Indiana University-Purdue University Indianapolis (IUPUI) / The time course and biological mechanisms by which breast cancer (BC) and/or alterations in estrogen status lead to cognitive and brain changes remain unclear. The studies presented here use neuroimaging, cognitive testing, genetics, and biomarkers to investigate how post-chemotherapy interval (PCI), chemotherapy-induced amenorrhea (CIA), and genetic variation in the estrogen pathway affect the brain. Chapter 1 examines the association of post-chemotherapy interval (PCI) with gray matter density (GMD) and working memory-related brain activation in BC survivors (mean PCI 6.4, range 3-10 years). PCI was positively associated with GMD and activation in the right frontal lobe, and GMD in this region was correlated with global neuropsychological function. In regions where BC survivors showed decreased GMD compared to controls, this was inversely related to oxidative DNA damage and learning and memory scores. This is the first study to show neural effects of PCI and relate DNA damage to brain alterations in BC survivors. Chapter 2 demonstrates prospectively, in an independent cohort, decreased combined magnitudes of brain activation and deactivation from pre-to post-chemotherapy in patients undergoing CIA compared to both postmenopausal BC patients undergoing chemotherapy and healthy controls. CIA’s change in activity magnitude was strongly correlated with change in processing speed, suggesting this activity increase reflects effective cognitive compensation. These results demonstrate that the pattern of change in brain activity from pre- to post-chemotherapy varies according to pre-treatment menopausal status. Chapter 3 presents the effects of variation in ESR1, the gene that codes for estrogen receptor-α, on brain structure in healthy older adults. ESR1 variation was associated with hippocampus and amygdala volumes, particularly in females. Single nucleotide polymorphism (SNP) rs9340799 influenced cortical GMD and thickness differentially by gender. Apolipoprotein E (APOE)-ε4 carrier status modulated the effect of SNP rs2234693 on amygdala volumes in women. This study showed that genetic variation in estrogen relates to brain morphology in ways that differ by sex, brain region and APOE-ε4 carrier status. The three studies presented here explore the interplay of BC, estrogen, and cognition, showing that PCI, CIA, and ESR1 genotype influence brain phenotypes. Cognitive correlates of neuroimaging findings indicate potential clinical significance of these results.

Student selection is particularly challenging in South Africa. Heterogeneous educational backgrounds require that it is necessary to assess prospective students' potential rather than their current abilities that crystallised from inadequate school education. Dynamic assessment assesses learning potential versus traditional psychometric measures, which are static measures of cognitive ability, measuring what a person has already learned. The aim was to determine the predictive validity of a selection battery. The following predictors were included in the study; matric results, Potential Index Battery, LPCAT, bridging course status and gender. The results confirmed that static measures of intelligence and matric results showed lower predictive validity than learning potential tests. The learning potential measure appeared to be a more valid predictor of academic performance and is suitable to include in a selection battery. Gender and bridging course factors did not reflect significant differences in academic performance. There were indications that students perform better in successive years of study, once they have adjusted to tertiary education. / Industrial and Organisational Psychology / M. Comm. (Industrial and Organisational Psychology)

The aim of this research was (1) to provide empirical data of learning potential and English language proficiency for work performance; (2) to establish whether race and gender influence work performance; (3) to evaluate practical utility and to propose recommendations for selection purposes. The Learning Potential Computerised Adaptive Test and the English Literacy Skills Assessment were used as measuring instruments to measure learning potential and English language proficiency respectively. Work performance data were obtained from the normal performance data system of the company where the research was conducted. ANOVA results showed differences between race and gender groupings. A regression analysis confirmed the predictive validity of learning potential and English language proficiency on work performance. The Spearman rho correlation coefficient (p < 0.05) showed a significant positive correlation between the investigated variables / Industrial and Organisational Psychology / M. A. (Industrial and Organisational Psychology)

Student selection is particularly challenging in South Africa. Heterogeneous educational backgrounds require that it is necessary to assess prospective students' potential rather than their current abilities that crystallised from inadequate school education. Dynamic assessment assesses learning potential versus traditional psychometric measures, which are static measures of cognitive ability, measuring what a person has already learned. The aim was to determine the predictive validity of a selection battery. The following predictors were included in the study; matric results, Potential Index Battery, LPCAT, bridging course status and gender. The results confirmed that static measures of intelligence and matric results showed lower predictive validity than learning potential tests. The learning potential measure appeared to be a more valid predictor of academic performance and is suitable to include in a selection battery. Gender and bridging course factors did not reflect significant differences in academic performance. There were indications that students perform better in successive years of study, once they have adjusted to tertiary education. / Industrial and Organisational Psychology / M. Comm. (Industrial and Organisational Psychology)

