Electroencephalography findings in menstrually-related mood disorders: A critical review.

The female reproductive years are characterized by fluctuations in ovarian hormones across the menstrual cycle, which have the potential to modulate neurophysiological and behavioral dynamics. Menstrually-related mood disorders (MRMDs) comprise cognitive-affective or somatic symptoms that are thought to be triggered by the rapid fluctuations in ovarian hormones in the luteal phase of the menstrual cycle. MRMDs include premenstrual syndrome (PMS), premenstrual dysphoric disorder (PMDD), and premenstrual exacerbation (PME) of other psychiatric disorders. Electroencephalography (EEG) non-invasively records in vivo synchronous activity from populations of neurons with high temporal resolution. The present overview sought to systematically review the current state of task-related and resting-state EEG investigations on MRMDs. Preliminary evidence indicates lower alpha asymmetry at rest being associated with MRMDs, while one study points to the effect being luteal-phase specific. Moreover, higher luteal spontaneous frontal brain activity (slow/fast wave ratio as measured by the delta/beta power ratio) has been observed in persons with MRMDs, while sleep architecture results point to potential circadian rhythm disturbances. In this review, we discuss the quality of study designs as well as future perspectives and challenges of supplementing the diagnostic and scientific toolbox for MRMDs with EEG.

A scoping review of hormonal clinical trials in menstrual cycle-related brain disorders: Studies in premenstrual mood disorder, menstrual migraine, and catamenial epilepsy.

Cyclic variations in hormones during the normal menstrual cycle underlie multiple central nervous system (CNS)-linked disorders, including premenstrual mood disorder (PMD), menstrual migraine (MM), and catamenial epilepsy (CE). Despite this foundational mechanistic link, these three fields operate independently of each other. In this scoping review (N = 85 studies), we survey existing human research studies in PMD, MM, and CE to outline the exogenous experimental hormone manipulation trials conducted in these fields. We examine a broad range of literature across these disorders in order to summarize existing diagnostic practices and research methods, highlight gaps in the experimental human literature, and elucidate future research opportunities within each field. While no individual treatment or study design can fit every disease, there is immense overlap in study design and established neuroendocrine-based hormone sensitivity among the menstrual cycle-related disorders PMD, MM, and CE. SCOPING REVIEW STRUCTURED SUMMARY: Background. The menstrual cycle can be a biological trigger of symptoms in certain brain disorders, leading to specific, menstrual cycle-linked phenomena such as premenstrual mood disorders (PMD), menstrual migraine (MM), and catamenial epilepsy (CE). Despite the overlap in chronicity and hormonal provocation, these fields have historically operated independently, without any systematic communication about methods or mechanisms. OBJECTIVE: Online databases were used to identify articles published between 1950 and 2021 that studied hormonal manipulations in reproductive-aged females with either PMD, MM, or CE. We selected N = 85 studies that met the following criteria: 1) included a study population of females with natural menstrual cycles (e.g., not perimenopausal, pregnant, or using hormonal medications that were not the primary study variable); 2) involved an exogenous hormone manipulation; 3) involved a repeated measurement across at least two cycle phases as the primary outcome variable. CHARTING METHODS: After exporting online database query results, authors extracted sample size, clinical diagnosis of sample population, study design, experimental hormone manipulation, cyclical outcome measure, and results from each trial. Charting was completed manually, with two authors reviewing each trial. RESULTS: Exogenous hormone manipulations have been tested as treatment options for PMD (N = 56 trials) more frequently than MM (N = 21) or CE (N = 8). Combined oral contraceptive (COC) trials, specifically those containing drospirenone as the progestin, are a well-studied area with promising results for treating both PMDD and MM. We found no trials of COCs in CE. Many trials test ovulation suppression using gonadotropin-releasing hormone agonists (GnRHa), and a meta-analysis supports their efficacy in PMD; GnRHa have been tested in two MM-related trials, and one CE open-label case series. Finally, we found that non-contraceptive hormone manipulations, including but not limited to short-term transdermal estradiol, progesterone supplementation, and progesterone antagonism, have been used across all three disorders. CONCLUSIONS: Research in PMD, MM, and CE commonly have overlapping study design and research methods, and similar effects of some interventions suggest the possibility of overlapping mechanisms contributing to their cyclical symptom presentation. Our scoping review is the first to summarize existing clinical trials in these three brain disorders, specifically focusing on hormonal treatment trials. We find that PMD has a stronger body of literature for ovulation-suppressing COC and GnRHa trials; the field of MM consists of extensive estrogen-based studies; and current consensus in CE focuses on progesterone supplementation during the luteal phase, with limited estrogen manipulations due to concerns about seizure provocation. We argue that researchers in any of these respective disciplines would benefit from greater communication regarding methods for assessment, diagnosis, subtyping, and experimental manipulation. With this scoping review, we hope to increase collaboration and communication among researchers to ultimately improve diagnosis and treatment for menstrual-cycle-linked brain disorders.

