Neuroimaging the Menstrual Cycle and Premenstrual Dysphoric Disorder

Abstract

Knowledge of gonadal hormone-related influences on human brain anatomy, function, and chemistry is scarce. The present review scrutinized organizational and functional neuroimaging correlates of the menstrual cycle and premenstrual dysphoric disorder (PMDD). Supportive evidence of cyclic short-term structural and functional brain plasticity in response to gonadal hormonal modulation is provided. The paucity of studies, sparsity and discordance of findings, and weaknesses in study design at present hinder the drawing of firm conclusions. Ideal study designs should comprise high-resolution multimodal neuroimaging (e.g., MRI, DTI, rs-fMRI, fMRI, PET), hormones, genetic, and behavioral longitudinal assessments of healthy women and PMDD patients at critical time points of the menstrual cycle phase (i.e., early follicular phase, late follicular phase, mid-luteal phase) in a counter-balanced setup. Studies integrating large-scale brain network structural, functional, and molecular neuroimaging, as well as treatment data, will deepen the understanding of neural state, disorder, and treatment markers.

Effects of GABA active steroids in the female brain with a focus on the premenstrual dysphoric disorder

“…Nonetheless, the current trend is to move away from trying to pin down functional abnormalities to individual brain areas and, instead, to focus on trying to understand how distributed foci operating in large‐scale networks contribute to psychopathology . The most recent hypothesis underlying affective dysregulation in PMDD suggests that exaggerated bottom‐up activation of the salience network, coupled with blunted top‐down regulation by fronto‐cingulate regions, and dysregulated functional coupling between the salience and executive control network, lies at the basis of the affective symptomatology in PMDD …”

“…52 The most recent hypothesis underlying affective dysregulation in PMDD suggests that exaggerated bottom-up activation of the salience network, coupled with blunted top-down regulation by fronto-cingulate regions, and dysregulated functional coupling between the salience and executive control network, lies at the basis of the affective symptomatology in PMDD. 55 Thus far, the most reliable finding in studies investigating menstrual cycle-linked differences in functional brain activity is that women with PMDD exhibit a higher reactivity in the amygdala during the luteal phase compared to asymptomatic controls. 56,57 In turn, increased amygdala reactivity during the luteal phase, in contrast to the follicular phase, has been reported in healthy naturally cycling women in response to negatively valenced pictures during facial expression discrimination tasks and when recalling negative emotionally arousing information.…”

Morphological brain measures of cortico‐limbic inhibition related to resilience

“…All subjects were right-handed and female subjects were premenopausal as confirmed by self-report. Due to the modulation of brain activity, structure, and function by gonadal steroid hormones (Comasco and Sundstrom-Poromaa, 2015), females were scanned during the follicular phase of their menstrual cycle as determined by the number of days since last menstrual period. All procedures were performed after approval from the University Institutional Review Board and all subjects provided written informed consent in accordance with the Declaration of Helsinki.…”

Treatment of Premenstrual Dysphoric Disorder: Therapeutic Challenges

“…the amygdala) and blunted top-down inhibition from frontocingulate cortical regions [8]. The differential sensitivity is likely in part genetically determined, with possible genetic polymorphisms in genes coding for serotonergic and BDNF function [8], type 1 5α-reductase [7], or the estrogen receptor alpha 1 [5].…”