Measurement of adolescent psychological wellbeing: A test of factor structure and measurement invariance.

Gains in holistic approaches to adult mental health have been associated with increasing interest in understanding psychological wellbeing (PWB) among adolescents. Empirical examination of measurement models for PWB in adolescence is lacking. Thus, the current study examined PWB in a longitudinal, diverse sample of 433 adolescents (non-Latinx Black: 37.6%; non-Latinx White: 25.9%; Latinx: 36.5%; Male adolescents: 50.1%). A one-factor, correlated six-factor and hierarchical models were examined across racial/ethnic (White, Black, and Hispanic) and gender (female, male) identities, after which the best fitting model was selected to undergo invariance testing. A one-factor structure was superior, and exhibited strict invariance across racial/ethnic and gender identities at each wave of the study, as well as longitudinal invariance within the entire sample.

A High Threshold of Biotherapeutic Aggregate Numbers is Needed to Induce an Immunogenic Response In Vitro, In Vivo, and in the Clinic.

BACKGROUND AND PURPOSE: There is concern that subvisible aggregates in biotherapeutic drug products pose a risk to patient safety. We investigated the threshold of biotherapeutic aggregates needed to induce immunogenic responses. METHODS AND RESULTS: Highly aggregated samples were tested in cell-based assays and induced cellular responses in a manner that depended on the number of particles. The threshold of immune activation varied by disease state (cancer, rheumatoid arthritis, allergy), concomitant therapies, and particle number. Compared to healthy donors, disease state patients showed an equal or lower response at the late phase (7 days), suggesting they may not have a higher risk of responding to aggregates. Xeno-het mice were used to assess the threshold of immune activation in vivo. Although highly aggregated samples (~ 1,600,000 particles/mL) induced a weak and transient immunogenic response in mice, a 100-fold dilution of this sample (~ 16,000 particles/mL) did not induce immunogenicity. To confirm this result, subvisible particles (up to ~ 18,000 particles/mL, containing aggregates and silicone oil droplets) produced under representative administration practices (created upon infusion of a drug product through an IV catheter) did not induce a response in cell-based assays or appear to increase the rate of adverse events or immunogenicity during phase 3 clinical trials. CONCLUSION: The ability of biotherapeutic aggregates to elicit an immune response in vitro, in vivo, and in the clinic depends on high numbers of particles. This suggests that there is a high threshold for aggregates to induce an immunogenic response which is well beyond that seen in standard biotherapeutic drug products.

Testing the temporal precedence of family functioning and child psychopathology in the LONGSCAN sample.

Family functioning may serve as protective or risk factors in the development of youth psychopathology. However, few studies have examined the potentially reciprocal relation between child psychopathology and family functioning. To fill this gap in the literature, this study tested for time-ordered associations between measures of family functioning (e.g., cohesion, conflict, and emotional expressiveness) and child psychopathology (e.g., total behavior problems, externalizing, and internalizing problems) using data from the Longitudinal Studies of Child Abuse and Neglect (LONGSCAN; N = 1143, 52.3% female, Nwaves = 5). We used a random-intercept cross-lagged panel model to identify whether child psychopathology preceded and predicted family functioning, the reverse, or both processes occurred simultaneously. At the between-person level, families who tended to have more cohesion, who lacked conflict, and who expressed their emotions had lower levels of child psychopathology. At the within-person level in childhood, we found minimal evidence for time-ordered associations. In adolescence, however, a clear pattern whereby early psychopathology consistently predicted subsequent family functioning emerged, and the reverse direction was rarely found. Results indicate a complex dynamic relation between the family unit and child that have important implications for developmental models that contextualize risk and resilience within the family unit.

Quantitative measurement of the requirement of diverse protein degradation pathways in MHC class I peptide presentation.

Peptides from degradation of intracellular proteins are continuously displayed by major histocompatibility complex (MHC) class I. To better understand origins of these peptides, we performed a comprehensive census of the class I peptide repertoire in the presence and absence of ubiquitin-proteasome system (UPS) activity upon developing optimized methodology to enrich for and quantify these peptides. Whereas most class I peptides are dependent on the UPS for their generation, a surprising 30%, enriched in peptides of mitochondrial origin, appears independent of the UPS. A further ~10% of peptides were found to be dependent on the proteasome but independent of ubiquitination for their generation. Notably, clinically achievable partial inhibition of the proteasome resulted in display of atypical peptides. Our results suggest that generation of MHC class I•peptide complexes is more complex than previously recognized, with UPS-dependent and UPS-independent components; paradoxically, alternative protein degradation pathways also generate class I peptides when canonical pathways are impaired.