Blunted Cortisol Response to Acute Psychosocial Stress in Women With Premenstrual Dysphoric Disorder.

BACKGROUND: Despite being considered a stress-related condition, it is not known whether the hypothalamic-pituitary-adrenal (HPA) axis is dysfunctional in response to acute psychosocial stress in premenstrual dysphoric disorder (PMDD). This is problematic because many women with PMDD report that they are not able to control their stress levels, and a blunted cortisol output has been identified in women with related psychiatric conditions, such as anxiety and depression. The present study is a part of the Premenstrual Hormonal and Affective State Evaluation (PHASE) project, and it aimed to characterize the cortisol trajectory in response to an acute psychosocial stress challenge. METHODS: Women with PMDD and healthy controls with confirmed ovulatory cycles underwent the Trier Social Stress Test (TSST) procedure in the mid-late luteal phase of the menstrual cycle, throughout which we collected serum samples of cortisol that we analyzed using ultra-performance liquid chromatography tandem mass spectrometry. RESULTS: The linear mixed model analysis indicated a significant time*diagnosis interaction (P = .008) such that women with PMDD displayed significantly lower serum cortisol levels at +40 through +90 minutes from the time of stress induction. CONCLUSION: This is the first study to show that women with PMDD have a blunted cortisol response to psychosocial stress. Combined with our earlier finding showing a greater parasympathetic nervous system withdrawal on heart oscillations in PMDD during acute stress, these and other results show that the dysregulated processing of stress in PMDD may be captured using objective study measures.

Is trait rumination associated with affective reactivity to the menstrual cycle? A prospective analysis.

BACKGROUND: A minority of naturally cycling individuals experience clinically significant affective changes across the menstrual cycle. However, few studies have examined cognitive and behavioral constructs that may maintain or worsen these changes. Several small studies link rumination with premenstrual negative affect, with authors concluding that a tendency to ruminate amplifies and perpetuates hormone-sensitive affective symptoms. Replication in larger samples is needed to confirm the validity of rumination as a treatment target. METHOD: 190 cycling individuals (M = 30.82 years; 61.1% Caucasian) were recruited for moderate perceived stress, a risk factor for cyclical symptoms. They completed the Rumination Response Scale at baseline, then reported daily affective and physical symptoms across 1-6 cycles. Multilevel growth models tested trait rumination as a predictor of baseline levels, luteal increases, and follicular decreases in symptoms. RESULTS: The degree of affective cyclicity was normally distributed across a substantial range, supporting feasibility of hypothesis tests and validating the concept of dimensional hormone sensitivity. Contrary to prediction, higher brooding did not predict levels or cyclical changes of any symptom. In a subsample selected for luteal increases in negative affect, brooding predicted higher baseline negative affect but still did not predict affective cyclicity. CONCLUSIONS: An individual's trait-like propensity to engage in rumination may not be a valid treatment target in premenstrual mood disorders. State-like changes in rumination should still be further explored, and well-powered prospective studies should explore other cognitive and behavioral factors to inform development of targeted psychological treatments for patients with cyclical affective symptoms.

Emotion-focused therapy for women with premenstrual dysphoric disorder: a randomized clinical controlled trial.

BACKGROUND: Premenstrual dysphoric disorder (PMDD) is a debilitating condition, affecting women of reproductive age. It is characterized by severe periodic physical and psychological symptoms, which end after the onset of menstruation. This study aimed to evaluate the effectiveness of emotion-focused therapy (EFT) for PMDD patients. METHODS: A total of 48 PMDD women, in the age range of 18-44 years, were randomly assigned to two intervention and control groups. The intervention group participated in 16 weeks of EFT treatment, while the control group was selected based on the waiting list (waitlist control group) and followed-up after three months. Forty-four patients finally completed this study. The participants completed the Premenstrual Syndrome Screening Tool (PSST), Difficulties in Emotion Regulation Scale (DERS), and Depression Anxiety Stress Scale-21 (DASS-21) in the first premenstrual period before treatment, the first premenstrual period after treatment, and the premenstrual period three months after treatment. RESULTS: Based on the repeated measure analysis of variances, the total score of DERS and the total score of PSST decreased significantly (P < 0.05). Also, in DASS-21, the scores of depression and stress subscales reduced significantly (P < 0.05), while there was no significant decrease in the score of anxiety subscale (P > 0.05). CONCLUSION: Based on the present results, EFT can be an effective treatment for alleviating the symptoms of PMDD. This treatment can reduce the emotion regulation difficulties of women with PMDD and alleviate the symptoms of depression and stress. TRIAL REGISTRATION: Iranian Registry of Clinical Trials, IRCT ID: IRCT20220920055998N1, Registered on: 12/2/2023.

