James L. Burns

Interaction of prenatal exposure to cigarettes and MAOA genotype in pathways to youth antisocial behavior

Genetic susceptibility to antisocial behavior may increase fetal sensitivity to prenatal exposure to cigarette smoke. Testing putative gene × exposure mechanisms requires precise measurement of exposure and outcomes. We tested whether a functional polymorphism in the gene encoding the enzyme monoamine oxidase A (MAOA) interacts with exposure to predict pathways to adolescent antisocial behavior. We assessed both clinical and information-processing outcomes. One hundred seventy-six adolescents and their mothers participated in a follow-up of a pregnancy cohort with well-characterized exposure. A sex-specific pattern of gene × exposure interaction was detected. Exposed boys with the low-activity MAOA 5′ uVNTR (untranslated region variable number of tandem repeats) genotype were at increased risk for conduct disorder (CD) symptoms. In contrast, exposed girls with the high-activity MAOA uVNTR genotype were at increased risk for both CD symptoms and hostile attribution bias on a face-processing task. There was no evidence of a gene–environment correlation (rGE). Findings suggest that the MAOA uVNTR genotype, prenatal exposure to cigarettes and sex interact to predict antisocial behavior and related information-processing patterns. Future research to replicate and extend these findings should focus on elucidating how gene × exposure interactions may shape behavior through associated changes in brain function.

Observational Assessment of Preschool Disruptive Behavior, Part II: validity of the Disruptive Behavior Diagnostic Observation Schedule (DB-DOS).

OBJECTIVE To examine the reliability of the Disruptive Behavior Diagnostic Observation Schedule (DB-DOS), a new observational method for assessing preschool disruptive behavior. METHOD The DB-DOS is a structured clinic-based assessment designed to elicit clinically salient behaviors relevant to the diagnosis of disruptive behavior in preschoolers. Child behavior is assessed in three interactional contexts that vary by partner (parent versus examiner) and level of support provided. Twenty-one disruptive behaviors are coded within two domains: problems in Behavioral Regulation and problems in Anger Modulation. A total of 364 referred and nonreferred preschoolers participated: interrater reliability and internal consistency were assessed on a primary sample (n = 335) and test-retest reliability was assessed in a separate sample (n = 29). RESULTS The DB-DOS demonstrated good interrater and test-retest reliability. Confirmatory factor analysis demonstrated an excellent fit of the DB-DOS multidomain model of disruptive behavior. CONCLUSIONS The DB-DOS is a reliable observational tool for clinic-based assessment of preschool disruptive behavior. This standardized assessment method holds promise for advancing developmentally sensitive characterization of preschool psychopathology.

Defining the developmental parameters of temper loss in early childhood: implications for developmental psychopathology

BACKGROUND Temper modulation problems are both a hallmark of early childhood and a common mental health concern. Thus, characterizing specific behavioral manifestations of temper loss along a dimension from normative misbehaviors to clinically significant problems is an important step toward identifying clinical thresholds. METHODS Parent-reported patterns of temper loss were delineated in a diverse community sample of preschoolers (n = 1,490). A developmentally sensitive questionnaire, the Multidimensional Assessment of Preschool Disruptive Behavior (MAP-DB), was used to assess temper loss in terms of tantrum features and anger regulation. Specific aims were: (a) document the normative distribution of temper loss in preschoolers from normative misbehaviors to clinically concerning temper loss behaviors, and test for sociodemographic differences; (b) use Item Response Theory (IRT) to model a Temper Loss dimension; and (c) examine associations of temper loss and concurrent emotional and behavioral problems. RESULTS Across sociodemographic subgroups, a unidimensional Temper Loss model fit the data well. Nearly all (83.7%) preschoolers had tantrums sometimes but only 8.6% had daily tantrums. Normative misbehaviors occurred more frequently than clinically concerning temper loss behaviors. Milder behaviors tended to reflect frustration in expectable contexts, whereas clinically concerning problem indicators were unpredictable, prolonged, and/or destructive. In multivariate models, Temper Loss was associated with emotional and behavioral problems. CONCLUSIONS Parent reports on a developmentally informed questionnaire, administered to a large and diverse sample, distinguished normative and problematic manifestations of preschool temper loss. A developmental, dimensional approach shows promise for elucidating the boundaries between normative early childhood temper loss and emergent psychopathology.

Unpacking the association: Individual differences in the relation of prenatal exposure to cigarettes and disruptive behavior phenotypes

Prenatal exposure to cigarettes has been robustly associated with disruptive behavior in diverse samples and across developmental periods. In this paper we aim to elucidate exposure related behavioral phenotypes and developmental pathways by testing: (a) differential associations of exposure and four disruptive behavior dimensional phenotypes: Aggression, Noncompliance, Temper Loss and Low Concern for Others; and (b) moderation of these pathways including sex differences and moderation by parental responsive engagement. Participants were 211 teens and their parents from the East Boston Family Study (EBFS), an adolescent follow-up of a pregnancy cohort over-sampled for exposure. A best estimate serum cotinine corrected score was used to characterize exposure. In multivariate models controlling for parental antisocial behavior, family adversity and secondhand exposure, exposure uniquely predicted Aggression and Noncompliance. Paternal responsiveness moderated exposure effects on disruptive behavior. There were no sex differences in these patterns. Phenotypic findings suggest the possibility of specific neural mechanisms. In conjunction with prior research, protective effects of parental responsiveness occurring as late as adolescence point to the potential benefit of parenting-based prevention efforts to reduce risk to exposed offspring.