Interpersonal Well-Being and Suicidal Outcomes in a Nationally Representative Study of Adolescents: A Translational Study.

Adolescent suicide continues to rise despite burgeoning research on interpersonal risk for suicide. This may reflect challenges in applying developmental psychopathology research into clinical settings. In response, the present study used a translational analytic plan to examine indices of social well-being most accurate and statistically fair for indexing adolescent suicide. Data from the National Comorbidity Survey Replication Adolescent Supplement were used. Adolescents aged 13-17 (N = 9,900) completed surveys on traumatic events, current relationships, and suicidal thoughts and attempts. Both frequentist (e.g., receiver operating characteristics) and Bayesian (e.g., Diagnostic Likelihood Ratios; DLRs) techniques provided insight into classification, calibration, and statistical fairness. Final algorithms were compared to a machine learning-informed algorithm. Overall, parental care and family cohesion best classified suicidal ideation, while these indices and school engagement best classified attempts. Multi-indicator algorithms suggested adolescents at high risk across these indices were approximately 3-times more likely to engage in ideation (DLR = 3.26) and 5-times more likely to engage in attempts (DLR = 4.53). Although equitable for attempts, models for ideation underperformed in non-White adolescents. Supplemental, machine learning-informed algorithms performed similarly, suggesting non-linear and interactive effects did not improve model performance. Future directions for interpersonal theories for suicide are discussed and clinical implications for suicide screening are demonstrated.

Recommendations for Imaging of the Temporomandibular Joint. Position Statement from the American Academy of Oral and Maxillofacial Radiology and the American Academy of Orofacial Pain.

This position statement was developed by an ad hoc committee of the American Academy of Oral and Maxillofacial Radiology and the American Academy of Orofacial Pain. The committee reviewed the pertinent literature and drafted recommendations for imaging. This joint statement provides evidence-based recommendations and clinical guidance for applying appropriate diagnostic imaging to evaluate the temporomandibular joint (TMJ). This manuscript guides the design of TMJ imaging examinations, addresses in-office CBCT imaging, and provides timely evidence-based recommendations to evaluate the TMJ bony components, also addressing the use of MRI and other modalities to evaluate TMJ involvement in different pathologic conditions.

Adolescent Loneliness during the COVID-19 Pandemic: The Role of Pre-Pandemic Risk Factors.

The COVID-19 pandemic is a global mental health crisis that disproportionately impacts adolescents. Loneliness is a particularly salient pandemic psychosocial outcome to understand; however, research to date on this outcome is sparse and largely cross-sectional. In response, we examined pre-pandemic risk factors for pandemic loneliness. Further, we examined how risk may differ based on key demographics, and whether mediation or moderation models best explained potential disparities in experiencing loneliness. Self-reported, pre-pandemic mental health, trauma exposure, and family conflict survey data were collected at Wave 1 in a diverse sample of 369 adolescents (54.5% female, 45.5% male; 30.1% White; 30.9% Black; 18.4% Hispanic; Mage = 15.04; SD age = 1.10). Subsequently, self-reported experiences of loneliness during the pandemic were collected 6 months (April-June 2020) and 12 months (October-December 2020) later. Using a regression-based framework (i.e., PROCESS), we tested (a) which pre-pandemic risks uniquely predicted prospective loneliness and (b) whether loneliness risk was elevated for certain identities (i.e., mediation models) or whether certain identities were more sensitive to specific risks (i.e., moderation models). Overall, pre-pandemic depressive and aggression symptoms predicted early pandemic loneliness (6-month follow-up), whereas anxiety symptoms specifically predicted mid-pandemic loneliness (12-month follow-up). Environmental stressors were moderated by gender, such that females with pre-pandemic trauma exposure were more likely to report pandemic loneliness. Further, pre-pandemic internalizing distress for girls and externalizing symptoms for boys, reflected gender-specific pathways for loneliness. Implications for mental health prevention in the wake of national disasters are discussed. Supplementary Information: The online version contains supplementary material available at 10.1007/s12187-022-09984-8.

