Dysbiosis exacerbates colitis by promoting ubiquitination and accumulation of the innate immune adaptor STING in myeloid cells.

Alterations in the cGAS-STING DNA-sensing pathway affect intestinal homeostasis. We sought to delineate the functional role of STING in intestinal inflammation. Increased STING expression was a feature of intestinal inflammation in mice with colitis and in humans afflicted with inflammatory bowel disease. Mice bearing an allele rendering STING constitutively active exhibited spontaneous colitis and dysbiosis, as well as progressive chronic intestinal inflammation and fibrosis. Bone marrow chimera experiments revealed STING accumulation in intestinal macrophages and monocytes as the initial driver of inflammation. Depletion of Gram-negative bacteria prevented STING accumulation in these cells and alleviated intestinal inflammation. STING accumulation occurred at the protein rather than transcript level, suggesting post-translational stabilization. We found that STING was ubiquitinated in myeloid cells, and this K63-linked ubiquitination could be elicited by bacterial products, including cyclic di-GMP. Our findings suggest a positive feedback loop wherein dysbiosis foments the accumulation of STING in intestinal myeloid cells, driving intestinal inflammation.

Prospection of Potential Actions during Visual Working Memory Starts Early, Is Flexible, and Predicts Behavior.

For visual working memory to serve upcoming behavior, it is crucial that we prepare for the potential use of working-memory contents ahead of time. Recent studies have demonstrated how the prospection and planning for an upcoming manual action starts early after visual encoding, and occurs alongside visual retention. Here, we address whether such "output planning" in visual working memory flexibly adapts to different visual-motor mappings, and occurs even when an upcoming action will only potentially become relevant for behavior. Human participants (female and male) performed a visual-motor working memory task in which they remembered one or two colored oriented bars for later (potential) use. We linked, and counterbalanced, the tilt of the visual items to specific manual responses. This allowed us to track planning of upcoming behavior through contralateral attenuation of ß band activity, a canonical motor-cortical EEG signature of manual-action planning. The results revealed how action encoding and subsequent planning alongside visual working memory (1) reflect anticipated task demands rather than specific visual-motor mappings, (2) occur even for actions that will only potentially become relevant for behavior, and (3) are associated with faster performance for the encoded item, at the expense of performance to other working-memory content. This reveals how the potential prospective use of visual working memory content is flexibly planned early on, with consequences for the speed of memory-guided behavior.SIGNIFICANCE STATEMENT It is increasingly studied how visual working memory helps us to prepare for the future, in addition to how it helps us to hold onto the past. Recent studies have demonstrated that the planning of prospective actions occurs alongside encoding and retention in working memory. We show that such early "output planning" flexibly adapts to varying visual-motor mappings, occurs both for certain and potential actions, and predicts ensuing working-memory guided behavior. These results highlight the flexible and future-oriented nature of visual working memory, and provide insight into the neural basis of the anticipatory dynamics that translate visual representations into adaptive upcoming behavior.

Longitudinal study of traumatic-stress related cellular and cognitive aging.

Traumatic stress is associated with both accelerated epigenetic age and increased risk for dementia. Accelerated epigenetic age might link symptoms of traumatic stress to dementia-associated biomarkers, such as amyloid-beta (Aß) proteins, neurofilament light (NFL), and inflammatory molecules. We tested this hypothesis using longitudinal data obtained from 214 trauma-exposed military veterans (85 % male, mean age at baseline: 53 years, 75 % White) who were assessed twice over the course of an average of 5.6 years. Cross-lagged panel mediation models evaluated measures of lifetime posttraumatic stress disorder and internalizing and externalizing comorbidity (assessed at Time 1; T1) in association with T1 epigenetic age (per the GrimAge algorithm) and T1 plasma markers of neuropathology along with bidirectional temporal paths between T1 and T2 epigenetic age and the plasma markers. Results revealed that a measure of externalizing comorbidity was associated with accelerated epigenetic age (ß = 0.30, p <.01), which in turn, was associated with subsequent increases in Aß-40 (ß = 0.20, p <.001), Aß-42 (ß = 0.18, p <.001), and interleukin-6 (ß = 0.18, p <.01). T1 advanced epigenetic age and the T1 neuropathology biomarkers NFL and glial fibrillary acidic protein predicted worse performance on T2 neurocognitive tasks assessing working memory, executive/attentional control, and/or verbal memory (ps = 0.03 to 0.009). Results suggest that advanced GrimAge is predictive of subsequent increases in neuropathology and inflammatory biomarkers as well as worse cognitive function, highlighting the clinical significance of this biomarker with respect to cognitive aging and brain health over time. The finding that advanced GrimAge mediated the association between psychiatric comorbidity and future neuropathology is important for understanding potential pathways to neurodegeneration and early identification of those at greatest risk.

