Life Sciences Commons^™

The Genomics Of Autism-Related Genes Il1rapl1 And Il1rapl2: Insights Into Their Cortical Distribution, Cell-Type Specificity, And Developmental Trajectories, Jacob Weaver

MUSC Theses and Dissertations

Neuropsychiatric disorders have a significant impact on modern society. These disorders affect a large percentage of the population: schizophrenia has a world-wide prevalence of 1% and autism spectrum disorders (ASD) affects 1 in 59 school-aged children in the US. There is substantial evidence that most neuropsychiatric disorders have a genetic component. Thus, with the advent of high throughput sequencing much effort has gone into identifying genetic variants associated with these disorders. The emerging picture from these studies is a complex one where hundreds of genes with small effects interact with a varied landscape of common variants to result in disease. …

Belonging Amidst Bias: Embracing Difference On The Path To Common Humanity, Alyssia Sheikh

Mindfulness Studies Theses

The mindfulness community prioritizes self-awareness and common humanity, but is often entrapped by the idea that oneness is equivalent to sameness. This inclination for objectivity is rooted in the same neural propensities that facilitate bias; the brain is a subjective organ, however, and so neurologically speaking, bias is inevitable. This paper asks: Is striving for sameness separating us from interconnectedness? A human experience is a subjective, diverse, and variable one. The path to shared humanity and social justice co-occurs with increasing cultural humility through mindful awareness and acknowledging our subjective nature. Exploring our neurological tendency to make assumptions, we …

Spanning The Auditory System: Subcortical And Cortical Auditory Processing Of Speech Sounds In Autistic And Typically Developing Children, Erin Stephanie Misato Matsuba

Theses - ALL

Autistic individuals often report atypical sensory processing, particularly in the auditory domain. However, the neural mechanisms that produce such symptoms are poorly understood. The Speech Auditory Brainstem Response (speech-ABR) and the Mismatch Negativity (MMN) are neurophysiological measures that capture different levels of auditory processing, such that the speech-ABR reflects processing at the subcortical level and the MMN measures cortical processing. The present study integrated both techniques in a multimethod approach, which spans both subcortical and cortical processing of speech sounds in a group of autistic children (n = 11) matched on chronological age and non-verbal IQ to their typically developing …

Gastrointestinal Alterations In Two Mouse Models Associated With Social Behavior Deficits, Gracie Leamon

Undergraduate Honors Theses

The gastrointestinal (GI) tract is a diverse habitat for multiple microorganisms. Disturbances in the microbiome of the GI tract have been associated with psychiatric disorders including autism spectrum disorder (ASD). Individuals with ASD, when compared to neurotypical individuals, have demonstrated differing gut species. Also, it has been shown that microbial transplant therapies impact ASD symptoms in patients. Animal models of behaviors associated with ASD might offer insight for the actual role these microbial differences may occupy regarding symptoms. Unfortunately, ASD does not have an accepted animal model where the GI alterations have been thoroughly explored. In this study, we sought …

Numerical Cognition And Autism Spectrum Traits In Adults, Benjamin Covington

All Graduate Theses and Dissertations, Spring 1920 to Summer 2023

Evidence suggests that individuals with high-functioning autism spectrum disorder (ASD) may be particularly inclined toward math proficiency, especially in adulthood. There is also evidence, however, that many of those with an ASD struggle in math as children compared to their typically-developing peers. These ostensibly inconsistent findings may indicate that individuals with an ASD struggle with number sense, a precursor to formal math, rather than with formal math per se. This account is compatible with evidence of a specific form of neural dysregulation, excitatory/inhibitory imbalance, in ASD that results in reduced signal-to-noise ratios (SNR) for processes that occur in downstream …

Facing Fears When Fearing Faces: Binocular Rivalry Perceptual Alternation And Approach-Avoidance In College-Aged Women With Autistic Traits And A History Of Adverse Experiences, Sarah Kamhout

Undergraduate Honors Theses

Women with Autism Spectrum Conditions (ASCs) may be more likely to experience symptoms of trauma exposure due to greater likelihood of facing adverse childhood experiences (ACEs). In order to gain a better understanding of the neural mechanisms involved with ASC and PTSD in women who experience difficulty with social interactions, I examined the ability of two vision tasks-- Binocular Rivalry Perceptual Alternation (BR) and Visual Approach/Avoidance by the Self Task (VAAST)-- to predict symptoms of both conditions as well as differentiate between them. I also examined differences in response to neutral or emotional (angry or fearful) faces under both paradigms. …