The role of hopelessness and procedural justice on depressogenic outcomes in serious adolescent offenders.

OBJECTIVE: Despite increasing depression and suicide rates in justice-system-involved youth, little is known about depressogenic risk factors in this population. Therefore, we explored how levels of and changes in hopelessness and perceptions of procedural justice predicted depressive and suicidal outcomes in justice-system-involved youth. HYPOTHESES: We hypothesized that higher levels and increasing trajectories of hopelessness, as well as of perceived injustice, would predict depressive symptoms and suicidal ideation across adolescence and emerging adulthood. We also expected that procedural injustice would explain the relation between hopelessness and these outcomes. Finally, we hypothesized that gender and race/ethnicity would moderate the influence of hopelessness and perceived injustice. METHOD: Data for the present study were collected as part of the Pathways to Desistance study. In total, 1,354 adolescents (Mage = 16.04 years; 86.4% male; 41.4% non-Hispanic Black, 33.5% Hispanic, 20.2% non-Hispanic White) convicted of serious offenses participated. For the present study, participants answered questions on measures of procedural justice, hopelessness, depression, and suicidal ideation across 11 time points over 7 years. RESULTS: Using latent growth curve modeling, we found partial support for our hypotheses. Specifically, baseline levels of hopelessness predicted depression levels and increases in depression during adolescence (ps < .01). Further, changes in hopelessness predicted corresponding changes in depression throughout adolescence and emerging adulthood (ps < .001). Similarly, procedural justice levels predicted levels of depression (p < .001), and changes in procedural justice corresponded to changes in depression during emerging adulthood (p = .01). With regard to suicidal ideation, levels of and changes in hopelessness in emerging adulthood predicted corresponding suicidal ideation outcomes (ps ≤ .01). Meanwhile, we found only marginal support for our mediation model (p = .05). Collectively, results did not vary across gender or race/ethnicity. CONCLUSIONS: Hopelessness and perceived injustice are unique predictors of depression for juvenile-justice-system-involved youth. Preventive interventions targeting both hopelessness and procedural justice could help attenuate elevated depression rates in this population. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Intersecting identities and adolescent depression: Patterns of depressed mood and anhedonia in the past decade.

BACKGROUND: Research suggests adolescent depression is increasing and certain adolescents may be uniquely vulnerable. However, limited conceptualizations of identity and time, as well as the reliance on unitary conceptualizations of depression, inhibits a nuanced perspective on these trends. In response, we examined how adolescent depressive symptoms, depressed mood, and anhedonia, vary across intersecting identities over time. METHODS: Secondary data analysis on the National Survey on Drug Use and Health between 2009 and 2017 was conducted. In total 145,499 nationally representative adolescents (ages 12-17) completed a diagnostic assessment for depression. Lifetime and past year reports of depressive symptoms, depressed mood, and anhedonia were treated as separate variables. A novel, mixed-level model in which participants were nested within identity (defined by one's age, gender, race/ethnicity, poverty level) and time was used to test our aims. RESULTS: Overall, the relation between depression outcomes and identity did not vary over time (p > .01). Further, identity's impact on depression was approximately ten-fold that of temporal effects. Multiracial, late adolescent, female adolescents were at particular risk. Findings concerning depressed mood and anhedonia were similar across analyses. LIMITATIONS: All facets of identity (e.g., sexual identity) were not included in the model and a unidimensional measure of poverty may have underestimated its depressogenic influence. CONCLUSION: Adolescent depression outcomes are mostly consistent across criterial symptom subtypes and time, but vary as a function of identity. Prevention protocols that highlight mechanisms of risk tethered to social identity, and include salient experiences of females, late adolescents, and multiracial youth in particular, need to be prioritized in mental health initiatives.

Recommendations for imaging of the temporomandibular joint. Position statement from the American Academy of Oral and Maxillofacial Radiology and the American Academy of Orofacial Pain.