The impact of comorbid premenstrual syndrome or premenstrual dysphoric disorder on the clinical characteristics of bipolar disorder among Han Chinese women.

Bipolar disorder (BD) is commonly comorbid with premenstrual syndrome (PMS) or premenstrual dysphoric disorder (PMDD). However, little is known about their relationship. This study aimed to assess the impact of comorbid PMS or PMDD on the clinical characteristics of BD. A cross-sectional study was conducted on 262 women with BD. PMS and PMDD were screened with the Premenstrual Symptoms Screening Tool (PSST). Symptomatic features were assessed with Hamilton Depression Scale (HAMD), Young Mania Rating Scale (YMRS), and atypical features by the depressive episode section of SCID-I/P. The rates of PMS and PMDD among BD were 57.6% and 20.6% according to PSST. No significant difference in the rates of PMS and PMDD was found between BD I, BD II, and BD-NOS. Compared to BD patients without PMS or PMDD, patients with comorbid BD and PMS or PMDD were younger, more educated, had a higher risk of OCD, had an earlier age of onset, scored higher on HAMD-17 and its sub-scale of anxiety/somatization, cognitive deficit, psychomotor retardation, and were more likely to have increased appetite and leaden paralysis. In addition, patients with comorbid BD and PMDD were less likely to experience traumatic life events, more likely to have family history of mental disorders and have inflammatory or autoimmune disease, scored higher on HMAD-17, particularly in its sub-scale of anxiety/somatization, cognitive deficit, psychomotor retardation, and sleep disturbance. Compared with BD without PMS or PMDD, BD with PMS or PMDD might be a specific subtype of BD characterized with earlier onset age, heavier genetic load, increased symptom severity, and atypical features.

Prevalence and correlates of premenstrual syndrome and premenstrual dysphoric disorder among women aged 18-25 in Turkey.

OBJECTIVE: Premenstrual syndrome (PMS) and premenstrual dysphoric disorder (PMDD) are experienced in the luteal phase among women of reproductive age and are known to affect quality of life. This study sought to determine the prevalence and correlates of PMS and PMDD in women aged 18-25 in Turkey. METHOD: A cross-sectional study was conducted between December 2022 and May 2023, which recruited 1125 female college students. A personal information form, the International Physical Activity Questionnaire, and the Premenstrual Syndrome Scale (PMSS) were administered. Participants who met criteria for PMS during three consecutive menstrual cycles based on the ACOG and PMSS scores were diagnosed as having PMS. Participants who met the criteria for PMDD during three consecutive menstrual cycles based on the DSM-V were diagnosed as having PMDD. Logistic regression analysis was used to determine correlates of PMS and PMDD. FINDINGS: PMS was found in 49.2% and PMDD in 48.0% of the participants. Women having a blood group type B compared to those with blood group type A were more likely to have PMS (OR = 151.8, 95% CI = 54.5-422.6). In addition, women with PMS were less likely to be physically active based on the metabolic equivalent of task score (OR = 0.99, 95% CI= 0.98-0.99). Menstrual cycle duration was also longer among those with PMDD (OR = 1.47, 95% CI= 1.25-1.72), as was daily caffeine intake (OR = 1.01, 95% CI= 1.00-1.01). PMDD score was also found to be associated with major depressive disorder (OR = 1.06,95% = 1.05-1.07). CONCLUSIONS: PMS and PMDD among young women in Turkey were associated with blood groups, MET scores, and other clinical characteristics that may help clinicians to identify these conditions.

Mental health and quality of life in patients with premenstrual exacerbation: a cross-sectional study in Japan.

BACKGROUND: In the classification of premenstrual disorders (PMDs), premenstrual exacerbation (PME) is listed as one of the variants of PMDs, along with core PMD. However, the incidence of PME and its impact on mental health and quality of life have not been investigated. Therefore, we investigated the proportion of PME among women seeking treatment for premenstrual symptoms in Japan and compared the levels of anxiety, depression and quality of life between women with PME and those with core PMD. METHODS: Women who presented to the Department of Obstetrics and Gynaecology of a single institute for treatment of premenstrual symptoms and were diagnosed with PMDs using patient diaries were included in the study. Based on the diagnosis, patients were divided into two groups (core PMD and PME) and their responses to a questionnaire on mental health and quality of life at the first visit were analysed. RESULTS: A total of 32 women were diagnosed with PMDs (22 with core PMD and 10 with PME). All underlying medical conditions in women with PME were psychiatric disorders. There were no significant differences in various factors between the two groups. In terms of mental health, the PME group had higher levels of anxiety and depression than the core PMD group. Regarding quality of life, the PME group had lower scores than the core PMD group in all domains except physical and social functioning. CONCLUSIONS: Patients seeking treatment for premenstrual symptoms included many PME. Women with PME were more anxious and depressed than those with core PMD, and their quality of life was low in both physical and psychological domains. Patients with PME should be diagnosed and treated more appropriately.

