Linking social reward responsiveness and affective responses to the social environment: An ecological momentary assessment study.

Social support is a key predictor of well-being, but not everyone experiences mental health benefits from receiving it. However, given that a growing number of interventions are based on social support, it is crucial to identify the features that make individuals more likely to benefit from social ties. Emerging evidence suggests that neural responses to positive social feedback (i.e., social reward) might relate to individual differences in social functioning, but potential mechanisms linking these neural responses to psychological outcomes are yet unclear. This study examined whether neural correlates of social reward processing, indexed by the reward positivity (RewP), relate to individuals' affective experience following self-reported real-world positive social support events. To this aim, 193 university students (71% females) underwent an EEG assessment during the Island Getaway task and completed a 10-day ecological momentary assessment where participants reported their positive and negative affects (PA, NA) nine times a day and the count of daily positive and negative events. Experiencing a higher number of social support positive events was associated with higher PA. The RewP moderated this association, such that individuals with greater neural response to social feedback at baseline had a stronger positive association between social support positive events count and PA. Individual differences in the RewP to social feedback might be one indicator of the likelihood of experiencing positive affect when receiving social support.

Spleen Tyrosine Kinase (SYK) negatively regulates ITAM-mediated human NK cell signaling and CD19-CAR NK cell efficacy.

NK cells express activating receptors that signal through ITAM-bearing adapter proteins. The phosphorylation of each ITAM creates binding sites for SYK and ZAP70 protein tyrosine kinases to propagate downstream signaling including the induction of Ca 2 + influx. While all immature and mature human NK cells co-express SYK and ZAP70, clonally driven memory or adaptive NK cells can methylate SYK genes and signaling is mediated exclusively using ZAP70. Here, we examined the role of SYK and ZAP70 in a clonal human NK cell line KHYG1 by CRISPR-based deletion using a combination of experiments and mechanistic computational modeling. Elimination of SYK resulted in more robust Ca + + influx after cross-linking of the CD16 and NKp30 receptors and enhanced phosphorylation of downstream proteins, whereas ZAP70 deletion diminished these responses. By contrast, ZAP70 depletion increased proliferation of the NK cells. As immature T cells express both SYK and ZAP70 but mature T cells often express only ZAP70, we transduced the human Jurkat cell line with SYK and found that expression of SYK increased proliferation but diminished TCR-induced Ca 2 + flux and activation. We performed transcriptional analysis of the matched sets of variant Jurkat and KHYG1 cells and observed profound alterations caused by SYK expression. As depletion of SYK in NK cells increased their activation, primary human NK cells were transduced with a CD19-targeting CAR and were CRISPR edited to ablate SYK or ZAP70. Deletion of SYK resulted in more robust cytotoxic activity and cytokine production, providing a new therapeutic strategy of NK cell engineering for cancer immunotherapy.

Neurophysiological responses to emotional faces predict dynamic fluctuations in affect in adolescents.

The ability to accurately identify and interpret others' emotions is critical for social and emotional functioning during adolescence. Indeed, previous research has identified that laboratory-based indices of facial emotion recognition and engagement with emotional faces predict adolescent mood states. Whether socioemotional information processing relates to real-world affective dynamics using an ecologically sensitive approach, however, has rarely been assessed. In the present study, adolescents (N = 62; ages 13-18) completed a Facial Recognition Task, including happy, angry, and sad stimuli, while EEG data were acquired. Participants also provided ecological momentary assessment (EMA) data probing their current level of happiness, anger, and sadness for 1-week, resulting in indices of emotion (mean-level, inertia, instability). Analyses focused on relations between (1) accuracy for and (2) prolonged engagement with (LPP) emotional faces and EMA-reported emotions. Greater prolonged engagement with happy faces was related to less resistance to changes in happiness (i.e., less happiness inertia), whereas greater prolonged engagement with angry faces associated with more resistance to changes in anger (i.e., greater anger inertia). Results suggest that socioemotional processes captured by laboratory measures have real-world implications for adolescent affective states and highlight potentially actionable targets for novel treatment approaches (e.g., just-in-time interventions). Future studies should continue to assess relations among socioemotional informational processes and dynamic fluctuations in adolescent affective states.

