Differences in mental health engagement and follow-up among Black and White patients after traumatic injury.

BACKGROUND: Severe injury necessitating hospitalization is experienced by nearly three million US adults annually. Posttraumatic stress disorder and depression are prevalent clinical outcomes. The mechanisms by which programs equitably promote mental health recovery among trauma-exposed patients are understudied. We evaluated clinical outcomes and engagement among a cohort of Black and White patients enrolled in the Trauma Resilience and Recovery Program (TRRP), a stepped-care model to accelerate mental health recovery after traumatic injury. METHODS: Trauma Resilience and Recovery Program is a four-step model that includes (1) bedside psychoeducation about mental health recovery following traumatic injury, (2) a text-messaging symptom tracking system, (3) a 30-day postinjury mental health screen, and (4) referrals to mental health services. Data describe 1,550 patients enrolled in TRRP within a Level I trauma center ( Mage = 40.86; SD, 17.32), 611 of whom identified as Black (74.5% male) and 939 of whom identified as White (67.7% male). RESULTS: Enrollment in TRRP was nearly universal (97.9%) regardless of race or injury mechanism. Enrollment and usage of the text-message system were statistically similar between Black (35.7%) and White patients (39.5%). Trauma Resilience and Recovery Program reengaged Black and White patients at a similar rate at the 30-day postinjury follow-up. However, Black patients were more likely to report peritraumatic distress at the bedside and clinical elevations in posttraumatic stress disorder and depression on the 30-day screen. Referrals were more likely to be accepted by Black patients relative to White patients with clinically elevated symptoms. CONCLUSION: Enrollment and engagement were comparable among Black and White patients served by TRRP. Data provide preliminary evidence to suggest that TRRP is feasible and acceptable and engages patients in mental health follow-up equitably. However, research that includes careful measurement of social determinants of health and long-term follow-up examining initiation, completion, and benefit from treatment is needed. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level III.

Frustration, Cognition, and Psychophysiology in Dysregulated Children: A Research Domain Criteria Approach.

OBJECTIVE: Dysregulated children experience significant impairment in regulating their affect, behavior, and cognitions and are at risk for numerous adverse sequelae. The unclear phenomenology of their symptoms presents a barrier to evidence-based diagnosis and treatment. METHOD: The cognitive, behavioral, and psychophysiological mechanisms of dysregulation were examined in a mixed clinical and community sample of 294 children ages 7-17 using the Research Domain Criteria constructs of cognitive control and frustrative nonreward. RESULTS: Results showed that caregivers of dysregulated children viewed them as having many more problems with everyday executive function than children with moderate or low levels of psychiatric symptoms; however, during standardized assessments of more complex cognitive control tasks, performance of dysregulated children differed only from children with low symptoms on tests of cognitive flexibility. In addition, when frustrated, dysregulated children performed more poorly on the Go/No-Go Task and demonstrated less autonomic flexibility as indexed by low respiratory sinus arrhythmia and pre-ejection period scores. CONCLUSION: The findings of this study suggest that autonomic inflexibility and impaired cognitive function in the context of frustration may be mechanisms underlying childhood dysregulation.

Tubulin Polymerization Promoting Protein (TPPP) gene methylation and corpus callosum measures in maltreated children.

The goal of the current study was to evaluate the impact of Tubulin Polymerization Promoting Protein (TPPP) methylation on structural and fractional anisotropy (FA) corpus callosum (CC) measures. TPPP is involved in the development of white matter tracts in the brain and was implicated in stress-related psychiatric disorders in an unbiased whole epigenome methylation study. The cohort included 63 participants (11.73 y/o ±1.91) from a larger study investigating risk and resilience in maltreated children. Voxel-based morphometry (VBM) was used to process the structural data, fractional anisotropy (FA) was determined using an atlas-based approach, and DNA specimens were derived from saliva in two batches using the 450 K (N = 39) and 850 K (N = 24) Illumina arrays, with the data from each batch analyzed separately. After controlling for multiple comparisons and relevant covariates (e.g., demographics, brain volume, cell composition, 3 PCs), 850 K derived TPPP methylation values, in interaction with a dimensional measure of children's trauma experiences, predicted left and right CC body volumes and genu, body and splenium FA (p < .007, all comparisons). The findings in the splenium replicated in subjects with the 450 K data. The results extend prior investigations and suggest a role for TPPP in brain changes associated with stress-related psychiatric disorders.

Social supports moderate the effects of child adversity on neural correlates of threat processing.