Premenstrual exacerbation of underlying medical conditions is one of the variants of premenstrual disorders. This study aimed to assess the proportion of premenstrual exacerbation among patients attending a gynaecological clinic for premenstrual symptoms and to evaluate their mental health and quality of life. Women diagnosed with premenstrual disorder were divided into the core premenstrual disorder group and the premenstrual exacerbation group. We compared the mental health and quality of life scores calculated from the questionnaire between the two groups. Among the patients diagnosed with premenstrual disorders, about one-third were patients with premenstrual exacerbation. The premenstrual exacerbation group were more anxious and depressed than the core premenstrual disorder group, and had lower quality of life scores in almost all domains. The results underscore the importance that health care providers should always consider the possibility of premenstrual exacerbation when managing patients with premenstrual symptoms and provide appropriate care for these patients.

The relationship between trauma, stress, and premenstrual symptoms: the role of attributional style and trait anger.

AIMS: The aim of this study was to examine potential mediators of the relationship between traumatic experiences, perceived stress, and the subjective, retrospectively measured, intensity of symptoms of premenstrual disorders. It was hypothesised that pessimistic attributional style and trait anger mediate the said relationship. METHODS: The study sample comprised 150 non-clinical subjects (aged 18-31; M = 21.82; SD = 2.19). Study variables were assessed with self-report questionnaires: the Premenstrual Symptoms Screening Tool (PSST); the Traumatic Experiences Checklist (TEC); the Perceived Stress Scale-4 Short Form (PSS-4); the Attributional Style Questionnaire (ASQ); and the State-Trait Anger Expression Inventory-2 (STAXI-2 - trait anger subscale). Correlation and mediation analyses were performed. RESULTS: The symptoms of premenstrual disorders were significantly and positively associated with both trait anger and pessimistic attributional style, as well as with trauma and stress. The correlations were moderate to strong, ranging from rho = 0.57 (pessimistic attributional style and trauma) to rho = 0.85 (stress and premenstrual symptoms). Both anger and pessimistic attributional style partially mediated the relationship between trauma and premenstrual symptoms and between stress and premenstrual symptoms. CONCLUSION: Although the design of the study does not allow to infer causality, it demonstrates strong, positive relationship between the symptoms of premenstrual disorders, trauma, stress, attributional style, and anger. The results of mediation analyses may point to some practical implications (e.g. for psychotherapeutic interventions) but further studies employing prospective methods are needed.

[Premenstrual syndrome and premenstrual dysphoric disorder-Overview on pathophysiology, diagnostics and treatment]. / Prämenstruelles Syndrom und prämenstruelle dysphorische Störung ­ Übersicht zu Pathophysiologie, Diagnostik und Therapie.

Premenstrual syndrome and premenstrual dysphoric disorder become episodically manifest during the second half of the female menstrual cycle and are characterized by psychological and physical symptoms causing relevant functional and social impairments. Mood swings, depression and dysphoria are associated depressive symptoms. Therefore, affective disorders should be considered as a differential diagnosis. Of women in reproductive age 3-8% suffer from premenstrual syndrome and 2% of women are affected by premenstrual dysphoric disorder. Genetic and sociobiographical risk factors are discussed. Furthermore, genetic polymorphisms of specific hormone receptors are considered to be genetic risk factors. From a pathophysiological perspective premenstrual syndrome and premenstrual dysphoric disorder are caused by a complex interaction between cyclic changes of ovarian steroids and central neurotransmitters. An imbalance of estrogen and progesterone in the luteal phase is believed to cause the symptoms. Therefore, the first treatment approach consists of regulation of the menstrual cycle or luteal support with progesterone or synthetic progestins even if their effectiveness has not yet been proven in randomized controlled studies and meta-analyses. The administration of combined oral contraceptives is also an option. Especially treatment with selective serotonin reuptake inhibitors (SSRI) represent an evidence-based approach. In severe cases the administration of gonadotropin releasing hormone (GnRH) agonists with add back treatment can also be considered. In the field of affective disorders premenstrual syndromes represent clinically relevant differential diagnoses and comorbidities, which confront the treating physician with particular clinical challenges. Therefore, this literature review gives the readership a clinical orientation for dealing with these disorders.