Capturing mood dynamics through adolescent smartphone social communication.

Most adolescents with depression remain undiagnosed and untreated-missed opportunities that are costly from both personal and public health perspectives. A promising approach to detecting adolescent depression in real-time and at a large scale is through their social communication on the smartphone (e.g., text messages, social media posts). Past research has shown that language from online social communication reliably indicates interindividual differences in depression. To move toward detecting the emergence of depression symptoms intraindividually, the present study tested whether sentiment (i.e., words connoting positive and negative affect) from smartphone social communication prospectively predicted daily mood fluctuations in 83 adolescents (Mage = 16.49, 73.5% female) with a wide range of depression severity. Participants completed daily mood ratings across a 90-day period, during which 354,278 messages were passively collected from social communication apps. Greater positive sentiment (i.e., more positive weighted composite valence score and a greater proportion of words expressing positive sentiment) predicted more positive next-day mood, controlling for previous-day mood. Moreover, greater proportions of positive and negative sentiment were, respectively, associated with lower anhedonia and greater dysphoria symptoms measured at baseline. Exploratory analyses of nonaffective linguistic features showed that greater use of social engagement words (e.g., friends and affiliation) and emojis (primarily consisting of hearts) predicted more positive changes in mood. Collectively, findings suggest that language from smartphone social communication can detect mood fluctuations in adolescents, laying the foundation for language-based tools to identify periods of heightened depression risk. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Risk factors for the intergenerational transmission of depression in women and girls: Understanding neural correlates of major depressive disorder and the role of early-onset maternal depression.

Deficits in neural reward processing have been implicated in the etiology of depression and have been observed in high-risk individuals. However, depression is a heterogeneous disorder, and not all depressed individuals exhibit blunted neural reward response, suggesting the need to examine more specific depression phenotypes. Early-onset depression, a well-defined phenotype, has been associated with greater intergenerational transmission of depression and appears more closely linked to neural reward processing deficits. The present study examined whether a maternal history of early-onset depression was associated with neural reward response among mothers and their daughters. Mothers with and without a history of depression, as well as their biological, adolescent daughters (N = 109 dyads), completed a monetary reward guessing task while electroencephalogram was collected. Analyses focused on the Reward Positivity (RewP), an event-related potential following reward receipt. Adjusting for current depressive symptoms, maternal early-onset depression was associated with a blunted RewP in the mothers and a numerically smaller RewP in their never-depressed, adolescent daughters. Maternal adult-onset depression was not statistically associated with a blunted RewP in mothers or daughters. Thus, a blunted RewP appears to be a trait-like vulnerability marker for depression that emerges before depression onset and relates to more specific depression phenotypes (e.g., early-onset depression). These findings have implications for early identification of individuals at risk of depression and for developing more targeted interventions.

Self-referential Processing in Remitted Depression: An Event-Related Potential Study.

Background: Identifying mechanisms of major depressive disorder that continue into remission is critical, as these mechanisms may contribute to subsequent depressive episodes. Biobehavioral markers related to depressogenic self-referential processing biases have been identified in adults with depression. Thus, we investigated whether these risk factors persisted during remission as well as contributed to the occurrence of stress and depressive symptoms over time. Methods: At baseline, adults with remitted depression (n = 33) and healthy control subjects (n = 33) were administered diagnostic and stress interviews as well as self-report symptom measures. In addition, participants completed a self-referential encoding task while electroencephalography data were acquired. Stress interviews and self-report symptom measures were readministered at the 6-month follow-up assessment. Results: Drift diffusion modeling showed that compared with healthy individuals, adults with remitted depression exhibited a slower drift rate to negative stimuli, indicating a slower tendency to reject negative stimuli as self-relevant. At the 6-month follow-up assessment, a slower drift rate to negative stimuli predicted greater interpersonal stress severity among individuals with remitted depression but not healthy individuals while controlling for both baseline depression symptoms and interpersonal stress severity. Highlighting the specificity of this effect, results were nonsignificant when predicting noninterpersonal stress. For self-relevant positive words endorsed, adults with remitted depression exhibited smaller left- than right-hemisphere late positive potential amplitudes; healthy control subjects did not show hemispheric differences. Conclusions: Self-referential processing deficits persist into remission. In line with the stress generation framework, these biases predicted the occurrence of interpersonal stress, which may provide insight about a potential pathway for the re-emergence of depressive symptoms.

