An Examination of Post-Traumatic Stress Symptoms and Aggression Among Children with a History of Adverse Childhood Experiences

Childhood aggression is associated with many deleterious outcomes and is a common reason for psychiatric referral (Card and Little 2006; Gurnani, Ivanov, and Newcorn 2016). One factor associated with childhood aggression is Adverse Childhood Experiences (ACEs; Felitti et al. 1998). However, existing research remains equivocal on which characteristics of ACEs (e.g., cumulative impact, typology, etc.) are significantly elated to aggression, especially when considering differential effects of ACEs on proactive aggression (PA) and reactive aggression (RA; Dodge and Coie, 1987). Post-traumatic stress symptoms (PTSS) are a common negative sequalae of ACEs and are characterized by disruptions in several cognitive, emotional, and behavioral processes similar to those associated with both RA and PA (e.g., Marsee 2008). As such, the examination of PTSS as an underlying mechanism of influence on the relation between ACEs, PA, and RA is warranted. The present study fills several gaps in the literature by examining ACE characteristics that might be related to PTSS, PA, and RA while also examining direct and indirect effects on the relation between ACEs, PTSS and PA and RA. Results indicated the type of ACE, specifically child maltreatment ACEs (CM-ACEs), was most strongly related to all outcome variables. Therefore, CM-ACEs were included in a path analysis with PTSS, PA, and RA. Results indicated a significant indirect effect for PTSS on the relation between CM-ACEs and RA (β = .18, p \u3c .01) but not PA. Findings have several implications for future research and clinical practice, especially for children with an extensive history of CM-ACEs

Pathways from Child Maltreatment to Proactive and Reactive Aggression: The Role of Post-Traumatic Stress Symptom Clusters

Objective: Childhood aggression is related to a myriad of negative concurrent and long-term outcomes. To mitigate the risks associated with childhood aggression, it is important to understand risk factors that might predispose one to aggressive behaviors. One risk factor commonly associated with aggression is the experience of child maltreatment. A common outcome associated with child maltreatment is the development of post-traumatic stress symptoms (PTSS). Several prevailing theoretical models of both post-traumatic stress and aggression indicate that these constructs have similar underlying cognitive, behavioral, and emotional mechanisms. Therefore, the present study examined the relations between and among child maltreatment, PTSS clusters, and proactive and reactive aggression in children. Method: Children between the ages of 6 and 14 who were enrolled in a residential treatment program completed self-report measures to evaluate variables of interest. These variables were included as multiple outcomes in a path analysis model in which individual PTSS clusters were examined as potential multiple mediators of the relations between child maltreatment and proactive and reactive aggression. Results: Direct effects of child maltreatment and PTSS clusters on aggression were observed. Significant indirect effects of the intrusion PTSS cluster on the relation between child maltreatment and reactive aggression was found. Conclusions: Findings suggest that symptoms associated with these specific PTSS clusters might help explain the relation between child maltreatment and reactive aggression and therefore present important implications for clinical practice and future research

The epigenetic clock is correlated with physical and cognitive fitness in the Lothian Birth Cohort 1936

Background: The DNA methylation-based 'epigenetic clock' correlates strongly with chronological age, but it is currently unclear what drives individual differences. We examine cross-sectional and longitudinal associations between the epigenetic clock and four mortality-linked markers of physical and mental fitness: lung function, walking speed, grip strength and cognitive ability. Methods: DNA methylation-based age acceleration (residuals of the epigenetic clock estimate regressed on chronological age) were estimated in the Lothian Birth Cohort 1936 at ages 70 (n=920), 73 (n=299) and 76 (n=273) years. General cognitive ability, walking speed, lung function and grip strength were measured concurrently. Cross-sectional correlations between age acceleration and the fitness variables were calculated. Longitudinal change in the epigenetic clock estimates and the fitness variables were assessed via linear mixed models and latent growth curves. Epigenetic age acceleration at age 70 was used as a predictor of longitudinal change in fitness. Epigenome-wide association studies (EWASs) were conducted on the four fitness measures. Results: Cross-sectional correlations were significant between greater age acceleration and poorer performance on the lung function, cognition and grip strength measures (r range: -0.07 to -0.05, P range: 9.7 x 10 to 0.024). All of the fitness variables declined over time but age acceleration did not correlate with subsequent change over 6 years. There were no EWAS hits for the fitness traits. Conclusions: Markers of physical and mental fitness are associated with the epigenetic clock (lower abilities associated with age acceleration). However, age acceleration does not associate with decline in these measures, at least over a relatively short follow-up