[Premenstrual dysphoric disorder (PMDD): Drug and psychotherapeutique management, a literature review]. / Trouble dysphorique prémenstruel : prises en charge médicamenteuses et psychothérapeutiques, une revue de littérature.

INTRODUCTION: Premenstrual Dysphoric Disorder (PMDD) was first recognised in July 2013 in the DSM-5 after a long journey to identify its existence. It was not until 1983 that the US National Institute of Mental Health determined research criteria for the study of PMS. In 1994, the term "premenstrual dysphoric disorder" (PMDD) replaced this term in the 4th edition of the Diagnostic System Manual (DSM). It was listed in the section "Mood Disorder Not Otherwise Specified" and remained under consideration until the DSM-5, in which it appeared in the depressive disorders section. The legitimisation of the psychiatric diagnosis as well as the determination of clear symptomatology criteria in 2013 opened up possibilities for management, development of clinical, pathophysiological, therapeutic and psychotherapeutic studies. This disabling disorder can affect personal, social, family and professional life. In 2019, the ICD-11 in turn introduced the diagnosis of premenstrual dysphoric disorder, which solidifies the recognition of the disorder. OBJECTIVE: (I) to review the existing treatments, both medicinal and psychotherapeutic, and (II) to review their effectiveness. At the end of this work we will formulate recommendations for the management of these patients. METHODOLOGY: A bibliographic search was carried out from 7 June 2021 to 7 July2021 on the databases (bases de données) Psychinfo APA, Scopus, PubMed, as well as the bases de données of the Cochrane organisation and the recommendation documents of the Haute Autorité de la santé. After an initial selection based on keywords, the full text of all articles were read to arrive at the final selection of 32 articles. RESULTS: Antidepressants and Cognitive Behavioural Therapies (CBT) appear to be the most commonly recommended treatments for PMDD. Other research shows the effectiveness of oral contraceptives including drospirenone. Selective serotonin reuptake inhibitors (SSRIs) were identified as an effective treatment for PMDD. These data are consistent with the current etiological hypothesis of PMDD which has a negative impact of natural hormonal fluctuations on certain neurotransmitters. CBT showed positive results in reducing the functional impact of PMDD. DISCUSSION: Selective serotonin reuptake inhibitor (SSRI) antidepressants were reported to be first-line treatments for PMDD (sertraline 50-150 mg/d, fluoxetine 10-20 mg/d, escitalopram 10-20 mg/d, paroxetine 12.5-25 mg/d). Drospirenone (EE 3 mg and EE 20 mg/d 24 days of hormonal pills, 4 days inactive) appears to have been a first or second line treatment depending on the articles. Current results clearly point to the effectiveness of CBT in helping to reduce: functional impairment, depressed mood, feelings of hopelessness, anxiety, mood swings, sensitivity, irritability, insomnia, conflict with others, impact of premenstrual symptoms on daily life, intensity of symptoms experienced, and symptom handicap. CBTs could also become a first-line treatment if there were to be more evidence of their effectiveness. In the future, it would seem useful to offer a psychotherapeutic treatment that can be reproduced and to multiply research with a high level of scientific comparability in order to clarify the place of CBT in the management of PMDD. Research on the etiopathology of the disorder and the optimal drug regimen is still ongoing. There is a need to develop appropriate psychotherapeutic techniques to support and accompany these patients. CONCLUSION: In order to better evaluate treatments for PMDD, there is a need to homogenise studies on the subject at several levels: design, treatment doses, psychotherapeutic techniques, and evaluation measures. At present, some studies include both premenstrual syndrome (PMS) and PMDD patients. PMS and PMDD do not include the same symptoms, nor the same severity and potentially the same aetiology in the patients studied. In order to propose rigorous research that evaluates the effectiveness of treatments for PMDD and to properly support people with both these disorders, it seems essential to distinguish the two conditions. The role of the health practitioner is to be able to identify PMDD by differentiating it from other clinically related disorders. The patient must then be accompanied to make a choice of treatment adapted to her symptoms, their severity, her history, her plans for procreation, contraindications and her preferences. In 2021, the French National Authority for Health did not offer any guidelines or recommendations for the management of premenstrual dysphoric disorder. There is a need to develop research in France.

Trauma and female reproductive health across the lifecourse: motivating a research agenda for the future of women's health.

