The proposed experiment will investigate the effects of increased cortisol secretion on developing memory functions in preschool children with age-adjusted symptoms of depression (the primary study population in the co-sponsor's laboratory). Memory impairments and increased cortisol activity are associated with Major Depressive Disorder in adolescents and adults. Animal models of very early depression suggest that increased glucocorticoid (GC) secretion in response to stressors may occur early and continue into adulthood, supporting the hypothesis that preschool children with depressive symptoms may experience persistent, stress related increases in cortisol secretion. GCs affect neuronal metabolism, physiology, and gene expression, and recent evidence indicates that GCs inhibit neural differentiation and growth of hippocampal cells. These results highlight the essential role that GCs play in the trajectory of the developing hippocampus a subcortical structure necessary for certain types of learning and memory. The sponsor's laboratory has previously reported that elevated plasma concentrations of cortisol can produce clinically significant decreases in verbal declarative memory performance in healthy young adults. Despite these important findings, the effects of increased cortisol secretion during young childhood, a critical window for rapid memory development, remain unknown. The proposed study design will investigate the effects of increased cortisol secretion in preschool children with symptoms of depression. The long-term objective of the candidate is to investigate the influence of GCs on the development of memory functions as well as the normal trajectory of memory development in preschool children. Specifically, this study aims to 1) determine whether preschool children with symptoms of depression demonstrate increased secretion of cortisol in response to the stress of cognitive testing as compared to controls; 2) investigate performance on specific neuropsychological functions in preschool-aged children with symptoms of depression as compared to controls; 3) determine whether increases in circulating cortisol concentrations impact declarative memory performance in preschool children with or without symptoms of depression. The proposed case-control study will assess declarative memory and other elements of cognitive function, as well as salivary cortisol secretion in response to stress in preschool children with and without depressive symptoms. The assessment will be conducted in one laboratory assessment, with the assessment process being the stressor. Factors such as depression and/or increased cortisol secretion may have an early adverse impact on the normal development of memory systems in the human brain. Increasing our understanding of factors involved in early disturbances in human memory performance may provide important targets for early interventions to prevent potential short- and long- term adverse effects on brain functions relevant to the development of memory in children.