The epigenetic clock and telomere length are independently associated with chronological age and mortality

Telomere length and DNA methylation have been proposed as biological clock measures that track chronological age. Whether they change in tandem, or contribute independently to the prediction of chronological age, is not known

Did a physician-targeted intervention that reduced potentially inappropriate prescribing to elderly patients also reduce related hospitalizations?

Objectives: To determine whether a general practitioner focused intervention aimed at decreasing PIM prescribing in the elderly can decrease the risk of PIM-related hospitalizations. Poster presented at 2016 ISPOR conference in Washington DC.https://jdc.jefferson.edu/jcphposters/1005/thumbnail.jp

Integration of datasets for individual prediction of DNA methylation-based biomarkers

BACKGROUND: Epigenetic scores (EpiScores) can provide biomarkers of lifestyle and disease risk. Projecting new datasets onto a reference panel is challenging due to separation of technical and biological variation with array data. Normalisation can standardise data distributions but may also remove population-level biological variation.RESULTS: We compare two birth cohorts (Lothian Birth Cohorts of 1921 and 1936 - nLBC1921 = 387 and nLBC1936 = 498) with blood-based DNA methylation assessed at the same chronological age (79 years) and processed in the same lab but in different years and experimental batches. We examine the effect of 16 normalisation methods on a novel BMI EpiScore (trained in an external cohort, n = 18,413), and Horvath's pan-tissue DNA methylation age, when the cohorts are normalised separately and together. The BMI EpiScore explains a maximum variance of R2=24.5% in BMI in LBC1936 (SWAN normalisation). Although there are cross-cohort R2 differences, the normalisation method makes a minimal difference to within-cohort estimates. Conversely, a range of absolute differences are seen for individual-level EpiScore estimates for BMI and age when cohorts are normalised separately versus together. While within-array methods result in identical EpiScores whether a cohort is normalised on its own or together with the second dataset, a range of differences is observed for between-array methods.CONCLUSIONS: Normalisation methods returning similar EpiScores, whether cohorts are analysed separately or together, will minimise technical variation when projecting new data onto a reference panel. These methods are important for cases where raw data is unavailable and joint normalisation of cohorts is computationally expensive.</p

GWAS on family history of Alzheimer’s disease

Alzheimer’s disease (AD) is a public health priority for the 21st century. Risk reduction currently revolves around lifestyle changes with much research trying to elucidate the biological underpinnings. We show that self-report of parental history of Alzheimer’s dementia for case ascertainment in a genome-wide association study of 314,278 participants from UK Biobank (27,696 maternal cases, 14,338 paternal cases) is a valid proxy for an AD genetic study. After meta-analysing with published consortium data (n = 74,046 with 25,580 cases across the discovery and replication analyses), three new AD-associated loci (P &lt; 5 × 10−8) are identified. These contain genes relevant for AD and neurodegeneration: ADAM10, BCKDK/KAT8 and ACE. Novel gene-based loci include drug targets such as VKORC1 (warfarin dose). We report evidence that the association of SNPs in the TOMM40 gene with AD is potentially mediated by both gene expression and DNA methylation in the prefrontal cortex. However, it is likely that multiple variants are affecting the trait and gene methylation/expression. Our discovered loci may help to elucidate the biological mechanisms underlying AD and, as they contain genes that are drug targets for other diseases and disorders, warrant further exploration for potential precision medicine applications

