Faculty Bibliography

Background Infants with critical congenital heart disease ( CCHD ) are more likely to be small for gestational age (GA). It is unclear how this affects mortality. The authors investigated the effect of birth weight Z score on 1-year mortality separately in preterm (GA <37 weeks), early-term (GA 37-38 weeks), and full-term (GA 39-42 weeks) infants with CCHD . Methods and Results Live-born infants with CCHD and GA 22 to 42 weeks born in California 2007-2012 were included in the analysis. The primary predictor was Z score for birth weight and the primary outcome was 1-year mortality. Multivariable logistic regression was used. Results are presented as adjusted odds ratios and 95% confidence intervals ( CIs ). The authors identified 6903 infants with CCHD . For preterm and full-term infants, only a Z score for birth weight <-2 was associated with increased mortality compared with the reference group ( Z score 0-0.5, adjusted odds ratio, 2.15 [95% CI , 1.1-4.21] and adjusted odds ratio, 3.93 [95% CI , 2.32-6.68], respectively). In contrast, in early-term infants, the adjusted odds ratios for Z scores <-2, -2 to -1, and -1 to -0.5 were 3.42 (95% CI , 1.93-6.04), 1.78 (95% CI , 1.12-2.83), and 2.03 (95% CI , 1.27-3.23), respectively, versus the reference group. Conclusions GA seems to modify the effect of birth weight Z score on mortality in infants with CCHD . In preterm and full-term infants, only the most severe small-for-GA infants ( Z score <-2) were at increased risk for mortality, while, in early-term infants, the risk extended to mild to moderate small-for-GA infants ( Z score <-0.5). This information helps to identify high-risk infants and is useful for surgical planning.

Although birth weight is a potential causal risk factor for attention-deficit/hyperactivity disorder (ADHD) symptoms, both the specificity of this association and its mediating pathways are largely unknown. We carefully assessed youth with and without ADHD (i.e., Wave 1), and followed them prospectively for 2 years (i.e., Wave 2). We (a) tested the association of birth weight with Wave 2 ADHD symptoms, and (b) evaluated biologically plausible neurocognitive functions from Wave 1 as temporally ordered mediators of birth weight and Wave 2 ADHD symptoms in a multiple mediation framework. At Wave 1, 222 ethnically diverse youth (30% female; ages 5-10) completed the Digit Span, Vocabulary, Symbol Search, and Arithmetic subtests of the Wechsler Intelligence Scale for Children-IV. At both Wave 1 and Wave 2 (ages 7-13), multiple informants (i.e., parents, teachers) rated youth ADHD symptoms and co-occurring psychopathology using multiple methods (i.e., structured interview, rating scale). Controlling for demographic factors, gestational age, and co-occurring externalizing and internalizing psychopathology, birth weight inversely predicted Wave 2 ADHD symptoms across multiple methods and informants. Additionally, controlling for Wave 1 ADHD symptoms and relevant covariates, Wave 1 Arithmetic uniquely mediated the association of birth weight with multi-method/informant Wave 2 ADHD symptoms. These findings suggest that birth weight is a relatively specific risk factor for youth ADHD symptoms and they implicate individual differences in fluid reasoning as a preliminary causal mediator of this association. We discuss implications for future research evaluating causal mechanisms underlying risk factors for ADHD.

Although gene × environment interactions contribute to youth attention-deficit/hyperactivity disorder (ADHD) symptoms, the pathways mediating these influences are unknown. We tested genetic moderation of indirect effects from parenting behavior to youth ADHD symptoms through multiple neurocognitive factors. Two hundred and twenty-nine youth with and without ADHD were assessed at baseline (Wave 1; ages 5-10) and at a 2-year follow-up (Wave 2; ages 7-13). At Wave 1, youth completed a neurocognitive battery including measures of response inhibition, visuospatial working memory, and fluid reasoning, and a standardized parent-child interaction task yielding observational measures of positive and negative parenting. At Wave 2, youth psychopathology was rated by parents and teachers using multiple methods (i.e., structured interview, rating scale). We employed moderated multiple mediation and compared conditional indirect effects across youth genotypes at two biologically plausible genetic loci. Controlling for parent ADHD symptoms as well as youth demographic factors and co-occurring externalizing symptoms, these genetic factors moderated the indirect effect from Wave 1 parenting to multi-method/informant Wave 2 ADHD symptoms through Wave 1 neurocognitive functioning. This preliminary study is the first to identify genetic moderation of mediated effects underlying ADHD symptoms and suggests that specific gene × parenting interactions may underlie neurocognitive functioning deficits and subsequent ADHD.