The aetiology behind many female reproductive disorders is poorly studied and incompletely understood despite the prevalence of such conditions and substantial burden they impose on women's lives. In light of evidence demonstrating a higher incidence of trauma exposure in women with many such disorders, we present a set of interlinked working hypotheses proposing relationships between traumatic events and reproductive and mental health that can define a research agenda to better understand reproductive outcomes from a trauma-informed perspective across the lifecourse. Additionally, we note the potential for racism to act as a traumatic experience, highlight the importance of considering the interaction between mental and reproductive health concerns, and propose several neuroendocrinological mechanisms by which traumatic experiences might increase the risk of adverse health outcomes in these domains. Finally, we emphasize the need for future primary research investigating the proposed pathways between traumatic experiences and adverse female reproductive outcomes.

Effects of cognitive emotion regulation strategies on mood and cortisol in daily life in women with premenstrual dysphoric disorder.

BACKGROUND: The psychological risk factors of premenstrual dysphoric disorder (PMDD) are not fully understood, but initial evidence points to a potential role of unfavorable cognitive emotion regulation (ER-) strategies. Given the symptom cyclicity of PMDD, ambulatory assessment is ideally suited to capture psychological and physiological processes across the menstrual cycle. Our study examines habitual ER-strategies in women with PMDD and their predictive value for the course of mood and basal cortisol across the cycle in affected women. METHODS: Women with and without PMDD (n = 61 each) were compared regarding habitual mindfulness, reappraisal, and repetitive negative thinking (RNT). Momentary affect and cortisol output were assessed over two consecutive days per cycle phase (menstrual, follicular, ovulatory, late luteal). RESULTS: Women with PMDD reported lower mindfulness, less use of reappraisal and stronger RNT than controls (ps < 0.035). In women with PMDD, higher mindfulness and reappraisal and lower RNT predicted decreased negative and increased positive affect across the menstrual cycle (ps < 0.027). However, women using more favorable ER-strategies displayed stronger mood cyclicity, resulting in stronger mood deterioration in the late luteal phase, thereby resembling women with more unfavorable ER-strategies toward the end of the cycle. Lower mindfulness predicted lower cortisol in the menstrual phase. CONCLUSIONS: Protective ER-strategies seem to be generally linked to better momentary mood in women with PMDD, but do not appear to protect affected women from premenstrual mood deterioration. Habitual mindfulness, in turn, seems to buffer blunted cortisol activity in women with PMDD, especially in the menstrual phase.

Agmatine prevents the manifestation of impulsive burying and depression-like behaviour in progesterone withdrawn female rats.

Premenstrual dysphoric disorder (PMDD) is characterized by various physical and affective symptoms, including anxiety, irritability, anhedonia, social withdrawal, and depression. The present study investigated the role of the agmatinergic system in animal model of progesterone withdrawal in female rats. Chronic progesterone exposure of female rats for 21 days and its abrupt withdrawal showed enhanced marble burying, increased immobility time, and reduced no. of entries in open arm as compared to control animals. The progesterone withdrawal-induced enhanced marble burying anxiety and immobility time was significantly attenuated by agmatine (5-20 mg/kg, i.p.), and its endogenous modulators like L-arginine (100 mg/kg, i.p.), amino-guanidine (25 mg/kg, i.p.) and arcaine (50 mg/kg, i.p.) by their once-daily administration from day 14-day 21 of the protocol. We have also analysed the levels of agmatine, progesterone, and inflammatory cytokines in the hippocampal region of progesterone withdrawn rats. There was a significant decline in agmatine and progesterone levels and an elevation in cytokine levels in the hippocampal region of progesterone withdrawn rats compared to the control animals. In conclusion, the present studies suggest the importance of the endogenous agmatinergic system in progesterone withdrawal-induced anxiety-like and depression-like behaviour. The data also projects agmatine as a potential therapeutic target for the premenstrual dysphoric disorder.

A 1-week sleep and light intervention improves mood in premenstrual dysphoric disorder in association with shifting melatonin offset time earlier.

