Dimensional Affective Sensitivity to Hormones across the Menstrual Cycle (DASH-MC): A transdiagnostic framework for ovarian steroid influences on psychopathology.

Fluctuations in progesterone (P4) and estradiol (E2) across the menstrual cycle can exert direct effects on biological systems implicated in neuropsychiatric disorders and represent a key biological source of variability in affective, cognitive, and behavioral disorders. Although these cyclical symptoms may be most readily identified when they occur exclusively in relation to the menstrual cycle, as in DSM-5 premenstrual dysphoric disorder, symptom changes of similar magnitude occur in a larger proportion of people with ongoing psychiatric disorders. Studies investigating cyclical regulation of brain and behavior often produce inconsistent results, which may be attributed to a lack of focus on specific hormonal events and individual differences in related sensitivities. We propose a transdiagnostic Dimensional Affective Sensitivity to Hormones across the Menstrual Cycle (DASH-MC) framework, postulating that atypical neural responses to several key hormonal events provoke specific temporal patterns of affective and behavioral change across the menstrual cycle. We review prospective and experimental evidence providing initial support for these dimensions, which include (1) luteal-onset negative affect caused by a sensitivity to E2 or P4 surges (mediated by neuroactive metabolites such as allopregnanolone), typified by irritability and hyperarousal; (2) perimenstrual-onset negative affect caused by a sensitivity to low or falling E2, typified by low mood and cognitive dysfunction; and (3) preovulatory-onset positive affect dysregulation caused by a sensitivity to E2 surges, typified by harmful substance use and other risky reward-seeking. This multidimensional, transdiagnostic framework for hormone sensitivity can inform more precise research on ovarian steroid regulation of psychopathology, including further mechanistic research, diagnostic refinement, and precision psychiatry treatment development. Additionally, given the high rates of hormone sensitivity across affective disorders, the DASH-MC may guide broader insights into the complex neurobiological vulnerabilities driving female-biased affective risk, as well as potential triggers and mechanisms of affective state change in psychiatric disorders.

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.

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.

Cumulative stressor exposure predicts menstrual cycle affective changes in a transdiagnostic outpatient sample with past-month suicidal ideation.

BACKGROUND: Affective responses to the menstrual cycle vary widely. Some individuals experience severe symptoms like those with premenstrual dysphoric disorder, while others have minimal changes. The reasons for these differences are unclear, but prior studies suggest stressor exposure may play a role. However, research in at-risk psychiatric samples is lacking. METHODS: In a large clinical sample, we conducted a prospective study of how lifetime stressors relate to degree of affective change across the cycle. 114 outpatients with past-month suicidal ideation (SI) provided daily ratings (n = 6187) of negative affect and SI across 1-3 menstrual cycles. Participants completed the Stress and Adversity Inventory (STRAIN), which measures different stressor exposures (i.e. interpersonal loss, physical danger) throughout the life course, including before and after menarche. Multilevel polynomial growth models tested the relationship between menstrual cycle time and symptoms, moderated by stressor exposure. RESULTS: Greater lifetime stressor exposure predicted a more pronounced perimenstrual increase in active SI, along with marginally significant similar patterns for negative affect and passive SI. Additionally, pre-menarche stressors significantly increased the cyclicity of active SI compared to post-menarche stressors. Exposure to more interpersonal loss stressors predicted greater perimenstrual symptom change of negative affect, passive SI and active SI. Exploratory item-level analyses showed that lifetime stressors moderated a more severe perimenstrual symptom trajectory for mood swings, anger/irritability, rejection sensitivity, and interpersonal conflict. CONCLUSION: These findings suggest that greater lifetime stressor exposure may lead to heightened emotional reactivity to ovarian hormone fluctuations, elevating the risk of psychopathology.

Attention-deficit/hyperactivity disorder and the menstrual cycle: Theory and evidence.

Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder that exhibits striking sex differences in symptoms, prevalence, and associated problems across development. Etiological factors and mechanisms underlying these sex differences remain one of the most understudied aspects of this disorder. The current paper seeks to provide a novel theoretical framework for understanding this phenomenon by reviewing evidence that females with ADHD may experience a "double whammy" of organizational and activational pubertal hormonal effects. We propose a novel theory of activational effects of cyclical circulating ovarian hormones on ADHD with increasing risk at times of rapid declines in estrogen. These declines may decrease executive function and trait control at two points of the cycle characterized by biphasic affective risk: (1) increases in approach/risk-taking behaviors at mid-cycle (periovulatory) and (2) increases in avoidance/negative affect perimenstrually. Low estrogen and control may then interact with increases in positive and negative affect, respectively, to increase hyperactivity-impulsivity symptoms post-ovulation and inattention symptoms perimenstrually. These interactions may be exacerbated by organizational pubertal effects on relatively overdeveloped limbic circuitry and adolescent-specific social pressures magnified in females with ADHD.

Associations of luteal phase changes in vagally mediated heart rate variability with premenstrual emotional changes.

BACKGROUND: A recent meta-analysis revealed that vagally mediated heart rate variability (vmHRV; a biomarker of emotion regulation capacity) significantly decreases in the luteal phase of the menstrual cycle. As two follow-up studies suggest, these vmHRV decreases are driven primarily by increased luteal progesterone (P4). However, analyses also revealed significant interindividual differences in vmHRV reactivity to the cycle, which is in line with longstanding evidence for interindividual differences in mood sensitivity to the cycle. The present study begins to investigate whether these interindividual differences in vmHRV cyclicity can explain who is at higher risk of showing premenstrual emotional changes. We expected a greater degree of midluteal vmHRV decrease to be predictive of a greater premenstrual increase in negative affect. METHODS: We conducted an observational study with a naturally cycling community sample (N = 31, M = 26.03 years). Over a span of six weeks, participants completed (a) daily ratings of negative affect and (b) counterbalanced lab visits in their ovulatory, midluteal, and perimenstrual phases. Lab visits were scheduled based on positive ovulation tests and included assessments of baseline vmHRV and salivary ovarian steroid levels. RESULTS: In line with previous research, multilevel models suggest that most of the sample shows ovulatory-to-midluteal vmHRV decreases which, however, were not associated with premenstrual emotional changes. Interestingly, it was only the subgroup with luteal increases in vmHRV whose negative affect markedly worsened premenstrually and improved postmenstrually. CONCLUSION: The present study begins to investigate cyclical changes in vmHRV as a potential biomarker of mood sensitivity to the menstrual cycle. The results demonstrate a higher level of complexity in these associations than initially expected, given that only atypical midluteal increases in vmHRV are associated with greater premenstrual negative affect. Potential underlying mechanisms are discussed, among those the possibility that luteal vmHRV increases index compensatory efforts to regulate emotion in those with greater premenstrual negative affect. However, future studies with larger and clinical samples and more granular vmHRV assessments should build on these findings and further explore associations between vmHRV cyclicity and menstrually related mood changes.

Menstrual cycle-driven vs noncyclical daily changes in sexual desire.

BACKGROUND: Past research on the association between sexual desire and the menstrual cycle has provided inconclusive results and has not considered the potential influence of psychological and physical changes that are frequently associated with the menstrual cycle. AIM: To test the strength of association between the menstrual cycle (and associated symptoms) and changes in sexual desire. METHODS: Prospective daily reports across 2 full menstrual cycles (2 months) from a sample of female university students (n = 213), were analysed. Analyses tested for average effects of the menstrual cycle on sexual desire, individual differences in these effects, and cyclical and noncyclical associations between sexual desire and the 9 menstrual cycle-related changes. Note that data presented in the current article come from a larger study from which other reports have been published. OUTCOMES: Target variables were (1) daily change in sexual desire and (2) daily reports of 5 psychological changes and 4 physical changes that are commonly associated with the menstrual cycle. RESULTS: Results showed that when considering average effects across participants, the menstrual cycle was associated with a small midcycle increase in sexual desire. However, multilevel analyses showed large individual differences in how the menstrual cycle influences sexual desire. Specifically, some participants showed a midcycle increase, others a perimenstrual increase, and others no change across the menstrual cycle. Moreover, results demonstrated that psychological changes were more important for predicting sexual desire as compared with physical changes. CLINICAL IMPLICATIONS: These results suggest that daily measurement of sexual desire across multiple menstrual cycles may be an important tool in the assessment of sexual desire among some females. STRENGTHS AND LIMITATIONS: Strengths of this study are the daily assessment of sexual desire and all symptoms for 2 menstrual cycles and multilevel analyses that allow the study of individual differences. Limitations include limited measurement of sexual desire based on only 2 questions and the lack of measures of relationship status and sexual orientation. CONCLUSION: Emphasis is placed on the need to apply more rigorous research methods and to abandon simplistic average-effects models that are based on outdated theories and stereotypes.

