes across early adulthood. The current study examined the role of coping in the association between depression and alcohol use across late adolescence and early adulthood. A control sample of adolescents (N = 498) from a longitudinal prevention trial completed the Brief Symptom Inventory, Life Events Coping Inventory, and a self-report survey on alcohol use at ages 17, 22, and 23, as well as the Composite International Diagnostic Interview at age 28-30. Path analyses integrated self-report and diagnostic measures. Although gender differences were observed in mean levels of depression, alcohol use, and the use of substances to cope, we did not find gender differences in structural relations across these domains over time. Substance use coping served as an intervening pathway in the association between alcohol use and depression both at the symptom level from age 17 to 23, and in predicting longer term diagnostic outcomes at ages 28-30. Depressive symptoms in early adulthood were indirectly related to major depressive disorder (MDD) through two independent paths, including the stability of depressive symptoms over time, and through the influence of depression on increasing the tendency to use substances to cope with stress. Our results underscore that coping effects provide unique predictive power across developmental transitions, over and above the stability of depressive symptoms and alcohol use, underscoring coping motives as a promising intervention target that may prevent co-occurring depression and substance use. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Long-term cross-over effects of the family check-up prevention program on child and adolescent depression: Integrative data analysis of three randomized trials.

OBJECTIVE: The present study examined prevention effects of the family check-up (FCU) prevention program on longitudinal changes in youth depression, using harmonized data collected across three prevention trials, including one trial initiated in early childhood and two initiated in early adolescence (total N = 2,322). METHOD: Data from parent and youth reports of youth depression were harmonized using Moderated Nonlinear Factor Analysis (MNLFA), which provides a robust means to examine differential item functioning (DIF) across subgroups of participants (e.g., age groups, ethnic groups), and creates scale scores based on all available items while accounting for individual differences. Long-term intervention effects were tested using a multi-informant growth model examining changes in depression from baseline to up to 14-year postbaseline. RESULTS: Across trials, significant long-term effects of the FCU on reductions in depression were observed, although effects were found to wane after approximately 10 years. CONCLUSION: FCU effects on depression across trials were attained with a relatively brief parenting program designed to reduce behavior problems and improve relational functioning that emphasized parental motivation to change while supporting positive parenting strategies. Implications of these results are discussed, along with directions for future work in this area. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Children's appraisals of maternal depression and responses to emotional faces in early-adolescence: An Event Related Potential (ERP) study.

BACKGROUND: Parental depression represents a significant risk for depression development in offspring. While cognitive mechanisms represent a central risk pathway, children's appraisals of parental symptoms have been understudied. This study examined associations between children's self-blame, threat, and frequency/duration appraisals for maternal symptoms in relation to cognitive control and emotional response processes. METHODS: Sixty mother-daughter (aged 10-14-years) pairs participated. Affective processing was assessed by three Event Related Potential (ERP) components, the N2, P3, and LPP, during an emotional Go/NoGo task. RESULTS: Threat-appraisals were associated with alterations in all three ERP components, independently of maternal diagnostic histories or youth depressive symptoms. Self-blame was associated with early attentional engagement towards calm faces. Independent effects of maternal depression history and youth symptoms were also observed. CONCLUSIONS: Results highlight the importance of youth perceptions of maternal depressive symptoms in models of depression-risk.

Physiological feelings.

The role of peripheral physiology in the experience of emotion has been debated since the 19th century following the seminal proposal by William James that somatic responses to stimuli determine subjective emotion. Subsequent views have integrated the forebrain's ability to initiate, represent and simulate such physiological events. Modern affective neuroscience envisions an interacting network of "bottom-up" and "top-down" signaling in which the peripheral (PNS) and central nervous systems both receive and generate the experience of emotion. "Feelings" serves as a term for the perception of these physical changes whether emanating from actual somatic events or from the brain's representation of such. "Interoception" has come to represent the brain's receipt and representation of these actual and "virtual" somatic changes that may or may not enter conscious awareness but, nonetheless, influence feelings. Such information can originate from diverse sources including endocrine, immune and gastrointestinal systems as well as the PNS. We here examine physiological feelings from diverse perspectives including current and historical theories, evolution, neuroanatomy and physiology, development, regulatory processes, pathology and linguistics.

Concordance between maternal recall of birth complications and data from obstetrical records.

