Dynamic processes in behavioral activation therapy for anhedonic adolescents: Modeling common and patient-specific relations.

OBJECTIVE: Behavioral activation (BA) is a brief intervention for depression encouraging gradual and systematic re-engagement with rewarding activities and behaviors. Given this treatment focus, BA may be particularly beneficial for adolescents with prominent anhedonia, a predictor of poor treatment response and common residual symptom. We applied group iterative multiple model estimation (GIMME) to ecological momentary assessment (EMA) treatment data to investigate common and person-specific processes during BA for anhedonic adolescents. METHOD: Thirty-nine adolescents (Mage = 15.7 years old, 67% female, 81% White) with elevated anhedonia (Snaith-Hamilton Pleasure Scale) were enrolled in a 12-week BA trial, with weekly anhedonia assessments. EMA surveys were triggered every other week (2-3 surveys per day) throughout treatment assessing current positive affect (PA) and negative affect (NA), engagement in pleasurable activities and social interactions, anticipatory pleasure, rumination, and recent pleasurable and stressful experiences. RESULTS: A multilevel model revealed significant decreases in anhedonia, t(25.5) = -4.76, p < .001, over the 12-week trial. GIMME results indicated substantial heterogeneity in variable networks across patients. PA was the variable with the greatest number (22% of all paths vs. 11% for NA) of predictive paths to other symptoms (i.e., highest out-degree). Higher PA (but not NA) out-degree was associated with greater anhedonia improvement, t(25.8) = -2.22, p = .035. CONCLUSIONS: Results revealed substantial heterogeneity in variable relations across patients, which may obscure the search for common processes of change in BA. PA may be a particularly important treatment target for anhedonic adolescents in BA. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Reward-related predictors of symptom change in behavioral activation therapy for anhedonic adolescents: a multimodal approach.

Anhedonia is a cardinal characteristic of depression which predicts worse treatment outcome and is among the most common residual symptoms following treatment. Behavioral Activation (BA) has been shown to be an effective treatment for depressed adults, and more recently, depressed adolescents. Given its emphasis on systematically and gradually increasing exposure to and engagement with rewarding activities and experiences, BA may be a particularly effective intervention for adolescents experiencing anhedonia and associated reward system dysfunction. In the present study, anhedonic adolescents (AA; n = 39) received 12 weekly sessions of BA and completed a multimodal (i.e., neural, behavioral, and self-report [ecological momentary assessment]) assessment of reward function at pre-treatment and post-treatment (as well as weekly self-report assessments of anhedonia). Typically developing adolescents (TDA; n = 41) completed the same measures at corresponding timepoints. Multilevel models tested pre-treatment reward-related predictors of anhedonia improvement, as well as change in reward measures over the course of BA. Analyses revealed significant reductions in anhedonia following BA treatment. Enhanced pre-treatment neural (striatal) reward responsiveness predicted greater anhedonia improvement. In contrast, baseline self-report and behavioral reward measures did not predict treatment outcome. A group x time interaction revealed greater increases in both reward- and loss-related neural responsiveness among AA relative to TDA adolescents. Consistent with a capitalization (rather than compensatory) model, pre-treatment neural - but not self-report or behavioral - measures of relatively enhanced reward responsiveness predicted better BA outcome. In addition to alleviating anhedonia, successful BA may also increase neural sensitivity to affectively salient (e.g., reward- and loss-related) stimuli among anhedonic youth.

Levels of soluble complement regulators predict severity of COVID-19 symptoms.

The SARS-CoV-2 virus continues to cause significant morbidity and mortality worldwide from COVID-19. One of the major challenges of patient management is the broad range of symptoms observed. While the majority of individuals experience relatively mild disease, a significant minority of patients require hospitalisation, with COVID-19 still proving fatal for some. As such, there remains a desperate need to better understand what drives this severe disease, both in terms of the underlying biology, but also to potentially predict at diagnosis which patients are likely to require further interventions, thus enabling better outcomes for both patients and healthcare systems. Several lines of evidence have pointed to dysregulation of the complement cascade as a major factor in severe COVID-19 outcomes. How this is underpinned mechanistically is not known. Here, we have focussed on the role of the soluble complement regulators Complement Factor H (FH), its splice variant Factor H-like 1 (FHL-1) and five Factor H-Related proteins (FHR1-5). Using a targeted mass spectrometry approach, we quantified these proteins in a cohort of 188 plasma samples from controls and SARS-CoV-2 patients taken at diagnosis. This analysis revealed significant elevations in all FHR proteins, but not FH, in patients with more severe disease, particularly FHR2 and FHR5 (FHR2: 1.97-fold, p<0.0001; FHR5: 2.4-fold, p<0.0001). Furthermore, for a subset of 77 SARS-CoV-2 +ve patients we also analysed time course samples taken approximately 28 days post-diagnosis. Here, we see complement regulator levels drop in all individuals with asymptomatic or mild disease, but regulators remain high in those with more severe outcomes, with elevations in FHR2 over baseline levels in this group. These data support the hypothesis that elevation of circulating levels of the FHR family of proteins could predict disease severity in COVID-19 patients, and that the duration of elevation (or lack of immune activation resolution) may be partly responsible for driving poor outcomes in COVID-19.

