Browsing by Subject "ASD"

Now showing 1 - 5 of 5
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    Differential Methylation Profile in Fragile X Syndrome-Prone Offspring Mice after in Utero Exposure to Lactobacillus Reuteri
    (MDPI, 2022-07-22) AlOlaby, Reem R.; Zafarullah, Marwa; Barboza, Mariana; Peng, Gang; Varian, Bernard J.; Erdman, Susan E.; Lebrilla, Carlito; Tassone, Flora; Medical and Molecular Genetics, School of Medicine
    Environmental factors such as diet, gut microbiota, and infections have proven to have a significant role in epigenetic modifications. It is known that epigenetic modifications may cause behavioral and neuronal changes observed in neurodevelopmental disabilities, including fragile X syndrome (FXS) and autism (ASD). Probiotics are live microorganisms that provide health benefits when consumed, and in some cases are shown to decrease the chance of developing neurological disorders. Here, we examined the epigenetic outcomes in offspring mice after feeding of a probiotic organism, Lactobacillus reuteri (L. reuteri), to pregnant mother animals. In this study, we tested a cohort of Western diet-fed descendant mice exhibiting a high frequency of behavioral features and lower FMRP protein expression similar to what is observed in FXS in humans (described in a companion manuscript in this same GENES special topic issue). By investigating 17,735 CpG sites spanning the whole mouse genome, we characterized the epigenetic profile in two cohorts of mice descended from mothers treated and non-treated with L. reuteri to determine the effect of prenatal probiotic exposure on the prevention of FXS-like symptoms. We found several genes involved in different neurological pathways being differentially methylated (p ≤ 0.05) between the cohorts. Among the key functions, synaptogenesis, neurogenesis, synaptic modulation, synaptic transmission, reelin signaling pathway, promotion of specification and maturation of neurons, and long-term potentiation were observed. The results of this study are relevant as they could lead to a better understanding of the pathways involved in these disorders, to novel therapeutics approaches, and to the identification of potential biomarkers for early detection of these conditions.
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    The impact of personality traits on outcomes of caregivers of individuals with Autism Spectrum Disorder in the transition period
    (2017) Yu, Yue; McGrew, John H.
    The study examined the impact of the “big 5” personality traits on caregiver burden during the period when individuals with ASD transition from high school. Participants (N = 117) were caregivers of individuals with ASD who either will graduate within two years or graduated from high school within the past two years. Participants completed questionnaires measuring study variables predicted to be associated with caregiver burden as guided by the Double ABCX model of family adaptation, i.e., autism symptom severity, problem behaviors, pile-up of life demands, personality traits, social support, cognitive appraisals, and coping strategies. Primary caregivers reported moderate burden in the transition period. Specifically, although caregivers experienced stress in the transition period, they were less overwhelmed than the period when one’s child first receive the ASD diagnosis. Increased problem behaviors, higher neuroticism, lower extraversion, conscientiousness, and agreeableness, lower levels of social support, fewer use of challenge appraisals, and greater use of threat appraisals and passive-avoidance coping strategies predicted greater caregiver burden. Passive-avoidance coping mediated the relationship between caregiving stress and four personality traits respectively (i.e., neuroticism, extraversion, conscientiousness, and agreeableness). The results support the potential importance of personality traits in explaining differences in caregiver stress in families of those with ASD and further indicated that the association between personality and burden was mediated by caregivers’ use of maladaptive coping strategies, i.e., passive-avoidance coping. The findings also have potential applicability for interventions to reduce caregiver burden. Several factors were identified that could help alleviate the stress. For example, parents should be encouraged to avoid using threat appraisals and passive-avoidance coping strategies. In addition, interventions could be developed to provide support or strategies to parents to handle child’s behavioral problems and thus reduce stress.
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    Neurodevelopmental disorders and microcephaly: how apoptosis, the cell cycle, tau and amyloid-β precursor protein APPly
    (Frontiers Media, 2023-09-22) Sokol, Deborah K.; Lahiri, Debomoy K.; Neurology, School of Medicine
    Recent studies promote new interest in the intersectionality between autism spectrum disorder (ASD) and Alzheimer’s Disease. We have reported high levels of Amyloid-β Precursor Protein (APP) and secreted APP-alpha (sAPP a ) and low levels of amyloid-beta (Aβ) peptides 1–40 and 1–42 (Aβ40, Aβ42) in plasma and brain tissue from children with ASD. A higher incidence of microcephaly (head circumference less than the 3rd percentile) associates with ASD compared to head size in individuals with typical development. The role of Aβ peptides as contributors to acquired microcephaly in ASD is proposed. Aβ may lead to microcephaly via disruption of neurogenesis, elongation of the G1/S cell cycle, and arrested cell cycle promoting apoptosis. As the APP gene exists on Chromosome 21, excess Aβ peptides occur in Trisomy 21-T21 (Down’s Syndrome). Microcephaly and some forms of ASD associate with T21, and therefore potential mechanisms underlying these associations will be examined in this review. Aβ peptides’ role in other neurodevelopmental disorders that feature ASD and acquired microcephaly are reviewed, including dup 15q11.2-q13, Angelman and Rett syndrome.
