Traumatic brain injury, working memory-related neural processing, and alcohol experimentation behaviors in youth from the ABCD cohort.

Adolescent traumatic brain injury (TBI) has long-term effects on brain functioning and behavior, impacting neural activity under cognitive load, especially in the reward network. Adolescent TBI is also linked to risk-taking behaviors including alcohol misuse. It remains unclear how TBI and neural functioning interact to predict alcohol experimentation during adolescence. Using Adolescent Brain Cognitive Development (ABCD) study data, this project examined if TBI at ages 9-10 predicts increased odds of alcohol sipping at ages 11-13 and if this association is moderated by neural activity during the Emotional EN-Back working memory task at ages 11-13. Logistic regression analyses showed that neural activity in regions of the fronto-basal ganglia network predicted increased odds of sipping alcohol by ages 11-13 (p < .05). TBI and left frontal pole activity interacted to predict alcohol sipping (OR = 0.507, 95% CI [0.303 - 0.846], p = .009) - increased activity predicted decreased odds of alcohol sipping for those with a TBI (OR = 0.516, 95% CI [0.314 - 0.850], p = .009), but not for those without (OR = 0.971, 95% CI [0.931 -1.012], p = .159). These findings suggest that for youth with a TBI, increased BOLD activity in the frontal pole, underlying working memory, may be uniquely protective against the early initiation of alcohol experimentation. Future work will examine TBI and alcohol misuse in the ABCD cohort across more time points and the impact of personality traits such as impulsivity on these associations.

Coronary Inflammation by Computed Tomography Pericoronary Fat Attenuation and Increased Cytokines in Young Male Anabolic Androgenic Steroid Users. / Inflamação Coronária Avaliada pela Atenuação de Gordura Pericoronária na Tomografia Computadorizada e Elevação de Citocinas em Usuários Jovens de Esteroides Anabólicos Androgênicos.

BACKGROUND: Anabolic androgenic steroid (AAS) abuse has been associated with coronary artery disease (CAD). Pericoronary fat attenuation (pFA) is a marker of coronary inflammation, which is key in the atherosclerotic process. OBJECTIVE: To evaluate pFA and inflammatory profile in AAS users. METHODS: Twenty strength-trained AAS users (AASU), 20 AAS nonusers (AASNU), and 10 sedentary controls (SC) were evaluated. Coronary inflammation was evaluated by mean pericoronary fat attenuation (mPFA) in the right coronary artery (RCA), left anterior descending coronary artery (LAD), and left circumflex (LCx). Interleukin (IL)-1 (IL-1), IL-6, IL-10, and TNF-alpha were evaluated by optical density (OD) in a spectrophotometer with a 450 nm filter. P<0.05 indicated statistical significance. RESULTS: AASU had higher mPFA in the RCA (-65.87 [70.51-60.70] vs. -78.07 [83.66-72.87] vs.-78.46 [85.41-71.99] Hounsfield Units (HU), respectively, p<0.001) and mPFA in the LAD (-71.47 [76.40-66.61] vs. -79.32 [84.37-74.59] vs. -82.52 [88.44-75.81] HU, respectively, p=0.006) compared with AASNU and SC. mPFA in the LCx was not different between AASU, AASNU, and SC (-72.41 [77.17-70.37] vs. -80.13 [86.22-72.23] vs. -78.29 [80.63-72.29] HU, respectively, p=0.163). AASU compared with AASNU and SC, had higher IL-1, (0.975 [0.847-1.250] vs. 0.437 [0.311-0.565] vs. 0.530 [0.402-0.780] OD, respectively, p=0.002), IL-6 (1.195 [0.947-1.405] vs. 0.427 [0.377-0.577] vs. 0.605 [0.332-0.950] OD, p=0.005) and IL-10 (1.145 [0.920-1.292] vs. 0.477 [0.382-0.591] vs. 0.340 [0.316-0.560] OD, p<0.001). TNF-α was not different between the AASU, AASNU, and SC groups (0.520 [0.250-0.610] vs. 0.377 [0.261-0.548] vs. 0.350 [0.182-430]), respectively. CONCLUSION: Compared with ASSNU and controls, AASU have higher mPFA and higher systemic inflammatory cytokines profile suggesting that AAS may induce coronary atherosclerosis through coronary and systemic inflammation.