Separating Family-Level and Direct Exposure Effects of Smoking During Pregnancy on Offspring Externalizing Symptoms: Bridging the Behavior Genetic and Behavior Teratologic Divide

AbstractMaternal smoking during pregnancy (MSDP) has been robustly associated with externalizing problems and their developmental precursors in offspring in studies using behavioral teratologic designs (Wakschlag et al., Am J Public Health 92(6):966–974, 2002; Espy et al., Dev Psychol 47(1):153–169, 2011). In contrast, the use of behavior genetic approaches has shown that the effects commonly attributed to MSDP can be explained by family-level variables (D’Onofrio et al., Dev Psychopathol 20(01):139–164, 2008). Reconciling these conflicting findings requires integration of these study designs. We utilize longitudinal data on a preschool proband and his/her sibling from the Midwest Infant Development Study-Preschool (MIDS-P) to test for teratologic and family level effects of MSDP. We find considerable variation in prenatal smoking patterns both within and across pregnancies within families, indicating that binary smoking measures are not sufficiently capturing exposure. Structural equation models indicate that both conduct disorder and oppositional defiant disorder symptoms showed unique effects of MSDP over and above family level effects. Blending high quality exposure measurement with a within-family design suggests that it is premature to foreclose the possibility of a teratologic effect of MSDP on externalizing problems. Implications and recommendations for future studies are discussed.

Health Literacy and Patient-Reported Outcomes: A Cross-Sectional Study of Underserved English- and Spanish-Speaking Patients With Type 2 Diabetes

This study examined associations between patient characteristics, health behaviors, and health outcomes and explored the role of health literacy as a potential mediator of outcomes. English- and Spanish-speaking adults with Type 2 diabetes used a bilingual multimedia touchscreen to complete questionnaires. The behavioral model for vulnerable populations guided multivariable regression and mediation testing. Dependent variables were diabetes self-care, health status, and satisfaction with communication. Independent variables included sociodemographic and clinical characteristics, health literacy, health beliefs, and self-efficacy. Spanish speakers had lower health literacy and poorer physical, mental, and overall health compared to English speakers. Higher health literacy was associated with less social support for diet, fewer diet and medication barriers, younger age, higher diabetes knowledge, and talking with health care professionals to get diabetes information. In contrast to expectations, health literacy was not associated with diabetes self-care, health status, or satisfaction with communication, and it did not mediate the effects of other factors on these outcomes. Diabetes self-efficacy was significantly associated with health behaviors and outcomes. The association between Spanish language preference and poorer health was not mediated by this groups lower health literacy. Increasing health-related self-efficacy might be an important clinical strategy for improving outcomes in underserved patients with Type 2 diabetes.

A longitudinal evaluation of oxidative stress in trauma patients

BACKGROUND The purpose of this study was to determine the course of oxidative stress in trauma patients as measured by antioxidant disappearance and modulation of DNA damage. The study also explored the role of injury severity and the effect of changes in plasma lipoprotein concentration as the result of hemodilution on lipid-soluble plasma antioxidant concentrations. METHODS The study population included 17 adult male trauma patients in an urban level-1 trauma hospital and 12 healthy adult male controls. Blood was collected immediately after admission in the emergency room, and on days 2, 3, 4, 6, and 8 of admission. Plasma antioxidant concentrations and total cholesterol concentrations were evaluated. DNA damage was evaluated using the ratio of 8-hydroxydeoxyguanosine to deoxyguanosine (8OhdG to dG). Admission data were compared with data from controls. RESULTS Plasma antioxidant concentrations (except alpha-tocopherol) significantly decreased by 9.9% to 34.3% in the 24 hours after trauma and remained depressed throughout day 8. Repeated measures regression analysis for trend showed a significant increase in unadjusted alpha-tocopherol from day 1 to day 8 (p < .008). No other unadjusted antioxidant or plasma cholesterol showed a significant change. After individually adjusting antioxidant concentrations by total cholesterol, only gamma-tocopherol (22.2%) and lycopene (22.6%) were decreased (p < .04) in the 24 hours after trauma. Repeated measures regression analysis for trend for the cholesterol-adjusted antioxidants showed a significant decrease from day 1 to day 8 for cholesterol-adjusted alpha-carotene (p < .007) and beta-carotene (p < .007). Trauma patients were divided into more and less severely injured groups based on Injury Severity Score (ISS). Decreases in antioxidant concentration from day 1 to day 2 were found for the patients in the more injured group, with no significant differences from day 1 to day 2 in the less severely injured group. Cholesterol-adjusted gamma-to copherol (29.7%, p < .003) and lycopene (32.7%, p < .05) decreased from day 1 to day 2 in the more severely injured group. Using repeated measures regression analysis for trend, the only antioxidant that was significantly different in the high versus low ISS groups from day 1 through day 6 was cholesterol-adjusted lutein-zeaxanthin (p < .02). Compared with controls, trauma patients had significantly lower (27.3% to 64.9%) concentrations of all cholesterol-adjusted antioxidants at day 1 except for lycopene. Trauma patients had higher leukocyte 8OhdG to dG ratios at admission (42.6%, p < .05), but 8OhdG to dG ratios tended to decrease over the 24 hours after trauma (p < .07). This decrease was greater in the 3 trauma patients with an admission 8OhdG to dG ratio greater than 6 x 10(-5) (59.3% versus 0.05%, p < .03). CONCLUSIONS The difference in antioxidant concentrations between trauma patients and controls may have been associated with oxidative stress or with a poorer diet. The difference between antioxidant concentrations and cholesterol-adjusted antioxidant concentrations is likely caused by hemodilution or by changes in plasma lipid levels as a result of trauma. Therefore, individually adjusting lipid-soluble antioxidant concentrations by total cholesterol concentrations is important in trauma patients. Leukocyte 8OhdG to dG ratios were already elevated in trauma patients on admission but returned nearly to control levels 24 hours later, indicating short-term responsiveness to DNA oxidation in trauma patients and an extensive capacity for DNA repair within 24 hours.

