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1.  Changes in Mood, Cognitive Performance and Appetite in the Late Luteal and Follicular Phases of the Menstrual Cycle in Women With and Without PMDD (Premenstrual Dysphoric Disorder) 
Hormones and behavior  2008;54(1):185-193.
Although it’s been reported that women with premenstrual dysphoric disorder (PMDD) have increased negative mood, appetite (food cravings and food intake), alcohol intake and cognitive deficits premenstrually, few studies have examined these changes concurrently within the same group of women or compared to women without PMDD. Thus, to date, there is not a clear understanding of the full range of PMDD symptoms. The present study concurrently assessed mood and performance tasks in 29 normally cycling women (14 women who met DSM-IV criteria for PMDD and 15 women without PMDD). Women had a total of ten sessions: two practice sessions, 4 sessions during the follicular phase and 4 sessions during the late luteal phase of the menstrual cycle. Each session, participants completed mood and food-related questionnaires, a motor coordination task, performed various cognitive tasks and ate lunch. There was a significant increase in dysphoric mood during the luteal phase in women with PMDD compared to their follicular phase and compared to Control women. Further, during the luteal phase, women with PMDD showed impaired performance on the Immediate and Delayed Word Recall Task, the Immediate and Delayed Digit Recall Task and the Digit Symbol Substitution Test compared to Control women. Women with PMDD, but not Control women, also showed increased desire for food items high in fat during the luteal phase compared to the follicular phase and correspondingly, women with PMDD consumed more calories during the luteal phase (mostly derived from fat) compared to the follicular phase. In summary, women with PMDD experience dysphoric mood, a greater desire and actual intake of certain foods and show impaired cognitive performance during the luteal phase. An altered serotonergic system in women with PMDD may be the underlying mechanism for the observed symptoms; correspondingly, treatment with specific serotonin reuptake inhibitors (SSRIs) remains the preferred treatment at this time.
PMCID: PMC2491904  PMID: 18413151
Cognitive Performance; Food; PMDD; Mood; Women
2.  Altered autonomic nervous system activity as a potential etiological factor of premenstrual syndrome and premenstrual dysphoric disorder 
Premenstrual syndrome (PMS) encompasses a wide variety of cyclic and recurrent physical, emotional, and behavioral symptoms occurring during the late luteal phase of the menstrual cycle and abating shortly following the beginning of menses. Although PMS is widely recognized, its etiopathogenesis is not yet understood. The present study investigates whether the activity of the autonomic nervous system, which plays a vital role in orchestrating physiological homeostasis within the human body, is altered during the menstrual cycle of women with different degrees of premenstrual symptomatology.
Sixty-two women in their 20s to 40s with regular menstrual cycles participated in this study. All subjects were examined during the follicular and late luteal phases. Cycle phase was determined by the onset of menstruation and oral temperature and was verified by concentrations of ovarian hormones, estrone, and pregnanediol in a urine sample taken early in the morning. Autonomic nervous system activity was assessed by means of heart-rate variability (HRV) power spectral analysis during supine rest. The Menstrual Distress Questionnaire was used to evaluate physical, emotional, and behavioral symptoms accompanying the menstrual cycle of the subjects. The subjects were categorized in three groups, Control, PMS, and premenstrual dysphoric disorder (PMDD) groups, depending on the severity of premenstrual symptomatology.
No intramenstrual cycle difference in any of the parameters of HRV was found in the Control group, which had no or a small increase in premenstrual symptoms. In contrast, Total power and high frequency power, which reflect overall autonomic and parasympathetic nerve activity, respectively, significantly decreased in the late luteal phase from the follicular phase in the PMS group. As for the PMDD group, which had more severe symptoms premenstrually, heart-rate fluctuation as well as all components of the power spectrum of HRV were markedly decreased regardless of the menstrual cycle compared to those of the other two groups.
Several theories have been proposed to explain the underlying mechanisms of PMS with its complex web of bio-psycho-social factors. Although causes and consequences continue to elude, the present study provides intriguing and novel findings that the altered functioning of the autonomic nervous system in the late luteal phase could be associated with diverse psychosomatic and behavioral symptoms appearing premenstrually. In addition, when symptoms become more severe (as seen in women with PMDD), the sympathovagal function might be more depressed regardless of the menstrual cycle.
