If maternal expressed emotion is an environmental risk factor for children's antisocial behavior problems, it should account for behavioral differences between siblings growing up in the same family even after genetic influences on children's behavior problems are taken into account. This hypothesis was tested in the Environmental Risk Longitudinal Twin Study with a nationally representative 1994-1995 birth cohort of twins. The authors interviewed the mothers of 565 five-year-old monozygotic (MZ) twin pairs and established which twin in each family received more negative emotional expression and which twin received more warmth. Within MZ pairs, the twin receiving more maternal negativity and less warmth had more antisocial behavior problems. Qualitative interviews were used to generate hypotheses about why mothers treat their children differently. The results suggest that maternal emotional attitudes toward children may play a causal role in the development of antisocial behavior and illustrate how genetically informative research can inform tests of socialization hypotheses.

IMPORTANCE Few pharmacotherapies have demonstrated sufficient efficacy in the treatment of posttraumatic stress disorder (PTSD), a chronic and disabling condition.OBJECTIVE To test the efficacy and safety of a single intravenous subanesthetic dose of ketamine for the treatment of PTSD and associated depressive symptoms in patients with chronic PTSD. DESIGN, SETTING, AND PARTICIPANTS Proof-of-concept, randomized, double-blind, crossover trial comparing ketamine with an active placebo control, midazolam, conducted at a single site (Icahn School of Medicine at Mount Sinai, New York, New York). Forty-one patients with chronic PTSD related to a range of trauma exposures were recruited via advertisements.INTERVENTIONS Intravenous infusion of ketamine hydrochloride (0.5 mg/kg) and midazolam (0.045 mg/kg). MAIN OUTCOMES AND MEASURESThe primary outcome measure was change in PTSD symptom severity, measured using the Impact of Event Scale-Revised. Secondary outcome measures included the Montgomery-Asberg Depression Rating Scale, the Clinical Global Impression-Severity and -Improvement scales, and adverse effect measures, including the Clinician-Administered Dissociative States Scale, the Brief Psychiatric Rating Scale, and the Young Mania Rating Scale.RESULTS Ketamine infusion was associated with significant and rapid reduction in PTSD symptom severity, compared with midazolam, when assessed 24 hours after infusion (mean difference in Impact of Event Scale-Revised score, 12.7 [95% CI, 2.5-22.8]; P = .02). Greater reduction of PTSD symptoms following treatment with ketamine was evident in both crossover and first-period analyses, and remained significant after adjusting for baseline and 24-hour depressive symptom severity. Ketamine was also associated with reduction in comorbid depressive symptoms and with improvement in overall clinical presentation. Ketamine was generally well tolerated without clinically significant persistent dissociative symptoms. CONCLUSIONS AND RELEVANCEThis study provides the first evidence for rapid reduction in symptom severity following ketamine infusion in patients with chronic PTSD. If replicated, these findings may lead to novel approaches to the pharmacologic treatment of patients with this disabling condition. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00749203

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The moderating effect of maternal warmth on the association between low birth weight and children's attention-deficit/hyperactivity disorder (ADHD) symptoms and low IQ was studied in 2,232 twins. Half of 5-year-old children had low birth weights, below 2,500 g. Maternal warmth, a component of expressed emotion, was coded from mothers' audiotaped descriptions of each child. Both parents and teachers rated children's ADHD symptoms, and the children were administered an IQ test. Results showed a significant interaction between children's birth weight and maternal warmth in predicting mothers' and teachers' ratings of ADHD. The interaction was not significant for IQ. The findings suggest that the effect of children's birth weight on their ADHD symptoms can be moderated by maternal warmth and that enhancing maternal warmth may prevent behavior problems among the increasing population of low-birth- weight children.

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.

Social skills are traditionally viewed as acquired through social environments including parenting. However, biopsychosocial models highlight the importance of genetic influences and gene-environment interactions (GϫEs) in child development. Extant GϫE investigations often fail to account for developmental changes in the phenotype or rigorously assess the social environment using observational measures. The present study prospectively assessed 110 children (44.5% female) and their parents to explore biologically plausible independent and interactive associations of the serotonin transporter-linked polymorphic region (5-HTTLPR) and observed positive and negative parenting in prediction of (a) initial levels of social skills at school entry (age 6 years) and (b) developmental changes in social skills across the early school years (ages 6 -9 years). Overall, the SS (vs. SL/LL) 5-HTTLPR genotype inversely predicted social skills across all domains, although parenting behavior moderated these associations wherein putative GϫE effects differed by developmental timing and social skills domain. Positive parenting positively predicted concurrent (age 6) overall social skills for children with SL/LL genotypes, but not the SS genotype. However, for the SS group only, age 6 positive parenting positively predicted prospective growth in social responsibility, although negative parenting positively predicted growth in social cooperation. Findings suggest that 5-HTTLPR may signal differential sensitivities to parenting styles and patterns of social development, which may help to inform targeted intervention approaches to enhance person-environment fit.

Although parenting behavior and friendship quality predict adolescent externalizing behaviors (EBs), individual differences in temperament may differentially affect susceptibility to these factors over time. In a multi-method and multi-informant study of 141 children followed prospectively from toddlerhood to adolescence, we tested the independent and interactive associations of age 3 reactive temperament (e.g., negative emotionality) and age 13 observed parenting (i.e., positive and negative behavior) and friendship (i.e., conflict and warmth), with multi-informant ratings of age 15 aggression and rule-breaking behavior. Negative parenting predicted growth in parent-rated EB, but only for adolescents with early reactive temperament. Temperament did not affect sensitivity to positive parenting or friendship. Results are discussed in the context of differential susceptibility theory and intervention implications for adolescents.

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.