BACKGROUND: Child abuse and other forms of adversity are associated with alterations in threat processing and emotion regulation brain circuits. OBJECTIVE: The goal of the current investigation is to determine if the availability of positive social support can ameliorate the negative impact of adversity on these brain systems. PARTICIPANTS AND SETTING: Subjects included 55 children ages 7-16 (X = 11.8, SD = 2.0). Approximately one-third of the cohort had no significant history of adversity, one-third had a history of moderate adversity, and one-third had a history of severe adversity. Brain imaging was conducted at the University of Vermont using a 3.0 T Philips scanner. METHODS: The Emotional Go-NoGo task with fearful and calm facial stimuli was used to assess the neural correlates of threat processing and emotion regulation in children during functional magnetic resonance imaging (fMRI). Dimensional measures of anxiety, social supports, and children's adverse experiences were also obtained. RESULTS: A conjunction analysis was used to test if trauma-related brain activation in responding to fearful vs. calm targets was impacted by social support. This approach identified multiple activation foci, including a cluster extending from the left amygdala to several other key brain regions involved in emotion regulation, including the orbitofrontal cortex, anterior cingulate cortex (ACC), anterior insula, nucleus accumbens, and frontal pole (Family Wise Error (FWE) correction, p < 0.05). CONCLUSIONS: Greater social support may reduce the effect that adversity has on neural processing of threat stimuli, consistent with the protective role of positive supports in promoting resilience and recovery demonstrated in the literature.

A multi-method and multi-informant approach to assessing post-traumatic stress disorder (PTSD) in children.

Trauma exposure is highly prevalent among children globally, and is associated with elevated rates of PTSD. The goal of this study was to systematically evaluate the effects of multiple informants and multiple screening measures on the identification of specific PTSD symptoms and rates of PTSD diagnoses. Participants in this study included 350 maltreated children from two cohorts, one recruited from Connecticut (n = 130), and the other from Vermont (n = 220). Both cohorts completed the Screen for Child Anxiety-Related Emotional Disorders (SCARED) before a PTSD self-report measure. The KSADS psychiatric interview was also completed with the Connecticut cohort, with best-estimate ratings generated using parent and child interview, child self-report, and teacher questionnaire data. In addition to the SCARED and PTSD self-report scale, parents of the Vermont cohort completed the Child Behavioural Checklist. Significant differences emerged between parent and child report of sleep, nightmares, concentration, and irritability problems, suggesting the need for multiple informants in PTSD screening. Children also under-reported nightmares when asked in the context of a trauma-specific screening tool. As child trauma is associated with a broad range of psychiatric sequelae, comprehensive assessment using both general symptomatology and trauma-specific measures is recommended, since children often shut down when completing trauma measures.

Adverse Childhood Experiences, Epigenetic Measures, and Obesity in Youth.

OBJECTIVE: To determine if measures of adverse childhood experiences and DNA methylation relate to indices of obesity in youth. STUDY DESIGN: Participants were derived from a cohort of 321 8 to 15-year-old children recruited for an investigation examining risk and resilience and psychiatric outcomes in maltreated children. Assessments of obesity were collected as an add-on for a subset of 234 participants (56% female; 52% maltreated). Illumina arrays were used to examine whole genome epigenetic predictors of obesity in saliva DNA. For analytic purposes, the cohort analyzed in the first batch comprised the discovery sample (n = 160), and the cohort analyzed in the second batch the replication sample (n = 74). RESULTS: After controlling for race, sex, age, cell heterogeneity, 3 principal components, and whole genome testing, 10 methylation sites were found to interact with adverse childhood experiences to predict cross-sectional measures of body mass index, and an additional 6 sites were found to exert a main effect in predicting body mass index (P < 5.0 × 10-7, all comparisons). Eight of the methylation sites were in genes previously associated with obesity risk (eg, PCK2, CxCl10, BCAT1, HID1, PRDM16, MADD, PXDN, GALE), with several of the findings from the discovery data set replicated in the second cohort. CONCLUSIONS: This study lays the groundwork for future longitudinal studies to elucidate these mechanisms further and identify novel interventions to alleviate the health burdens associated with early adversity.

Methylation in OTX2 and related genes, maltreatment, and depression in children.