PMCID: PMC2253548  PMID: 18096034
3.  Work Stress, Premenstrual Syndrome and Dysphoric Disorder: Are There Any Associations? 
Women with recurrent and severe symptoms are diagnosed as having premenstrual syndrome (PMS), and if they suffer from severe affective symptoms, a diagnosis of premenstrual dysphoric disorder (PMDD) is made. The purpose of this study was to determine the association of work stress with PMS and PMDD.
Fifty-five female medical students in their internship program (ten 24-hour shifts per month) and 38 third-year female medical students without any shift duties were asked to participate in this study. A questionnaire was used to record demographic information and a self-report inventory was used to measure 13 symptoms relevant to PMS and PMDD according to DSM-IV criteria. All participants were asked to complete the inventory every night around midnight for those on shifts or before going to bed at home for 60 consecutive nights.
Out of 55 volunteers in the shift-work group, 31 (56%) fulfilled the diagnostic criteria for PMS in contrast to 12 (32%) in the control group. The frequency of PMDD was 12 (22%) in the intern group and 5 (13%) in the control group. Twenty one students (55%) from the control group did not have PMS or PMDD, compared to 12 (22%) students from the shift workers. Decreased energy (70.9%) and irritability (65.4%) were the most frequent symptoms during the luteal phase in the shift-work group.
Work stress and an increase in responsibility may produce or exacerbate PMS. Self-help approaches to induce self-awareness, along with psychological and psychiatric interventions, may help susceptible women to overcome this cyclic condition in order to increase their productivity as well as their quality of life.
PMCID: PMC3371938  PMID: 22737463
Premenstrual syndrome; Premenstrual dysphoric disorder; Work stress; Female; Medical students
4.  Premenstrual syndrome and premenstrual dysphoric disorder: guidelines for management 
The inclusion of research diagnostic criteria for premenstrual dysphoric disorder (PMDD) in the Diagnostic and Statistical Manual of Mental Disorders, 4th edition, recognizes the fact that some women have extremely distressing emotional and behavioural symptoms premenstrually. PMDD can be differentiated from premenstrual syndrome (PMS), which presents with milder physical symptoms, headache, and more minor mood changes. In addition, PMDD can be differentiated from premenstrual magnification of physical or psychological symptoms of a concurrent psychiatric or medical disorder. As many as 75% of women with regular menstrual cycles experience some symptoms of PMS, according to epidemiologic surveys. PMDD is much less common; it affects only 3% to 8% of women in this group. The etiology of PMDD is largely unknown, but the current consensus is that normal ovarian function (rather than hormone imbalance) is the cyclical trigger for PMDD-related biochemical events within the central nervous system and other target organs. The serotonergic system is in a close reciprocal relation with the gonadal hormones and has been identified as the most plausible target for interventions. Thus, beyond conservative treatment options such as lifestyle and stress management, other non-antidepressant treatments, or the more extreme intervneitons that eliminate ovulation altogether, selective serotonin reuptake inhibitors (SSRIs) are emerging as the most effective treatment option. Results from several randomized, placebo-controlled trials in women with PMDD have clearly demonstrated that SSRIs have excellent efficacy and minimal side effects. More recently, several preliminary studies indicate that intermittent (premenstrual only) treatment with selective SSRIs is equally effective in these women and, thus, may offer an attractive treatment option for a disorder that is itself intermittent.
PMCID: PMC1408015  PMID: 11109297
5.  Examination of premenstrual symptoms as a risk factor for depression in postpartum women 
Archives of women's mental health  2013;16(3):219-225.
Postpartum depression (PPD) is a significant public health concern with prevalence of major and minor depression reaching 20% in the first three postpartum months. Sociodemographic and psychopathology correlates of PPD are well-established; however, information on the relationship between premenstrual disorders and the development of PPD is less well-established. Thus, the aim of this study was to examine the role of premenstrual syndrome (PMS)/premenstrual dysphoric disorder (PMDD) as a risk factor for PPD.