Trauma exposure and transdiagnostic distress: Examining shared and posttraumatic stress disorder-specific associations.

We examined transdiagnostic and posttraumatic stress disorder (PTSD)-specific associations with multiple forms of trauma exposure within a nationwide U.S. sample (N = 1,649, 50.0% female) of military veterans overselected for PTSD. A higher-order Distress factor was estimated using PTSD, major depressive disorder (MDD), and generalized anxiety disorder (GAD) symptoms as indicators. A structural equation model spanning three assessment points over an average of 3.85 years was constructed to examine the unique roles of higher-order Distress and PTSD-specific variance in accounting for the associations between trauma exposure, measured using the Life Events Checklist (LEC) and Deployment Risk and Resiliency Inventory Combat subscale (DRRI-C), and psychosocial impairment. The results suggest the association between trauma exposure and PTSD symptoms was primarily mediated by higher-order distress (70.7% of LEC effect, 63.2% of DRRI-C effect), but PTSD severity retained a significant association with trauma exposure independent of distress, LEC: ß = .10, 95% CI [.06, .13]; DRRI-C: ß = .11, 95% CI [.07, .14]. Both higher-order distress, ß = .31, and PTSD-specific variance, ß = .36, were necessary to account for the association between trauma exposure and future impairment. Findings suggest that trauma exposure may contribute to comorbidity across a range of internalizing symptoms as well as to PTSD-specific presentations.

MMPI-2-RF Profiles of Treatment-Seeking Veterans in a VA Pain Clinic and Associations with Markers of Physical Performance.

Chronic pain is a debilitating condition for many military Veterans and is associated with posttraumatic stress disorder (PTSD). This study examined the Minnesota Multiphasic Personality Inventory-2-Restructured Form (MMPI-2-RF) in 144 Veterans (88.2% male, mean age = 57.95 years) recruited from a VA outpatient pain clinic and associations with self-reported pain severity, pain-related interference in daily activities, prescription opioid use, and objective metrics of physical performance on tasks impacted by pain (walking, stair climbing, grip strength, indexed by a single latent variable). Among the cohort with valid responses on the MMPI-2-RF (n = 117) and probable PTSD, mean Somatic Complaints (RC1) and Ideas of Persecution (RC6) scores were clinically elevated. All MMPI-2-RF scales were more strongly correlated with self-reported pain interference than severity. Regressions revealed associations between self-rated pain interference (but not pain or PTSD severity) and physical performance scores (ß = .36, p = .001). MMPI-2-RF overreporting Validity and Higher-Order scales contributed incremental variance in predicting physical performance, including Infrequent Psychopathology Responses (ß = .33, p = .002). PTSD severity was associated with prescription opioid use when accounting for the effects of over-reported somatic and cognitive symptoms (odds ratio 1.05, p ≤ .025). Results highlight the role of symptom overreporting and perceptions of functional impairment to observable behaviors among individuals with chronic pain.

Substance Use and Adherence to HIV Pre-Exposure Prophylaxis in Studies Enrolling Men Who Have Sex with Men and Transgender Women: A Systematic Review.