This position statement was developed by an ad hoc committee of the American Academy of Oral and Maxillofacial Radiology and the American Academy of Orofacial Pain. The committee reviewed pertinent literature and drafted recommendations for imaging. The statement provides evidence-based recommendations and clinical guidance to apply appropriate diagnostic imaging to evaluate the temporomandibular joint.

Engineered IL13 variants direct specificity of IL13Rα2-targeted CAR T cell therapy.

IL13Rα2 is an attractive target due to its overexpression in a variety of cancers and rare expression in healthy tissue, motivating expansion of interleukin 13 (IL13)-based chimeric antigen receptor (CAR) T cell therapy from glioblastoma into systemic malignancies. IL13Rα1, the other binding partner of IL13, is ubiquitously expressed in healthy tissue, raising concerns about the therapeutic window of systemic administration. IL13 mutants with diminished binding affinity to IL13Rα1 were previously generated by structure-guided protein engineering. In this study, two such variants, termed C4 and D7, are characterized for their ability to mediate IL13Rα2-specific response as binding domains for CAR T cells. Despite IL13Rα1 and IL13Rα2 sharing similar binding interfaces on IL13, mutations to IL13 that decrease binding affinity for IL13Rα1 did not drastically change binding affinity for IL13Rα2. Micromolar affinity to IL13Rα1 was sufficient to pacify IL13-mutein CAR T cells in the presence of IL13Rα1-overexpressing cells in vitro. Interestingly, effector activity of D7 CAR T cells, but not C4 CAR T cells, was demonstrated when cocultured with IL13Rα1/IL4Rα-coexpressing cancer cells. While low-affinity interactions with IL13Rα1 did not result in observable toxicities in mice, in vivo biodistribution studies demonstrated that C4 and D7 CAR T cells were better able to traffic away from IL13Rα1+ lung tissue than were wild-type (WT) CAR T cells. These results demonstrate the utility of structure-guided engineering of ligand-based binding domains with appropriate selectivity while validating IL13-mutein CARs with improved selectivity for application to systemic IL13Rα2-expressing malignancies.

Is ACEs Screening for Adolescent Mental Health Accurate and Fair?

Increasingly, adversity-focused assessment tools are being introduced into preventive mental health screening protocols. However, few studies have explicitly examined whether use of these instruments serves as equitable, clinically useful measures of mental health risk in adolescents. In response, the present study examined whether an adverse childhood experiences (ACEs) measure was accurate and fair as an index of environmental risk for adolescent mental health diagnoses. Secondary data analyses were conducted on the National Comorbidity Survey-Adolescent Supplement. Adolescents (N = 10,148; AgeMean = 15.20; 51.3% male; 65.6% White, 15.1% Black, and 14.4% Hispanic) answered ten questions concerning childhood adversities and completed diagnostic interviews for PTSD, depression, and externalizing disorders. In the overall sample, ACEs showed some clinical utility (e.g., area under the curve (AUCs) ≥ 0.64), diagnostic likelihood ratios (DLRs) > 4.0) and acceptable calibration (i.e., expected/observed indices' confidence intervals included 1) across diagnoses. Within subpopulations, however, predictive validity varied. The AUCs were lower for multiple diagnoses in Black male and Hispanic female adolescents and DLRs suggested greater clinical utility for indexing mental health in White, female adolescents. Finally, models were not well-calibrated between adolescent subpopulations, suggesting recommended ACEs screening can potentially produce biased results when used to inform mental health policy and prevention. Reasons for why results from ACEs screening may vary across adolescent subpopulations and the importance of testing statistical fairness for preventive mental health screening are discussed.

Testing the factor structure and measurement invariance of the Temporal Experience of Pleasure Scale in adolescents across time, gender, and race/ethnicity.