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    Shared and divergent mental health characteristics of ADNP-, CHD8- and DYRK1A-related neurodevelopmental conditions
    (Springer Nature, 2024-04-15) Neuhaus, Emily; Rea, Hannah; Jones, Elizabeth; Benavidez, Hannah; Miles, Conor; Whiting, Alana; Johansson, Margaret; Eayrs, Curtis; Kurtz‑Nelson, Evangeline C.; Earl, Rachel; Bernier, Raphael A.; Eichler, Evan E.; Pediatrics, School of Medicine
    Background: Neurodevelopmental conditions such as intellectual disability (ID) and autism spectrum disorder (ASD) can stem from a broad array of inherited and de novo genetic differences, with marked physiological and behavioral impacts. We currently know little about the psychiatric phenotypes of rare genetic variants associated with ASD, despite heightened risk of psychiatric concerns in ASD more broadly. Understanding behavioral features of these variants can identify shared versus specific phenotypes across gene groups, facilitate mechanistic models, and provide prognostic insights to inform clinical practice. In this paper, we evaluate behavioral features within three gene groups associated with ID and ASD - ADNP, CHD8, and DYRK1A - with two aims: (1) characterize phenotypes across behavioral domains of anxiety, depression, ADHD, and challenging behavior; and (2) understand whether age and early developmental milestones are associated with later mental health outcomes. Methods: Phenotypic data were obtained for youth with disruptive variants in ADNP, CHD8, or DYRK1A (N = 65, mean age = 8.7 years, 40% female) within a long-running, genetics-first study. Standardized caregiver-report measures of mental health features (anxiety, depression, attention-deficit/hyperactivity, oppositional behavior) and developmental history were extracted and analyzed for effects of gene group, age, and early developmental milestones on mental health features. Results: Patterns of mental health features varied by group, with anxiety most prominent for CHD8, oppositional features overrepresented among ADNP, and attentional and depressive features most prominent for DYRK1A. For the full sample, age was positively associated with anxiety features, such that elevations in anxiety relative to same-age and same-sex peers may worsen with increasing age. Predictive utility of early developmental milestones was limited, with evidence of early language delays predicting greater difficulties across behavioral domains only for the CHD8 group. Conclusions: Despite shared associations with autism and intellectual disability, disruptive variants in ADNP, CHD8, and DYRK1A may yield variable psychiatric phenotypes among children and adolescents. With replication in larger samples over time, efforts such as these may contribute to improved clinical care for affected children and adolescents, allow for earlier identification of emerging mental health difficulties, and promote early intervention to alleviate concerns and improve quality of life.
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    Using a model of family adaptation to examine outcomes of caregivers of individuals with autism spectrum disorder transitioning into adulthood
    (Elsevier, 2018-10) Yu, Yue; McGrew, John H.; Rand, Kevin L.; Mosher, Catherine E.; Psychology, School of Science
    Background The study examined the burden of caring for individuals with autism spectrum disorder (ASD) transitioning from high school and factors associated with burden derived from the Double ABCX model of family adaptation (i.e., autism symptom severity, problem behaviors, pile-up life demands, personality traits, social support, cognitive appraisals, and coping strategies). In particular, we were interested in the potential association between the “big 5” personality traits and burden. Method Participants (N = 105) were caregivers of individuals with ASD within two years pre- or post-graduation from high school. Results Primary caregivers reported moderate levels of burden. As hypothesized, burden was significantly associated with both child (i.e., increased autism symptom severity and problem behaviors) and caregiver characteristics (i.e., greater neuroticism, lower levels of extraversion, conscientiousness, agreeableness, and social support, and increased use of threat appraisals and passive-avoidance coping strategies). Using multiple regression, increased child behavior problems and increased caregiver use of passive-avoidance coping were identified as independent predictors of burden. Passive-avoidance coping mediated the relationship between caregiver burden and individual personality traits (i.e., neuroticism, extraversion, conscientiousness). Conclusions The results suggest that proximal variables, such as caregivers’ use of maladaptive coping strategies, explain the associations between burden and personality. Suggestions for interventions to relieve burden are discussed.