Search

Background and Objective: Autism spectrum disorder (ASD) is a heterogeneous disorder. Research has explored potential ASD subgroups with preliminary evidence supporting the existence of behaviorally and genetically distinct subgroups; however, research has yet to leverage machine learning to identify phenotypes on a scale large enough to robustly examine treatment response across such subgroups. The purpose of the present study was to apply Gaussian Mixture Models and Hierarchical Clustering to identify behavioral phenotypes of ASD and examine treatment response across the learned phenotypes.Materials and Methods: The present study included a sample of children with ASD (N = 2400), the largest of its kind to date. Unsupervised machine learning was applied to model ASD subgroups as well as their taxonomic relationships. Retrospective treatment data were available for a portion of the sample (n  = 1034). Treatment response was examined within each subgroup via regression.Results: The application of a Gaussian Mixture Model revealed 16 subgroups. Further examination of the subgroups through Hierarchical Agglomerative Clustering suggested 2 overlying behavioral phenotypes with unique deficit profiles each composed of subgroups that differed in severity of those deficits. Furthermore, differentiated response to treatment was found across subtypes, with a substantially higher amount of variance accounted for due to the homogenization effect of the clustering.Discussion: The high amount of variance explained by the regression models indicates that clustering provides a basis for homogenization, and thus an opportunity to tailor treatment based on cluster memberships. These findings have significant implications on prognosis and targeted treatment of ASD, and pave the way for personalized intervention based on unsupervised machine learning. [ABSTRACT FROM AUTHOR]

The percentage of children in the United States with obesity has more than tripled since the 1970s. Despite considerable work in this area, there has been limited success in the long-term treatment and prevention of childhood obesity. In order for intervention approaches to be successful, it will be crucial to study individual variation and the underlying mechanisms that impact human ingestive behavior. Research in my laboratory has focused on identifying behavioral phenotypes for childhood obesity which may be used to develop targeted intervention approaches that are tailored to a child's individual predisposition. This work has included studying select appetitive traits among weight-discordant siblings and unrelated children to elucidate potential differences in children's ability to regulate short-term energy intake and susceptibility to eating in response to food cues in the environment. I am greatly honored to be the recipient of the 2017 Alan N. Epstein Research Award from the Society for the Study of Ingestive Behavior (SSIB). I want to acknowledge and express my sincere gratitude to my mentors and colleagues who have supported me and provided guidance throughout my research career and to my research team and students for their hard work on our studies. [ABSTRACT FROM AUTHOR]

A large volume of behavioral research has explored the variable number of tandem repeat (VNTR) polymorphism on the dopamine receptor D4 gene ( DRD4 ). However, findings are inconsistent and there is no agreement about what constitutes “functional” and “less functional” variants at this locus. First, we systematically review studies exploring biological differences between DRD4 VNTRs ( k = 21). Second, we systematically review studies relating DRD4 variation to behavioral traits in population-based, non-clinical samples of children and adolescents ( k = 46; N = 13,195), highlighting the various genotypic classifications previously used. Third, we use meta-analyses to examine associations of DRD4 VNTRs with five broadly-defined behavioral outcomes (externalizing and attention problems, executive function, social/emotional development, and “reactive” temperament). We identify a significant association of “longer” DRD4 variants with lower levels of executive function and social/emotional development, but not independent of the choice of genotypic classification. We suggest that until the functionality of DRD4 VNTRs is established, researchers should report all genotypic classifications to ensure full transparency and allow for further meta-analytic work. [ABSTRACT FROM AUTHOR]