The Influence Of Autism Linked Gene Topoisomerase 3b (Top3b) On Neural Development In Zebrafish, Sydney Doolittle

Honors College Theses

Autism Spectrum Disorder is a class of developmental disabilities characterized by a spectrum of social, communication, and behavioral impairments in affected individuals. Studies have shown these defects stem from abnormal brain development during critical periods during early development. The underlying genetic cause of these impairments is not well understood but is believed to be a combination of a complex pairing of genetic and environmental factors. One of the genetic factors that has been recognized to influence the phenotypic symptoms of ASD is the enzyme topoisomerase 3β (top3β.) Topoisomerases are responsible for the prevention of supercoiling during DNA replication. Top3β is …

Computational Analysis Of Non-Cpg Dna Methylation In The Mammalian Nervous System, Dennis Yawen Wu

Arts & Sciences Electronic Theses and Dissertations

Noncanonical forms of DNA methylation, especially non-CpG DNA methylation, play essential roles in the neuronal epigenome, and have only recently begun to be characterized. While most DNA methylation within mammals is found in a CG context and maintained by DNMT1, neurons contain uniquely high levels of non-CpG methylation, such that the total amounts of methylation in non-CpG contexts equals or surpasses the total amounts of methylation in CG contexts. Non-CpG methylation, unlike CpG methylation, cannot be maintained by DNMT1, and must be established by the de novo methyltransferase DNMT3A.One unique characteristic of non-CpG methylation compared to canonical CpG methylation is …

Roles Of Autism Gene Arid1b In Murine Brain Development And Behavior, Amanda L. Smith

Theses & Dissertations

Autism spectrum disorder (ASD) and intellectual disability (ID) are highly prevalent neurodevelopmental disorders characterized by social and communication deficits, stereotyped behaviors, cognitive dysfunction, and deficits in adaptive behaviors. The pathogenesis underlying these disorders remains unknown, and thus no pharmacologic or genetic therapies are currently available. Recent progress in the field has shown that haploinsufficiency of the AT-rich interactive domain-containing 1B (ARID1B) gene is a genetic cause of ASD and ID. Our lab recently developed an Arid1b knockout mouse model to better study its role in the pathogenesis of these disorders. One theory regarding the cause of neurodevelopmental disorders …

An Autism-Causing Variant Misregulates Selective Autophagy To Alter Axon Targeting And Behavior, Tyler Buddell

Theses and Dissertations

Neurodevelopmental disorders cause debilitating disruptions to the cellular mechanisms that underlie development of the brain. Unfortunately, the complexities of neurodevelopmental disorders make them difficult to study, and the molecular mechanisms perturbed by these disorders remain elusive. Better understanding of neurodevelopmental mechanisms, and the related genes involved, will likely yield new insight into neurodevelopmental disorders. A gene that has been associated with a number of neurodevelopmental disorders is the calcium voltage-gated channel subunit alpha1 C (CACNA1C) gene. Common and rare variants of the CACNA1C gene have been associated with autism and other neurodevelopmental disorders including schizophrenia, bipolar disorder and ADHD. However, …

Investigating The Role Of Integrin Beta 3 In Dendritic Arborization In The Supragranular Developing Cerebral Cortex, Zachary Logan Holley

Senior Honors Projects, 2010-2019

Integrin subunits have been implicated in axonal and dendritic outgrowth. In particular, a strong positive association has been found between mutations in integrin beta 3 (Itgb3) and autism spectrum disorder, but little is known about neuronal Itgb3 function in vivo. Many forms of autism spectrum disorder are thought to arise from dysfunctional dendritic arborization and synaptic pruning. Global knockout of Itgb3 in mice leads to autistic-like behaviors. Itgb3^-/- mice also have reduced callosal volume, a key neuroanatomical correlate of autism. Here, we test the hypothesis that Itgb3 is required for normal dendritic arborization in layer II/III pyramidal …