All the Pringle ladies: Neural and behavioral responses to high-calorie food rewards in young adult women.

Reward processing is vital for learning and survival, and can be indexed using the Reward Positivity (RewP), an event-related potential (ERP) component that is larger for rewards than losses. Prior work suggests that heightened motivation to obtain reward, as well as greater reward value, is associated with an enhanced RewP. However, the extent to which internal and external factors modulate neural responses to rewards, and whether such neural responses motivate reward-seeking behavior, remains unclear. The present study investigated whether the degree to which a reward is salient to an individual's current motivational state modulates the RewP, and whether the RewP predicts motivated behaviors, in a sample of 133 women. To elicit the RewP, participants completed a forced-choice food reward guessing task. Data were also collected on food-related behaviors (i.e., type of food chosen, consumption of the food reward) and motivational salience factors (i.e., self-reported hunger, time since last meal, and subjective "liking" of food reward). Results showed that hungrier participants displayed an enhanced RewP compared to less hungry individuals. Further, self-reported snack liking interacted with RewP magnitude to predict behavior, such that when participants reported low levels of snack liking, those with a smaller RewP were more likely to consume their snacks than those with a larger RewP. Our data suggest that food-related motivational state may increase neural sensitivity to food reward in young women, and that neural markers of reward sensitivity might interact with subjective reward liking to predict real-world eating behavior.

Spontaneous suppression in dating couples: Social and physiological correlates of suppressing negative and positive emotions during negative and positive conversations.

Suppression (i.e., inhibiting one's emotional expression) has typically been associated with social and physiological costs. However, recent theorizing calls into question the inevitability of these costs. The present study takes a more nuanced approach and examines the social and physiological correlates of spontaneous (i.e., uninstructed) suppression when considering two potentially critical factors: the valence of the suppressed emotions (i.e., negative vs. positive) and the valence of the emotional context in which emotions are suppressed (i.e., negative conversation vs. positive conversation). Specifically, dating couples (N = 196 couples) completed both a negatively-valenced and a positively-valenced conversation in the laboratory while their autonomic-physiological responses were recorded. After each conversation, participants rated 1) the extent to which they had suppressed their negative and positive emotions, 2) the quality of the conversation, and 3) how connected they felt with their partner. We used Actor-Partner Interdependence Models to estimate actor effects (e.g., association of one's own suppression and one's own connectedness) and partner effects (e.g., association of one's partner's suppression and one's own connectedness). Suppression was associated with lower conversation quality and connectedness for the actors but largely not for the partners, regardless of the valence of the suppressed emotions and of the context, even when adjusting for felt emotion. Additionally, suppression was consistently not associated with physiological responses of actors or partners. Together, these findings suggest that, during emotional conversations with one's romantic partner, spontaneous (unlike instructed) suppression is associated with social but not physiological costs for the self but not one's partner.

Neurophysiological predictors of gaze-contingent music reward therapy among adults with social anxiety disorder.

