The ecocultural context and child behavior problems: A qualitative analysis in rural Nepal.

Commonly used paradigms for studying child psychopathology emphasize individual-level factors and often neglect the role of context in shaping risk and protective factors among children, families, and communities. To address this gap, we evaluated influences of ecocultural contextual factors on definitions, development of, and responses to child behavior problems and examined how contextual knowledge can inform culturally responsive interventions. We drew on Super and Harkness' "developmental niche" framework to evaluate the influences of physical and social settings, childcare customs and practices, and parental ethnotheories on the definitions, development of, and responses to child behavior problems in a community in rural Nepal. Data were collected between February and October 2014 through in-depth interviews with a purposive sampling strategy targeting parents (N = 10), teachers (N = 6), and community leaders (N = 8) familiar with child-rearing. Results were supplemented by focus group discussions with children (N = 9) and teachers (N = 8), pile-sort interviews with mothers (N = 8) of school-aged children, and direct observations in homes, schools, and community spaces. Behavior problems were largely defined in light of parents' socialization goals and role expectations for children. Certain physical settings and times were seen to carry greater risk for problematic behavior when children were unsupervised. Parents and other adults attempted to mitigate behavior problems by supervising them and their social interactions, providing for their physical needs, educating them, and through a shared verbal reminding strategy (samjhaune). The findings of our study illustrate the transactional nature of behavior problem development that involves context-specific goals, roles, and concerns that are likely to affect adults' interpretations and responses to children's behavior. Ultimately, employing a developmental niche framework will elucidate setting-specific risk and protective factors for culturally compelling intervention strategies.

The Role of TET Proteins in the Epigenetic Regulation of Neural Gene Expression and Behavior

Understanding how genes affect behavior is critical to develop precise therapies for human behavioral disorders. The ability to investigate the relationship between genes and behavior has been greatly advanced over the last few decades due to progress in gene-targeting technology. Recently, the Tet gene family was discovered and implicated in epigenetic modification of DNA methylation by converting 5-methylcytosine to 5-hydroxymethylcytosine (5hmC). 5hmC and its catalysts, the TET proteins, are highly abundant in the postnatal brain but with unclear functions. To investigate their neural functions, we generated new lines of Tet1 and Tet3 mutant mice using a gene targeting approach. We designed both mutations to cause a frameshift by deleting the largest coding exon of Tet1 (Tet1Δe4) and the catalytic domain of Tet3 (Tet3Δe7-9). As Tet1 is also highly expressed in embryonic stem cells (ESCs), we generated Tet1 homozygous deleted ESCs through sequential targeting to compare the function of Tet1 in the brain to its role in ESCs. To test our hypothesis that TET proteins epigenetically regulate transcription of key neural genes important for normal brain function, we examined transcriptional and epigenetic differences in the Tet1Δe4 mouse brain. The oxytocin receptor (OXTR), a neural gene implicated in social behaviors, is suggested to be epigenetically regulated by an unknown mechanism. Interestingly, several human studies have found associations between OXTR DNA hypermethylation and a wide spectrum of behavioral traits and neuropsychiatric disorders including autism spectrum disorders. Here we report the first evidence for an epigenetic mechanism of Oxtr transcription as expression of Oxtr is reduced in the brains of Tet1Δe4-/- mice. Likewise, the CpG island overlapping the promoter of Oxtr is hypermethylated during early embryonic development and persists into adulthood. We also discovered altered histone modifications at the hypermethylated regions, indicating the loss of TET1 has broad effects on the chromatin structure at Oxtr. Unexpectedly, we discovered an array of novel mRNA isoforms of Oxtr that are selectively reduced in Tet1Δe4-/- mice. Additionally, Tet1Δe4-/- mice display increased agonistic behaviors and impaired maternal care and short-term memory. Our findings support a novel role for TET1 in regulating Oxtr expression by preventing DNA hypermethylation and implicate TET1 in social behaviors, offering novel insight into Oxtr epigenetic regulation and its role in neuropsychiatric disorders.

Adults with autism spectrum disorders exhibit decreased sensitivity to reward parameters when making effort-based decisions.

BACKGROUND: Efficient effort expenditure to obtain rewards is critical for optimal goal-directed behavior and learning. Clinical observation suggests that individuals with autism spectrum disorders (ASD) may show dysregulated reward-based effort expenditure, but no behavioral study to date has assessed effort-based decision-making in ASD. METHODS: The current study compared a group of adults with ASD to a group of typically developing adults on the Effort Expenditure for Rewards Task (EEfRT), a behavioral measure of effort-based decision-making. In this task, participants were provided with the probability of receiving a monetary reward on a particular trial and asked to choose between either an "easy task" (less motoric effort) for a small, stable reward or a "hard task" (greater motoric effort) for a variable but consistently larger reward. RESULTS: Participants with ASD chose the hard task more frequently than did the control group, yet were less influenced by differences in reward value and probability than the control group. Additionally, effort-based decision-making was related to repetitive behavior symptoms across both groups. CONCLUSIONS: These results suggest that individuals with ASD may be more willing to expend effort to obtain a monetary reward regardless of the reward contingencies. More broadly, results suggest that behavioral choices may be less influenced by information about reward contingencies in individuals with ASD. This atypical pattern of effort-based decision-making may be relevant for understanding the heightened reward motivation for circumscribed interests in ASD.