The efficacy of playing a virtual reality game in modulating pain for children with acute burn injuries: A randomized controlled trial [ISRCTN87413556]

BACKGROUND: The management of burn injuries is reported as painful, distressing and a cause of anxiety in children and their parents. Child's and parents' pain and anxiety, often contributes to extended time required for burns management procedures, in particular the process of changing dressings. The traditional method of pharmacologic analgesia is often insufficient to cover the burnt child's pain, and it can have deleterious side effects [1,2]. Intervention with Virtual Reality (VR) games is based on distraction or interruption in the way current thoughts, including pain, are processed by the brain. Research on adults supports the hypothesis that virtual reality has a positive influence on burns pain modulation. METHODS: This study investigates whether playing a virtual reality game, decreases procedural pain in children aged 5–18 years with acute burn injuries. The paper reports on the findings of a pilot study, a randomised trial, in which seven children acted as their own controls though a series of 11 trials. Outcomes were pain measured using the self-report Faces Scale and findings of interviews with parent/carer and nurses. RESULTS: The average pain scores (from the Faces Scale) for pharmacological analgesia only was, 4.1 (SD 2.9), while VR coupled with pharmacological analgesia, the average pain score was 1.3 (SD 1.8) CONCLUSION: The study provides strong evidence supporting VR based games in providing analgesia with minimal side effects and little impact on the physical hospital environment, as well as its reusability and versatility, suggesting another option in the management of children's acute pain

Cognitive control in infancy: attentional predictors using a tablet-based measure

Cognitive control is a predictor of later-life outcomes and may underpin higher order executive processes. The present study examines the development of early cognitive control during the first 24-months. We evaluated a tablet-based assessment of cognitive control among infants aged 18- and 24-months. We also examined concurrent and longitudinal associations between attentional disengagement, general cognitive skills and cognitive control. Participants (N=60, 30 female) completed the tablet-task at 18- and 24-months of age. Attentional disengagement and general cognitive development were assessed at 5-, 8-, 12-, 18- and 24-months using an eye-tracking measure and the Mullen Scales of Early Learning (MSEL), respectively. The cognitive control task demonstrated good internal consistency, sensitivity to age-related change in performance and stable individual differences. No associations were found between infant cognitive control and MSEL scores longitudinally or concurrently. The eye-tracking task revealed that slower attentional disengagement at 8-months, but faster disengagement at 18-months, predicted higher cognitive control scores at 24-months. This task may represent a useful tool for measuring emergent cognitive control. The multifaceted relationship between attention and infant cognitive control suggests that the rapid development of the attentional system in infancy results in distinct attentional skills, at different ages, being relevant for cognitive control development

Clustered Coding Variants in the Glutamate Receptor Complexes of Individuals with Schizophrenia and Bipolar Disorder

Current models of schizophrenia and bipolar disorder implicate multiple genes, however their biological relationships remain elusive. To test the genetic role of glutamate receptors and their interacting scaffold proteins, the exons of ten glutamatergic ‘hub’ genes in 1304 individuals were re-sequenced in case and control samples. No significant difference in the overall number of non-synonymous single nucleotide polymorphisms (nsSNPs) was observed between cases and controls. However, cluster analysis of nsSNPs identified two exons encoding the cysteine-rich domain and first transmembrane helix of GRM1 as a risk locus with five mutations highly enriched within these domains. A new splice variant lacking the transmembrane GPCR domain of GRM1 was discovered in the human brain and the GRM1 mutation cluster could perturb the regulation of this variant. The predicted effect on individuals harbouring multiple mutations distributed in their ten hub genes was also examined. Diseased individuals possessed an increased load of deleteriousness from multiple concurrent rare and common coding variants. Together, these data suggest a disease model in which the interplay of compound genetic coding variants, distributed among glutamate receptors and their interacting proteins, contribute to the pathogenesis of schizophrenia and bipolar disorders