Social anxiety disorder (SAD) is associated with fear of negative evaluation and heightened performance monitoring. The best-established treatments help only a subset of patients, and there are no well-established predictors of treatment response. The current study investigated whether individual differences in processing errors might predict response to gaze-contingent music reward therapy (GC-MRT). At baseline, healthy control subjects (HC; n = 20) and adults with SAD (n = 29), ages 19-43 years, completed the Flanker Task while electroencephalography (EEG) data were recorded. SAD participants then received up to 12 sessions over 8 weeks of GC-MRT, designed to train participants' attention away from threatening and toward neutral faces. Clinical assessments were completed 9- (post-treatment) and 20-weeks (follow-up) after initiating the treatment. At baseline, compared to HC, SAD performed the task more accurately and exhibited increased error-related negativity (ERN) and delta power to error commission. After controlling for age and baseline symptoms, more negative ERN and increased frontal midline theta (FMT) predicted reduced self-reported social anxiety symptoms at post-treatment, and FMT also predicted clinician-rated and self-reported symptom reduction at the follow-up assessment. Hypervigilance to error is characteristic of SAD and warrants further research as a predictor of treatment response for GC-MRT.

Neural Correlates Associated With Suicide and Nonsuicidal Self-injury in Youth.

There is no definitive neural marker of suicidal thoughts and behaviors (STBs) or nonsuicidal self-injury (NSSI), and relative to adults, research in youth is more limited. This comprehensive review focuses on magnetic resonance imaging studies reporting structural and functional neural correlates of STBs and NSSI in youth to 1) elucidate shared and independent neural alternations, 2) clarify how developmental processes may interact with neural alterations to confer risk, and 3) provide recommendations based on convergence across studies. Forty-seven articles were reviewed (STBs = 27; NSSI = 20), and notably, 63% of STB articles and 45% of NSSI articles were published in the previous 3 years. Structural magnetic resonance imaging research suggests reduced volume in the ventral prefrontal and orbitofrontal cortices among youth reporting STBs, and there is reduced anterior cingulate cortex volume related to STBs and NSSI. With regard to functional alterations, blunted striatal activation may characterize STB and NSSI youth, and there is reduced frontolimbic task-based connectivity in suicide ideators and attempters. Resting-state functional connectivity findings highlight reduced positive connectivity between the default mode network and salience network in attempters and show that self-injurers exhibit frontolimbic alterations. Together, suicidal and nonsuicidal behaviors are related to top-down and bottom-up neural alterations, which may compromise approach, avoidance, and regulatory systems. Future longitudinal research with larger and well-characterized samples, especially those integrating ambulatory stress assessments, will be well positioned to identify novel targets that may improve early identification and treatment for youth with STBs and NSSI.

Neurophysiological Markers Related to Negative Self-referential Processing Differentiate Adolescent Suicide Ideators and Attempters.

Background: Adolescent suicide is a major public health concern, and presently, there is a limited understanding of the neurophysiological correlates of suicidal behaviors. Cognitive models of suicide indicate that negative views of the self are related to suicidal thoughts and behaviors, and this study investigated whether behavioral and neural correlates of self-referential processing differentiate suicide ideators from recent attempters. Methods: Adolescents with depression reporting current suicidal ideation and no lifetime suicide attempts (suicide ideators, n = 30) and past-year suicide attempts (recent attempters, n = 26) completed a self-referential encoding task while high-density electroencephalogram data were recorded. Behavioral analyses focused on negative processing bias (i.e., tendency to attribute negative information as being self-relevant) and drift rate (i.e., slope of reaction time and response type that corresponds to how quickly information is accumulated to make a decision about whether words are self-referent). Neurophysiological markers probing components reflecting early semantic monitoring (P2), engagement (early late positive potential), and effortful encoding (late late positive potential) also were tested. Results: Adolescent suicide ideators and recent suicide attempters reported comparable symptom severity, suicide ideation, and mental disorders. Although there were no behavioral differences, compared with suicide ideators, suicide attempters exhibited greater P2 amplitudes for negative versus positive words, which may reflect enhanced attention and arousal in response to negative self-referential stimuli. There were no group differences for the early or late late positive potential. Conclusions: Enhanced sensory arousal in response to negative stimuli-that is, attentional orienting to semantic, emotional, and self-relevant features-differentiates adolescent suicide attempters from ideators and thus may signal risk for suicidal behavior.

