Toddlers with Developmental Delays and Challenging Behaviors

Behavior problems and parental expectations and practices were studied in a sample of 58 toddlers with developmental disabilities who were consecutively referred to a mental health clinic. The majority of children (70.7%) exceeded the clinical cut-off score for significant behavior problems including tantrums, aggression, defiance, and hyperactivity, and 77.6% met the DSM-IV criteria for a psychiatric diagnosis with oppositional defiant disorder being the most common. Consistent with previous research, child behavior problems were related to parental use of verbal and corporal punishment and were detrimental to the quality of the parent-child relationship. A new finding was that parental expectations also were positively related to the emergence of early child behavior problems

Training Community-Based Professionals to Implement an Empirically Supported Parenting Program

Professionals representing 14 community-based organizations were trained at three different sites serving urban and rural families to implement an empirically supported parenting program for families of young children with challenging behaviors. Of the 44 practitioners trained, 23 successfully completed the program, which involved passing a knowledge test and facilitating the entire 10session program with a family. A total of 28, primarily low-income families completed the program. The family outcomes obtained by the facilitators, based on multiple pre-program and post-program measures, were comparable with those reported previously in the literature for facilitators trained in university settings. The challenges inherent in efforts to increase the community’s capacity to implement empirically supported programs are addressed

A Mental Health Clinic for Toddlers with Developmental Delays and Behavior Problems

A mental health clinic was developed for toddlers with developmental disabilities and significant behavior problems from families living in poverty. The clinic was a collaborative effort between a community-based Birth-to-Three agency and a university. The purpose of this clinic was threefold: to provide direct mental health services for these young children, to train graduate students to work with this population, and to begin to contribute to the limited research available in this area. This paper describes the clinical intake procedures and outcomes for the 81 children served by the clinic over a 2-year period. Referral concerns included tantrums, aggression, oppositional behaviors, hyperactivity, and self-injury. The children came from a diverse group of families living in poverty; single mothers with less than a high school education headed most of the households. The clinical intake included direct observations of parent–child interactions, child behavior assessments, and parental interviews and self-report measures. For the present sample, 77% of the children met the criteria for a developmental disability and nearly 70% also met the criteria for a psychiatric disorder. The most common diagnosis was oppositional defiant disorder. Discussion regarding the challenges inherent in working with families of toddlers with developmental delays and psychiatric disorders living in low-income circumstances is included

Mutations in the E2 glycoprotein and the 3\u27 untranslated region enhance chikungunya virus virulence in mice

Chikungunya virus (CHIKV) is a mosquito-transmitted alphavirus that causes debilitating musculoskeletal pain and inflammation and can persist for months to years after acute infection. Although studies of humans and experimentally infected animals suggest that CHIKV infection persists in musculoskeletal tissues, the mechanisms for this remain poorly understood. To evaluate this further, we isolated CHIKV from the serum of persistently infected Rag1 -/- mice at day 28. When inoculated into naive wild-type (WT) mice, this persistently circulating CHIKV strain displayed a capacity for earlier dissemination and greater pathogenicity than the parental virus. Sequence analysis revealed a nonsynonymous mutation in the E2 glycoprotein (E2 K200R) and a deletion within the 3' untranslated region (3'-UTR). The introduction of these changes into the parental virus conferred enhanced virulence in mice, although primary tropism for musculoskeletal tissues was maintained. The E2 K200R mutation was largely responsible for enhanced viral dissemination and pathogenicity, although these effects were augmented by the 3'- UTR deletion. Finally, studies with Irf3/Irf7 -/- and Ifnar1 -/- mice suggest that the E2 K200R mutation enhances viral dissemination from the site of inoculation independently of interferon regulatory factor 3 (IRF3)-, IRF7-, and IFNAR1-mediated responses. As our findings reveal viral determinants of CHIKV dissemination and pathogenicity, their further study should help to elucidate host-virus interactions that determine acute and chronic CHIKV infection

Early deprivation alters structural brain development from middle childhood to adolescence

Hypotheses concerning the biologic embedding of early adversity via developmental neuroplasticity mechanisms have been proposed on the basis of experimental studies in animals. However, no studies have demonstrated a causal link between early adversity and neural development in humans. Here, we present evidence from a randomized controlled trial linking psychosocial deprivation in early childhood to changes in cortical development from childhood to adolescence using longitudinal data from the Bucharest Early Intervention Project. Changes in cortical structure due to randomization to foster care were most pronounced in the lateral and medial prefrontal cortex and in white matter tracts connecting the prefrontal and parietal cortex. Demonstrating the causal impact of exposure to deprivation on the development of neural structure highlights the importance of early placement into family-based care to mitigate lasting neurodevelopmental consequences associated with early-life deprivation

Forced Abstinence from Cocaine Self-Administration is Associated with DNA Methylation Changes in Myelin Genes in the Corpus Callosum: a Preliminary Study

Background: Human cocaine abuse is associated with alterations in white matter integrity revealed upon brain imaging, an observation that is recapitulated in an animal model of continuous cocaine exposure. The mechanism through which cocaine may affect white matter is unknown and the present study tested the hypothesis that cocaine self-administration results in changes in DNA methylation that could result in altered expression of several myelin genes that could contribute to the effects of cocaine on white matter integrity. Methods: In the present study, we examined the impact of forced abstinence from cocaine self-administration on chromatin associated changes in white matter. To this end, rats were trained to self-administer cocaine (0.75 mg/kg/0.1 mL infusion) for 14 days followed by forced abstinence for 1 day (n = 6) or 30 days (n = 6) before sacrifice. Drug-free, sham surgery controls (n = 7) were paired with the experimental groups. Global DNA methylation and DNA methylation at specific CpG sites in the promoter regions ofmyelin basic protein (Mbp), proteolipid protein-1 (Plp1), and SRY-related HMG-box-10 (Sox10) genes were analyzed in DNA extracted from corpus callosum. Results: Significant differences in the overall methylation patterns of the Sox10 promoter region were observed in the corpus callosum of rats at 30 days of forced abstinence from cocaine self-administration relative to sham controls; the −189, −142, −93, and −62 CpG sites were significantly hypomethylated point-wise at this time point. After correction for multiple comparisons, no differences in global methylation or the methylation patterns of Mbp or Plp1 were found. Conclusion: Forced abstinence from cocaine self-administration was associated with differences in DNA methylation at specific CpG sites in the promoter region of the Sox10 gene in corpus callosum. These changes may be related to reductions in normal age related changes in DNA methylation and could be a factor in white matter alterations seen after withdrawal from repeated cocaine self-administration. Further research is warranted examining the effects of cocaine on DNA methylation in white matter