The serotonin transporter-linked polymorphic region (5-HTTLPR) is associated with caregiving in nonhuman animals and with affective and cognitive correlates of human parenting, yet its association with human parenting is largely unknown. Using a well-characterized sample of parents and offspring, we evaluated the association of parental 5-HTTLPR with observed positive and negative parenting behavior, as well as its biologically plausible moderation of child-related stress and disruptive child behavior as predictors of parenting. One hundred and sixty-two parents (86% mothers) and their 6- to 9-year-old children with and without attention-deficit/hyperactivity disorder were ascertained using multiple methods including structured interviews, rating scales, and observed parent-child interaction, yielding strong measures of key constructs. Controlling for multiple youth-level (e.g., sex, 5-HTTLPR genotype, disruptive behavior) and parent-level (e.g., demographics, depression, attention-deficit/hyperactivity disorder) factors, parents with an S allele exhibited significantly less observed positive parenting than those with the LL genotype. Significant Gene × Environment interactions were also observed: Child-related stress was negatively associated with observed parental negativity among SS/SL genotype parents but not LL genotype parents; next, observed disruptive child behavior was positively associated with parental negativity for both genotypes, but the effect was strongest in SS/SL parents. These preliminary findings suggest that parental 5-HTTLPR is uniquely associated with positive and negative parenting behavior, with more specific patterns according to child-related stress and disruptive child behavior. We consider implications for future research evaluating genetic influences on parenting as well as considerations for designing and delivering parenting-based interventions.

Although individual differences in fluid reasoning reliably mediate predictions of attention-deficit/hyperactivity disorder (ADHD) symptoms from birth weight in youth with typical cognitive development (TD), it is unknown if this indirect effect operates similarly in the development of ADHD symptoms secondary to intellectual disability (ID). Thus, we evaluated mediation by fluid reasoning in a longitudinal sample of 163 youth (45% female) with (n = 52) or without (n = 111) ID who were followed prospectively from age 5 to age 13. At age 9, youth completed the Arithmetic subtest of the Wechsler Intelligence Scale for Children, a measure of fluid reasoning. At ages 9 and 13, mothers and teachers separately rated youth ADHD symptoms and mothers completed a diagnostic interview. Mediation was tested via path analysis with bootstrapped confidence intervals, and moderated mediation estimated whether indirect effects differed between ID and TD youth or based on youth IQ. Controlling for demographic factors and age 9 ADHD symptoms, age 9 Arithmetic mediated birth weight and multi-method/informant age 13 ADHD symptoms, such that birth weight positively predicted Arithmetic, which negatively predicted ADHD symptoms. Neither ID status nor IQ moderated the observed indirect effect through Arithmetic, suggesting that it was similar for ID and TD youth as well as across the range of youth IQs. These findings support previous evidence that fluid reasoning, as measured by Arithmetic, may causally mediate birth weight and ADHD symptoms, and suggest that this pathway operates similarly with respect to the development of ADHD symptoms in youth with ID.

