Functional and Structural Neuroplasticity in Depression

Abstract

The brain has the capacity to modify itself structurally and functionally, to adapt to novel circumstances. Adaptive changes in neural circuitry that become intransigent, such as continued hypervigilance after resolution of a threat situation, become maladaptive and may facilitate development of psychiatric disorders such as Major Depressive Disorder (MDD). Although MDD pathogenesis is unclear, hypothalamic-pituitary-adrenal axis dysregulation may facilitate the neuroplastic changes observed in MDD. Whether these neuroplastic changes facilitate the development of MDD or develop due to MDD remains unclear. The characterization of neuroplastic changes in MDD has resulted in sometimes contradictory findings. There are gaps in understanding the timing of neuroplastic changes in MDD, and how and when they are affected by antidepressant treatment. Characterization of neuroplasticity in MDD may uncover different phenotypes and aid in the discovery of a predictive biomarker of antidepressant treatment response. This dissertation presents the results of a series of neuroimaging studies. Chapter 1 provides an introduction to neuroplasticity and MDD. In Chapter 2 results of a study examining hippocampal memory function in treatment naïve patients with MDD are presented. Chapter 3 exhibits findings from a study examining effects of an acute tryptophan depletion paradigm in midlife women receiving estrogen-based treatment on an emotional conflict task. Chapter 4 discusses results from an examination of unmedicated patients with MDD and healthy control participants on an emotional conflict task. Chapter 5 presents longitudinal data of the sample from Chapter 4, and the effect of 8 weeks of treatment with antidepressant escitalopram on performance on an emotional conflict task. In Chapter 6 a case study is presented of a patient with long-standing overt ventriculomegaly, whose chief complaint was of mood and cognitive impairments. Chapter 7 summarizes the findings and contributions of this body of research and discusses clinical implications and future directions.