FUNDAMENTO: O uso abusivo de esteroides anabólicos androgênicos (EAA) tem sido associado à doença arterial coronariana (DAC). A atenuação de gordura pericoronária (AGp) é um marcador de inflamação coronária, a qual exerce um papel chave no processo aterosclerótico. OBJETIVO: Avaliar AGp e perfil inflamatório em usuários de EAA. MÉTODO: Vinte indivíduos que realizavam treinamento de força, usuários de EAA (UEAA), 20 não usuários de EAA (NUEAA), e 10 indivíduos sedentários controle (SC) foram avaliados. Inflamação coronária foi avaliada por atenuação de gordura pericoronária média (AGPm) artéria coronária direita (ACD), artéria descendente anterior esquerda (ADA) e artéria circunflexa (ACX). Interleucina (IL)-1 (IL-1), IL-6, IL-10, e TNF-alfa foram avaliados por densidade ótica (DO) em um espectrofotômetro com um filtro de 450 nm. Um p<0,05 indicou significância estatística. RESULTADOS: Os UEAA apresentaram maior AGPm na ACD [-65,87 (70,51-60,70) vs. -78,07 (83,66-72,87) vs.-78,46 (85,41-71,99] unidades Hounsfield (HU), respectivamente, p<0,001) e AGPm na ADA [-71,47 (76,40-66,610 vs. -79,32 (84,37-74,59) vs. -82,52 (88,44-75,81) HU, respectivamente, p=0,006) em comparação aos NUEAA e CS. A AGPm na ACX não foi diferente entre os grupos UEAA, NUEAA e CS [-72,41 (77,17-70,37) vs. -80,13 (86,22-72,23) vs. -78,29 (80,63-72,29) HU, respectivamente, p=0,163). Em comparação aos NUEAA e aos CS, o grupo UEAA apresentaram maiores níveis de IL-1 [0,975 (0,847-1,250) vs. 0,437 (0,311-0,565) vs. 0,530 (0,402-0,780) DO, respectivamente, p=0,002), IL-6 [1,195 (0,947-1,405) vs. 0,427 (0,377-0,577) vs. 0,605 (0,332-0,950) DO, p=0,005) e IL-10 [1,145 (0,920-1,292) vs. 0,477 (0,382-0,591) vs. 0,340 (0,316-0,560) DO, p<0,001]. TNF-α não foi diferente entre os grupos UEAA, NUEAA e CS [0,520 (0,250-0,610) vs. 0,377 (0.261-0,548) vs. 0,350 (0,182-430)]. CONCLUSÃO: Em comparação aos NUEAA e controles, os UEAA apresentam maior AGPm e maior perfil de citocinas inflamatórias sistêmicas, sugerindo que os EAA podem induzir aterosclerose por inflamação coronária e sistêmica.

Hispanic/Latinx ethnic differences in the relationships between behavioral inhibition, anxiety, and substance use in youth from the ABCD cohort.

Introduction: Elevated levels of behavioral inhibition (BI) may connote risk for both anxiety and substance use disorders. BI has consistently been shown to be associated with increased levels of anxiety, while the association between BI and substance use has been mixed. It is possible that the relationship between BI and substance use varies by individual difference factors. Hispanic/Latinx (H/L) youth in particular may have stronger relationships between BI, anxiety, and substance use. Methods: The present study therefore evaluated (1) the prospective relationships between BI [assessed via self-reported behavioral inhibition system (BIS) scale scores], anxiety, and substance use in youth (n = 11,876) across baseline, 1-, and 2-year follow-ups of the Adolescent Brain Cognitive Development (ABCD) Study (ages 9-12) and (2) whether these relationships differed by H/L ethnicity while covarying for average behavioral approach system scores, race, sex, age, highest parental income, highest parental education, and past-year substance use (for analyses involving substance use outcomes). Results: Baseline levels of BIS scores predicted increased anxiety symptoms at both 1- and 2-year follow-ups and did not differ by H/L ethnicity. Baseline levels of BIS scores also prospectively predicted increased likelihood of substance use at 2-year follow-up, but only for H/L youth and not at 1-year follow-up. Discussion: High scores on the BIS scale contribute risk to anxiety across ethnicities and may uniquely contribute to risk for substance use in H/L youth.