Optimal adherence to pre-exposure prophylaxis (PrEP) is critical, but challenging. Men who have sex with men and transgender women have high rates of HIV incidence and substance use. Substance use is associated with reduced adherence to other medications, but associations between substance use and adherence to PrEP are less clear. Thus, the current review 1) systematically evaluates the measurement of substance use and PrEP adherence in studies examining both and 2) summarizes reported findings. Peer-reviewed articles published between 2010 - April 2021 examining associations between substance use and PrEP adherence were reviewed. Fifty studies met inclusion criteria. Assessment of substance use (i.e., mostly via self-reports at baseline) and PrEP adherence (i.e., often via tenofovir diphosphate [TFV-DP] concentration levels at follow-up) varied considerably across studies. Many studies used categorical variables (e.g., substance use: yes/no). Studies using TFV-DP levels defined adherence consistently (i.e., TFV-DP ≥ 700 fmol/punch), with slight variations. Qualitative studies (n = 10) indicated that substance use (mainly alcohol) is related to poorer PrEP adherence. While quantitative findings to date are equivocal for alcohol, there is a pattern of findings linking stimulant use with poorer PrEP adherence. This review reveals four methodological gaps, which can be addressed in future research by: 1) use of uniform benchmarks for substance use measures, 2) prospective assessment for substance use, 3) use of continuous outcome variables wherever possible, and 4) more extensive consideration of potential confounders. Addressing these methodological gaps may help us reach more definitive conclusions regarding associations between substance use and PrEP adherence.

Ranavirus infection-induced avoidance behaviour in wood frog juveniles: do amphibians socially distance?

Hosts may limit exposure to pathogens through changes in behaviour, such as avoiding infected individuals or contaminated areas. Here, we tested for a behavioural response to ranavirus infection in juvenile wood frogs (Rana sylvatica) because the majority of dispersal between populations occurs during this life stage. We hypothesized that if infections are transmissible and detectable at this life stage, then susceptibles would display avoidance behaviours when introduced to an infected conspecific. Despite no apparent signs of infection, we observed a greater distance between susceptible-infected pairs, compared to pairs of either two infected or two susceptible animals. Further, distances between susceptible-infected pairs were positively related to the infection intensity of the focal exposed frog, suggesting the cue to avoid infected conspecifics may become more detectable with more intense infections. Although we did not quantify whether the transmission was affected by their distancing, our findings suggest that juvenile frogs have the potential to reduce terrestrial transmission of ranaviruses through avoidance behaviours.

PTSD, major depression, and advanced transcriptomic age in brain tissue.

BACKGROUND: Psychiatric disorders have been associated with advanced epigenetic age in DNA methylation, yet this relationship has not been studied in the brain transcriptome. We examined transcriptomic age using an RNA-based algorithm recently developed by Ren and Kuan ("RNAAgeCalc") and the associations between posttraumatic stress disorder (PTSD), major depressive disorder (MDD), and alcohol use disorder with age-adjusted RNA age ("RNA age residuals") in three brain regions: dorsolateral prefrontal cortex, ventromedial prefrontal cortex (vmPFC), and motor cortex. METHODS: RNA sequencing was used to measure gene expression in postmortem brain tissue from the VA National PTSD Brain Bank (n = 94; 59% male). RESULTS: Linear models revealed that diagnoses of PTSD and/or MDD were positively associated with RNA age residuals in vmPFC only (p-adj = 0.012). Three genes in the RNAAgeCalc algorithm (KCNJ16, HYAL2, and CEBPB) were also differentially expressed in association with PTSD/MDD in vmPFC (p-adj = 6.45E-05 to 0.02). Enrichment analysis revealed that inflammatory and immune-related pathways were overrepresented (p-adj < 0.05) among the 43 genes in RNAAgeCalc that were also at least nominally associated with PTSD/MDD in vmPFC relative to the 448 RNAAgeCalc genes. Endothelial and mural cells were negatively associated with RNA age residuals in vmPFC (both p-adj = 0.028) and with PTSD/MDD (both p-adj = 0.017). CONCLUSIONS: Results highlight the importance of inflammation and immune system dysregulation in the link between psychopathology and accelerated cellular aging and raise the possibility that blood-brain barrier degradation may play an important role in stress-related accelerated brain aging.

Methylation of the AIM2 gene: An epigenetic mediator of PTSD-related inflammation and neuropathology plasma biomarkers.