Life stress influences the relationship between sex hormone fluctuation and affective symptoms in peripubertal female adolescents.

Female adolescents have a greatly increased risk of depression starting at puberty, which continues throughout the reproductive lifespan. Sex hormone fluctuation has been highlighted as a key proximal precipitating factor in the development of mood disorders tied to reproductive events; however, hormone-induced affective state change is poorly understood in the pubertal transition. The present study investigated the impact of recent stressful life events on the relationship between sex hormone change and affective symptoms in peripubertal female participants. Thirty-five peripubertal participants (ages 11-14, premenarchal, or within 1 year of menarche) completed an assessment of stressful life events, and provided weekly salivary hormone collections [estrone, testosterone, dehydroepiandrosterone (DHEA)] and mood assessments for 8 weeks. Linear mixed models tested whether stressful life events provided a context in which within-person changes in hormones predicted weekly affective symptoms. Results indicated that exposure to stressful life events proximal to the pubertal transition influenced the directional effects of hormone change on affective symptoms. Specifically, greater affective symptoms were associated with increases in hormones in a high stress context and decreases in hormones in a low stress context. These findings provide support for stress-related hormone sensitivity as a diathesis for precipitating affective symptoms in the presence of pronounced peripubertal hormone flux.

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.

Using self-report RDoC measures to identify transdiagnostic translational targets for perinatal affective disorders.

Perinatal depression affects 6.5-12.9% of women, with high rates in women of color and comorbid perinatal anxiety in up to 50% of cases. The Research Domain Criteria (RDoC) provides a translational framework for identifying transdiagnostic psychiatric symptoms, but its application in perinatal affective disorders (PNAD) is yet limited. Here, we identified RDoC-based transdiagnostic features of PNAD in 140 primarily low-income Black and Hispanic women at 272 total longitudinal visits across the perinatal period. Women completed RDoC self-report measures of potential threat and reward valuation-Behavioral Inhibition System/Behavioral Activation System scale (BIS/BAS) and Intolerance of Uncertainty Scale (IUS)-and measures of depression (Patient Health Questionnaire-9; PHQ-9) and anxiety (Generalized Anxiety Disorder-7; GAD-7). Longitudinal mixed effects models assessed associations of between-person ("trait-like") and within-person ("state-like") measures of potential threat (BIS/IUS) and reward valuation (BAS-Drive) with depression and anxiety symptoms. Higher "trait-like" BIS (standardized b = 2.33, p < .001) and IUS (b = 2.97, p < .001) scores, higher "state-like" BIS (b = .71, p < .001), and lower "state-like" BAS-Drive (b = - .58, p = .04) scores were associated with worse depressive symptoms. Higher "trait-like" BIS (b = 2.22, p < .001) and IUS (b = 2.73, p < .001) and higher "state-like" BIS scores (b = .92, p < .001) were associated with worse anxiety symptoms. Potential threat may be a prominent, transdiagnostic feature of perinatal anxiety and depression, whereas reward valuation may be a non-transdiagnostic, weaker feature of perinatal depression. Potential threat is important as both a "trait-like" feature that is sustained across the perinatal period and a "state-like" feature that varies within a woman across pregnancy. Grounded in RDoC, this work reveals neurobiological targets for translational research into PNAD.

Mood sensitivity to estradiol predicts depressive symptoms in the menopause transition.