Inflamação Coronária Avaliada pela Atenuação de Gordura Pericoronária na Tomografia Computadorizada e Elevação de Citocinas em Usuários Jovens de Esteroides Anabólicos Androgênicos / Coronary Inflammation by Computed Tomography Pericoronary Fat Attenuation and Increased Cytokines in Young Male Anabolic Androgenic Steroid Users

Resumo Fundamento O uso abusivo de esteroides anabólicos androgênicos (EAA) tem sido associado à doença arterial coronariana (DAC). A atenuação de gordura pericoronária (AGp) é um marcador de inflamação coronária, a qual exerce um papel chave no processo aterosclerótico. Objetivo Avaliar AGp e perfil inflamatório em usuários de EAA. Método Vinte indivíduos que realizavam treinamento de força, usuários de EAA (UEAA), 20 não usuários de EAA (NUEAA), e 10 indivíduos sedentários controle (SC) foram avaliados. Inflamação coronária foi avaliada por atenuação de gordura pericoronária média (AGPm) artéria coronária direita (ACD), artéria descendente anterior esquerda (ADA) e artéria circunflexa (ACX). Interleucina (IL)-1 (IL-1), IL-6, IL-10, e TNF-alfa foram avaliados por densidade ótica (DO) em um espectrofotômetro com um filtro de 450 nm. Um p<0,05 indicou significância estatística. Resultados Os UEAA apresentaram maior AGPm na ACD [-65,87 (70,51-60,70) vs. -78,07 (83,66-72,87) vs.-78,46 (85,41-71,99] unidades Hounsfield (HU), respectivamente, p<0,001) e AGPm na ADA [-71,47 (76,40-66,610 vs. -79,32 (84,37-74,59) vs. -82,52 (88,44-75,81) HU, respectivamente, p=0,006) em comparação aos NUEAA e CS. A AGPm na ACX não foi diferente entre os grupos UEAA, NUEAA e CS [-72,41 (77,17-70,37) vs. -80,13 (86,22-72,23) vs. -78,29 (80,63-72,29) HU, respectivamente, p=0,163). Em comparação aos NUEAA e aos CS, o grupo UEAA apresentaram maiores níveis de IL-1 [0,975 (0,847-1,250) vs. 0,437 (0,311-0,565) vs. 0,530 (0,402-0,780) DO, respectivamente, p=0,002), IL-6 [1,195 (0,947-1,405) vs. 0,427 (0,377-0,577) vs. 0,605 (0,332-0,950) DO, p=0,005) e IL-10 [1,145 (0,920-1,292) vs. 0,477 (0,382-0,591) vs. 0,340 (0,316-0,560) DO, p<0,001]. TNF-α não foi diferente entre os grupos UEAA, NUEAA e CS [0,520 (0,250-0,610) vs. 0,377 (0.261-0,548) vs. 0,350 (0,182-430)]. Conclusão Em comparação aos NUEAA e controles, os UEAA apresentam maior AGPm e maior perfil de citocinas inflamatórias sistêmicas, sugerindo que os EAA podem induzir aterosclerose por inflamação coronária e sistêmica.

Abstract Background Anabolic androgenic steroid (AAS) abuse has been associated with coronary artery disease (CAD). Pericoronary fat attenuation (pFA) is a marker of coronary inflammation, which is key in the atherosclerotic process. Objective To evaluate pFA and inflammatory profile in AAS users. Methods Twenty strength-trained AAS users (AASU), 20 AAS nonusers (AASNU), and 10 sedentary controls (SC) were evaluated. Coronary inflammation was evaluated by mean pericoronary fat attenuation (mPFA) in the right coronary artery (RCA), left anterior descending coronary artery (LAD), and left circumflex (LCx). Interleukin (IL)-1 (IL-1), IL-6, IL-10, and TNF-alpha were evaluated by optical density (OD) in a spectrophotometer with a 450 nm filter. P<0.05 indicated statistical significance. Results AASU had higher mPFA in the RCA (-65.87 [70.51-60.70] vs. -78.07 [83.66-72.87] vs.-78.46 [85.41-71.99] Hounsfield Units (HU), respectively, p<0.001) and mPFA in the LAD (-71.47 [76.40-66.61] vs. -79.32 [84.37-74.59] vs. -82.52 [88.44-75.81] HU, respectively, p=0.006) compared with AASNU and SC. mPFA in the LCx was not different between AASU, AASNU, and SC (-72.41 [77.17-70.37] vs. -80.13 [86.22-72.23] vs. -78.29 [80.63-72.29] HU, respectively, p=0.163). AASU compared with AASNU and SC, had higher IL-1, (0.975 [0.847-1.250] vs. 0.437 [0.311-0.565] vs. 0.530 [0.402-0.780] OD, respectively, p=0.002), IL-6 (1.195 [0.947-1.405] vs. 0.427 [0.377-0.577] vs. 0.605 [0.332-0.950] OD, p=0.005) and IL-10 (1.145 [0.920-1.292] vs. 0.477 [0.382-0.591] vs. 0.340 [0.316-0.560] OD, p<0.001). TNF-α was not different between the AASU, AASNU, and SC groups (0.520 [0.250-0.610] vs. 0.377 [0.261-0.548] vs. 0.350 [0.182-430]), respectively. Conclusion Compared with ASSNU and controls, AASU have higher mPFA and higher systemic inflammatory cytokines profile suggesting that AAS may induce coronary atherosclerosis through coronary and systemic inflammation.