Premenstrual symptoms were assessed retrospectively using the Premenstrual Symptoms Screening Tool (PSST) and depression was diagnosed according to DSM-IV criteria and assessed using the HDRS. A two-stage screening procedure was applied. In the first stage, the PHQ-9 was employed. In the second stage, women endorsing ≥ 5 symptoms on the PHQ-9 were administered the SCID, HDRS, and PSST.
Hierarchical linear regression showed that history of depression and PMS/PMDD contributed an additional 2% of the variance (p < .001), beyond that of sociodemographic factor effects. The full model accounted for 13% of the variance in postpartum depressive symptoms. Using logistic regression, a significant association also emerged between PMS/PMDD and PPD (OR=1.97).
The findings of this study suggest that PMS/PMDD is an important risk factor for PPD. Women endorsing a history of PMS/PMDD should be monitored during the perinatal period.
PMCID: PMC3663927  PMID: 23296333
Postpartum depression; Risk factors; Premenstrual syndrome (PMS); Premenstrual dysphoric disorder (PMDD); Premenstrual symptoms screening tool (PSST)
6.  Neuroimaging Evidence of Cerebellar Involvement in Premenstrual Dysphoric Disorder 
Biological psychiatry  2010;69(4):374-380.
Premenstrual dysphoric disorder (PMDD) is a debilitating cyclic disorder that is characterized by affective symptoms, including irritability, depression, and anxiety which arise in the luteal phase of the menstrual cycle and resolve soon after the onset of menses. Despite a prevalence of up to 8% in women of reproductive age, few studies have investigated the brain mechanisms that underlie this disorder.
We used positron emission tomography with [18F] fluorodeoxyglucose and self-report questionnaires to assess cerebral glucose metabolism and mood in 12 women with PMDD and 12 healthy comparison subjects in the follicular and late luteal phases of the menstrual cycle. The primary biological endpoint was incorporated regional cerebral radioactivity (scaled to the global mean) as an index of glucose metabolism. Relationships between regional brain activity and mood ratings were assessed. Blood samples were taken before each session for assay of plasma estradiol and progesterone concentrations.
There were no group differences in hormone levels in either the follicular or late luteal phase, but the groups differed in the effect of menstrual phase on cerebellar activity. Women with PMDD, but not comparison subjects, showed an increase in cerebellar activity (particularly in the right cerebellar vermis) from the follicular phase to the late luteal phase (p = 0.003). In the PMDD group, this increase in cerebellar activity was correlated with worsening of mood (p = 0.018).
These findings suggest that the midline cerebellar nuclei, which have been implicated in other mood disorders, also contribute to negative mood in PMDD.
PMCID: PMC3053132  PMID: 21092938
premenstrual dysphoric disorder; premenstrual syndrome; positron emission tomography; fluorodeoxyglucose; cerebellum; neuroimaging
Journal of affective disorders  2013;150(3):1234-1237.
Premenstrual dysphoric disorder (PMDD) is a chronic condition that significantly affects a woman’s well-being on a monthly basis. Although co-occurrence of PMDD and major depressive disorder (MDD) is common, most studies examine whether women with PMDD are at risk for depression and investigations of PMDD in depressed women are scant. Therefore, the present study examined rates of PMDD in young depressed women.
PMDD was assessed using a structured clinical interview (SCID-PMDD) in a sample of 164 young women with (n=85) and without (n=79) any history of depression.
Rates of PMDD were elevated among women with MDD in this sample. This result held true regardless of participants’ MDD status (current, lifetime or past history-only symptoms of MDD) and regardless of whether all or most DSM-IV-TR PMDD criteria were met.
Sample size in the present study was relatively small, and daily diary data were not available to confirm a PMDD diagnosis.
The current study highlights the need for clinicians to assess for PMDD in young female patients with major depression. Depressed women experiencing the added physical and psychological burden of PMDD may have a more severe disease course, and future studies will need to identify appropriate treatments for this subset of depressed women.