Global Proteomic Profiling of Embryonic Stem Cells Using iTRAQ Isobaric Tags with LC-MS/MS Quantification.

In this methods chapter, we describe the use of isobaric tags for relative and absolute quantification (iTRAQ) for the differential expression analysis of global proteins between embryonic stem cell samples. This protocol describes how proteins are collected from cell culture, digested and prepared so that peptides are labeled with these isobaric tags. Labeled digests are pooled, fractionated offline, and quantified using liquid chromatography-mass spectrometry (LC-MS). This offline fractionation allows for a greater separation and thus increased identification/quantification of peptides. This combined method enables large-scale, deep penetration into the proteome of embryonic stem cells. During quantification, the relative intensities of label-derived reporter ions represent the relative amount of peptide in each sample. Using search algorithms that integrate the generated data for the identified and quantified peptides allows the relative quantification of proteins in the samples. The isobaric tags can be used in a 4 or 8 multiplexed manner; however, using an 8-plex experimental setup allows for the simultaneous analysis of biological and technical replicates within the same mass spectrometry run, thus minimizing experimental variation and increasing the confidence in any identified expression differences.

Spontaneous Thought Characteristics are Differentially Related to Heightened Negative Affect vs. Blunted Positive Affect in Adolescents: An Experience Sampling Study.

Background: Mind-wandering has been linked to negative affect and depressive symptoms in adolescents. However, mind-wandering is an extremely broad and heterogenous cognitive construct. Some features of spontaneous thought may be related to increased negative affect, whereas others may improve affect, or have no emotional influence. We used ecological momentary assessment (EMA) to investigate the characteristics of spontaneous thoughts in adolescents and their differential relations with moment-to-moment affect. Method: One-hundred and sixteen adolescents (ages 13-18; Typical Mood (TM) = 58; Low Mood (LM) = 58) completed 5 days (2-3 times/day) of EMA (total 1,037 surveys) assessing current positive and negative affect (PA and NA) and dimensions of spontaneous thought. Multilevel models tested the relation between thought characteristics and affect. Results: Relative to the TM group, LM adolescents had a higher frequency of mind-wandering (38% vs. 56%) and negatively-valanced thoughts during episodes of mind-wandering (21% vs. 37%). Negatively-valenced, self-referential and past-oriented thoughts were each associated with higher NA, even when controlling for plausible confounds (e.g., engagement in an unpleasant activity or social interaction, depressive symptom severity). In contrast, task-focused and positively-valenced thoughts were uniquely linked to higher PA. Conclusion: Characteristics of spontaneous thought - including temporal orientation, self-referential quality, and task-relatedness - were differentially related to NA vs. PA in adolescents. If replicated, these findings could inform more nuanced assessments of and targeted interventions for specific dimensions of mind-wandering contributing to high NA vs. blunted PA in teens.

Beyond factor H: The impact of genetic-risk variants for age-related macular degeneration on circulating factor-H-like 1 and factor-H-related protein concentrations.

Age-related macular degeneration (AMD) is a leading cause of vision loss; there is strong genetic susceptibility at the complement factor H (CFH) locus. This locus encodes a series of complement regulators: factor H (FH), a splice variant factor-H-like 1 (FHL-1), and five factor-H-related proteins (FHR-1 to FHR-5), all involved in the regulation of complement factor C3b turnover. Little is known about how AMD-associated variants at this locus might influence FHL-1 and FHR protein concentrations. We have used a bespoke targeted mass-spectrometry assay to measure the circulating concentrations of all seven complement regulators and demonstrated elevated concentrations in 352 advanced AMD-affected individuals for all FHR proteins (FHR-1, p = 2.4 × 10-10; FHR-2, p = 6.0 × 10-10; FHR-3, p = 1.5 × 10-5; FHR-4, p = 1.3 × 10-3; FHR-5, p = 1.9 × 10-4) and FHL-1 (p = 4.9 × 10-4) when these individuals were compared to 252 controls, whereas no difference was seen for FH (p = 0.94). Genome-wide association analyses in controls revealed genome-wide-significant signals at the CFH locus for all five FHR proteins, and univariate Mendelian-randomization analyses strongly supported the association of FHR-1, FHR-2, FHR-4, and FHR-5 with AMD susceptibility. These findings provide a strong biochemical explanation for how genetically driven alterations in circulating FHR proteins could be major drivers of AMD and highlight the need for research into FHR protein modulation as a viable therapeutic avenue for AMD.

Food-related advertisements and food intake among adult men and women.