To test the hypothesis that 1 week of combined sleep and light interventions (SALI), which phase-advance (shift earlier) melatonin circadian rhythms, improves mood significantly more than phase-delay (shift later) SALI. After a 2-month diagnostic evaluation for premenstrual dysphoric disorder (PMDD per DSM-5 criteria) in a university clinical research setting, 44 participants enrolled in baseline studies were randomized in the luteal phase at home to (A) a phase-advance intervention (PAI): 1 night of late-night wake therapy (LWT: sleep 9 pm-1 am) followed by 7 days of the morning (AM) bright white light (BWL), or (B) a phase-delay intervention (PDI): 1 night of early-night wake therapy (EWT: sleep 3-7 am) plus 7 days of the evening (PM) BWL. After a month of no intervention, participants underwent the alternate intervention. Outcome measures were mood, the melatonin metabolite, 6-sulfatoxymelatonin (6-SMT), and actigraphy (to assess protocol compliance). At baseline, atypical depression correlated positively with phase delay in 6-SMT offset time (r = .456, p = .038). PAI advanced 6-SMT offset from baseline more than PDI (p < .05), and improved raw mood scores more than PDI (p < .05). As hypothesized, percent improvement in mood correlated positively with a phase advance from baseline in 6-SMT offset time (p < .001). Treatment with 1 night of advanced/restricted sleep followed by 7 days of AM BWL (PAI) was more efficacious in reducing PMDD depression symptoms than a PDI; mood improvement occurred in association with phase advance in 6-SMT offset time. Combined SALIs offer safe, efficacious, rapid-acting, well-tolerated, non-pharmacological, non-hormonal, affordable, repeatable home interventions for PMDD. Clinical Trials.gov NCT # NCT01799733.

Attention, response inhibition, impulsivity, and decision-making within luteal phase in women with premenstrual dysphoric disorder.

Cognitive impairment is a key feature of depressive disorder. Various forms of cognitive function have yet to be investigated in women with premenstrual dysphoric disorder (PMDD) during early luteal (EL) and late luteal (LL) phases. Therefore, we evaluated response inhibition and attention in PMDD in these two phases. We also examined the associations between cognitive functions, impulsivity, decision-making style, and irritability. There is a total of 63 female participants with PMDD and 53 controls, as determined through psychiatric diagnostic interviewing and a weekly symptoms checklist. The participants completed a Go/No-go task, Dickman's impulsivity inventory, Preference for Intuition and Deliberation scale, and the Buss-Durkee Hostility Inventory: Chinese Version-Short Form at the EL and LL phases. The women with PMDD had poorer attention in the Go trials at the LL phase and poorer response inhibition in the No-go trials at the EL and LL phases. Repeated measures analysis of variance revealed an LL exacerbation of deficit in attention among PMDD group. In addition, impulsivity negatively correlated with response inhibition at the LL phase. Preference for deliberation correlated with attention at the LL phase. Women with PMDD experienced LL declined attention and impaired response inhibition across the luteal phase. Response inhibition is linked to impulsivity. The deficit in attention links preference for deliberation among women with PMDD. These results reveal the different courses in different domains of cognitive impairment in PMDD. Further studies are required to elucidate the mechanism underlying cognitive dysfunction in PMDD.

Limbic self-neuromodulation as a novel treatment option for emotional dysregulation in premenstrual dysphoric disorder (PMDD); a proof-of-concept study.

AIM: To assess the efficacy of a novel neurofeedback (NF) method, targeting limbic activity, to treat emotional dysregulation related to premenstrual dysphoric disorder (PMDD). METHODS: We applied a NF probe targeting limbic activity using a functional magnetic resonance imaging-inspired electroencephalogram model (termed Amyg-EFP-NF) in a double-blind randomized controlled trial. A frontal alpha asymmetry probe (AAS-NF), served as active control. Twenty-seven participants diagnosed with PMDD (mean age = 33.57 years, SD = 5.67) were randomly assigned to Amyg-EFP-NF or AAS-NF interventions with a 2:1 ratio, respectively. The treatment protocol consisted of 11 NF sessions through three menstrual cycles, and a follow-up assessment 3 months thereafter. The primary outcome measure was improvement in the Revised Observer Version of the Premenstrual Tension Syndrome Rating Scale (PMTS-OR). RESULTS: A significant group by time effect was observed for the core symptom subscale of the PMTS-OR, with significant improvement observed at follow-up for the Amyg-EFP group compared with the AAS group [F(1, 15)=4.968, P = 0.042]. This finding was specifically robust for reduction in anger [F(1, 15) = 22.254, P < 0.001]. A significant correlation was found between learning scores and overall improvement in core symptoms (r = 0.514, P = 0.042) suggesting an association between mechanism of change and clinical improvement. CONCLUSION: Our preliminary findings suggest that Amyg-EFP-NF may serve as an affordable and accessible non-invasive treatment option for emotional dysregulation in women suffering from PMDD. Our main limitations were the relatively small number of participants and the lack of a sham-NF placebo arm.

Current status and problems in the diagnosis and treatment of premenstrual syndrome and premenstrual dysphoric disorder from the perspective of obstetricians and gynecologists in Japan.