The Role Of Ash1l During Human Neurodevelopment, Anna Bagnell

Senior Theses

Autism spectrum disorders (ASD) are associated with defects in neuronal connectivity and are highly heritable. A significant proportion of ASD cases are of complex genetic etiology; complexity which might reflect the impact of gene-environment interactions. However, there is a gap in our understanding of the mechanisms that underlie the gene-environment interaction in autism complex etiology. Genome wide association studies in large ASD cohorts identified high risk variants associated with autism in genes that regulate histone modifications and remodel chromatin. These findings highlight the relevance of chromatin regulatory mechanisms in the pathology of ASD. Changes in Histone H3 methylation have been …

Effect Of Propionic Acid-Derivative Ibuprofen On Neural Stem Call Differentiation; A Potential Link To Autism Spectrum Disorder, Aseelia Samsam

Honors Undergraduate Theses

Propionic acid (PPA) is a short chain fatty acid that is produced by the human gut microbiome. Propionate, butyrate and acetates are the end products of the fermentation of the complex carbohydrates by human gut friendly microbiome and are being used as sources of energy in our body. PPA is used as a food preservative against molds in various daily products and has been implicated in the pathogenesis of autism. In a recent study we showed that PPA in human neuronal stem cell (NSC) culture increases the astrocyte population and decreases the neuronal number and increases the inflammatory cytokines. In …

Arid1b And Macf1 In Murine Brain Development And Behavior, Jeffrey Jay Moffat

Theses & Dissertations

Intellectual disability (ID) and autism spectrum disorder (ASD) affect between one and three percent of the global population. These disorders represent a significant emotional and financial burden for affected individuals and their families. Treatment for these conditions remains limited because many of the key molecular factors and associated pathogenic mechanisms are still poorly understood.

In this report we examine two genes related to ASD and ID, AT-rich interactive domain-containing protein 1B (ARID1B) and Microtubule-actin crosslinking factor 1 (MACF1). ARID1B is a subunit of the mammalian BRG1/BRM associated factor (BAF) chromatin-remodeling complex, which broadly regulates gene expression. ARID1B also …

Increased Contagious Itch In Children With Autism Spectrum Disorder (Asd), Molly Schineller

Senior Theses and Projects

It has been previously demonstrated that contagion of yawning and laughter is significantly reduced in individuals with Autism Spectrum Disorder (ASD) in comparison to age-matched typically developing (TD) children, but contagion of itch has not been studied in this population. In this study, 55 children with ASD and 55 TD children, all aged 9-14, were exposed to video clips depicting actors yawning, laughing, and itching. In line with previous data, children with ASD demonstrated decreased contagious yawning and laughter in comparison to their TD peers. Surprisingly, they demonstrated increased contagious itch compared to their TD peers. However, susceptibility to contagion …

Using Parent-Identified Strengths Of Autistic Children To Advance Strength-Based Intervention, Angelique Francesca Trigueros

Walden Dissertations and Doctoral Studies

Questions remain about the range of abilities autistic children possess and what constitutes effective treatment. Strength-based intervention contrasts with traditional autistic intervention approaches that focus on children's deficits. Studies on strength-based intervention approaches have not revealed how children's strengths are identified and have not used the insights of parents for this purpose. Neurodiversity serves as the conceptual framework because the tenets of neurodiversity align with those of strength-based approaches and hold that autism is a variation of the human condition rather than a disability. The purpose of this qualitative interpretive phenomenological study was to explore how the parent-identified strengths of …

Interactive Physical And Cognitive Exercise System (Ipaces™): The Neuropsychological Effects For Youth On The Autism Spectrum, Michaela Haller

Honors Theses

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder that affects 1 in 68 children in the United States (Center for Disease Control, 2016). The disorder is characterized by deficits in social interaction, verbal communication, restricted interests, and repetitive behaviors (DSM- V, 2013). While the apparent cause of ASD is biological, the diagnosis remains based on social deficits (Hapé & Frith, 1996). Exercise has been found to improve executive function for children with an Autism Spectrum Disorder, but motivation is an issue and exergames hold promise. This pilot study evaluated an interactive Physical and Cognitive Exercise System (iPACES™), wherein children pedal …

Computational Modeling Of Facial Response For Detecting Differential Traits In Autism Spectrum Disorders, Manar D. Samad