PMCID: PMC3759648  PMID: 23800446
pre-menstrual dysphoric disorder; major depressive disorder; comorbidity
8.  Neuroticism-related personality traits are related to symptom severity in patients with premenstrual dysphoric disorder and to the serotonin transporter gene-linked polymorphism 5-HTTPLPR 
Archives of Women's Mental Health  2010;13(5):417-423.
Neuroticism has been linked to a functional polymorphism in the serotonin transporter gene (5-HTTLPR), with short-allele carriers being overrepresented among high-scorers on neuroticism. Studies evaluating neuroticism-related personality traits in relation to the 5-HTTLPR polymorphism among patients with premenstrual dysphoric disorder (PMDD) and are lacking. The primary aim of this study was to evaluate the relationship between PMDD and neuroticism-related personality traits, and secondly, to relate the personality trait scores of PMDD patients to experienced symptom severity and to the 5-HTTLPR short allele. Thirty PMDD patients and 55 asymptomatic healthy controls were included in the study. The Swedish Universities Scale of Personality was used to evaluate personality traits. Genotype analyses were available in 27 PMDD patients and 18 healthy controls. Women with PMDD displayed higher levels of neuroticism-related personality traits (psychic trait anxiety, somatic trait anxiety, embitterment, stress susceptibility and mistrust) than healthy controls, and these effects were most prominent in women with more severe luteal phase symptoms. Furthermore, PMDD patients with at least one copy of the short allele of the 5-HTTLPR polymorphism scored higher on psychic trait anxiety and lack of assertiveness than PMDD patients who were homozygous for the long allele. PMDD patients who suffer from more severe luteal phase symptoms also display increased scores of neuroticism-related personality traits in comparison with healthy controls. Within the group of PMDD patients, differences in certain personality trait scores are associated with the short allele of the 5-HTTLPR polymorphism.
PMCID: PMC2941046  PMID: 20440524
Personality; Neuroticism; Premenstrual dysphoric disorder; Swedish universities scale of personality; 5-HTTPLPR
9.  Timing of Alcohol Use and the Incidence of Premenstrual Syndrome and Probable Premenstrual Dysphoric Disorder 
Journal of Women's Health  2009;18(12):1945-1953.
Relatively little is known about factors that influence the initial development of premenstrual syndrome (PMS) and premenstrual dysphoric disorder (PMDD), although these conditions are common in reproductive age women and are associated with substantial impairment. Previous studies have observed higher alcohol use in prevalent PMS/PMDD patients compared with controls, but it is unknown if drinking predisposes women to developing these disorders or is instead influenced by symptom experience.
To address this, we conducted a case-control study nested within the prospective Nurses' Health Study II (NHS2). Participants were a subset of women aged 27–44 and free from PMS at baseline (1991), including 1057 women who developed PMS over 10 years of follow-up, 762 of whom also met criteria consistent with PMDD, and 1968 control women. Alcohol use at various time periods, before and after onset of menstrual symptoms, was assessed by questionnaire.
Overall, alcohol use was not strongly associated with the incidence of PMS and probable PMDD. Relative risks (RR) for women with the highest cumulative alcohol use vs. never drinkers were 1.19 (95% confidence interval [CI] 0.84-1.67) for PMS and 1.28 (95% CI 0.86-1.91) for PMDD, although results did suggest a positive relationship in leaner women (p trend = 0.002). Women who first used alcohol before age 18 had an RR of PMS of 1.26 (95% CI 0.91-1.75) compared with never drinkers; the comparable RR for PMDD was 1.35 (95% CI 0.93-1.98).
These findings suggest alcohol use is not strongly associated with the development of PMS and PMDD, although early age at first use and long-term use may minimally increase risk.
PMCID: PMC2828255  PMID: 20044856
10.  Persistent Alterations in Biological Profiles in Women With Abuse Histories: Influence of Premenstrual Dysphoric Disorder 
To examine dysregulation in biological measures associated with histories of abuse in women and whether women with premenstrual dysphoric disorder (PMDD) differ in their dysregulation.
Twenty-five women meeting prospective criteria for PMDD and 42 non-PMDD controls underwent structured interview to determine abuse histories and lifetime Axis I diagnoses, excluding those with current Axis I disorders or using medications.