Background and Aim: There is mounting evidence highlighting that Cornelia de Lange Syndrome (CdLS) and Rubinstein-Taybi Syndrome's (RSTS) behavioral phenotypes are not stable over individual developmental trajectories and that several psychiatric disorders might arise with age. Our study aims to examine the specific hallmarks of psychopathology and behavioral phenotypes in four different age ranges: infancy and toddlerhood, early childhood, middle childhood, and adolescence, in both genetic syndromes.Method: The sample included 44 patients with CdLS (48% boys, age = 6.67 ± 4.36) and 31 with RSTS (48% boys, age = 6.89 ± 4.58) recruited through follow-ups. Cognitive, behavioral, and autism assessments were carried out with Griffith's scales or the Leiter-R, the Child Behavior Checklist, and the Child Autism Rating Scales 2. Multiple ANOVA 2 × 4 were run to outline behavioral phenotypic age-related syndromic markers and ANCOVA to value the weight of IQ and ASD-related traits on the psychopathological outcome.Results: Findings showed that anxiety is a crucial phenotypic hallmark, independent of IQ but associated with autistic traits, that increases from infancy to adolescence in both CdLS and RSTS.Conclusion and Implications: Being aware of the developmental challenges that growing children are called to face is essential for drawing up proper standards of assessment turning into target age-related interventions, ensuring these patients personalized healthcare and improvement in life quality. [ABSTRACT FROM AUTHOR]

Humans are ubiquitously exposed to neurotoxicants in air pollution, causing increased risk for psychiatric outcomes. Effects of prenatal exposure to air pollution on early emerging behavioral phenotypes that increase risk of psychopathology remain understudied. We review animal models that represent analogues of human behavioral phenotypes that are risk markers for internalizing and externalizing problems (behavioral inhibition, behavioral exuberance, irritability), and identify commonalities among the neural mechanisms underlying these behavioral phenotypes and the neural targets of three types of air pollutants (polycyclic aromatic hydrocarbons, traffic-related air pollutants, fine particulate matter < 2.5 µm). We conclude that prenatal exposure to air pollutants increases risk for behavioral inhibition and irritability through distinct mechanisms, including altered dopaminergic signaling and hippocampal morphology, neuroinflammation, and decreased brain-derived neurotrophic factor expression. Future studies should investigate these effects in human longitudinal studies incorporating complex exposure measurement methods, neuroimaging, and behavioral characterization of temperament phenotypes and neurocognitive processing to facilitate efforts aimed at improving long-lasting developmental benefits for children, particularly those living in areas with high levels of exposure. • Air pollution alters dopamine, BDNF, and hippocampal structure in animal models. • Neural mechanisms of risk markers of psychopathology are vulnerable to exposure. • Exposure may increase risk for social anxiety and irritability via these mechanisms. [ABSTRACT FROM AUTHOR]

Fragile X syndrome (FXS) is a monogenic disease caused by mutations in the FMR1 gene. The Fmr1 knockout (KO) mice show many aspects of FXS-related phenotypes, and have been used as a major pre-clinical model for FXS. Although FXS occurs in both male and female patients, most studies on the mouse model use male animals. Few studies test whether gender affects the face validity of the mouse model. Here, we examined multiple behavioral phenotypes with male hemizygous and female homozygous Fmr1 KO mice on C57BL/6 background. For each behavioral paradigm, we examined multiple cohorts from different litters. We found that both male and female Fmr1 KO mice displayed significant audiogenic seizures, hyperactivity in the open field test, deficits in passive avoidance and contextual fear memory, and significant enhancement of PPI at low stimulus intensity. Male and female Fmr1 KO mice also showed more transitional movement between the lit and dark chambers in the light-dark tests. The lack of gender effects suggests that the Fmr1 KO mouse is a reasonable tool to test the efficacy of potential FXS therapies. [ABSTRACT FROM AUTHOR]

Abstract: The expression of emotions and internal states by individuals with severe or profound intellectual disabilities is a comparatively under-researched area. Comprehensive or standardized methods of assessing or understanding the emotions and internal states within this population, whose ability to communicate is significantly compromised, do not exist. The literature base will be discussed and compared to that applicable to the general population. Methods of assessing broader internal states, notably depression, anxiety, and pain within severe or profound intellectual disabilities are also addressed. Finally, this review will examine methods of assessing internal states within genetic syndromes, including hunger, social anxiety, and happiness within Prader–Willi, Fragile-X and Angelman syndrome. This will allow for identification of robust methodologies used in assessing the expression of these internal states, some of which may be useful when considering how to assess emotions within individuals with intellectual disabilities. [Copyright &y& Elsevier]