Television viewing may contribute to obesity via promotion of sedentary behavior and exposure to food-related commercials. However, the mechanisms by which food-related commercials promote food intake are not well understood. Therefore, the purpose of the present study was to examine the impact of television advertisements on food intake according to sex and transportability, or the tendency to become engrossed in what one is viewing. Eighty-three undergraduate students, free of disordered eating symptoms, were stratified by sex and randomly assigned to one of three conditions (food-related advertisements, neutral advertisements, or no advertisements). They were then identified as high or low in transportability according to a median split. A significant interaction was found between advertisement condition and transportability such that those high in transportability ate more in the food than other advertisement conditions. A second interaction was found between sex and transportability with women high in transportability eating more food than women low in transportability irrespective of advertisement condition. No significant main effects of advertisement condition, sex, or transportability were found. Results suggest the importance of studying the impact of individual difference variables on the relationship between food-related advertising and food intake.

St. Louis Initiative for Integrated Care Excellence (SLI(2)CE): integrated-collaborative care on a large scale model.

The primary care health setting is in crisis. Increasing demand for services, with dwindling numbers of providers, has resulted in decreased access and decreased satisfaction for both patients and providers. Moreover, the overwhelming majority of primary care visits are for behavioral and mental health concerns rather than issues of a purely medical etiology. Integrated-collaborative models of health care delivery offer possible solutions to this crisis. The purpose of this article is to review the existing data available after 2 years of the St. Louis Initiative for Integrated Care Excellence; an example of integrated-collaborative care on a large scale model within a regional Veterans Affairs Health Care System. There is clear evidence that the SLI(2)CE initiative rather dramatically increased access to health care, and modified primary care practitioners' willingness to address mental health issues within the primary care setting. In addition, data suggests strong fidelity to a model of integrated-collaborative care which has been successful in the past. Integrated-collaborative care offers unique advantages to the traditional view and practice of medical care. Through careful implementation and practice, success is possible on a large scale model.

The effects of social support and coping on the relationship between social anxiety and eating disorders.

The current study examined the hypotheses that social support and coping moderate and or mediate the relationship between a broad and a narrow form of social anxiety and eating disorder symptoms. One hundred sixty-nine female undergraduates at a private Midwestern university, completed measures of social support, coping, social anxiety, fear of negative evaluation, and disordered eating attitudes and behaviors. Results of hierarchical multiple regression analyses indicated that higher levels of social support are associated with a weaker association between social anxiety and eating disorder symptomatology. Low use of task- and avoidant-oriented (distraction) coping and increased use of emotion-oriented coping are associated with a stronger association between social anxiety and eating disorder symptomatology. Implications for research and clinical intervention are discussed.

Segregating YKU80 and TLC1 alleles underlying natural variation in telomere properties in wild yeast.

In yeast, as in humans, telomere length varies among individuals and is controlled by multiple loci. In a quest to define the extent of variation in telomere length, we screened 112 wild-type Saccharomyces sensu stricto isolates. We found extensive telomere length variation in S. paradoxus isolates. This phenotype correlated with their geographic origin: European strains were observed to have extremely short telomeres (<150 bp), whereas American isolates had telomeres approximately three times as long (>400 bp). Insertions of a URA3 gene near telomeres allowed accurate analysis of individual telomere lengths and telomere position effect (TPE). Crossing the American and European strains resulted in F1 spores with a continuum of telomere lengths consistent with what would be predicted if many quantitative trait loci (QTLs) were involved in length maintenance. Variation in TPE is similarly quantitative but only weakly correlated with telomere length. Genotyping F1 segregants indicated several QTLs associated with telomere length and silencing variation. These QTLs include likely candidate genes but also map to regions where there are no known genes involved in telomeric properties. We detected transgressive segregation for both phenotypes. We validated by reciprocal hemizygosity that YKU80 and TLC1 are telomere-length QTLs in the two S. paradoxus subpopulations. Furthermore, we propose that sequence divergence within the Ku heterodimer generates negative epistasis within one of the allelic combinations (American-YKU70 and European-YKU80) resulting in very short telomeres.

Interpersonal sensitivity predicts bulimic symptomatology cross-sectionally and longitudinally.

Individuals who experience interpersonal sensitivity (IPS) may be at an increased risk for developing eating disorder symptomatology. The purpose of the present study was to assess the predictive capacity of IPS and related constructs in the development of bulimic symptomatology both cross-sectionally and longitudinally while controlling for depressive symptoms. Participants were 119 female undergraduate psychology students attending a private mid-size Midwestern university. Data were collected at both the beginning and end of the academic semester. Participants completed the Center for Epidemiological Study - Depression Scale, Brief Fear of Negative Evaluation Scale, Interpersonal Sensitivity Measure, and the Bulimia Test - Revised. The Fragile Inner Self subscale of the IPSM was found to significantly account for additional variability in BULIT-R scores after controlling for depression both cross-sectionally and longitudinally (8% and 2%, respectively). IPS is a suitable candidate for inclusion in the dual pathway model of bulimic symptomatology.