BACKGROUND: The risk for depression markedly rises during the 5-6 years leading up to the cessation of menstruation, known as the menopause transition. Exposure to extreme estradiol levels may help explain this increase but few studies have examined individual sensitivity to estradiol in predicting perimenopausal depression. METHOD: The current study recruited 101 perimenopausal women. During Phase 1, we quantified each woman's sensitivity to changes in estradiol using 12 weekly measures of estrone-3-glucuronide (E1G), a urinary metabolite of estradiol, and concurrent depressive symptoms. The weekly cortisol awakening response was measured to examine the hypothalamic-pituitary-adrenal (HPA) axis in mediating mood sensitivity to estradiol. In Phase 2, depressive symptoms and major depression diagnoses were assessed monthly for 9 months. The relationship between Phase 1 E1G sensitivity and Phase 2 depressive symptoms and major depressive episodes was examined. Several baseline characteristics were examined as potential moderators of this relationship. RESULTS: The within-person correlation between weekly E1G and mood varied greatly from woman to woman, both in strength and direction. Phase 1 E1G mood sensitivity predicted the occurrence of clinically significant depressive symptoms in Phase 2 among certain subsets of women: those without a prior history of depression, reporting a low number of baseline stressful life events, and reporting fewer months since their last menstrual period. HPA axis sensitivity to estradiol fluctuation did not predict Phase 2 outcomes. CONCLUSION: Mood sensitivity to estradiol predicts risk for perimenopausal depression, particularly among women who are otherwise at low risk and among those who are early in the transition.

Are there temporal subtypes of premenstrual dysphoric disorder?: using group-based trajectory modeling to identify individual differences in symptom change.

BACKGROUND: Premenstrual dysphoric disorder (PMDD) is a new Diagnostic and Statistical Manual of Mental Disorders (DSM)-5 diagnosis characterized by the cyclical emergence of emotional and physical symptoms in the luteal phase of the menstrual cycle, with symptom remission in the follicular phase. Converging evidence highlights the possibility of distinct subtypes of PMDD with unique pathophysiologies, but temporal subgroups have yet to be explored in a systematic way. METHODS: In the current work, we use group-based trajectory modeling to identify unique trajectory subgroups of core emotional and total PMDD symptoms across the perimenstrual frame (days -14 to +9, where day 0 is menstrual onset) in a sample of 74 individuals prospectively diagnosed with DSM-5 PMDD. RESULTS: For the total daily symptom score, the best-fitting model was comprised of three groups: a group demonstrating moderate symptoms only in the premenstrual week (65%), a group demonstrating severe symptoms across the full 2 weeks of the luteal phase (17.5%), and a group demonstrating severe symptoms in the premenstrual week that were slow to resolve in the follicular phase (17.5%). CONCLUSIONS: These trajectory groups are discussed in the context of the latest work on the pathophysiology of PMDD. Experimental work is needed to test for the presence of possible pathophysiologic differences in trajectory groups, and whether unique treatment approaches are needed.

Differential effects of the menstrual cycle on reactive and proactive aggression in borderline personality disorder.

Borderline personality disorder (BPD) is characterized by rapidly shifting symptoms, including intense anger and aggressive behavior. Understanding how fluctuations in ovarian hormones across the menstrual cycle may contribute to symptom instability is key for accurate assessment of BPD symptoms and effective interventions. Reactive and proactive aggression, as well as anger-in and anger-out, were assessed daily in 15 physically healthy, unmedicated naturally cycling female individuals meeting criteria for BPD across 35 days. Urine luteinizing hormone surge and salivary progesterone were used to confirm ovulation and verify the cycle phase. Multilevel models evaluated cyclical differences of symptoms between cycle phases. Both forms of aggressive behavior demonstrated marked cycle effects, with reactive aggression highest during the midluteal cycle phase, co-occurring with initial increases in anger and irritability and followed by perimenstrual peaks in anger and anger-in. In contrast, highest levels of proactive aggression were observed during the follicular and ovulatory phases, when emotional symptoms and anger were otherwise at lowest levels. These findings highlight the importance of identifying the function of aggression when considering potential psychological and biological influences. Naturally cycling individuals with BPD may be at elevated risk for luteal worsening of a range of interpersonally reactive symptoms, including reactive aggression, whereas proactive aggression may occur more in phases characterized by less emotional and cognitive vulnerability and greater reward sensitivity. Research on aggression in this population should consider cycle effects. Cycling individuals with BPD attempting to reduce aggressive behavior may benefit from cycle-tracking to increase awareness of these effects and to develop appropriate strategies.

Does higher-than-usual stress predict nonsuicidal self-injury? Evidence from two prospective studies in adolescent and emerging adult females.