Adjuvant treatment for patients with FIGO stage I uterine serous carcinoma confined to the endometrium.

OBJECTIVES: The role of adjuvant treatment for early-stage uterine serous carcinoma is not defined. The goal of this study was to investigate the impact of adjuvant treatment on survival of patients with tumors confined to the endometrium. METHODS: Patients diagnosed with stage I uterine serous carcinoma with no myometrial invasion between January 2004 and December 2015 who underwent hysterectomy with at least 10 lymph nodes removed were identified from the National Cancer Database. Adjuvant treatment patterns defined as receipt of chemotherapy and/or radiotherapy within 6 months from surgery were investigated and overall survival was evaluated using Kaplan-Meier curves, and compared with the log-rank test for patients with at least one month of follow-up. A Cox analysis was performed to control for confounders. RESULTS: A total of 1709 patients were identified; 833 (48.7%) did not receive adjuvant treatment, 348 (20.4%) received both chemotherapy and radiotherapy, 353 (20.7%) received chemotherapy only, and 175 (10.2%) received radiotherapy only. Five-year overall survival rates for patients who did not receive adjuvant treatment (n=736) was 81.9%, compared with 91.3% for those who had chemoradiation (n=293), 85.1% for those who received radiotherapy only (n=143), and 91.0% for those who received chemotherapy only (n=298) (p<0.001). After controlling for age, insurance status, type of treatment facility, tumor size, co-morbidities, and history of another tumor, patients who received adjuvant chemotherapy (HR 0.64, 95% CI 0.42, 0.96), or chemoradiation (HR 0.55, 95% CI 0.35, 0.88) had better survival compared with those who did not receive any adjuvant treatment, while there was no benefit from radiotherapy alone (HR 0.85, 95% CI 0.53, 1.37). There was no survival difference between chemoradiation and chemotherapy only (HR 1.15, 95% CI 0.65, 2.01). CONCLUSION: Adjuvant chemotherapy (with or without radiotherapy) is associated with a survival benefit for uterine serous carcinoma confined to the endometrium.

Assessment of poor functional status and post-acute care needs following primary ovarian cancer debulking surgery.

INTRODUCTION: Poor baseline functional status is associated with adverse surgical outcomes. Additionally, decline in the postoperative setting may result in the delay of additional treatments, impacting overall survival. This study assesses the incidence and risk factors for functional decline following primary ovarian cancer debulking surgery in previously independent women using discharge location as a surrogate. METHODS: All patients with a postoperative diagnosis of ovarian cancer who underwent surgical debulking and had documentation of discharge location were identified using the 2011-2012 American College of Surgeons National Surgical Quality Improvement Program database. Patients were excluded if their baseline functional status was dependent or partially dependent, or if they died before discharge. Discharge destination was dichotomized as home versus non-home. Descriptive data included demographics, comorbidities, and perioperative outcomes. Multivariable logistic regression was used to evaluate the association of clinical and surgical factors on discharge destination. RESULTS: 1786 patients met the criteria for analysis; 120 (6.7%) patients were discharged to non-home. Differences between home and non-home discharges included age (53.2% vs 83.3% ≥60), body mass index (26.5 vs 27.8 median), comorbidities (45.2% vs 64.2% with ≥1), and complications (8.6% vs 30.0% with ≥1, all p<0.05). In multivariable logistic regression analyses, only increasing age and complications were independently associated with discharge to non-home. Those age ≥70 had 9.0 times the risk (95% CI 3.5 to 23.4; p<0.001) as age <50. The presence of one or more postoperative complications carried 4.5 times (95% CI 2.9 to 7.0; p<0.001) the risk of those without complications. 30 day mortality was also increased in patients discharged to non-home. DISCUSSION: 6.7% of previously independent ovarian cancer patients were discharged to non-home following surgery. Major risk factors for non-home include older age, comorbidities, and postoperative complications. Efforts to optimize baseline functional status and minimize surgical complications may improve discharge rates to non-home and postoperative functional status.