Major Outcome Measures
Plasma cortisol and norepinephrine (NE), heart rate (HR), blood pressure (BP), and vascular resistance index (VRI) were assessed at rest and in response to mental stress.
A greater proportion of PMDD women had prior abuse compared with non-PMDD women. Regardless of PMDD status, all abused women had lower plasma NE and higher HRs and tended to have lower plasma cortisol at rest and during stress. Abused women also reported more severe daily emotional and physical symptoms. Greater VRI and BP at rest and during stress were seen only in PMDD women with abuse.
There is persistent dysregulation in stress-responsive systems in all abused women that cannot be accounted for by current psychiatric illness or medications, and PMDD women may be differentially more vulnerable to the impact of abuse on measures reflecting α-adrenergic receptor function.
PMCID: PMC2750879  PMID: 17385972
premenstrual dysphoric disorder; abuse; stress; norepinephrine; cortisol
11.  Elevated Gray Matter Volume of the Emotional Cerebellum in Women with Premenstrual Dysphoric Disorder Disorder 
Journal of affective disorders  2012;146(2):266-271.
Premenstrual dysphoric disorder (PMDD) is characterized by severe, negative mood symptoms during the luteal phase of each menstrual cycle. We recently reported that women with PMDD show a greater increase in relative glucose metabolism in the posterior cerebellum from the follicular to the luteal phase, as compared with healthy women, and that the phase-related increase is proportional to PMDD symptom severity. We extended this work with a study of brain structure in PMDD.
High-resolution magnetic resonance imaging (MRI) scans were obtained from 12 women with PMDD and 13 healthy control subjects (whole-brain volume-corrected p<.05). Voxel-based morphometry was used to assess group differences in cerebral grey-matter volume (GMV), using a statistical criterion of p<.05, correcting for multiple comparisons in the whole-brain volume.
PMDD subjects had greater GMV than controls in the posterior cerebellum but not in any other brain area. Age was negatively correlated with GMV within this region in healthy women, but not in women with PMDD. The group difference in GMV was significant for women over age 30 (p=.0002) but not younger participants (p>.1).
PMDD appears to be associated with reduced age-related loss in posterior cerebellar GMV. Although the mechanism underlying this finding is unclear, cumulative effects of symptom-related cerebellar activity may be involved.
PMCID: PMC3529750  PMID: 22868063
premenstrual dysphoric disorder; premenstrual syndrome; cerebellum; neuroimaging; voxel-based morphometry; brain aging
12.  Premenstrual symptoms in young adults born preterm at very low birth weight - from the Helsinki Study of Very Low Birth Weight Adults 
BMC Women's Health  2011;11:25.
Clinically significant premenstrual symptoms are common among young women. Premenstrual syndrome (PMS) is characterized by emotional, behavioural and physical symptoms that consistently occur during the luteal phase of the menstrual cycle. Premenstrual dysphoric disorder (PMDD) is a severe form of PMS. Individual variation in stress responsiveness may be involved in the pathophysiology of premenstrual symptoms. Preterm birth at very low birth weight (VLBW, < 1500g) has a multitude of consequences that extend to adult life, including altered stress responsiveness which could affect the prevalence of premenstrual symptoms.
In this cohort study, we compared 75 VLBW women with 95 women born at term (mean age 22.5). We used a standardized retrospective questionnaire assessing the presence and severity of a variety of symptoms before and after menses. The symptom scores were used both as continuous and as dichotomized variables, with cutoffs based on DSM-IV criteria for PMDD and ACOG criteria for PMS, except prospective daily ratings could not be used. We used multiple linear and logistic regression to adjust for confounders.
There was no difference in the continuous symptom score before menses (mean difference VLBW-term -18.3%, 95% confidence interval -37.9 to 7.5%) or after menses. The prevalence of premenstrual symptoms causing severe impairment to daily life was 13.3% for VLBW women and 14.7% for control women. For PMDD, it was 8.0% and 4.2%, and for PMS, 12.0% and 11.6%, respectively. These differences were not statistically significant (p > 0.1).
Our findings suggest that the severity of premenstrual symptoms and the prevalence of PMDD and PMS among young women born preterm at VLBW is not higher than among those born at term.
