Background: Major depression is one of the most prevalent, disabling, and costly illnesses worldwide. Despite a 400% increase in antidepressant medication use since 1988, fewer than half of treated depression patients experience a clinically meaningful reduction in symptoms and uncertainty exists regarding how to successfully obtain symptom remission. Identifying homogenous subgroups based on clinically observable characteristics could improve the ability to efficiently predict who will benefit from which treatments. Methods: Latent class analysis and latent transition analysis (LTA) were applied to data from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study to explore how to efficiently identify subgroups comprised of the multiple dimensions of depression and examine changes in subgroup membership during treatment. The specific aims of this dissertation were to: 1) evaluate latent depression subgroups for men and women prior to antidepressant treatment; 2) examine transitions in these subgroups over 12 weeks of citalopram treatment; and 3) examine differences in functional impairment between women’s depression subgroups throughout treatment. Results: Four subgroups of depression were identified for men and women throughout this work. Men’s subgroups were distinguished by depression severity and psychomotor agitation and retardation. Severity, appetite changes, insomnia, and psychomotor disturbances characterized women’s subgroups. Psychiatric comorbidities, especially anxiety disorders, were related to increased odds of membership in baseline moderate and severe depression subgroups for men and women. After 12 weeks of citalopram treatment, depression severity and psychomotor agitation were related to men’s chances of improving. Severity and appetite changes were related to women’s likelihood of improving during treatment. When functional impairment was incorporated in LTA models for women, baseline functional impairment levels were related to both depression subgroups at baseline and chances of moving to a different depression subgroup after treatment. Conclusion: Depression severity, psychomotor disturbances, appetite changes, and insomnia distinguished depression subgroups in STAR*D. Gender, functional impairment, comorbid psychiatric disorders, and likelihood of transitioning to subgroups characterized by symptom improvement differed between these subgroups. The results of this work highlight how relying solely on summary symptom rating scale scores during treatment obscures changes in depression that might be informative for improving treatment response.

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)

In recent years, hypersomnia patients and researchers alike have increasingly discussed the possibility of heightened comorbidities, or co-occurrences, of autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) with the central disorders of hypersomnolence: idiopathic hypersomnia (IH) and narcolepsy (N). While a few scarce studies have investigated a link between ADHD and N, there has been no research on the co-occurrence of these conditions with IH. This study, using data from the Hypersomnia Foundation’s CoRDS Patient Registry, is the first to identify self-reported rates of ASD and ADHD diagnoses by people with idiopathic hypersomnia. Four chi-square tests were conducted to determine whether ASD or ADHD occurred at a significantly higher rate in IH than in the general population. People with IH reported ASD diagnoses at a frequency of 0.59% in the primary ASD test and 1.59% in the secondary test, while ADHD diagnoses were reported at a frequency of 25.84% in the primary ADHD test and 21.84% in the secondary test. The chi-square tests failed to confirm a statistically significant relationship, but the rate of ADHD diagnosis was high compared to general prevalence rates. Further research is required to obtain a more accurate measure of ASD’s co-occurrence with IH. The literature review for this study identified three commonalities shared by ASD, ADHD, and IH: excessive daytime sleepiness (EDS), memory and attention problems, and circadian rhythm abnormalities.

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.