PMDD

This research is being done to examine epigenetic markers and mood changes across the menstrual cycle, particularly in premenstrual dysphoric disorder (PMDD). The investigators previously identified epigenetic biomarkers of postpartum depression, another reproductive affective disorder, and in this study aim to determine if these biomarkers also distinguish PMDD cases from healthy controls at different points in the menstrual cycle. By collecting biological samples (such as blood) and monitoring mood changes across the menstrual cycle, the investigators will be able to determine whether these epigenetic markers are associated with PMDD. The investigators plan to study these epigenetic markers during the follicular phase (roughly the first half of the menstrual cycle, from menses until ovulation) and the luteal phase (roughly the second half of the menstrual cycle, from ovulation to menses). The investigators will study this in two groups: 1) individuals who do NOT have premenstrual mood symptoms, and 2) individuals with premenstrual syndrome/premenstrual dysphoric disorder (PMS/PMDD). The results will provide a comprehensive view of the changes in these systems across the menstrual cycle. This will add to the investigators understanding of the mechanisms that may cause PMS/PMDD.

Premenstrual Dysphoric Disorder (PMDD) is a cyclical mood disorder characterized by emotional, cognitive, physical, and sleep-related symptoms that occur in the days leading up to menstruation and improve shortly after menstruation begins. Although medications are commonly used to treat PMDD, many individuals experience side effects, do not benefit from medication, or prefer non-medication-based approaches. Sleep difficulties are very common in individuals with PMDD and may contribute to mood symptoms, emotional regulation difficulties, and functional impairment. Psychological interventions that focus on sleep, such as sleep psychoeducation and cognitive-behavioural strategies for insomnia, are effective in other mood and anxiety disorders but have not been well studied in PMDD. This study aims to evaluate the feasibility, acceptability, and preliminary effects of a brief, sleep-focused psychoeducation workshop tailored for individuals with PMDD or severe premenstrual symptoms. Information collected in this study may help inform future research and may improve care for individuals with PMDD.

Premenstrual dysphoric disorder (PMDD) is a sex-specific depressive disorder where depressive symptom severity drastically changes in relation to menstrual cycle phase. It is characterized by late luteal phase symptoms of affective lability, irritability, depressed mood, and anxiety. A lot remains unclear and further studies are needed in order to improve the understanding of PMDD and to differentiate it from major depressive disorder (MDD). To date, and in contrast to MDD, the neural correlates of PMDD have been sparsely and poorly investigated. The aim of this study is therefore to investigate the neural correlates of PMDD as compared to MDD and to relate them to stress reactivity. Therefore, three groups of naturally cycling women will be investigated and compared, namely (1) women with MDD, (2) women with PMDD, and (3) healthy control women. Stress and HPA axis activity are assumed to play a crucial role in the development of many mental disorders, including MDD. How stress reactivity and HPA axis activity are connected to PMDD still needs to be investigated. Furthermore, the HPA axis can affect or suppress the activity of the hypothalamic-pituitary-gonadal (HPG) axis, which is involved mainly in the reproductive, but also the immune system, making it an important candidate for the investigation of sex-specific differences in stress reactivity. There are sex-specific differences in stress reactivity, but also in the prevalence of stress-related diseases. Women are twice as likely to suffer from depression than men and the first onset of MDD usually peaks during the reproductive years. As to why these differences exist, a recent theory suggests that ovarian hormone fluctuations function as modulators of women's susceptibility to stress and that altered reactivity to stressors during different cycle phases plays a role in the etiology of depressive disorders. This hypothesis extends the Social Signal Transduction Theory of Depression which first and foremost relates depression to inflammation. They postulate a critical role of cytokines for understanding the pathogenesis of depression. Therefore, ovarian hormone fluctuations, but also inflammation in regard to MDD and PMDD and stress reactivity will be investigated in this study.

The investigators aim to investigate the role of the serotonin 2A receptor in women with premenstrual disorders. This study uses a double-blind, randomized, controlled design with 3 arms: Intervention 1: 10 micg LSD for \~10 days during the late luteal phase (for 3 cycles) Intervention 2: 10 micg LSD every other day for \~10 days during the late luteal phase (for 3 cycles) Control intervention: Placebo for \~10 days during the late luteal phase (for 3 cycles) Each participant will be treated in only one arm. The study employs a parallel design with three treatment arms and consists of a two-cycle observational phase followed by a three-cycle treatment phase.