Event-related potentials to acoustic startle probes during unpredictable threat are associated with individual differences in intolerance of uncertainty.

Individual differences in sensitivity to unpredictable threat may be a critical mechanism for internalizing psychopathology phenotypes. The present study examined whether the startle probe-elicited N100 and P300 during unpredictable threat - two event-related potentials indexing early and elaborative attentional processing of unpredictable threat - may be endophenotypes for internalizing psychopathology, including fear and distress/misery disorders and intolerance of uncertainty (IU), a clinical trait that is transdiagnostically associated with internalizing disorders. A large sample of adult siblings (N = 375) completed the no, predictable, and unpredictable threat task, during which the N100 and P300 were recorded. Relative to the no threat condition, N100 was more strongly enhanced in anticipation of unpredictable than predictable threat while P300 was suppressed to both predictable and unpredictable threat. While neither N100 enhancement nor P300 suppression to unpredictable threat was associated with fear or distress/misery disorders, they were negatively linked to inhibitory IU (a facet of IU). Thus, individuals high in inhibitory IU showed reduced attentional engagement with the threatening context when it was unpredictable. Further, N100 enhancement and, to a lesser degree, P300 suppression to unpredictable threat showed familial aggregation - a key criterion for determining whether a biomarker is an endophenotype. In sum, N100 enhancement and P300 suppression to unpredictable threat may be endophenotypes for dimensional measures of internalizing psychopathology.

Ethnic differences in behavioral and physiological indicators of sensitivity to threat.

The clinical presentation of anxiety may differ between Hispanics/Latinx (H/L) and non-H/L, although findings on ethnic differences in self-reported anxiety symptoms have been mixed. Fewer studies have focused on ethnic differences in quick and relatively automatic laboratory-assessed indicators of anxiety symptoms, which have the potential to be more objective indicators than self-report. Therefore, the present study examined ethnic differences in two laboratory-assessed indicators of threat sensitivity (an important transdiagnostic mechanism of anxiety): attentional bias to threat and electromyography startle reactivity to threat. White H/L (n = 117) and White non-H/L (n = 168) adults who were matched on demographics and lifetime psychopathology (including anxiety) completed a dot-probe task to assess attentional bias to threat and the No-Predictable-Unpredictable threat (NPU) task to assess startle reactivity to threat. Results indicated that H/L displayed less Slow OrientationRB (ß = -0.27, p = 0.032, R2ß∗ = 0.02), and increased Slow DisengagementRB (ß = 0.31, p = 0.016, R2ß∗ = 0.02) compared to non-H/L. H/L exhibited blunted overall startle compared to non-H/L (ß = -0.30, p = 0.014, R2ß∗ = 0.02), but groups did not differ in startle reactivity to either predictable or unpredictable threat. In summary, H/L and non-H/L may differ in their experience and presentation of anxiety symptoms and such differences may vary across indicators of sensitivity to threat.

An Uncommon Presentation of Cryptococcal Meningitis in an Immunocompetent Patient: A Case Report.

INTRODUCTION: Meningitis is a serious and potentially life-threatening infection of the central nervous system. Cryptococcus neoformans is a rare fungal cause of meningitis that commonly presents with atypical symptoms. Although this infection is most common in immunocompromised patients, it also occurs in immunocompetent patients. This case report describes an atypical presentation of cryptococcal meningitis in a seemingly immunocompetent patient. CASE REPORT: A 40-year-old immunocompetent patient with no significant past medical history had visited the emergency department (ED) five times within a span of 30 days reporting dental pain and headache. Throughout each of the visits, no clear symptoms signaling the need for a meningitis workup were observed, as the patient had been afebrile, displayed no nuchal rigidity, and his presenting symptoms subsided within the ED after treatment. A lumbar puncture was performed after emergency medical services brought the patient in for his sixth ED visit, initially for stroke-like symptoms and altered mental status. Spinal fluid was indicative of cryptococcal meningitis. CONCLUSION: This case highlights the challenge of identifying cryptococcal meningitis in the ED, particularly in immunocompetent patients who do not display classic meningitis symptoms. It also highlights the importance of keeping a broad differential and carefully ruling out diagnoses when patients return to the ED multiple times for the same complaint.