Indiana University-Purdue University Indianapolis (IUPUI) / The substantial interpersonal and economic costs of depression make it imperative to better understand the predictors and moderators of depressive symptoms. The ability to use social support protects people from depressive symptoms, but individuals high in attachment avoidance tend not to use others as sources of support. Research has found that attachment avoidance is related to depressive symptoms in some samples but not in others (Mikulincer & Shaver, 2007; Shea, 2011). Thus, there appear to be factors that moderate the relationship between attachment avoidance and depressive symptoms. The present study examined if cognitive abilities that facilitate effective emotion regulation strategies moderate the relationship between attachment avoidance and depressive symptoms. Using a sample of college students, attachment avoidance, cognitive abilities, depressive symptoms, and other indices of psychological distress and well-being were measured and examined for evidence of moderation via hierarchical linear regression. The hypothesis that cognitive abilities moderate the relationship between attachment avoidance and depressive symptoms was not supported (ΔR2 = 0.02, p = .68). Factors contributing to the null findings are discussed and conceptual and methodological suggestions are offered for future research.

Indiana University-Purdue University Indianapolis (IUPUI) / Down syndrome (DS) is caused by three copies of human chromosome 21 (Hsa21) and results in an array of phenotypes including intellectual disability. Ts65Dn mice, the most extensively studied DS model, have three copies of ~50% of the genes on Hsa21 and display many phenotypes associated with DS, including cognitive deficits. DYRK1A is found in three copies in humans with Trisomy 21 and in Ts65Dn mice, and is involved in a number of critical pathways including CNS development and osteoclastogenesis. Epigallocatechin-3-gallate (EGCG), the main polyphenol in green tea, inhibits Dyrk1a activity. We have shown that a three-week EGCG treatment (~10mg/kg/day) during adolescence normalizes skeletal abnormalities in Ts65Dn mice, yet the same dose did not rescue deficits in the Morris water maze spatial learning task (MWM) or novel object recognition (NOR). Others have reported that An EGCG dose of 2-3 mg per day (90mg/ml) improved hippocampal-dependent task deficits in Ts65Dn mice. The current study investigated deficits in a radial arm maze pattern separation task in Ts65Dn mice. Pattern separation requires differentiation between similar memories acquired during learning episodes; distinguishing between these similar memories is thought to depend on distinctive encoding in the hippocampus. Pattern separation has been linked to functional activity of newly generated granule cells in the dentate gyrus. Recent studies in Ts65Dn mice have reported significant reductions in adult hippocampal neurogenesis, and after EGCG treatment, enhanced hippocampal neurogenesis. Thus, it was hypothesized that Ts65Dn mice would be impaired in the pattern separation task, and that EGCG would alleviate the pattern separation deficits seen in trisomic mice, in association with increased adult hippocampal neurogenesis. At weaning, Ts65Dn mice and euploid littermates were randomly assigned to the water control, or EGCG [0.4 mg/mL], with both treatments yielding average daily intakes of ~50 mg/kg/day. Beginning on postnatal day 75, all mice were trained on a radial arm maze-delayed non-matching-to-place pattern separation task. Euploid mice performed significantly better over training than Ts65Dn mice, including better performance at each of the three separations. EGCG did not significantly alleviate the pattern separation deficits in Ts65Dn mice. After the behavioral testing commenced, animals were given ad libitum food access for five days, received a 100mg/kg injection of BrdU, and were perfused two hours later. Coronal sections through the dorsal hippocampus were processed for BrdU labeling, and cells were manually counted throughout the subgranular zone of the dentate gyrus. The euploid controls had significantly more BrdU labeled cells than Ts65Dn mice, however, EGCG does not appear to increase proliferation of the hippocampal neuroprogenitor cells. This is the first report of deficits in Ts65Dn mice on a pattern separation task. To the extent that pattern separation depends on the functional involvement of newly generated neurons in an adult dentate gyrus, this approach in Ts65Dn mice may help identify more targeted pharmacotherapies for cognitive deficits in individuals with DS.