<p> <b>Purpose:</b> Sleep-disordered breathing (SDB) is a spectrum disorder that is estimated to effect a significant proportion of the pediatric population (1-3% in USA). SDB is able to disrupt and fragment sleep through frequent arousals and intermittent hypoxia. In addition, the long term effects of SDB in pediatrics have been well-documented; decreases in intelligence quotient (IQ), executive function, school performance, and alertness have all been observed. Although surgical treatments can be quite effective, there are no widely accepted prophylactic measures to prevent SDB development. Recently, breastfeeding duration in infancy has been demonstrated to be correlated with reduced SDB (lower AHI, RAI, and higher SpO2), as well as increases in IQ, executive function, and school performance (independent of SDB). The overarching goal of this dissertation was to examine the potential effects of both breastfeeding duration and SDB severity on the neurological underpinnings associated with observed behavioral and cognitive deficits; namely, correlations with white matter structural volume and fractional anisotropy (FA) scores through diffusion tensor imaging (DTI). Here, I proposed a unique developmental hypothesis where breastfeeding may ultimately reduce SDB, enabling the preservation of rapid eye movement (REM) sleep, and leading to healthier neurological white matter development. </p><p> <b>Method:</b> Twenty-four children with SDB and 19 healthy controls were imaged using MR techniques. White matter volume was measured using the central 13 millimeters of the corpus callosum (CC). DTI of major white matter tracts was also conducted. The SDB group received neurocognitive testing to assess cognitive performance; the control group was assessed using real-world academic report cards. Finally, REM sleep was quantified in infants using overnight polysomnography (PSG), with SDB metrics and infant feeding method also measured. Results: There was no correlation between infant feeding methods and CC volume in either group, nor a significant differences between CC volumes in children with SDB versus those without. However, increased breastfeeding duration was correlated with increased left superior longitudinal fasciculus (LSLF) and left angular bundle (LAB) FA scores in healthy controls. In 8-9 month old infants, increased breastfeeding duration was also correlated with a reduced proportion of REM sleep (%TST), and children with exclusive breastfeeding had reduced SDB in infancy compared to children with any formula feeding. Finally, exclusively formula-fed infants were diagnosed with &ldquo;primary snoring&rdquo; more often than those with any amount of breastfeeding. </p><p> <b>Conclusions:</b> The findings in this dissertation revealed associations between breastfeeding, SDB, REM sleep, and white matter integrity in the brain. These results support the hypothesis that certain cognitive effects associated with SDB and infant feeding methods may have common underlying anatomical brain changes that subserve these observed phenomena.</p>

<p> Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impairments in social interaction and communication, is of unknown etiology, and has a prevalence of 1.5% in the U.S. Atypical language patterns and anatomical findings of brain asymmetry differences between neurotypical and individuals with ASD suggest involvement of brain lateralization aberrations in autism etiology. The literature suggests an increased frequency of non-right handedness (NRH) in ASD. This dissertation aimed to study the association between hand preference and ASD in a cohort of children with ASD using a large, well-designed, population-based case-control study, CHARGE (<i>CH</i>ildhood <i> A</i>utism <i>R</i>isks from <i>G</i>enetics and the <i>E</i>nvironment). </p><p> In Chapter 1, we evaluated the association between handedness and ASD in 2- to 5-year old children. Chapter 2 longitudinally evaluated handedness outcome of the children from Chapter 1 at age 7 and older. We then investigated the utility of a parent-reported handedness assessment of children at ages 2-5 years using established hand preference at age 7+ years as the gold standard. Finally, we investigated the association between the intronic variant rs7799109 on theFOXP2 gene and ASD as well as the gene&rsquo;s interaction effect on the association between NRH and ASD. </p><p> Our findings indicate that children with neurodevelopmental disorders show a delayed establishment of handedness lateralization in early stages of childhood with a subset of these children still remaining NRH at age 7 years. Language deficits in children at ages 2 to 5 years are associated with NRH and ASD, and is a determinant of NRH in ASD at age 7 years and older. Our study also supports current literature that hand preference may have genomic underpinnings in ASD.</p>

<p>Children are commonly prescribed fluoxetine to manage their depressive symptoms, although evidence suggests many fail to respond to this treatment. Recently, low doses of ketamine were shown to work as a fast-acting and long-lasting antidepressant, however, it is unclear what the long-term effects are of using ketamine in pediatric populations. Thus, this thesis examined whether early-life exposure to ketamine influences the rewarding effects of nicotine in male and female adolescent Sprague- Dawley rats using conditioned place preference. Rats were pretreated with ketamine (0.0 or 20.0 mg/kg) from postnatal day (PD) 21-30 and then assessed for nicotine (0.0, 0.03, 0.1, 0.3, or 0.6 mg/kg) preference during adolescence (PD 32-42). Results indicate that female adolescent rats find nicotine to be more rewarding than male rats, however ketamine pretreatment did not affect nicotine?s effects. These findings suggest that ketamine as an antidepressant in children and adolescents may not produce adverse increases in nicotine reward.

<p> Through a mixed methodology of hermeneutic and heuristic inquiry, this thesis examines the influence of early childhood numinous, or profound spiritual, experience on the developing psyche and its relationship to repetitive compulsion over the lifespan. A dual lens of depth psychology and neuroscience is employed to explore the interstitial spaces between theories on the numen, early psychological development, and the repetition compulsion, comparing the literature with personal and clinical examples. Findings illustrated that numinous experiences are intimately connected with repetitive symptomology and that certain individuals are genetically predisposed to numinous experience. The hypothesis was proposed that repetition compulsion engendered by early numinous experiences, and perhaps all repetition phenomena, might reflect an unconscious <i> telos</i>, or the aim of an integral part of one&rsquo;s psyche seeking expression, integration, and relationship in the world.</p><p>