PMCID: PMC3127835  PMID: 21639914
13.  Premenstrual Syndrome and Premenstrual Dysphoric Disorder in Perimenopausal Women 
Journal of Menopausal Medicine  2014;20(2):69-74.
To evaluate the prevalence of premenstrual syndrome (PMS) and premenstrual dysphoric disorder (PMDD) of perimenopausal women at a university hospital along with their menstrual characters.
A questionnaire survey regarding premenstrual symptoms was carried out in 100 perimenopausal women (43 to 53, years). The pattern of menstruation and, the intensity of dysmenorrhea were assessed; and further, the symptoms were classified according to their number, intensity, and persistence. The PMS criteria of American College of Obstetrics and Gynecology (ACOG) and PMDD criteria by American Psychiatric Association (APA) were evaluated.
The approximate prevalence of PMS criteria was 95% and that of PMDD criteria was 23%. The most dominant symptoms were 'breast tenderness', 'abdominal bloating', 'and headache'. PMDD was significantly associated with the severity of dysmenorrhea (P = 0.020). There was no significant relation with age, height, weight, body mass index and the cycle of menstruation.
Most women experience PMS and PMDD, which and have a significant impact on the activity of perimenopause women. However in most women that do not know well about PMS and PMDD. We should educate and inform women of PMS and PMDD, thus helping them increase their quality of life.
PMCID: PMC4207004  PMID: 25371896
Perimenopause; Premenstrual syndrome; Prevalence; Severity of illness index
14.  Effects and treatment methods of acupuncture and herbal medicine for premenstrual syndrome/premenstrual dysphoric disorder: systematic review 
During their reproductive years about 10% of women experience some kind of symptoms before menstruation (PMS) in a degree that affects their quality of life (QOL). Acupuncture and herbal medicine has been a recent favorable therapeutic approach. Thus we aimed to review the effects of acupuncture and herbal medicine in the past decade as a preceding research in order to further investigate the most effective Korean Medicine treatment for PMS/PMDD.
A systematic literature search was conducted using electronic databases on studies published between 2002 and 2012. Our review included randomized controlled clinical trials (RCTs) of acupuncture and herbal medicine for PMS/PMDD. Interventions include acupuncture or herbal medicine. Clinical information including statistical tests was extracted from the articles and summarized in tabular form or in the text. Study outcomes were presented as the rate of improvement (%) and/or end-of-treatment scores.
The search yielded 19 studies. In screening the RCTs, 8 studies in acupuncture and 11 studies in herbal medicine that matched the criteria were identified. Different acupuncture techniques including traditional acupuncture, hand acupuncture and moxibustion, and traditional acupuncture technique with auricular points, have been selected for analysis. In herbal medicine, studies on Vitex Agnus castus, Hypericum perforatum, Xiao yao san, Elsholtzia splendens, Cirsium japonicum, and Gingko biloba L. were identified. Experimental groups with Acupuncture and herbal medicine treatment (all herbal medicine except Cirsium japonicum) had significantly improved results regarding PMS/PMDD.
Limited evidence supports the efficacy of alternative medicinal interventions such as acupuncture and herbal medicine in controlling premenstrual syndrome and premenstrual dysphoric disorder. Acupuncture and herbal medicine treatments for premenstrual syndrome and premenstrual dysphoric disorder showed a 50% or better reduction of symptoms compared to the initial state. In both acupuncture and herbal medical interventions, there have been no serious adverse events reported, proving the safety of the interventions while most of the interventions provided over 50% relief of symptoms associated with PMS/PMDD. Stricter diagnostic criteria may have excluded many participants from some studies. Also, depending on the severity of symptoms, the rate of improvement in the outcomes of the studies may have greatly differed.
PMCID: PMC3898234  PMID: 24410911
Premenstrual syndrome; Premenstrual dysphoric disorder; Acupuncture; Herbal medicine; TCM; CAM; PMS; PMDD
15.  Reduced Phase-Advance of Plasma Melatonin after Bright Morning Light in the Luteal, but not Follicular, Menstrual Cycle Phase in Premenstrual Dysphoric Disorder: An Extended Study 
Chronobiology International  2011;28(5):415-424.
