Background: Up to 55% of patients administered ketamine, experience an emergence phenomena (EP) that closely mimics schizophrenia and increases their risk of injury. While genetics accounts for about 50% of severe adverse drug reactions, no studies have investigated genetic association of ketamine-induced EP in healthy patients. Ketamine is metabolized by CYP 2B6 enzymes and CYP 2B^8^ allele significantly alter ketamine metabolism. In addition, ketamine exerts most of its effects by inhibiting the N-methyl-D-aspartate receptor (NMADR), and NMDAR genes (GRIN2B) are associated with learning and memory impairment and schizophrenia. Purpose: To investigate the relationship between CYP2B6*6 and GRIN2B single nucleotide polymorphisms (SNPs) and ketamine-induced emergence phenomena (EP). Methods: This cross-sectional pharmacogenetic study recruited 75 patients having minor orthopedic, hand, foot, anorectal surgeries from two outpatient surgical centers. EP was measured with the Clinician Administered Dissociative State Scale (CADSS). DNA was genotyped using standard Taqman assays and protocols. Genetic association of CYP2B6*6 and GRIN2B (rs1019385 & rs1806191) SNPs and ketamine induced EP occurrence and severity were tested using multivariate logistic and linear regression, adjusting for age, ketamine dose, duration of anesthesia, and time since ketamine administration. Results: Forty-seven patients (63%) received ketamine and were genotyped. Nineteen EP cases were identified (CADSS > 4), leaving 28 non-EP controls. For our population, CADSS has an internal consistency reliability Cronbach’s alpha of 0.82, and could reliably distinguish ketamine from non-ketamine cases. Occurrence and severity of EP were not associated with CYP2B6*6 or GRIN2B (p > 0.1). Models removing genotype and containing age, ketamine dose, duration of v anesthesia, and time since ketamine administration significantly predicted EP occurrence (p = 0.001) and severity (p = 0.007). Presence and severity of EP did not affect patient satisfaction with care. Discussion: Younger age, higher dose and longer duration of anesthesia significantly predicted EP occurrence and severity among our sample. This study provides effect size estimates useful for the design of adequately powered future genetic association studies. The feasibility of recruitment from patients undergoing elective, outpatient surgeries and ease of post-operative EP assessment with CADSS supports our approach. However, the small sample size may have limited about ability to determine significant differences. Conclusion: Fully powered studies are needed to investigate this important phenomena. Determining factors for anesthesia-related EP symptoms may reduce risks and costs associated with this adverse medication effect.

Alcohol consumption among college students is a well-established phenomenon, as is the observation that they often do not abide by safe consumption practices. Of particular concern is the association between college students’ heavy drinking practices, reduced understanding and practice of sexual consent, and sexual aggression (e.g., coercion, unwanted physical contact, or rape). The aim of this study was to expand the current literature by assessing the degree to which college students’ self report of no, low/moderate, and heavy alcohol consumption was associated with (1) self reports of experiencing or committing sexually aggressive behavior, and (2) their understanding of what constitutes sexual consent between individuals. Understanding these issues may assist with the development of future prevention programs aimed at reducing the link between college students’ consumption of alcohol and risky sexual behaviors.

Experiencing the death of a family member at a young age is a confusing time for many children. Some clinicians have reported that parental death is the most stressful life event for children, and some studies have traced adults' mental health difficulties to unresolved childhood grief (Balk, 1983; Krahnstoever, 2006). Despite the hardships endured after a family member's death, some children manage to endure the pain of loss better than others because they are resilient due to a variety of protective factors (Masten, 2003; Bonanno, 2004). The present study examined the relationships between childhood grief, potential protective factors (social support, physical and academic self-concept, parent-child relationship quality) and adolescent outcomes (depression, social satisfaction, and academic achievement). Longitudinal data from the National Institute of Child Health and Human Development (NICHD) Study of Early Child Care (SECC) was utilized in the present study. The sample consisted of 1,364 children, including 261 children who experienced the death of at least one family member in third or fifth grade. There were twelve moderation analyses that were used to examine buffering effects in the present study. Findings in the present study did not support the hypotheses that the psychosocial factors examined could be protective factors between experiencing the death of a family member and the adolescent outcomes examined. Results also revealed a significant main effect of social support, parent-child relationship quality, and physical and academic self-concept whereby those with higher levels of these psychosocial factors tend to have lower levels of depression. Having higher physical and academic self-concept was found to be positively associated with academic achievement. Contrary to what might be expected, a main effect of having higher levels of social support, parent-child relationship quality, physical self-concept, and academic self-concept were associated with lower levels of social satisfaction. Although the hypotheses were not supported in the present study, it is still important that the topic was examined and findings from the present study can guide future research in further exploring possible protective factors for children who experienced the death of a family member.