Abstract: The research literature notes both biological and operant theories of behavior disorder in individuals with intellectual disabilities. These two theories of genetic predisposition and operant reinforcement remain quite distinct; neither theory on its own is sufficient to explain challenging behavior in genetic syndromes and an integrated approach is required. This literature review integrates the two approaches by exploring how environmental factors can influence problem behavior in genetic syndromes associated with intellectual disability. Particular attention is paid to studies that describe evidence that problem behaviors in syndromes that are considered to be phenotypic are associated with other aspects of an established behavioral phenotype. The review highlights how the study of phenotype–environment interactions within syndromes can promote understanding of the aetiology of problem behaviors both within genetic syndromes and, ultimately, the wider population of individuals with severe intellectual disabilities. The review also evaluates the current status of research and the methods typically employed. Implications for intervention, future research and extending existing causal models of challenging behavior are discussed. [Copyright &y& Elsevier]

Abstract: F1 and F2 mouse hybrids derived from different parental strains are becoming a useful tool in behavioral research, underlining the importance of their in-depth behavioral phenotyping. 129S1/SvImJ (S1), C57BL/6 (B6), NMRI (N) and BALB/c (BC) mice are commonly used in behavioral neuroscience, demonstrating marked behavioral differences. Here, we assess behavioral phenotypes of male mice of S1 and several hybrid strains (S1B6, S1N, S1BC) in a battery of behavioral tests, including the open field, novel odor exposure, novelty-induced grooming, horizontal rod (Suok) and the elevated plus maze tests. In addition, we assessed aggression and social barbering in these strains. Overall, the substantial differences observed here between these strains allow us to determine the influence of different genetic backgrounds on mouse behaviors, and more fully understand how different strain-specific behaviors overlap in the F1 progeny. Our results imply complex interplay between parental genotypes in anxiety, activity, grooming, aggression and barbering of their F1 progeny, further confirming the utility of F1 hybrids in behavioral neurogenetics. [Copyright &y& Elsevier]

Abstract: An obesigenic environment is a potent force for promoting weight gain. However, not all people exposed to such an environment become obese; some remain lean. This means that some people are susceptible to weight gain (in a weight-promoting environment) and others are resistant. Identifying the characteristics of appetite control and food motivation in these two groups could throw light on the causes of weight gain and how this can be either treated or prevented. We have investigated the issue experimentally by identifying people who habitually consume a high-fat diet (greater than 43% fat energy). These individuals have been termed high-fat phenotypes. We have compared individuals, of the same age (mean=37 years old) and gender (male), who have gained weight (BMI=34) or who have remained lean (BMI=22). The susceptible individuals are characterised by a cluster of characteristics including a weak satiety response to fatty meals, a maintained preference for high-fat over low-energy foods in the post-ingestive satiety period, a strong hedonic attraction to palatable foods and to eating, and high scores on the TFEQ factors of Disinhibition and Hunger. The analysis of large databases suggests that this profile of factors contributes to an average daily positive energy balance from food of approximately 0.5 MJ. This profile of characteristics helps to define the symptomatology of a thrifty phenotype. [Copyright &y& Elsevier]

Background: The rate of habituation to food and reinforcing value of food are processes that are related to food intake and body weight. Reinforcing value of food provides an index of the motivation to eat, while habituation provides an index on how repeated presentations of food relate to reduced behavioral and physiological responses to that food.Objective: To investigate the relationship between habituation phenotypes to salty, sweet and savory foods and reinforcing value of those foods.Design: A sample of 229 8-12-year-old children at risk for obesity completed reinforcing value and habituation tasks for foods that varied in savory, sweet or salty tastes. Multivariate Group Based Trajectory Modeling was used to create four unique patterns of habitation to foods based on detailed 10 s epochs of responding for food over a 24 min task. Differences in reinforcing value of food were assessed for these habituation phenotypes.Results: Results showed a graded relationship between the overall habituation phenotypes and reinforcing value of food, as those with the relatively flat habituation phenotype found food more reinforcing than those with phenotypes that showed rapidly decelerating responding across all taste categories.Conclusions: Those who habituated slower found food more reinforcing than those with a rapid habituation phenotype. Implications of these phenotypes for understanding how habituation relates to food intake are discussed. [ABSTRACT FROM AUTHOR]