OBJECTIVE:Supratherapeutic doses of methylphenidate activate μ-opioid receptors, which are linked to euphoria. This study assessed whether naltrexone, a mixed μ-opioid antagonist, may attenuate the euphoric effects of stimulants, thereby minimizing their abuse potential in subjects with attention-deficit/hyperactivity disorder (ADHD). METHODS:We conducted a 6-week, double-blind, placebo-controlled, randomized clinical trial of naltrexone in adults with DSM-IV ADHD receiving open treatment with a long-acting formulation of methylphenidate (January 2013 to June 2015). Spheroidal Oral Drug Absorption System methylphenidate (SODAS-MPH) was administered twice daily, was titrated to ~1 mg/kg/d over 3 weeks, and was continued for 3 additional weeks depending on response and adverse effects. Subjects were adults with ADHD preselected for having experienced euphoria with an oral test dose of 60 mg of immediate-release methylphenidate (IR-MPH). The primary outcome measure was Question 2 (Liking a Drug Effect) on the Drug Rating Questionnaire, Subject version, which was assessed after oral test doses of 60 mg of IR-MPH were administered after the third and sixth weeks of treatment with SODAS-MPH. RESULTS:Thirty-seven subjects who experienced stimulant-induced (mild) euphoria at a baseline visit were started in the open trial of SODAS-MPH and randomized to naltrexone 50 mg/d or placebo. Thirty-one subjects completed through week 3, and 25 completed through week 6. Naltrexone significantly diminished the euphoric effect of IR-MPH during the heightened-risk titration phase (primary outcome; first 3 weeks) (χ² = 5.07, P = .02) but not the maintenance phase (weeks 4-6) (χ² = 0.22, P = .64) of SODAS-MPH treatment. CONCLUSIONS:Preclinical findings are extended to humans showing that naltrexone may mitigate stimulant-associated euphoria. Our findings provide support for further studies combining opioid receptor antagonists with stimulants to reduce abuse potential. TRIAL REGISTRATION:ClinicalTrials.gov identifier: NCT01673594.

Disruptive mood dysregulation disorder (DMDD) is a new diagnosis in the Diagnostic and Statistical Manual of Mental Disorders (DSM-5). We compared juvenile justice involved youths with DMDD to those with disruptive behavior disorders (DBDs) and other mood disorders, to clarify the differences and to investigate differential correlates to DMDD relative to DBDs or mood disorders. Diagnostic and demographic data were available for 9,819 youths served by 57 juvenile justice sites. A subsample of 2,498 youths had data relevant to our study. The youths self-assessed mental health status on the Voice Diagnostic Interview Schedule for Children (V-DISC), and we retrofitted the V-DISC data to derive an approximate DMDD diagnosis. The retrofitted criteria for DMDD were met by 3.3 percent of justice-involved youths. Results from multinomial regression showed that, after adjustment for covariates, those with DMDD had fewer differences compared with those with other mood disorders than did those meeting criteria for DBDs. Consistent with the DSM-5 classification of DMDD as a depressive disorder, those with DMDD shared more characteristics with youths with mood disorders than with those reporting DBDs. Externalizing behaviors leading to justice involvement may overshadow internalizing symptoms of DMDD, but mood-related conditions should be identified and treated in this population.

Pediatric psychiatric emergency care is delivered in different settings with vastly different resources around the country. Training programs lack guidance on developing optimal curricula for this highly variable but crucial setting. A model curriculum for child and adolescent psychiatry trainees may be helpful to provide such guidance; its components include recommendations for assessing baseline knowledge, identifying and teaching core subject content, encouraging development of essential skills, and building in supervision for learners. Future directions include further study in current pediatric emergency psychiatry education and expanding the scope of curricula to include different learners and delivery models.

Early academic achievement has been shown to predict high school completion, but there have been few studies of the predictors of early academic success focused on Latino students. Using longitudinal data from 750 Mexican and Dominican American families, this study examined a cultural model of parenting and early academic achievement. While Latino students were achieving in the average range as a whole, certain subgroups (e.g., Dominicans, boys) were at higher risk for underachievement. Results highlighted the protective role of authoritative parenting, which was associated with academic and social-emotional school readiness, both of which predicted higher achievement at the end of first grade. The role of respeto and authoritarian parenting practices in academic achievement at first grade differed between Mexican and Dominican American families. Findings advance understanding of early achievement and parenting among Latino families from a cultural perspective.