Electrical & Computer Engineering Theses & Dissertations

This dissertation proposes novel computational modeling and computer vision methods for the analysis and discovery of differential traits in subjects with Autism Spectrum Disorders (ASD) using video and three-dimensional (3D) images of face and facial expressions. ASD is a neurodevelopmental disorder that impairs an individual’s nonverbal communication skills. This work studies ASD from the pathophysiology of facial expressions which may manifest atypical responses in the face. State-of-the-art psychophysical studies mostly employ na¨ıve human raters to visually score atypical facial responses of individuals with ASD, which may be subjective, tedious, and error prone. A few quantitative studies use intrusive sensors on …

Changes In Synaptic Protein Content And Signaling In A Mouse Model Of Fragile X Syndrome, Kelly Birch, Peter W. Vanderklish Phd

Undergraduate Honors Theses

Fragile X Syndrome--the most common inherited form of intellectual disability--is characterized by low IQ, impaired social interaction, hyperactivity and impulsivity, and abnormal physical traits including an elongated face and protruding ears. Nearly half of all children with Fragile X also meet diagnostic criteria for autism spectrum disorder. Fragile X is caused by a trinucleotide repeat expansion on the X chromosome, leading to silencing of the Fragile X mental retardation gene (FMR1) and thus lack of expression of Fragile X mental retardation protein (FMRP). As a key translational suppressor, FMRP is crucial for normal neural development and synaptic function. The current …

Messenger Rna Transport And Translation Regulated By The 3' Utrs Of Dendritic Mrnas And Abnormal Alternative Splicing Of Neuroligin1 In The Fmr1 Ko Mouse Hippocampus, Tianhui Zhu

Dissertations, Theses, and Capstone Projects

Fragile X Syndrome (FXS) is one of the most commonly inherited mental retardations. It is caused by the loss of functional fragile X mental retardation protein (FMRP). Loss of functional FMRP is the most widespread single-gene cause of autism. The most prominent phenotype of FXS patients is an IQ ranging from 20 to 70. FMRP is an RNA binding protein, widely expressed in almost all tissues and highly expressed in brain. As a RNA binding protein, 85-90 % of FMRP in the brain is associated with polyribosomes. Approximately 4 % of total mRNA is associated with FMRP, which functions in …

Neurodevelopmental Defects Associated With Gestational Exposure To Low Levels Of Dbp In Mice, Françoise Sidime

Dissertations, Theses, and Capstone Projects

The etiology of autism is thought to involve the complex interplay among genetic and environmental factors. Patterns of inheritance suggest an epigenetic component to the development of autism. A variety of environmental risk factors are known to induce epigenetic changes in DNA, affecting many genes including those autism-associated genes (AAG). The plasticizer dibutyl phthalate (DBP; CAS 84-74-2) is a developmental and reproductive toxin that causes a broad range of birth defects resulting in neurological impairments.

To date, although the effect of DBP as an endocrine and a reproductive disruptor are established, there are only few studies that address the effects …

From Rainman To Rainmaker: A Presentation Of Jim’S Journey And Rapidly Advancing Technologies: Integrating Proven Behavioral Therapies With Emergent Measurement And Testing Advances Will Result In Transformational Progress In Autistic Individuals, Richard Zajac

CMC Senior Theses

The autism treatment status quo was reviewed and accompanied by a narrative contextualizing past and present progress with my younger brother Jim’s journey with the condition, sharing proposed next steps for bettering the current state of affairs in the space. The impetus for this piece was to share in the lessons of Jim’s life thus far and the revelations of those who have supported him, as well as to determine ways to create more impactful, lasting change in the limited window of early intervention therapy whilst empowering individuals on the spectrum to optimize for their skills and talents rather than …

Effects Of Ketogenic Diets On Autistic Symptoms Of Female El Mice, Subrina N. Bisnauth

Senior Theses and Projects

The ketogenic diet (KD) is a restricted carbohydrate, high fat and sufficient protein metabolic therapy that elevates ketones as an alternative fuel source, and that reduces seizures in persons with epilepsy which is often comorbid with autism. Autism is characterized by communication deficits, decreased sociability and repetitive behaviours. A restrictive KD reverses symptoms in the BTBR mouse model of autism but its severity is a factor in its clinical applicability. In a study with the EL mouse model of epilepsy and autism, sex-dependent effects were found where only females displayed the behavioural effects of the KD. In the current study, …

The Influence Of Prenatal Stress On Behaviors Associated With Schizophrenia And Autism Spectrum Disorder., Harold Bauerle