BACKGROUND: Posttraumatic stress disorder (PTSD) is associated with inflammation and various forms of chronic disease. The Absent in Melanoma 2 (AIM2) gene has been implicated in mechanisms of inflammation and anxiety, and methylation at a particular locus in this gene (cg10636246) has previously been shown to influence the association between PTSD and elevated C-reactive protein levels in blood. METHOD: We tested if this association might extend to other indicators of inflammation and to plasma-based measures of neuropathology in a cohort of post-9/11 US military veterans. Using a Bayesian approach, mediation models were tested cross-sectionally (n = 478) and longitudinally (n = 298). Peripheral markers of inflammation and neuropathology were measured with ultra-sensitive Single Molecule Array (Simoa®) technology. RESULTS: Analyses revealed indirect effects of PTSD symptom severity on peripheral indices of both inflammation (interleukin [IL]6, IL-10, tumor necrosis factor-α; indirect standardized [std.] ß range = 0.018-0.023, all p-values adjusted for multiple testing [padj ] < 0.05) and neuropathology (neurofilament light [NFL]; indirect std. ß = -0.018, padj = 0.02) via AIM2 methylation. This indirect effect was also evident when predicting IL-10 at a follow-up assessment (indirect std. ß = -0.018, padj = 0.04) controlling for baseline IL-10. CONCLUSIONS: Given that AIM2 methylation mediated the association between PTSD symptoms and multiple inflammatory and neuropathology markers, our results suggest that AIM2 methylation may offer clinical utility for indexing risk for adverse health outcomes associated with these peripheral indices of inflammation and neuropathology. Results also suggest a possible shared etiology underlying the frequent co-occurrence of inflammation and neuropathology.

Premorbid traumatic stress and veteran responses to the COVID-19 pandemic.

The COVID-19 pandemic has had unprecedented effects on lifestyle stability and physical and mental health. We examined the impact of preexisting posttraumatic stress disorder (PTSD), alcohol use disorder (AUD), and depression on biopsychosocial responses to the pandemic, including psychiatric symptoms, COVID-19 exposure, and housing/financial stability, among 101 U.S. military veterans enrolled in a longitudinal study of PTSD, a population of particular interest given veterans' trauma histories and defense-readiness training. Participants (83.2% male, 79.2% White, Mage  = 59.28 years) completed prepandemic, clinician-administered psychiatric diagnostic interviews and a phone-based assessment between May and September 2020 using a new measure, the Rapid Assessment of COVID-19-Related Experiences (RACE), which was used to assess pandemic responses and its effects on mental and physical health; COVID-19 diagnosis and testing were also extracted from electronic medical records. Multivariate regressions showed that, controlling for demographic characteristics, prepandemic PTSD, ß = .332; p = .003, and AUD symptoms, ß = .228; p = .028, were associated with increased pandemic-related PTSD symptoms. Prepandemic AUD was associated with increased substance use during the pandemic, ß = .391; p < .001, and higher rates of self-reported or medical record-based COVID-19 diagnosis, ß = .264; p = .019. Minority race was associated with pandemic-related housing/financial instability, ß = -.372; p < .001, raising concerns of population inequities. The results suggest that preexisting PTSD and AUD are markers for adverse pandemic-related psychiatric outcomes and COVID-19 illness. These findings carry implications for the importance of targeting prevention and treatment efforts for the highest-risk individuals.

An in-depth look at latent classes of DSM-5 psychiatric comorbidity among individuals with PTSD: Clinical indicators and treatment utilization.

OBJECTIVE: Posttraumatic stress disorder (PTSD) is associated with high comorbidity rates across the full range of psychiatric disorders. However, little is known about how psychiatric comorbidity manifests among people with PTSD, particularly with regard to concurrent diagnoses. METHOD: Latent class analysis (LCA) was used to characterize discrete classes of PTSD comorbidity using past year DSM-5 diagnostic standards among a large nationally representative epidemiologic sample of U.S. adults. Follow-up analyses compared participant characteristics across latent classes. RESULTS: The LCA was best characterized by five classes: low comorbidity, distress-fear, distress-externalizing, mania-fear-externalizing, and mania-externalizing. Excluding the low comorbidity class, proportions of borderline and schizotypal personality disorder were high across classes. CONCLUSION: Participant characteristics across classes of past year PTSD comorbidity are explored through the lens of case conceptualization and treatment planning utility.

The Contribution of Text Characteristics to Reading Comprehension: Investigating the Influence of Text Emotionality.