The Temporal Experience of Pleasure Scale (TEPS) is a self-report measure designed to assess anticipatory and consummatory pleasure, two facets of anhedonic predispositions. Despite its widespread use, the factor structure of the TEPS has yet to be tested in adolescents, who are at increased risk for psychopathology and undergoing rapid changes in reward-related processes. In response, the present study aimed to test the factor structure and measurement invariance of the TEPS across time, gender, and race/ethnicity in a diverse adolescent sample. Adolescents (N = 441; Mage = 14.98; 223 female) who identified as either Black (37%), Hispanic (37%), or White (26%), completed the TEPS at Baseline, 6-month, and 12-month follow-ups. Factor analyses were conducted to examine the factor structure of the TEPS, while configural, metric, scalar, and strict invariance were tested across time and demographics. Findings supported the two-factor structure of the TEPS, above and beyond other conceptualizations (e.g., 4-factor, bifactor), full longitudinal invariance, and partial invariance across gender and race/ethnicity. Examination of mean differences suggested no temporal, gender nor race/ethnic differences for anticipatory pleasure. For consummatory pleasure, no differences were found for gender, but results suggested higher levels over time and lower levels in Black adolescents. Our findings provide preliminary support for reliable cross-group interpretations of anticipatory and consummatory anhedonic predispositions as measured through the TEPS. Together, results provide support for the clinical utility of the TEPS for anhedonic-related psychopathology risk assessment in adolescence. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Childhood Maltreatment and Anhedonic Symptoms: Test of a Dual-risk Model in Emerging Adults.

Anhedonia, defined as deficits in positive affect and approach related behaviors, remains an understudied trauma response. As anhedonic responses to interpersonal violence are associated with a more severe course of psychopathology that is more difficult to treat, an increased focus on risk factors for anhedonia is necessary. The present study sought to address this gap in the literature by testing a theoretical model that highlights two transdiagnostic pathways leading to anhedonic responses in emerging adults attending college. Specifically, our study examined how childhood maltreatment subtypes (a) uniquely associate with depressive and post-traumatic stress (PTS) manifestations of anhedonia and (b) how temperament (i.e., anticipatory positive affect) and distress (i.e., negative mood) explain these relations. At baseline, a racially diverse sample of 462 emerging adults (AgeMean = 19.45; 75.5% female; 45.5% White) completed self-report forms on childhood abuse and neglect, anticipatory positive affect, negative mood, and anhedonia. Individuals completed measures of temperament and psychological distress again 6-weeks, and 12-weeks later. Latent growth curve models were utilized to test our model. Consistent with hypotheses, deficits in anticipatory positive affect uniquely explained the relation between neglect and depressive/PTS anhedonic symptoms. Meanwhile, negative mood mediated the relation between abuse and both forms of anhedonia. These findings support the theory that two separate risk pathways lead to anhedonia. Support for our model suggests that distinguishing between pathways for anhedonic responses may be the key to a more targeted, transdiagnostic, trauma-informed approach for treating and preventing these deleterious, treatment-resistant, internalizing symptoms.

Use of cone beam computed tomography imaging for airway measurement to predict obstructive sleep apnea.

Objective: This retrospective chart review examined whether airway parameters were correlated with scores on the STOP-Bang questionnaire.Methods: Minimal upper airway area, upper airway volume, minimal retropalatal area, retropalatal volume, minimal retroglossal area, and retroglossal volume were calculated from cone beam computed tomography (CBCT) images. Patients were grouped based on their STOP-Bang scores (<3 or ≥3) for obstructive sleep apnea (OSA), and airway parameters were compared across the 2 groups.Results: Thirty-one (43%) of 72 patients with a minimal upper airway area of <110 mm2 had STOP-Bang scores of ≥3. Most patients (90%) with STOP-Bang scores of ≥3 had minimal retropalatal areas of <110 mm2. Differences were found between groups for minimal upper airway area (p = 0.03), upper airway volume (p = 0.04), and minimal retropalatal area (p = 0.001).Discussion: To assess OSA risk, dentists should compare CBCT images with STOP-Bang scores.

Short-Term and Long-Term Resilience Among At-Risk Adolescents: The Role of Family and Community Settings.