We previously observed blunted phase-shift responses to morning bright light in women with Premenstrual Dysphoric Disorder (PMDD). The aim of this study was to determine if we could replicate these findings using a higher intensity, shorter duration light pulse and to compare these results with the effects of an evening bright light pulse.
In 17 PMDD patients and 14 normal control (NC) subjects, we measured plasma melatonin at 30 minute intervals from 18:00–10:00 h in dim (< 30 lux) or dark conditions the night before (night 1) and after (night 3) a bright light pulse (administered on night 2) in both follicular and luteal menstrual cycle phases. The bright light (either 3,000 lux for 6 h or 6,000 lux for 3 h) was given either in the AM, 7 h after the Dim Light Melatonin Onset (DLMO) measured the previous month, or in the PM, 3 h after the DLMO.
In the luteal, but not in the follicular, phase, AM light advanced melatonin offset between night 1 and night 3 significantly less in PMDD than in NC subjects. The effects of PM light were not significant, nor were there significant effects of the light pulse on melatonin measures of onset, duration, peak or area under the curve.
These findings replicated our previous finding of a blunted phase-shift response to morning bright light in the luteal, but not the follicular, menstrual cycle phase in PMDD compared with NC women, using a brighter (6,000 vs. 3,000 lux) light pulse for a shorter duration (3 vs. 6 h). As the effect of PM bright light on melatonin phase-shift responses did not differ between groups or significantly alter other melatonin measures, these results suggest that in PMDD there is a luteal phase subsensitivity or an increased resistance to morning bright light cues which are critical in synchronizing human biological rhythms. The resulting circadian rhythm malsynchonization may contribute to the occurrence of luteal phase depressive symptoms in women with PMDD.
PMCID: PMC3377494  PMID: 21721857
light; phase-shift; melatonin; women; PMDD; menstrual cycle
16.  Magnesium (Mg) Retention and Mood Effects After Intravenous Mg Infusion in Premenstrual Dysphoric Disorder 
Biological psychiatry  2005;59(4):327-333.
Background: Conflicting data exist regarding the presence of magnesium (Mg) deficiency and the therapeutic efficacy of Mg in premenstrual syndrome or premenstrual dysphoric disorder (PMDD).
Methods: The % Mg retention was determined using 24-hour urinary Mg excretion and the total dose of Mg given intravenously. In women with (n = 17) and without (n = 14) prospectively diagnosed PMDD, several blood measures of Mg and mood were obtained before, immediately after, and the day following an intravenous Mg (.1 mmol/kg) loading dose. A positive mood response was seen under open conditions; as open Mg infusion improved mood, subsequent PMDD patients (n = 10) were randomized in a double-blind, placebo-controlled, crossover fashion.
Results: Patients (31.5%) and control subjects (27.5%) retained comparable mean percentages of Mg. Neither group differed in measures of mean Mg before, immediately after, or the day following Mg infusion. Although there was a time effect for all mood measures in the patient group (p <.01 for all), there was neither a treatment nor time-by-treatment effect.
Conclusions: Contrary to prior reports, we found no evidence of Mg deficiency in women with PMDD compared with control subjects. Furthermore, Mg was not superior to placebo in the mitigation of mood symptoms in women with PMDD.
PMCID: PMC1509101  PMID: 16197921
PMDD; magnesium; magnesium loading test
17.  Abnormalities of Dorsolateral Prefrontal Function in Women With Premenstrual Dysphoric Disorder: A Multimodal Neuroimaging Study 
The American journal of psychiatry  2013;170(3):305-314.
To investigate the neural substrate of premenstrual dysphoric disorder (PMDD), the authors used [15O]H2O positron emission tomography (PET) regional cerebral blood flow (rCBF) and blood-oxygen-level-dependent (BOLD) functional MRI (fMRI) signal measurements during working memory in conjunction with a 6-month hormone manipulation protocol.