Through unbiased transcriptomics and multiple molecular tools, transient downregulation of the Orthodenticle homeobox 2 (OTX2) gene was recently causatively associated with the development of depressive-like behaviors in a mouse model of early life stress. The analyses presented in this manuscript test the translational applicability of these findings by examining peripheral markers of methylation of OTX2 and OTX2-regulated genes in relation to measures of depression and resting-state functional connectivity data collected as part of a larger study examining risk and resilience in maltreated children. The sample included 157 children between the ages of 8 and 15 years (χ = 11.4, SD = 1.9). DNA specimens were derived from saliva samples and processed using the Illumina 450 K beadchip. A subset of children (N = 47) with DNA specimens also had resting-state functional MRI data. After controlling for demographic factors, cell heterogeneity, and three principal components, maltreatment history and methylation in OTX2 significantly predicted depression in the children. In terms of the imaging data, increased OTX2 methylation was found to be associated with increased functional connectivity between the right vmPFC and bilateral regions of the medial frontal cortex and the cingulate, including the subcallosal gyrus, frontal pole, and paracingulate gyrus-key structures implicated in depression. Mouse models of early stress hold significant promise in helping to unravel the mechanisms by which child adversity confers risk for psychopathology, with data presented in this manuscript supporting a potential role for OTX2 and OTX2-related (e.g., WNT1, PAX6) genes in the pathophysiology of stress-related depressive disorders in children.

Appendix.

This article is designed to serve as a reference for researchers and clinicians interested in extant evidence-based programs designed to promote healthy youth development. This article begins with a review of 2 freely available online registries of evidence-based youth development programs. Both registries compile information on healthy youth development programs and rate such programs on pre-established criteria. This article also outlines several specific model programs, which intervene on a variety of targets to promote healthy youth development. Lastly, this article also outlines emerging youth development programs. The model and emerging programs reviewed have resulted in myriad positive outcomes.

Child abuse, depression, and methylation in genes involved with stress, neural plasticity, and brain circuitry.

OBJECTIVES: To determine whether epigenetic markers predict dimensional ratings of depression in maltreated children. METHOD: A genome-wide methylation study was completed using the Illumina 450K BeadChip array in 94 maltreated and 96 healthy nontraumatized children with saliva-derived DNA. The 450K BeadChip does not include any methylation sites in the exact location as sites in candidate genes previously examined in the literature, so a test for replication of prior research findings was not feasible. RESULTS: Methylation in 3 genes emerged as genome-wide-significant predictors of depression: DNA-Binding Protein Inhibitor ID-3 (ID3); Glutamate Receptor, Ionotropic N-methyl-D-aspartate (NMDA) 1 (GRIN1); and Tubulin Polymerization Promoting Protein (TPPP) (p < 5.0 × 10(-7), all analyses). These genes are all biologically relevant with ID3 involved in the stress response, GRIN1 involved in neural plasticity, and TPPP involved in neural circuitry development. Methylation in CpG sites in candidate genes were not predictors of depression at significance levels corrected for whole genome testing, but maltreated and control children did have significantly different ß values after Bonferroni correction at multiple methylation sites in these candidate genes (e.g., BDNF, NR3C1, FKBP5). CONCLUSIONS: This study suggests that epigenetic changes in ID3, GRIN1, and TPPP genes, in combination with experiences of maltreatment, may confer risk for depression in children. The study adds to a growing body of literature supporting a role for epigenetic mechanisms in the pathophysiology of stress-related psychiatric disorders. Although epigenetic changes are frequently long lasting, they are not necessarily permanent. Consequently, interventions to reverse the negative biological and behavioral sequelae associated with child maltreatment are briefly discussed.

Phencyclidine (PCP) produces sexually dimorphic effects on voluntary sucrose consumption and elevated plus maze behavior.

Previous research in our laboratory indicates that the psychotomimetic drug phencyclidine (PCP) reduces voluntary sucrose consumption in male rats, potentially modeling the schizophrenic symptom of anhedonia. Given reports from the clinical literature that schizophrenia has a later age of onset and more favorable outcome in females, PCP might be expected to have sexually dimorphic effects in animal models of schizophrenia such as PCP-induced decreases in voluntary sucrose consumption. Young adult (66 days old) and adult (109 days old) male and female rats were trained to drink sucrose during a 30 min/day presentation protocol. On the day prior to the test day, animals were treated with PCP (15 mg/kg) or saline four hours after the onset of the sucrose presentation (20 h prior to the sucrose on the test day). PCP decreased sucrose consumption on the test day similarly in adult males and females, although females also showed decreased water consumption. In young animals, PCP decreased sucrose consumption in males but not in females. These results are consistent with the prediction that females will be less sensitive to the schizophrenia-like behavioral effects of PCP. In a separate study, the same animals were tested in an elevated plus maze one to two months after testing for voluntary sucrose consumption. Significant sex x drug interaction effects on a number of measures in the elevated plus maze indicated that prior exposure to PCP had an anxiolytic effect in females and an anxiogenic effect in males. While unexpected, this finding indicates an additional sexually dimorphic effect of PCP on behavior and its potential relevance to the PCP model of schizophrenia is discussed.