BACKGROUND: Nonsuicidal self-injury (NSSI) is highly prevalent among adolescent and emerging adult females. Most studies examining the relationship between stress and NSSI largely have relied on aggregate self-report measures of stress and between-person models. Using data from two prospective samples, this manuscript tests the hypothesis that within-person models of NSSI provide better clinical markers of risk for NSSI than between-person models of NSSI. METHODS: Two samples (Sample 1: 220 high-risk girls, M age = 14.68, SD = 1.36, baseline assessment and 3-month follow-ups for 18 months; Sample 2: 40 emerging adult females with a history of NSSI, M age = 21.55, SD = 2.14, 14 days with daily retrospective reports) were followed prospectively and completed validated measures of stress and NSSI. Models were adjusted for age and depression. RESULTS: In Sample 1, a within-person model demonstrated that higher-than-usual (but not average) stress levels predicted NSSI within the same 3-month wave. In Sample 2, results from a within-person model with daily diary assessment data showed that higher-than-usual stress (but not average daily stress) predicted same-day NSSI. CONCLUSIONS: Together, our results suggest that higher-than-usual stress, relative to one's typical stress level, but not average stress levels, signals times of enhanced risk for NSSI. These results highlight the clinical utility of repeated assessments of stress.

Ovarian Hormones as a Source of Fluctuating Biological Vulnerability in Borderline Personality Disorder.

PURPOSE OF REVIEW: To examine the potential role of ovarian hormones in biological vulnerability to borderline personality disorder (BPD). The review focuses primarily on research examining the menstrual cycle as a source of short-term lability of BPD symptom expression, while discussing the currently understudied possibility of ovarian hormone influence in the developmental course of BPD. FINDINGS: Several patterns of menstrual cycle effects on BPD symptoms and relevant features in non-clinical samples have been observed in empirical studies. Most symptoms demonstrated patterns consistent with perimenstrual exacerbation; however, timing varied between high and low arousal symptoms, potentially reflecting differing mechanisms. Symptoms are typically lowest around ovulation, with an exception for proactive aggression and some forms of impulsive behaviors. Preliminary evidence suggests ovarian hormones may exert strong effects on BPD symptom expression, and further research is warranted examining mechanisms and developing interventions. Recommendations for researchers and clinicians working with BPD are provided.

Perimenstrual exacerbation of symptoms in borderline personality disorder: evidence from multilevel models and the Carolina Premenstrual Assessment Scoring System.

BACKGROUND: Individuals with a borderline personality disorder (BPD) suffer from a constellation of rapidly shifting emotional, interpersonal, and behavioral symptoms. The menstrual cycle may contribute to symptom instability among females with this disorder. METHODS: Fifteen healthy, unmedicated females with BPD and without dysmenorrhea reported daily symptoms across 35 days. Urine luteinizing hormone and salivary progesterone (P4) were used to confirm ovulation and cycle phase. Cyclical worsening of symptoms was evaluated using (1) phase contrasts in multilevel models and (2) the Carolina Premenstrual Assessment Scoring System (C-PASS), a protocol for evaluating clinically significant cycle effects on symptoms. RESULTS: Most symptoms demonstrated midluteal worsening, a perimenstrual peak, and resolution of symptoms in the follicular or ovulatory phase. Post-hoc correlations with person-centered progesterone revealed negative correlations with most symptoms. Depressive symptoms showed an unexpected delayed pattern in which baseline levels of symptoms were observed in the ovulatory and midluteal phases, and exacerbations were observed during both the perimenstrual and follicular phases. The majority of participants met C-PASS criteria for clinically significant (⩾30%) symptom exacerbation. All participants met the emotional instability criterion of BPD, and no participant met DSM-5 criteria for premenstrual dysphoric disorder (PMDD). CONCLUSIONS: Females with BPD may be at elevated risk for perimenstrual worsening of emotional symptoms. Longitudinal studies with fine-grained hormonal measurement as well as hormonal experiments are needed to determine the pathophysiology of perimenstrual exacerbation in BPD.

Suicide Risk and the Menstrual Cycle: a Review of Candidate RDoC Mechanisms.

PURPOSE OF REVIEW: Risk for suicidal behavior may fluctuate across the menstrual cycle. Here, we use the RDoC framework to review potential mechanisms by which the cycle may increase acute suicide risk. RECENT FINDINGS: The menstrual cycle impacts the majority of RDoC constructs linked to suicide risk, particularly among hormone-sensitive women, such as those with premenstrual dysphoric disorder or premenstrual exacerbation of a psychiatric disorder. Despite this, there are no published studies examining suicidal ideation, planning, or behavior longitudinally across the cycle. More work is needed to understand how hormone sensitivity may relate to both trait and state suicide risk. Intensive multilevel investigations of cyclical hormone effects on suicide risk through specific RDoC mechanisms are suggested. This is a fertile research area and may provide key insights regarding the mechanisms of acute suicide risk.