Objective: Given the severe consequences associated with maltreatment, establishing an understanding of pathways to resilience among trauma-exposed youth is a critical public health aim. Longitudinal research has either examined short-term or long-term responses to traumatic events, which prevents testing for a) individual differences between resilience subtypes and b) consistency of short-term, resilient responses over time. Additionally, post-traumatic stress and depression represent the two most common symptom patterns in youth exposed to maltreatment, however few studies have simultaneously investigated resilience to these outcomes. In response, the current study employs a dimensional analytic approach to distinguish between short-term (the ability to demonstrate adaptive responses to ongoing adversities) and long-term (lack of distress over several years in response to a prior adversity) resilience. Consistent with an ecological perspective, the study examines whether family- and community-level protective factors are similarly or uniquely associated with different resilience subtypes.Method: Participants included 943 individuals (469 male, 474 female) from a nationally-representative, at-risk sample of adolescents who completed self-report measures of maltreatment exposure, depressive symptoms and post-traumatic stress symptoms at ages 12, 16, and 18. During the age 12 visit, participants' caregivers completed self-report measures of family routines and neighborhood social cohesion.Results: Overall, we found that family routines uniquely buffered against trauma-related distress across resilience conceptualizations, while social cohesion played a role in short-term resilience to depressive symptoms (p <.05). Participant gender did not moderate these results (p > .05).Conclusion: These findings highlight the importance of understanding resilience dimensionally for adolescents exposed to maltreatment.

Cardiac autonomic functioning across stress and reward: Links with depression in emerging adults.

The autonomic nervous system (ANS) has received much attention as a potential low-cost, peripheral indicator of depression. Despite theoretical support, however, results have been mixed as to whether indices of the ANS reliably index depression. In response, the present study sought to clarify the relation between ANS activity and depression by examining cardiac autonomic balance (CAB) and cardiac autonomic regulation (CAR), two composite indices of the parasympathetic and sympathetic nervous system, within both a stressful and rewarding context. We hypothesized that CABStress, representing the difference between the parasympathetic and sympathetic branches in response to stress, and CARReward, representing the summation of the two branches in response to reward, will be most indicative of depressogenic risk. We examined the parasympathetic (i.e., respiratory sinus arrhythmia) and sympathetic (i.e., pre-ejection period) responses of 97 emerging adults (Mage = 18.93) for a stress (i.e., negative mood induction) and reward (i.e., probabilistic learning) task, as well as their depressive symptoms at baseline, 3-week, and 6-week follow-up. Analyses found partial support for our hypotheses, revealing greater CARReward (i.e., coactivation of both branches) was related to lower depressive symptoms. Further, exploratory analyses examining gender differences found lower CABStress (i.e., sympathetically-oriented response) was predictive of an increasing trajectory of depression, but only among males. Overall, the current study highlights the importance of simultaneously examining both branches of the ANS across various environmental contexts. Research and clinical implications of the current findings are discussed.

Developmental consequences of emotional abuse and neglect in vulnerable adolescents: A multi-informant, multi-wave study.

BACKGROUND: Extant research and theory posit that emotional abuse and emotional neglect-exposure is uniquely harmful during adolescence. Yet, these findings are mostly based on mono-informant, retrospective studies with unselected adults that examine emotional maltreatment in the aggregate. This prevents inferences concerning the unique, prospective risk emotional abuse and neglect, as reported by multiple informants, may confer within at-risk, adolescent samples. OBJECTIVE: In response, the present study examined how emotional abuse and emotional neglect-exposure in adolescence uniquely related to psychological symptoms and social impairment. PARTICIPANTS AND SETTING: Our aims were tested in a child welfare system (CWS)-involved sample of adolescents (N = 657; AgeM = 12.49 at baseline) who were participating in a longitudinal study. METHODS: A multi-informant approach was used to assess emotional abuse/neglect and mental health. Physical abuse and lifetime CWS contact represented covariates in growth curve models. RESULTS: Emotional abuse predicted symptoms within informant, such that youth-reported emotional abuse predicted youth-reported internalizing, ß = 0.21, p = .001, and externalizing, ß=0.35, p = .001, symptoms while parent-reported emotional abuse predicted parent-reported externalizing, ß=0.30, p < .001, and internalizing ß=0.29, p < .001, symptoms. Meanwhile, youth-reported emotional neglect predicted heightened self-reported internalizing symptoms, ß=0.29, p < .001, parent-reported externalizing symptoms, ß=0.15, p = .002 and social impairment across youth, ß=-0.17, p = .01 and parent, ß=-0.24, p < .001, report. CONCLUSIONS: This study shows the importance of distinguishing between these maltreatment subtypes in adolescence and provides measurement recommendations for future maltreatment research. The manuscript concludes by discussing adolescent emotional abuse and neglect-exposure as a maintenance, as opposed to causal risk, factors.