AIM: To investigate the current status and problems in the diagnosis and treatment of premenstrual syndrome (PMS) and premenstrual dysphoric disorder (PMDD) from the perspective of obstetricians and gynecologists (OB/GYNs) in Japan, the Japanese Society of Obstetrics and Gynecology (JSOG) conducted a national-wide survey. METHODS: An email survey was sent to all JSOG members (16 732) and a web-based survey was conducted using a Google form between September and November 2021. The current status and problems in PMS/PMDD diagnosis and treatment were surveyed in this cross-sectional study. RESULTS: In total, 1312 respondents (7.8% of all JSOG members) completed the questionnaire. In terms of diagnoses and treatment, OB/GYN was preferred over psychiatrist for PMS (91.4% vs. 45%); however, no differences were noted for PMDD (76.1% vs. 73.7%). A total of 1267 (96.6%) respondents engaged in routine PMS/PMDD treatment. Regarding the general diagnosis procedure, 84.4% respondents answered "only a vague medical interview," 8.4% kept a two-cycle symptom diary, and 10.3% used a screening questionnaire. The most commonly used medication was oral contraceptive pills (OCPs) (98.1%), followed by the Kampo, traditional Japanese herbal medicines, Kamishoyosan (73.6%). Concerning first-line drugs for treatment, OCPs were the most common (76.8%), followed by Kampo medicine (19.5%); selective serotonin reuptake inhibitors (SSRIs) were less frequently used (2.6%). Regarding first-line drugs among OCPs, 65.1% respondents reported drospirenone-ethinylestradriol use. CONCLUSIONS: This study indicates that only a few OB/GYNs practicing PMS/PMDD in Japan use a prospective diary, which is an essential diagnostic criterion for PMS/PMDD. Regarding treatment, SSRIs were used less frequently.

Women's Health Care Committee, Japan Society of Obstetrics and Gynecology: Annual report-2023.

The Women's Health Care Committee was established in 2010 with the goal of improving women's health. In the current academic year, there are six subcommittees focusing on conducting the following surveys: (1) the current status of pregnancy-associated breast cancer in Japan; (2) surgery for disorders of sex development; (3) diagnosis and treatment of premenstrual syndrome and premenstrual dysphoric disorder; (4) obstetrics and gynecology-based treatment for patients with eating disorders in Japan; (5) multi-drug-resistant bacterial infections in the field of obstetrics and gynecology; and (6) changing the methodology of the treatment of dysmenorrhea and continuing medical education. The activities of each subcommittee are described below. This report is based on the Japanese version of the annual report (Acta Obst Gynaec Jpn 2023;75(6):662-86).

Prevalence of lifetime self-injurious thoughts and behaviors in a global sample of 599 patients reporting prospectively confirmed diagnosis with premenstrual dysphoric disorder.

BACKGROUND: Suicide is the second leading cause of death among Americans ages 10 to 34, with alarming recent increases in suicide rates among those assigned female at birth. A large body of evidence points to menstrual cycle influences on self-injurious thoughts and behaviors (STBs), suggesting that neurobiological hormone sensitivities, such as in premenstrual dysphoric disorder (PMDD), may drive suicide risk in females. However, existing studies of STBs in PMDD use cross-sectional self-report measures of PMDD with poor validity. As a first step to establish accurate prevalence rates of STBs in PMDD, we examined the lifetime prevalence of STBs in a large global survey of patients reporting a diagnosis of PMDD based on daily ratings. METHOD: Individuals with self-reported PMDD symptoms were invited to an online survey through online support groups for PMDD and social media posts from PMDD awareness accounts. Participants reported demographics, whether they had been diagnosed with PMDD by a healthcare provider using daily ratings, STBs using the Columbia Suicide Severity Rating Scale, and history of lifetime comorbid psychiatric diagnoses. RESULTS: Of 2,689 survey completers, 599 (23%) reported a diagnosis with PMDD based on two months of daily ratings and were included in analyses. We observed high rates of lifetime active suicidal ideation (72%), planning (49%), intent (42%), preparing for an attempt (40%), and attempt (34%), as well as non-suicidal self-injury (51%). The majority (70%) of the sample reported at least one lifetime comorbid psychiatric diagnosis. Predictors of lifetime active suicidal ideation included nulliparity, low-to-moderate (vs. high) income, and history of diagnosis with major depression or post-traumatic stress disorder. Predictors of lifetime attempts among those reporting lifetime active ideation included older age, nulliparity, lower income, and history of diagnosis with post-traumatic stress disorder or borderline personality disorder. CONCLUSIONS: These data indicate high rates of STBs among those reporting prospective diagnosis of PMDD and highlight the need for prospective research on mechanisms and prevention of STBs in PMDD. Clinical practice guidelines for PMDD should accommodate comorbidities and recommend frequent screenings for STB risk. STBs should be considered for inclusion in future iterations of the DSM PMDD diagnostic criteria.