Evaluating the criterion validity of hierarchical psychopathology dimensions across models: Familial aggregation and associations with research domain criteria (sub)constructs.

The Hierarchical Taxonomy of Psychopathology (HiTOP) posits that psychopathology is a hierarchy of correlated dimensions. Numerous studies have examined the validity of these dimensions using bifactor models, in which each disorder loads onto both a general and specific factor (e.g., internalizing, externalizing). Although bifactor models tend to fit better than alternative models, concerns have been raised about bifactor model selection, factor reliability, and interpretability. Therefore, we compared the reliability and validity of several higher-order HiTOP dimensions between bifactor and correlated factor models using familial aggregation and associations with Research Domain Criteria (RDoC; sub)constructs as validators. Lifetime psychopathology was assessed in a community sample (N = 504) using dimensional disorder severity scales calculated from semistructured interview data. A series of unidimensional, correlated factor, and bifactor models were fit to model several HiTOP dimensions. A bifactor model with two specific factors (internalizing and disinhibited externalizing) and a correlated two-factor model provided the best fit to the data. HiTOP dimensions had adequate reliability in the correlated factor model, but suboptimal reliability in the bifactor model. The disinhibited externalizing dimension was highly correlated across the two models and was familial, yet largely unrelated to RDoC (sub)constructs in both models. The internalizing dimension in the correlated factor model and the general factor in the bifactor model were highly correlated and had similar validity patterns, suggesting the general factor was largely redundant with the internalizing dimension in the correlated factor model. These findings support concerns about the interpretability of psychopathology dimensions in bifactor models. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

The emotion-elicited late positive potential is stable across five testing sessions.

Many studies have examined associations between neural and behavioral markers of attention to emotion and individual differences in affective functioning. However, the majority of these studies are cross-sectional, and examine associations between brain, behavior, and individual differences at one or two time-points, limiting our understanding of the extent to which these neural responses reflect trait-like patterns of attention. The present study used the Emotional Interrupt paradigm, and examined the stability and trajectory of behavioral (i.e., reaction time to targets following task-irrelevant appetitive, neutral, and aversive images), and neural responses to images (i.e., the late positive potential or LPP), across five sessions separated by one week in 86 individuals. Additionally, we examined the extent to which the LPP and behavioral measures were sensitive to naturally occurring daily fluctuations in positive and negative affect. Results indicate that, though the magnitude of the conditional LPP waveforms decreased over time, the degree of emotional modulation (i.e., differentiation of emotional from neutral) did not; in fact, differentiation of appetitive from neutral increased over time. Behavioral responses were similarly stable across sessions. Additionally, we largely did not observe significant effects of state positive and negative affect on the LPP or behavior over time. Finally, the LPP elicited by appetitive images significantly predicted reaction time to targets following these images. These data suggest that neural and behavioral markers of attention to motivationally salient cues may be trait-like in nature, and may be helpful in future studies seeking to identify markers of vulnerability for diverse forms of psychopathology.

Sacubitril/valsartan versus enalapril on exercise capacity in patients with heart failure with reduced ejection fraction: A randomized, double-blind, active-controlled study.

Sacubitril/valsartan reduces mortality in patients with heart failure with reduced ejection fraction (HFrEF) when compared with enalapril. However, it is unknown the effect of both treatments on exercise capacity. We compared sacubitril/valsartan versus enalapril in patients with HFrEF based on peak oxygen consumption (VO2) and 6-minute walk test (6-MWT). METHODS: We included 52 participants with HFrEF with a left ventricular ejection fraction <40% to receive either sacubitril/valsartan (target dose of 400 mg daily) or enalapril (target dose of 40 mg daily). Peak VO2 was measured by using cardiopulmonary exercise testing. Six-minute walk test was also performed. RESULTS: At 12 weeks, the sacubitril/valsartan (mean dose 382.6 ± 57.6 mg daily) group had increased peak VO2 of 13.1% (19.35 ± 0.99 to 21.89 ± 1.04 mL/kg/min) and enalapril (mean dose 34.4 ± 9.2 mg daily) 5.6% (18.58 ± 1.19 to 19.62 ± 1.25 mL/kg/min). However, no difference was found between groups (P = .332 interaction). At 24 weeks, peak VO2 increased 13.5% (19.35 ± 0.99 to 21.96 ± 0.98 mL/kg/min) and 12.0% (18.58 ± 1.19 to 20.82 ± 1.18 mL/kg/min) in sacubitril/valsartan (mean dose 400 ± 0 mg daily) and enalapril (mean dose 32.7 ± 11.0 mg daily), respectively. However, no differences were found between groups (P= .332 interaction). At 12 weeks, 6-MWT increased in both groups (sacubitril/valsartan: 459 ± 18 to 488 ± 17 meters [6.3%] and enalapril: 443 ± 22 to 477 ± 21 meters [7.7%]). At 24 weeks, sacubitril/valsartan increased 18.3% from baseline (543 ± 26 meters) and enalapril decreased slightly to 6.8% (473 ± 31 meters), but no differences existed between groups (P= .257 interaction). CONCLUSIONS: Compared to enalapril, sacubitril/valsartan did not substantially improve peak VO2 or 6-MWT after 12 or 24 weeks in participants with HFrEF. (NEPRIExTol-HF Trial, ClinicalTrials.gov number, NCT03190304).