BACKGROUND: Prenatal complications are associated with poor outcomes in the offspring. Access to medical records is limited in the United States and investigators often rely on maternal report of prenatal complications. STUDY DESIGN AND AIMS: We tested concordance between maternal recall and birth records in a community-based sample of mothers participating in a longitudinal study in order to determine the accuracy of maternal recall of perinatal complications. SUBJECTS: Participants were 151 biological mothers, who were interviewed about gestational age at birth, birthweight, and the most commonly occurring birth complications: nuchal cord and meconium aspiration when the female child was on average 6years old, and for whom birth records were obtained. OUTCOME MEASURES: Concordance between reports was assessed using one-way random intra-class coefficients for continuous measures and kappa coefficients for dichotomous outcomes. Associations between maternal demographic and psychological factors and discrepancies also were tested. RESULTS: Concordance was excellent for continuously measured birthweight (ICC=0.85, p<0.001) and good for gestational age (ICC=0.68, p<0.001). Agreement was good for low birthweight (<2500g) (kappa=0.67, p<0.001), fair for preterm delivery (<37weeks gestation) (kappa=0.44, p<0.001), and poor for nuchal cord or meconium aspiration. Most discrepancies were characterized by presence according to birth record and absence according to maternal recall. Receipt of public assistance was associated with a decrease in discrepancy in report of nuchal cord. CONCLUSIONS: Concordance between maternal retrospective report and medical birth records varies across different types of perinatal events. There was little evidence that demographic or psychological factors increased the risk of discrepancies. Maternal recall based on continuous measures of perinatal factors may yield more valid data than dichotomous outcomes.

The effect of prenatal docosahexaenoic acid supplementation on infant outcomes in African American women living in low-income environments: A randomized, controlled trial.

IMPORTANCE: African American women living in urban, low-income environments are at high risk for poor nutrition during pregnancy and birth complications. OBJECTIVE: To test the effectiveness of prenatal docosahexaenoic acid (DHA) supplementation on birth outcomes and infant development in a sample of African American women with Medicaid insurance and living in the city of Pittsburgh. DESIGN: The Nutrition and Pregnancy Study (NAPS) is a double-blind, randomized controlled trial of prenatal DHA supplementation conducted between 2012 and 2014. SETTING: Participants were recruited from obstetric clinics at the University of Pittsburgh Medical Center. PARTICIPANTS: Sixty-four pregnant, African American women were enrolled at 16-21 weeks of gestation and randomized to either 450mg/day of DHA (22:6n-3)(n=43) or a soybean placebo (n=21). Four women (6.3%) withdrew from the study: two participants from each study arm; complete data were obtained for 49 infants (76.5%) at the 3-month assessment. INTERVENTIONS: Supplementation with DHA or placebo continued from the beginning of enrollment through delivery. MAIN OUTCOME AND MEASURES: Data on birth outcomes were collected from medical records. At approximately 3 months post-partum, mothers brought their infants to the laboratory where the Bayley Scales of Infant Development (BSID-III) were administered and cortisol response to the Face-to-Face Still-Face (FFSF) paradigm was assessed. RESULTS: Infants of mothers who received DHA supplementation had higher birth weight (3.174g versus 2.890g) than infants of mothers receiving placebo (F [2.40]=6.09, p=0.018, eta=0.36), and were more likely to have a 1-min Apgar score greater than 8 (OR=5.99 [95% CI=1.25-28.75], p=0.025). Infants of mothers who received DHA compared with infants of mothers receiving placebo had lower levels of cortisol in response to the FFSF paradigm (F [1.32]=5.36, p=0.018, eta=0.36). None of the scores on the BSID-III differed as a function of active supplement versus placebo. CONCLUSIONS: Infants of women living in urban, low-income environments who received DHA supplementation had more optimal birth outcomes and more modulated cortisol response to a stressor. DHA supplementation may be effective in attenuating the negative effects of prenatal stress on offspring development.

Peripheral blood cytokine and chemokine profiles in juvenile localized scleroderma: T-helper cell-associated cytokine profiles.

OBJECTIVE: To evaluate peripheral blood T-helper (TH) cell-associated cytokine and chemokine profiles in localized scleroderma (LS), and correlate them with clinical disease features, including disease activity parameters. METHODS: A 29-plex Luminex platform was used to analyze the humoral profile of plasma samples from 69 pediatric LS patients and 71 healthy pediatric controls. Cytokine/chemokine levels were compared between these two groups and within LS patients, focusing on validated clinical outcome measures of disease activity and damage in LS. RESULTS: Plasma levels of IP-10, MCP-1, IL-17a, IL-12p70, GM-CSF, PDGF-bb, IFN-α2, and IFN-γ were significantly higher in LS subjects compared to healthy controls. Analysis within the LS group demonstrated IP-10, TNF-α, and GM-CSF correlated with clinical measures of disease activity. Several cytokines/chemokines correlated with anti-histone antibody, while only a few correlated with positive ANA and single-stranded DNA antibody. CONCLUSION: This is the first time that multiple cytokines and chemokines have been examined simultaneously in LS. In general, a TH1 (IFN-γ) and TH17 (IL-17a) predominance was demonstrated in LS compared to healthy controls. There is also an IFN-γ signature with elevated IP-10, MCP-1, and IFN-γ, which has been previously demonstrated in systemic sclerosis, suggesting a shared pathophysiology. Within the LS patients, those with active disease demonstrated IP-10, TNF-α, and GM-CSF, which may potentially serve as biomarkers of disease activity in the clinical setting.