Neural Correlates of Premenstrual Dysphoric Disorder in Women with Bipolar Disorder

Abstract

Introduction: Women with bipolar disorder (BD) have higher rates of premenstrual syndrome (PMS) and premenstrual dysphoric disorder (PMDD). The primary goal of this thesis was to examine the neural correlates of bipolar disorder and comorbid PMDD and identify changes in brain structure or function that may mediate emotional and cognitive dysregulation in the late luteal phase. Results: In healthy women with no history of PMDD, absolute levels of estradiol, progesterone, allopregnanolone and dehydroepiandrosterone sulfate (DHEAS) were correlated with patterns of functional coupling in multiple regions associated with emotional and cognitive processes, in the mid-follicular and late luteal menstrual phases. A systematic review of the literature on resting state functional connectivity (Rs-FC) in BD during euthymia highlighted consistent patterns of resting state functional connectivity (Rs-FC) using ICA and SBA; including stability of the default mode network (DMN), salience network (SN) and fronto-parietal network (FPN) relative to controls. Available literature largely failed to control for sex, menstrual cycle phase or menstrual cycle disorders. Thus, we conducted the first fMRI studies to control for menstrual cycle phase in BD. During the mid-follicular phase, we found increased Rs-FC between critical nodes of the default mode and frontoparietal networks in BD compared to controls and increased functional connectivity between the somatosensory cortex and the insular cortex, inferior prefrontal gyrus and frontal orbital cortex in BD compared to controls. Voxel based morphometry analysis showed decreased gray matter in the somatosensory cortex in the same population compared to controls. Finally, women with BD and co-morbid PMDD displayed different patterns of Rs-FC using the right and left hippocampi as seed regions than women with BD without comorbid PMDD and controls with PMDD. Differences in cortical thickness between controls with and without PMDD and with and without BD were also found in regions central to emotional regulation and cognitive processing. Conclusions: Results highlight the influence of sex hormones on Rs-FC and support the need to control for menstrual phase and PMDD diagnosis. Differences in structural and functional connectivity, and the clinical profile of women with BD and those with BD and co-morbid PMDD highlights the impact of PMDD on BD and the need for future research in this area.