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.

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.

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.

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).

Interferon-gamma inducible protein-10 as a potential biomarker in localized scleroderma.

INTRODUCTION: The purpose of this study was to evaluate the presence and levels of interferon-gamma inducible protein-10 (IP-10) in the plasma and skin of pediatric localized scleroderma (LS) patients compared to those of healthy pediatric controls and to determine if IP-10 levels correlate to clinical disease activity measures. METHODS: The presence of IP-10 in the plasma was analyzed using a Luminex panel in 69 pediatric patients with LS and compared to 71 healthy pediatric controls. Of these patients, five had available skin biopsy specimens with concurrent clinical and serological data during the active disease phase, which were used to analyze the presence and location of IP-10 in the skin by immunohistochemistry (IHC). RESULTS: IP-10 levels were significantly elevated in the plasma of LS patients compared to that of healthy controls and correlated to clinical disease activity measures in LS. Immunohistochemistry staining of IP-10 was present in the dermal infiltrate of LS patients and was similar to that found in psoriasis skin specimens, the positive disease control. CONCLUSIONS: Elevation of IP-10 levels in the plasma compared to those of healthy controls and the presence of IP-10 staining in the affected skin of LS patients indicates that IP-10 is a potential biomarker in LS. Furthermore, significant elevation of IP-10 in LS patients with active versus inactive disease and correlations between IP-10 levels and standardized disease outcome measures of activity in LS strongly suggest that IP-10 may be a biomarker for disease activity in LS.