This study investigated nicotine conditioned place preference (CPP) in two different ages of adolescence using a rodent model of schizophrenia. Both 2- and 3-chambered CPP apparatuses were used to test whether the CPP was due to an aversion to the white chamber. Animals were neontally treated with the dopamine D2/D3 agonist, quinpirole, or saline and raised to either early postweanling age (P 22) or adolescence (P 29). Rats were conditioned to prefer the white chamber using nicotine. Results showed that nicotine induced CPP and appeared to alleviate an increased stress response in D2 primed animals, which appeared to diminish over time. Additionally, adult D2 and non-D2 primed rats were tested on the elevated T-maze. Results revealed that D2 primed rats demonstrated a significant increase in unconditioned fear. This study showed that nicotine induced CPP in D2 and non-D2 primed rats regardless of age, and D2 primed rats appear to demonstrate an increase in stress levels that was alleviated by nicotine.

<p>This thesis presents research investigating structural neural correlates of major depressive disorder (MDD). Although there are clear clinical differences between early- and late-onset MDD, they are still subject to the same diagnostic criteria and treatment strategy. Whether these differences translate into differences in cortical structure was examined in this study. By directly comparing early-onset (EOD) and late-onset (LOD) patients, we test whether age-of-onset results in changes in the extent or spatial pattern of cortical thinning.</p> <p>Chapter 1 provides a general background on the cerebral cortex, followed with a focus on cortical thickness. Chapter 2 presents a comprehensive review of the clinical and neurobiological literature on major depressive disorder as it pertains to age-of-onset. Three working hypotheses regarding the differences between early- and late-onset depression are presented and discussed.</p> <p>The results presented in this thesis show that there are both differences and similarities in cortical thickness between patients with EOD and LOD, with differences reflecting spatial extent, region-specificity, and magnitude of thickness differences. We confirmed the hypothesis of greater thinning in the dorsal lateral prefrontal cortex in depressed patients compared to healthy controls. We also correlated cortical thickness with clinical variables, which resulted in the finding of a positive correlation in the posterior cingulate cortex with illness severity.</p> <p>Few studies have used age-of-onset as a factor, which may account for some of the heterogeneity and inconsistent results seen in studies of MDD. We found that depression onset in early life is associated with greater disturbances in cortical thickness than LOD, possibly reflecting atypical development. These results provide novel insights into vulnerability and how development of depression is differentially affected by age.</p> / Master of Science (MSc)

This study tested the utility of three different models of personality, namely the social and personality model, the pathological personality traits model, and the psychological dysregulation model, in predicting overt aggression, relational aggression, and delinquency in a sample of detained boys (ages 12 to 18; M age = 15.31; SD = 1.16). Results indicated that the three personality approaches demonstrated different unique associations with aggression and delinquency. The psychological dysregulation approach, composed of behavioral dysregulation, emotional dysregulation, and cognitive dysregulation, emerged as the overall best predictor of overt aggression, relational aggression, and delinquency. After controlling for the Big Five personality traits, psychological dysregulation accounted for significant variance in overt aggression and delinquency, but not relational aggression. After controlling for callous-unemotional traits and narcissistic traits, psychological dysregulation also accounted for significant variance in overt aggression, relational aggression, and delinquency. Psychological dysregulation did not account for significant variance in aggression or delinquency after controlling for borderline traits. The pathological personality traits approach, comprised of callous-unemotional traits, narcissistic traits, and borderline traits performed second best. In particular, within this approach borderline traits accounted for the most unique variance, followed by narcissistic traits, then callous-unemotional traits. Borderline traits accounted for significant variance in overt aggression, relational aggression, and delinquency when controlling for the Big Five traits, but not after controlling for psychological dysregulation. Narcissistic traits only accounted for significant variance in overt aggression and relational aggression after controlling for the Big Five personality traits, but not after controlling for psychological dysregulation. CU traits only accounted for significant variance in overt aggression after controlling for the Big Five personality traits, but not after controlling for psychological dysregulation. The social and personality model, represented by the Big Five personality traits accounted for the least amount of variance in the prediction of aggression and delinquency, on its own, and when pitted against the other two personality approaches. The exception was that the Big Five personality traits accounted for significant variance in relational aggression beyond narcissistic traits, as well as psychological dysregulation. These findings have implications for assessment and intervention with aggressive and antisocial youth.