In the current study, we examined relations between text features (e.g., word concreteness, referential cohesion) and reading comprehension using multilevel logistic models. The sample was 158 native English-speaking students between 8 years 8 months and 11 years 2 months of age with a wide range of reading ability. In line with the simple view of reading, decoding ability and language comprehension were associated with reading comprehension performance. Text characteristics, including indices of word frequency, number of pronouns, word concreteness, and deep cohesion, also predicted unique variance in reading comprehension performance over and above the simple view's components. Additionally, the emotional charge of text (i.e., lexical ratings of arousal) predicted reading comprehension beyond traditional person-level and text-based characteristics. These findings add to a small but growing body of evidence suggesting that it is important to consider emotional charge in addition to person-level and text-based characteristics to better understand reading comprehension performance.

One Thing Leads to Another: Anticipating Visual Object Identity Based on Associative-Memory Templates.

Probabilistic associations between stimuli afford memory templates that guide perception through proactive anticipatory mechanisms. A great deal of work has examined the behavioral consequences and human electrophysiological substrates of anticipation following probabilistic memory cues that carry spatial or temporal information to guide perception. However, less is understood about the electrophysiological substrates linked to anticipating the sensory content of events based on recurring associations between successive events. Here, we demonstrate behavioral and electrophysiological signatures of using associative-memory templates to guide perception, while equating spatial and temporal anticipation (experiments 1 and 2), as well as target probability and response demands (experiment 2). By recording the electroencephalogram in the two experiments (N = 55; 24 females), we show that two markers in human electrophysiology implicated in spatial and temporal anticipation also contribute to the anticipation of perceptual identity, as follows: attenuation of alpha-band oscillations and the contingent negative variation (CNV). Together, our results show that memory-guided identity templates proactively impact perception and are associated with anticipatory states of attenuated alpha oscillations and the CNV. Furthermore, by isolating object-identity anticipation from spatial and temporal anticipation, our results suggest a role for alpha attenuation and the CNV in specific visual content anticipation beyond general changes in neural excitability or readiness.SIGNIFICANCE STATEMENT Probabilistic associations between stimuli afford memory templates that guide perception through proactive anticipatory mechanisms. The current work isolates the behavioral benefits and electrophysiological signatures of memory-guided identity-based anticipation, while equating anticipation of space, time, motor responses, and task relevance. Our results show that anticipation of the specific identity of a forthcoming percept impacts performance and is associated with states of attenuated alpha oscillations and the contingent negative variation, extending previous work implicating these neural substrates in spatial and temporal preparatory attention. Together, this work bridges fields of attention, memory, and perception, providing new insights into the neural mechanisms that support complex attentional templates.

Admission Psychosocial Characteristics of Critically Ill Children and Acute Stress.

OBJECTIVES: Children are at increased risk for developing acute stress and post-traumatic stress following admission to the PICU. The primary objective of this investigation was to explore the prehospitalization psychosocial characteristics of children admitted to the PICU and their association with acute stress. DESIGN: Observational. SETTING: The PICU at an urban, academic, pediatric medical center. PATIENTS: Children, 8-17 years old with an expected PICU stay greater than 24 hours were recruited. MEASUREMENTS AND MAIN RESULTS: During the admission, they completed questionnaires and a semistructured interview evaluating prehospitalization psychosocial symptoms, including prehospitalization post-traumatic stress, quality of life, and current acute stress. One hundred eleven children were enrolled (mean age = 12.9 yr; 60% male; 58% Latino). Half (51%) reported a prehospitalization history of trauma and nearly all (96%) of these children had post-traumatic stress. They had significant impairment on all domains of quality of life. Children reported high rates of acute stress during their hospitalization, 74.8% acute stress symptoms, and 6% met diagnostic criteria for acute stress disorder. Univariate analysis showed associations between child age, quality of life, chronic illness, and post-traumatic stress with more severe acute stress. Multiple linear regression modeling of acute stress was done accounting for child age, acute versus chronic illness, quality of life, and post-traumatic stress; prehospitalization quality of life and post-traumatic stress remained significantly associated with the development of inhospital acute stress and accounted for 34% of the variance of the model. CONCLUSIONS: The current investigation is a novel evaluation of the prehospitalization psychosocial characteristics of children admitted to a PICU. The children enrolled reported high rates of acute stress, which was associated with a history of post-traumatic stress and worsened quality of life. The relation with post-traumatic stress is consistent with prior research into complex post-traumatic stress disorder and increases concerns about long-term psychosocial outcomes. Our data advance understanding of the factors contributing to acute stress during hospitalizations and may add to recognizing the importance of models integrating psychosocial support.