Unique longitudinal relationships between symptoms of psychopathology in youth: A cross-lagged panel network analysis in the ABCD study.

BACKGROUND: The network theory suggests that psychopathology may reflect causal relationships between individual symptoms. Several studies have examined cross-sectional relationships between individual symptoms in youth. However, these studies cannot address the directionality of the temporal relationships hypothesized by the network theory. Therefore, we estimated the longitudinal relationships between individual internalizing, externalizing, and attention symptoms in youth. METHODS: Data from 4,093 youth participants in the Adolescent Brain Cognitive Development (ABCD) study were used. Symptoms were assessed using the Brief Problem Monitor, which was administered at three time points spaced six months apart. Unique longitudinal relationships between symptoms at T1 and T2 were estimated using cross-lagged panel network modeling. Network replicability was assessed by comparing this network to an identically estimated replication network of symptoms at T2 predicting symptoms at T3. RESULTS: After controlling for all other symptoms and demographic covariates, depressed mood, inattention, and worry at T1 were most predictive of other symptoms at T2. In contrast, threats of violence and destructiveness at T2 were most prospectively predicted by other symptoms at T1. The reciprocal associations between depressed mood and worthlessness were among the strongest bivariate relationships in the network. Comparisons between the original network and the replication network (correlation between edge lists = .61; individual edge replicability = 64%-84%) suggested moderate replicability. CONCLUSIONS: Although causal inferences are precluded by the observational design and methodological considerations, these findings demonstrate the directionality of relationships between individual symptoms in youth and highlight depressed mood, inattention, and worry as potential influencers of other symptoms.

Distress Tolerance as a Familial Vulnerability for Distress-Misery Disorders.

Low perceived distress tolerance (DT), a trait-like individual difference factor reflecting one's perceived ability to withstand aversive affective states, has been linked with current internalizing and substance use disorders (SUDs). However, perceived DT has not been systematically evaluated as a familial, transdiagnostic vulnerability factor for internalizing and SUDs. The current study tested whether perceived DT runs in families and whether it is reduced among individuals with versus without remitted internalizing/SUD psychopathology. Perceived DT and internalizing/SUDs were measured in 638 individuals (nested within 256 families). Analyses also adjusted for the effects of neuroticism to test whether DT was a specific vulnerability factor independent of temperamental negative affect. Analyses revealed that perceived DT was lower in individuals with remitted distress (i.e., major depression, generalized anxiety disorder, posttraumatic stress disorder) but not fear disorders (i.e., panic disorder, social anxiety disorder, specific phobia, obsessive-compulsive spectrum disorders) relative to healthy controls, and the effect of distress-misery disorder history remained significant when adjusting for neuroticism. Perceived DT was not significantly different among individuals with versus without a remitted SUD. There were no effects for comorbid SUD and distress-misery disorders. Finally, perceived DT was also significantly correlated within families, suggesting that it runs in families. Overall, results suggest that independent of neuroticism, low perceived DT is a familial vulnerability for distress (but not fear or substance use) disorders.

The Relation Between Posttraumatic Stress Symptom Severity and Startle Potentiation to Predictable and Unpredictable Threat.

Aberrant threat reactivity has been implicated in the pathophysiology of posttraumatic stress disorder (PTSD); however, the literature on this association is mixed. One factor that may contribute to this inconsistent association is differences in severity of posttraumatic stress symptoms (PTSSs) across studies, but no studies have tested this hypothesis. The relation between PTSD and threat reactivity may also differ between unpredictable threats (U-threats) and predictable threats (P-threats), given burgeoning evidence to support a particular role for aberrant responding to U-threat in PTSD. The present study examined how PTSS severity relates to startle potentiation to U-threat and P-threat in a trauma-exposed community sample (N = 258). There was a negative linear, but not quadratic, relation between PTSS severity and startle potentiation to U-threat, but not P-threat. Blunted defensive responding to U-threat may therefore contribute to higher levels of PTSSs and may represent a novel treatment target for higher levels of PTSSs.