Graduate College Dissertations and Theses

Disorders such as schizophrenia (SCZ) and austism spectrum disorder (ASD) have long been associated with prenatal stress. In these three experiments, we attempted to correlate stress during gestation with behaviors considered to have good facial validity with SCZ and ASD in both juvenile and adult animals. To differentiate the effects of prenatal stress (PS) from the effects of early life stress due to a dam's behavior (MS), half of offspring animals were cross fostered to dams treated in the alternative condition as the offspring during pregnancy in experiments 2 and 3. In experiment 1, but not in 2 or 3, …

Biological Motion Processing In Typical Development And In The Autism Spectrum, Aaron Krakowski

Dissertations, Theses, and Capstone Projects

Biological motion (BM) analysis and interpretation is a fundamental process of human neurocognition that has been only minimally explored neurophysiologically. In addition to its importance in understanding the underlying roots and development of social cognition, BM processing is a prime candidate domain for exploring the underlying etiology of social cognitive disorders such as the autism spectrum.

In an initial experiment, typical adults observed BM point-light displays of a human actor (UM) as well as their spatially scrambled counterparts (SM), in both an unattended distractor task as well as an explicit attention task. Results showed a neurophysiological response manifested as three …

The Effects Of Even- And Odd-Numbered Medium Chain Triglyceride Ketogenic Diets On Autistic Behaviors In A Mouse Model, Lisa Saa

Senior Theses and Projects

BACKGROUND: A ketogenic diet (KD), which has restricted carbohydrates, sufficient protein, and a very high fat content, causes the body to switch from a glucose-based metabolism to a ketone-based metabolism. The KD has been effective at reducing seizures in epileptic patients. Autism is comorbid with epilepsy and characterized by restricted and repetitive behaviors, low sociability, and deficits in communication. A strict version of the long-chain triglyceride (LCT) KD has been effective at reducing autistic symptoms in BTBR T+tf/J, an autistic model of mice. However, a more moderate and clinically relevant version of the LCT KD has been shown to be …

The Neurodevelopment Of Basic Sensory Processing And Integration In Autism Spectrum Disorder, Alice Brown Brandwein

Dissertations, Theses, and Capstone Projects

This thesis presents three studies that together explore the neurophysiological basis for the sensory processing and integration abnormalities that have been observed in autism spectrum disorder (ASD) since the disorder was first described over half a century ago. In designing these studies we seek to fill a hole that currently exists in the research community‟s knowledge of the neurodevelopment of basic multisensory integration -- both in children with autism and as well as in those with typical development. The first study applied event related potentials (ERPs) and behavioral measures of multisensory integration to a large group of healthy participants ranging …

Magnetic Resonance Imaging Of Brain Tissue Abnormalities: Transverse Relaxation Time In Autism And Tourette Syndrome And Development Of A Novel Whole-Brain Myelin Mapping Technique, Yann Gagnon

Electronic Thesis and Dissertation Repository

The transverse relaxation time (T2) is a fundamental parameter of magnetic resonance imaging sensitive to tissue microstructure and water content, thus offering a non-invasive approach to evaluate abnormalities of brain tissue in-vivo. Prevailing hypotheses of two childhood psychiatric disorders were tested using quantitative T2 imaging and automated region of interest (ROI) analyses. In autism, the under-connectivity theory, which proposes aberrant connectivity within white matter (WM) was assessed, finding T2 to be eleveted in the frontal and parietal lobes, while dividing whole brain data into neurodevelopmentally relevant WM ROIs found increased T2 in bridging and radiate WM. In Tourette syndrome, tissue …

Btbr-Fvb Chromosome 4 Congenic Displays Rescue Of Behavior And Neuro-Anatomical Phenotypes, Jessica F. Gracias

Legacy Theses & Dissertations (2009 - 2024)

Autism is commonly called the most genetic of neuropsychiatric disorders. Currently, the only diagnostic test is a behavioral evaluation performed by trained physicians and psychologists. There is an urgent need for biomarkers to diagnose autism instead of just relying on behavior and there is also a need to understand the basis of this disorder. One of the theories is that malformation of the corpus callosum is one of the factors that lead to the behavior deficits seen in autism. This theory is based on the fact that human MRI studies have shown that the corpus callosum is absent or malformed …