A Systematic Review of the Self-Medication Hypothesis in the Context of Posttraumatic Stress Disorder and Comorbid Problematic Alcohol Use.

Posttraumatic stress disorder (PTSD) and alcohol use disorder (AUD) commonly co-occur and are associated with many negative public health outcomes. There are several etiological models that explain the overlap between PTSD and AUD, including shared genetic risk and phenotypic causality, but the predominant model of etiologic association is the drinking-to-cope self-medication model. Although the self-medication model is conceptually appealing and has been widely accepted within the literature examining alcohol use and anxiety (e.g., PTSD) phenotypes, the findings are inconsistent and there is a lack of rigorous empirical evidence in support of this model. This review, which was, to our knowledge, the first systematic review of the self-medication model in relation to PTSD to date, aimed to synthesize the current literature on the association between PTSD and problematic alcohol use within the context of the self-medication model. In total, 24 studies met the inclusion criteria for the review and assessed the self-medication hypothesis using a variety of measurement instruments and data analytic approaches, such as mediation, moderation, and regression. Overall, the included studies provide evidence for the self-medication hypothesis but are limited in rigor due to methodological limitations. These limitations, which include issues with the operationalization (or lack thereof) of trauma-related drinking to cope, are discussed, and directions for future research are presented.

Functional biases in attentional templates from associative memory.

In everyday life, attentional templates-which facilitate the perception of task-relevant sensory inputs-are often based on associations in long-term memory. We ask whether templates retrieved from memory are necessarily faithful reproductions of the encoded information or if associative-memory templates can be functionally adapted after retrieval in service of current task demands. Participants learned associations between four shapes and four colored gratings, each with a characteristic combination of color (green or pink) and orientation (left or right tilt). On each trial, observers saw one shape followed by a grating and indicated whether the pair matched the learned shape-grating association. Across experimental blocks, we manipulated the types of nonmatch (lure) gratings most often presented. In some blocks the lures were most likely to differ in color but not tilt, whereas in other blocks this was reversed. If participants functionally adapt the retrieved template such that the distinguishing information between lures and targets is prioritized, then they should overemphasize the most commonly diagnostic feature dimension within the template. We found evidence for this in the behavioral responses to the lures: participants were more accurate and faster when responding to common versus rare lures, as predicted by the functional-but not the strictly veridical-template hypothesis. This shows that templates retrieved from memory can be functionally biased to optimize task performance in a flexible, context-dependent, manner.

Examination of a novel measure of trauma-related drinking to cope.

OBJECTIVES: The present study sought to fill a gap in the current literature by developing a concise self-report questionnaire assessing drinking motives specific to coping with symptoms of posttraumatic stress disorder (PTSD). This new four-item questionnaire is called the Trauma Related Drinking questionnaire (TRD). METHOD: Using structural equation modeling, the latent structure of the TRD items and how they relate to other variables of interest were explored among a sample of 1,896 college undergraduates from a large public university. RESULTS: Broadly, we found evidence to suggest that TRD is a more specific measure of drinking to cope motives compared to the commonly used Drinking Motives Questionnaire coping subscale. Additionally, findings demonstrate support for the external validation of TRD, both with regard to PTSD and alcohol consumption and related problems. CONCLUSIONS: Results support the use of TRD in future self-medication research and as a clinically useful screening tool.

The relationship between cognitive skills and reading comprehension of narrative and expository texts: A longitudinal study from Grade 1 to Grade 4.