Research suggests that trauma has an impact on eating disorders. While prior research has demonstrated that the trauma from abuse has a significant impact on eating disorders, research has failed to explore other types of trauma. In addition, previous studies have stopped short of examining the impact trauma has on functioning among individuals with an eating disorder. This study aimed to address that gap in the literature. The purpose of this study is to examine whether traumatic life events impact psychosocial functioning among individuals living with an eating disorder. Furthermore, this study aimed to identify which traumas are shown to have the strongest impact on psychosocial functioning. A quantitative design was used for this investigation, using measurement scales that have been shown to be valid and reliable in measuring the constructs of trauma and psychosocial functioning among individuals with an eating disorder. Participants completed a single survey of the combined measurement scales. A non-random purposive sample was collected from online social media cites Tumblr, Facebook, eating disorder message boards, and an outpatient eating disorder treatment center. Using a study sample of N= 2,319 descriptive and inferential statistics were conducted using SPSS. Based on the results of correlation and multiple regression analyses, a statistically significant relationship was found between traumatic life events and psychosocial impairment among those with eating disorders. The findings of this study have the potential to impact the way social work policies address the relationship between trauma and eating disorders, and influence the way social work clinicians implement strategies to treat both trauma and eating psychopathology.

This thesis is an examination of euthanasia, eugenics, the ethic of patient care, and linguistic propaganda in the Second World War. The examination of euthanasia discusses not only the history and involvement of the facility at Hadamar in Germany, but also discuss the current euthanasia debate. Euthanasia in World War II arose out of the Nazi desire to cleanse the Reich and was greatly influenced by the American eugenics movement of the early 20th century. Eugenics was built up to include anyone considered undesirable and unworthy of life and killed many thousands of people before the invasion of allied troops in 1944. Paramount to euthanasia is forced sterilization, the ethic of patient care, and how the results of the research conducted on euthanasia victims before their deaths should be used. The Nazis were able to change the generally accepted terms that researchers use to describe their experiments and this change affected how modern doctors and researchers use the terms in current research. This thesis includes research conducted in Germany and the United States from varied resources.

Manipulation of stories and events expose issues of false representation and stereotyping within the mainstream media. This research examined the media’s role in shaping the behaviors and experiences of African American male athletes while using Critical Race Theory as the framework in conducting research. A focus group consisting of six former African American male student athletes was conducted. A semi-structured interview schedule was used in order to allow for open discussion. The Constant Comparison Method was instrumental in thematizing the data while QDA Miner software was used to analyze the data. The findings suggested that African American male athletes feel they are portrayed negatively in relation to leadership abilities as well as being portrayed as thugs and rappers. African American male athletes do feel pressured to challenge certain stereotypes presented by the media in order to become better role models for the African American community. Future research should explore the media’s impact on younger generations of African American male athletes as well as African American female athletes to compare whether similarities exists between the groups.

The dissertation describes a novel method for plant drug discovery based on mutation and selection of plant cells. Despite the industry focus on chemical synthesis, plants remain a source of potent and complex bioactive metabolites. Many of these have evolved as defensive compounds targeted on key proteins in the CNS of herbivorous insects, for example the insect dopamine transporter (DAT). Because of homology with the human DAT protein some of these metabolites have high abuse potential, but others may be valuable in treating drug dependence. This dissertation redirects the evolution of a native Lobelia species toward metabolites with greater activity at this therapeutic target, i.e. the human DAT. This was achieved by expressing the human DAT protein in transgenic plant cells and selecting gain-of-function mutants for survival on medium containing a neurotoxin that is accumulated by the human DAT. This created a sub-population of mutants with increased DAT inhibitory activity. Some of the active metabolites in these mutants are novel (i.e. not detectable in wild-type cells). Others are cytoprotective, and also protect DAergic neurons against the neurotoxin. This provides proof-of-concept for a novel plant drug discovery platform, which is applicable to many different therapeutic target proteins and plant species.