The replicability and generalizability of internalizing symptom networks across five samples.

The popularity of network analysis in psychopathology research has increased exponentially in recent years. Yet, little research has examined the replicability of cross-sectional psychopathology network models, and those that have used single items for symptoms rather than multiitem scales. The present study therefore examined the replicability and generalizability of regularized partial correlation networks of internalizing symptoms within and across 5 samples (total N = 2,573) using the Inventory for Depression and Anxiety Symptoms, a factor analytically derived measure of individual internalizing symptoms. As different metrics may yield different conclusions about the replicability of network parameters, we examined both global and specific metrics of similarity between networks. Correlations within and between nonclinical samples suggested considerable global similarities in network structure (rss = .53-.87) and centrality strength (rss = .37-.86), but weaker similarities in network structure (rss = .36-.66) and centrality (rss = .04-.54) between clinical and nonclinical samples. Global strength (i.e., connectivity) did not significantly differ across all 5 networks and few edges (0-5.5%) significantly differed between networks. Specific metrics of similarity indicated that, on average, approximately 80% of edges were consistently estimated within and between all 5 samples. The most central symptom (i.e., dysphoria) was consistent within and across samples, but there were few other matches in centrality rank-order. In sum, there were considerable similarities in network structure, the presence and sign of individual edges, and the most central symptom within and across internalizing symptom networks estimated from nonclinical samples, but global metrics suggested network structure and symptom centrality had weak to moderate generalizability from nonclinical to clinical samples. (PsycINFO Database Record (c) 2020 APA, all rights reserved).

The time course of responding to aversiveness in females with a history of non-suicidal self-injury.

Non-suicidal self-injury is a risk factor for suicidal behavior, particularly in females. Two prominent theories of suicide suggest that habituation to the psychophysiological aversiveness of NSSI is a mechanism by which NSSI exposure may lead to increased risk for suicide. Several laboratory studies examining the relationship between physiological habituation and suicide attempt history have yielded mixed results, potentially due to their use of broad measures of physiological arousal and/or focus on specific psychopathologies. However, no studies have examined the association between the time course (e.g., habituation, initial reactivity) of responding to aversiveness and NSSI, which may help to elucidate psychophysiological mechanisms of NSSI. Therefore, we examined habituation and initial reactivity to aversiveness (indexed by the time course of acoustic startle reflex, a well-validated measure of defensive responding) in three groups of young adult females - those with a history of NSSI, psychiatric controls matched on potential confounds (e.g., psychopathology, trauma history, demographics), and healthy controls. Results indicated that individuals with a history of NSSI exhibited blunted initial reactivity and marginally slower habituation to aversiveness relative to the two control groups. The NSSI group's insensitivity to aversiveness may reflect prior psychophysiological habituation, and may be a mechanism through which prior NSSI exposure leads to increased risk for suicidal behavior.

Startle during threat longitudinally predicts functional impairment independent of DSM diagnoses.

Heightened responsivity to unpredictable, and perhaps predictable, threat characterizes some internalizing disorders and may be vulnerability factors for psychopathology as well. However, few studies have directly tested whether individual differences in unpredictable and/or predictable threat responding longitudinally predict symptoms of psychopathology and functional outcomes. Examining functioning is particularly important given that functioning is separable from symptoms of psychopathology. The present study examined whether electromyography startle measures of predictable and/or unpredictable threat responding was associated with interviewer-assessed symptoms of internalizing psychopathology and functional impairment at baseline (n = 409) and one-year follow-up (n = 104). Elevated startle responding to unpredictable and predictable threat longitudinally predicted a worsening of functioning over time and this effect was independent of change of symptoms over time. Importantly, threat responding at baseline predicted functional impairment during the follow-up independent of the effects of DSM-defined fear-based (e.g., panic disorder) or distress-misery (e.g., major depressive disorder) internalizing disorders. These findings provide initial support for the incremental validity of neurobiological vulnerability markers of threat responding over and above DSM disorders and highlight the importance of distinguishing functional outcomes from symptom outcomes.

The role of intolerance of uncertainty in current and remitted internalizing and externalizing psychopathology.