Following the increased emphasis on expository text in early grades, this study examined narrative and expository reading comprehension growth in a sample of children who were followed longitudinally from grades 1 to 4, with the goals of explaining potential differences in children's overall performance and growth of narrative and expository text comprehension and identifying the cognitive factors that distinctly contribute to comprehension for each text type. We hypothesized that differences in reading comprehension growth of narrative and expository texts would be explained by various cognitive factors, specifically those related to executive functions (EF; e.g., working memory, planning/organization, shifting, and inhibition). At four annual time points, children (n= 94) read, retold (Recall), and answered questions (CompQ) about expository and narrative passages. Growth curve modeling was used to explore reading comprehension development across the two types of text. On average, results showed that children scored better on reading comprehension of narrative passages than they did on expository passages across all time points. After controlling for socioeconomic status (SES), vocabulary in 1st grade predicted 4th grade comprehension scores (Recall) for both narrative and expository passages, while word reading efficiency (WRE) in 1st grade predicted 4th grade comprehension scores (CompQ) for expository passages only. Additionally, WRE was associated with the growth of expository reading comprehension: children with higher WRE showed a faster growth rate for expository CompQ. The contribution of EF to text comprehension was largely confined to expository text, although planning and organization (measured using a direct cognitive assessment) in 1st grade also predicted 4th grade comprehension scores for narrative text Recall. For expository text comprehens ion, working memory, planning and organization, shifting, and inhibition (measured using a parent rating scale), predicted reading comprehension outcomes. Critically, 1st grade shifting and inhibition not only predicted 4th grade expository text comprehension (CompQ), but also modulated its growth rate: children with stronger shifting and inhibition had faster rates of growth. Together, these findings suggest that expository reading comprehension is (1) more difficult than narrative reading comprehension and (2) is associated with unique cognitive skills.

The Effects of Family Functioning on the Development of Posttraumatic Stress in Children and Their Parents Following Admission to the PICU.

OBJECTIVES: To report the rate of acute stress and posttraumatic stress among children and parents following PICU admission and the relation between family function and posttraumatic stress. DESIGN: Prospective, longitudinal, multi-informant observational study. Pediatric patients (n = 69) and parents were recruited in the ICU. They completed measures evaluating acute stress and posttraumatic stress during their hospitalization and at 3-month follow-up. Parents completed measures of family functioning during the hospitalization. Pearson correlations and multiple regression models were used to examine the relations between family functioning and acute stress and posttraumatic stress. SETTING: An academic, urban, pediatric hospital in California. PATIENTS: Children, 8-17 years old, admitted to the PICU for greater than 24 hours and their English- or Spanish-speaking parents. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: All children endorsed acute stress during their PICU admission, with 51% meeting criteria for acute stress disorder. At 3-month follow-up, 53% of the children continued to endorse posttraumatic stress with 13% meeting criteria for posttraumatic stress disorder. Among parents, 78% endorsed acute stress during admission with 30% meeting criteria for acute stress disorder, and at follow-up, 35% endorsed posttraumatic stress with 10% meeting criteria for posttraumatic stress disorder. In multiple linear regression modeling, child acute stress significantly predicted child posttraumatic stress (ß = 0.36; p < 0.01). In the parent model, parent acute stress (ß = 0.29; p < 0.01) and parent education (ß = 0.59; p < 0.00) positively predicted parent's posttraumatic stress. Family function was not a predictor of either's posttraumatic stress. CONCLUSIONS: Both children and parents have alarmingly high rates of acute stress and posttraumatic stress following the child's PICU admission. Although family function did not emerge as a predictor in this study, further understanding of the influence of the family and the interplay between child and parent posttraumatic stress is needed to improve our understanding of the model of development of posttraumatic stress in this population to inform the intervention strategies.

Replication of the Interaction of PRKG1 and Trauma Exposure on Alcohol Misuse in an Independent African American Sample.

In the present study, we sought to replicate recent findings of Polimanti et al. (2017), who conducted a genome-wide gene-by-environment interaction study (GEWIS) and identified a gene-by-trauma interaction that predicts alcohol misuse among African Americans.  Consistent with the findings published by Polimanti and colleagues, results of the current study demonstrated an interaction effect, b = 0.41, of trauma exposure and rs1729578 in the intron of PRKG1 on alcohol misuse in a subsample of ancestral African Americans. The minor allele (rs1729578*C) was positively associated with increased alcohol use disorder symptoms in trauma-exposed subjects and negatively associated in non-trauma-exposed subjects.  This effect, however, was only significant for one out of three alcohol outcome measures we investigated, suggesting the interaction may be most salient when predicting higher severity of alcohol misuse. Additionally, the effect did not remain significant after we accounted for testing the effect on three different outcome variables. Also in line with the original study, the gene-by-environment effect was not demonstrated among the ancestral European subsample.  The findings suggest this gene variant may increase an individual's susceptibility to environmental influences, both adverse and supportive.