Validating Neuro-QoL short forms and targeted scales with people who have multiple sclerosis

Background: Multiple sclerosis (MS) is a chronic, progressive, and disabling disease of the central nervous system with dramatic variations in the combination and severity of symptoms it can produce. The lack of reliable disease-specific health-related quality of life (HRQL) measures for use in clinical trials prompted the development of the Neurology Quality of Life (Neuro-QOL) instrument, which includes 13 scales that assess physical, emotional, cognitive, and social domains, for use in a variety of neurological illnesses. Objective: The objective of this research paper is to conduct an initial assessment of the reliability and validation of the Neuro-QOL short forms (SFs) in MS. Methods: We assessed reliability, concurrent validity, known groups validity, and responsiveness between cross-sectional and longitudinal data in 161 recruited MS patients. Results: Internal consistency was high for all measures (α = 0.81–0.95) and ICCs were within the acceptable range (0.76–0.91); concurrent and known groups validity were highest with the Global HRQL question. Longitudinal assessment was limited by the lack of disease progression in the group. Conclusions: The Neuro-QOL SFs demonstrate good internal consistency, test-re-test reliability, and concurrent and known groups validity in this MS population, supporting the validity of Neuro-QOL in adults with MS.

Contextual variation in young children's observed disruptive behavior on the DB‐DOS: implications for early identification

BACKGROUND Contextual variation in child disruptive behavior is well documented but remains poorly understood. We first examine how variation in observed disruptive behavior across interactional contexts is associated with maternal reports of contextual variation in oppositional-defiant behavior and functional impairment. Second, we test whether child inhibitory control explains the magnitude of contextual variation in observed disruptive behavior. METHODS Participants are 497 young children (mean age = 4 years, 11 months) from a subsample of the MAPS, a sociodemographically diverse pediatric sample, enriched for risk of disruptive behavior. Observed anger modulation and behavioral regulation problems were coded on the Disruptive Behavior Diagnostic Observation Schedule (DB-DOS) during interactions with parent and examiner. Oppositional-defiant behavior, and impairment in relationships, with parents and nonparental adults, were measured with the Preschool Age Psychiatric Assessment (PAPA) interview with the mother. Functional impairment in the home and out-and-about was assessed with the Family Life Impairment Scale (FLIS), and expulsion from child care/school was measured with the baseline survey and FLIS. RESULTS Observed disruptive behavior on the DB-DOS Parent Context was associated with oppositional-defiant behavior with parents, and with impairment at home and out-and-about. Observed disruptive behavior with the Examiner was associated with oppositional-defiant behavior with both parents and nonparental adults, impairment in relationships with nonparental adults, and child care/school expulsion. Differences in observed disruptive behavior in the Parent versus Examiner Contexts was related to the differences in maternal reports of oppositional-defiant behavior with parents versus nonparental adults. Children with larger decreases in disruptive behavior from Parent to Examiner Context had better inhibitory control and fewer attention-deficit/hyperactivity disorder symptoms. CONCLUSIONS The DB-DOS showed clinical utility in a community sample for identifying contextual variation that maps onto reported oppositional-defiant behavior and functioning across contexts. Elucidating the implications of contextual variation for early identification and targeted prevention is an important area for future research.

Feasibility, acceptability and preliminary psychological benefits of mindfulness meditation training in a sample of men diagnosed with prostate cancer on active surveillance: results from a randomized controlled pilot trial.

In a pilot randomized controlled trial, examine the feasibility and preliminary efficacy of an 8‐week, mindfulness training program (Mindfulness Based Stress Reduction) in a sample of men on active surveillance on important psychological outcomes including prostate cancer anxiety, uncertainty intolerance and posttraumatic growth.