Intolerance of uncertainty (IU) is a putative key, transdiagnostic factor in internalizing psychopathologies. However, it is unclear if elevated levels of IU, as measured by the Intolerance of Uncertainty Scale, short form (IUS-12) and its subscales (prospective and inhibitory IU), persist into remission of internalizing psychopathologies (or particular types of internalizing psychopathologies; e.g., fear vs. distress-misery disorders). It is also unknown if IU is specifically characteristic of internalizing (vs. externalizing) psychopathology and whether this relationship is independent of neuroticism/negative affectivity (N/NA). A large community sample (n = 517) completed a diagnostic interview and self-report measures of IU and N/NA. Results indicated that, independent of N/NA, IU was elevated in current fear and distress/misery disorders, but not externalizing disorders. Individuals with remitted fear disorders also displayed significantly elevated levels of IU in comparison to healthy controls after adjusting for levels of N/NA. In terms of subscales, elevated levels of inhibitory IU, and not prospective IU, demonstrated more reliable relationships with internalizing psychopathologies. In summary, IU was more consistently related to fear disorders, demonstrated incremental validity over and above the effects of N/NA, and may be a key, transdiagnostic mechanism in fear disorders.

Mimosine accumulation in Leucaena leucocephala in response to stress signaling molecules and acute UV exposure.

Mimosine is a non-protein amino acid of Fabaceae, such as Leucaena spp. and Mimosa spp. Several relevant biological activities have been described for this molecule, including cell cycle blocker, anticancer, antifungal, antimicrobial, herbivore deterrent and allelopathic activities, raising increased economic interest in its production. In addition, information on mimosine dynamics in planta remains limited. In order to address this topic and propose strategies to increase mimosine production aiming at economic uses, the effects of several stress-related elicitors of secondary metabolism and UV acute exposure were examined on mimosine accumulation in growth room-cultivated seedlings of Leucaena leucocephala spp. glabrata. Mimosine concentration was not significantly affected by 10 ppm salicylic acid (SA) treatment, but increased in roots and shoots of seedlings treated with 84 ppm jasmonic acid (JA) and 10 ppm Ethephon (an ethylene-releasing compound), and in shoots treated with UV-C radiation. Quantification of mimosine amidohydrolase (mimosinase) gene expression showed that ethephon yielded variable effect over time, whereas JA and UV-C did not show significant impact. Considering the strong induction of mimosine accumulation by acute UV-C exposure, additional in situ ROS localization, as well as in vitro antioxidant assays were performed, suggesting that, akin to several secondary metabolites, mimosine may be involved in general oxidative stress modulation, acting as a hydrogen peroxide and superoxide anion quencher.

Corrigendum: Reference Genes for qPCR Analysis in Resin-Tapped Adult Slash Pine As a Tool to Address the Molecular Basis of Commercial Resinosis.

[This corrects the article on p. 849 in vol. 7, PMID: 27379135.].

Reference Genes for qPCR Analysis in Resin-Tapped Adult Slash Pine As a Tool to Address the Molecular Basis of Commercial Resinosis.

Pine oleoresin is a major source of terpenes, consisting of turpentine (mono- and sesquiterpenes) and rosin (diterpenes) fractions. Higher oleoresin yields are of economic interest, since oleoresin derivatives make up a valuable source of materials for chemical industries. Oleoresin can be extracted from living trees, often by the bark streak method, in which bark removal is done periodically, followed by application of stimulant paste containing sulfuric acid and other chemicals on the freshly wounded exposed surface. To better understand the molecular basis of chemically-stimulated and wound induced oleoresin production, we evaluated the stability of 11 putative reference genes for the purpose of normalization in studying Pinus elliottii gene expression during oleoresinosis. Samples for RNA extraction were collected from field-grown adult trees under tapping operations using stimulant pastes with different compositions and at various time points after paste application. Statistical methods established by geNorm, NormFinder, and BestKeeper softwares were consistent in pointing as adequate reference genes HISTO3 and UBI. To confirm expression stability of the candidate reference genes, expression profiles of putative P. elliottii orthologs of resin biosynthesis-related genes encoding Pinus contorta ß-pinene synthase [PcTPS-(-)ß-pin1], P. contorta levopimaradiene/abietadiene synthase (PcLAS1), Pinus taeda α-pinene synthase [PtTPS-(+)αpin], and P. taeda α-farnesene synthase (PtαFS) were examined following stimulant paste application. Increased oleoresin yields observed in stimulated treatments using phytohormone-based pastes were consistent with higher expression of pinene synthases. Overall, the expression of all genes examined matched the expected profiles of oleoresin-related transcript changes reported for previously examined conifers.