Emotion-related impulsivity and rumination predict the perimenstrual severity and trajectory of symptoms in women with a menstrually related mood disorder.

OBJECTIVE: Women with menstrually related mood disorders (MRMDs) demonstrate clinically significant distress during the premenstrual week that remits with the onset of menses. Relatively little is known about psychosocial mechanisms of MRMDs. Given the core affective and behavioral symptoms of MRMDs, dysfunctional responses to emotion (e.g., difficulties with awareness and regulation of emotion; rumination and impulsive or maladaptive behavior in response to emotion) may be important factors to explore as cognitive and behavioral mechanisms in MRMDs. The purpose of the present study was to examine the associations of various dysfunctional responses to emotion (as measured using the Difficulties in Emotion Regulation Scale [DERS] and brooding on the Ruminative Responses Scale [RRS]) with premenstrual symptom severity and trajectory. METHOD: A total of 54 women (mean age = 38.11; 65% Caucasian) with prospectively confirmed MRMDs completed the DERS and RRS, and provided 2-4 menstrual cycles of daily symptom reports. RESULTS: Only the emotion-related impulsivity subscale of the DERS was robustly associated with premenstrual symptom severity. Brooding rumination predicted a more rapid premenstrual increase and slower postmenstrual remission of some symptoms. CONCLUSION: Both rumination and emotion-related impulsivity may be important treatment targets in cognitive behavioral interventions aimed at reducing symptom severity and cyclicity in MRMDs.

Treatment of premenstrual dysphoria with continuous versus intermittent dosing of oral contraceptives: Results of a three-arm randomized controlled trial.

BACKGROUND: Although traditionally dosed combined oral contraceptives (COCs) (21 days of active pills, 7 days of inactive pills) have not been demonstrated as superior to placebo for the treatment of premenstrual dysphoria (PMD), some randomized controlled trials (RCTs) indicate that oral contraceptives administered with a shortened or eliminated hormone-free interval are superior to placebo. However, results of such trials are mixed, and no existing studies have directly compared continuous and intermittent dosing schedules of the same oral contraceptive. The present study compared placebo, intermittent dosing of oral contraceptives, and continuous dosing of contraceptives for the treatment of PMD. METHODS: Fifty-five women with prospectively confirmed PMD completed a three-arm, RCT in which they were randomized to 3 months of placebo (n = 22), intermittent drospirenone/ethinyl estradiol dosed on a 21-7 schedule (n = 17), or continuous drospirenone/estradiol (n = 16) following a baseline assessment month. RESULTS: All three groups demonstrated similar, robust reductions in premenstrual symptoms over time. A marked placebo response was observed. CONCLUSIONS: The study fails to replicate a uniquely beneficial effect of continuous COC on PMD. Additional work is needed to understand the psychosocial context bolstering the placebo response in women with PMD.

High trait shame undermines the protective effects of prevalence knowledge on state shame following HPV/CIN diagnosis in women.

Human papillomavirus (HPV), and the related, cervical intraepithelial neoplasia (CIN), are common yet poorly understood physical conditions. The diagnosis of HPV often elicits shame and guilt, which in turn may undermine psychological and physical health. The current study compared shame and guilt responses to diagnosis among two groups: women diagnosed with HPV/CIN and women diagnosed with Epstein-Barr Virus (EBV/IM). Eighty women recently diagnosed with HPV/CIN or EBV/IM completed measures of shame- and guilt-proneness, shame and guilt following diagnosis, and disease knowledge including prevalence estimates (HPV and EBV, respectively). HPV/CIN (vs. EBV/IM) predicted more diagnosis-related shame and guilt. Estimates of high prevalence interacted with diagnosis and shame-proneness to predict diagnosis-related shame. Simple slope analyses indicated that in women with HPV/CIN reporting low-to-average shame-proneness, high prevalence estimates reduced diagnosis-related shame; however, women high in shame-proneness experienced high diagnosis-related shame regardless of more accurate prevalence estimates. Women high in shame-proneness appear to be particularly vulnerable to HPV-related shame even when they are aware that it is very common.