Faculty Bibliography

Although the search for quantitative trait loci for behaviour remains a considerable challenge, the complicated genetic architecture of quantitative traits is beginning to be understood. The current project utilised heterogeneous stock (HS) male mice (n = 580) to investigate the genetic basis for brain weights, activity, anxiety and cognitive phenotypes. We identified 126 single nucleotide polymorphisms (SNPs) in genes involved in regulation of neurotransmitter systems, nerve growth/death and gene expression, and subsequently investigated their associations with changes in behaviour and/or brain weights in our sample. We found significant associations between four SNP-phenotype pairs, after controlling for multiple testing. Specificity protein 2 (Sp2, rs3708840), tryptophan hydroxylase 1 (Tph1, rs262731280) and serotonin receptor 3A (Htr3a, rs50670893) were associated with activity/anxiety behaviours, and microtubule-associated protein 2 (Map2, rs13475902) was associated with cognitive performance. All these genes except for Tph1 were expressed in the brain above the array median, and remained significantly associated with relevant behaviours after controlling for the family structure. Additionally, we found evidence for a correlation between Htr3a expression and activity. We discuss our findings in the light of the advantages and limitations of currently available mouse genetic tools, suggesting further directions for association studies in rodents.

OBJECTIVE:Advanced paternal age (APA) at conception has been linked with autism and schizophrenia in offspring, neurodevelopmental disorders that affect social functioning. The current study explored the effects of paternal age on social development in the general population. METHOD/METHODS:We used multilevel growth modeling to investigate APA effects on socioemotional development from early childhood until adolescence, as measured by the Strengths and Difficulties Questionnaire (SDQ) in the Twins Early Development Study (TEDS) sample. We also investigated genetic and environmental underpinnings of the paternal age effects on development, using the Additive genetics, Common environment, unique Environment (ACE) and gene-environment (GxE) models. RESULTS:In the general population, both very young and advanced paternal ages were associated with altered trajectory of social development (intercept: p = .01; slope: p = .03). No other behavioral domain was affected by either young or advanced age at fatherhood, suggesting specificity of paternal age effects. Increased importance of genetic factors in social development was recorded in the offspring of older but not very young fathers, suggesting distinct underpinnings of the paternal age effects at these two extremes. CONCLUSION/CONCLUSIONS:Our findings highlight that the APA-related deficits that lead to autism and schizophrenia are likely continuously distributed in the population.

Advanced paternal age (APA) at conception has been associated with negative outcomes in offspring, raising concerns about increasing age at fatherhood. Evidence from evolutionary and psychological research, however, suggests possible link between APA and a phenotypic advantage. We defined such advantage as educational success, which is positively associated with future socioeconomic status. We hypothesised that high IQ, strong focus on the subject of interest and little concern about 'fitting in' will be associated with such success. Although these traits are continuously distributed in the population, they cluster together in so-called 'geeks'. We used these measures to compute a 'geek index' (GI), and showed it to be strongly predictive of future academic attainment, beyond the independent contribution of the individual traits. GI was associated with paternal age in male offspring only, and mediated the positive effects of APA on education outcomes, in a similar sexually dimorphic manner. The association between paternal age and GI was partly mediated by genetic factors not correlated with age at fatherhood, suggesting contribution of de novo factors to the 'geeky' phenotype. Our study sheds new light on the multifaceted nature of the APA effects and explores the intricate links between APA, autism and talent.

Children with autism have atypical gaze behavior but it is unknown whether gaze differs during distinct types of reciprocal interactions. Typically developing children (N = 20) and children with autism (N = 20) (4-13 years) made similar amounts of eye contact with an examiner during a conversation. Surprisingly, there was minimal eye contact during interactive play in both groups. Gaze behavior was stable across 8 weeks in children with autism (N = 15). Lastly, gaze behavior during conversation but not play was associated with autism social affect severity scores (ADOS CSS SA) and the Social Responsiveness Scale (SRS-2). Together findings suggests that eye contact in typical and atypical development is influenced by subtle changes in context, which has implications for optimizing assessments of social communication skills.

Caregiver report is the most common measure of change in pediatric psychiatry. Yet, placebo response rates pose significant challenges to reliably detect a treatment response. The present study simulated an eight-week clinical trial protocol for Autism Spectrum Disorder (ASD) for the purpose of testing the feasibility and validity of several outcome measures. Twenty caregivers answered questions about their child's behavior on their smartphone each week and completed a battery of paper questionnaires during weeks one and eight. No treatment was administered. Caregivers reported a significant decrease in problem behaviors on the Aberrant Behavior Checklist (ABC) (29% decrease) and general ASD behaviors on the Social Responsiveness Scale (SRS) (7% decrease). There was also a trend of behavior improvement from smartphone questions but no significant changes in clinical ratings of core diagnostic features of ASD. Participation in a comprehensive protocol in the absence of a particular treatment significantly influenced how caregivers perceived the severity of their children's problem behaviors. These placebo-like effects represent substantial challenges for randomized controlled trials (RCTs) that use treatment as usual and have implications for future behavioral and pharmacological treatment trial designs. Autism Res 2017, 10: 1567-1572. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.

Purpose The African American church has long been recognized as a valuable partner for health interventions in the community. While an extensive literature exists documenting the potential efficacy of diabetes education programs in church settings, there has yet to be an effort to leverage spiritual beliefs and practices to promote diabetes self-management and shared decision making within a faith-based framework that is culturally tailored to the African American church. The purpose of this article is to describe the translation of a clinic-based diabetes education program into faith-based education curriculum tailored for use in the African American church. Conclusions Themes extracted from focus groups and input from a faith-based community partner provided a methodical and patient-informed foundation for culturally tailoring and piloting a diabetes self-management curriculum for the African American church setting. This study illustrates how spirituality can be incorporated into interventions to enhance health promotion and behavioral change among African Americans with diabetes. Participants in our study described how religious beliefs play an active role in many aspects of diabetes care, including self-management behaviors, coping strategies, and patient/provider communication. In addition, this intervention can serve as a model for the development of patient-centered health interventions.

Joint attention, or the shared focus of attention between objects or events and a social partner, is a crucial milestone in the development of social communication and a notable area of deficit in children with autism spectrum disorder. While valid parent-report screening measures of social communication are available, the majority of these measures are designed to assess a wide range of behaviors. Targeted assessment of joint attention and related skills is primarily limited to semi-structured, examiner-led interactions, which are time-consuming and laborious to score. The Pictorial Infant Communication Scale is an efficient parent-report measure of joint attention that can be used as a complement to structured assessments in fully characterizing early social communication development. This study examined the psychometric properties of the Pictorial Infant Communication Scale. Results revealed a high degree of internal consistency and strong intercorrelations between subscales. Additionally, confirmatory factor analysis supported a three-factor model of joint attention. Furthermore, significant correlations between the Pictorial Infant Communication Scale and direct clinical measures of child joint attention, language skills, and autism spectrum disorder symptom severity were suggestive of concurrent validity. Findings suggest that the Pictorial Infant Communication Scale is a promising tool for measuring joint attention skills in preschool-aged children with autism spectrum disorder.