PET and fMRI scans were obtained from women with prospectively confirmed PMDD and asymptomatic comparison subjects while they completed the n-back task during three hormone conditions: ovarian suppression induced by the gonadotropin-releasing hormone agonist leuprolide acetate, leuprolide plus estradiol, and leuprolide plus progesterone. Fifteen patients and 15 matched comparison subjects underwent PET imaging. Fourteen patients and 14 comparison subjects underwent fMRI. For each hormone condition, rCBF was measured with [15O]H2O PET, and BOLD signal was measured with fMRI, both during an n-back working memory paradigm. Global Assessment of Functioning Scale (GAF) scores and clinical characteristics were obtained for each patient before hormone manipulation, and symptoms were measured before and during the protocol.
In both the PET and fMRI studies, a main effect of diagnosis was observed, with PMDD patients showing greater prefrontal activation than comparison subjects. In the patient group, the degree to which dorsolateral prefrontal cortex activation was abnormally increased correlated with several dimensions of disease: disability as indicated by GAF scores, age at symptom onset, duration of PMDD, and differences in pre- and postmenses PMDD symptoms.
Abnormal working memory activation in PMDD, specifically in the dorsolateral prefrontal cortex, is related to PMDD severity, symptoms, age at onset, and disease burden. These results support the clinical relevance of the findings and the proposal that dorsolateral prefrontal cortex dysfunction represents a substrate of risk for PMDD. The concordance of the fMRI and PET data attests to the neurobiological validity of the results.
PMCID: PMC3968942  PMID: 23361612
18.  Lifetime Discrimination Associated with Greater Likelihood of Premenstrual Dysphoric Disorder 
Journal of Women's Health  2011;20(6):923-931.
To evaluate whether the stressor of perceived discrimination was associated with premenstrual dysphoric disorder (PMDD) and premenstrual symptoms among minority women. This study builds on previous research that found perceived discrimination was positively associated with other psychiatric illnesses.
Participants were 2718 Asian, Latina, and black premenopausal women aged 18–40 years who completed the World Mental Health Composite International Diagnostic Interview for the National Latino and Asian American Survey or the National Survey of American Life. Perceived discrimination was assessed with the Everyday Discrimination Scale. DSM-IV-based diagnostic algorithms generated a provisional lifetime diagnosis of PMDD.
Eighty-three percent of the participants reported experiencing discrimination (due to race, gender, age, height or weight, or other reasons) in their lifetimes. The frequency of perceived discrimination was positively associated with PMDD (odds ratio [OR] 1.08, 95% confidence interval [CI] 1.05-1.10) and premenstrual symptoms (OR 1.04, 95% CI 1.02-1.05), independent of demographic covariates and social desirability. Women reporting gender discrimination (OR 5.18, 95% CI 1.80-14.90), race discrimination (OR 4.14, 95% CI 1.54-11.11), and other forms of discrimination (OR 6.43, 95% CI 2.11-19.65) were significantly more likely than women without experiences of discrimination to have PMDD. Subtle discrimination was more strongly associated with PMDD (OR 1.12, 95% CI 1.01-1.23) than was blatant discrimination (OR 1.04, 95% CI 0.94-1.15).
This study is the first to demonstrate that perceived discrimination is associated with PMDD and premenstrual symptoms. These findings suggest that the prevalence of these conditions may be lessened by reducing discrimination in women's lives.
PMCID: PMC3159126  PMID: 21671777
19.  Luteal-Phase Accentuation of Acoustic Startle Response in Women with Premenstrual Dysphoric Disorder 
Alterations in central nervous system response to menstrual cycle-related fluctuations in neuroactive steroids are thought to underlie the emergence of negative affect in the luteal phase of the menstrual cycle in women with premenstrual dysphoric disorder (PMDD). Such changes in the neuroendocrine milieu may lead to heightened arousal and response to stress in women with PMDD. Using the acoustic startle paradigm, we sought to determine whether women with PMDD have an accentuated physiologic response to a mildly aversive stimulus during the luteal compared to follicular phase. Further, we also examined the impact of visual affective stimuli on acoustic startle response (ASR) magnitude. During the follicular and luteal phases of the menstrual cycle, acoustic stimuli (103 dB) were delivered to 15 women with PMDD and 14 healthy menstruating women of similar age. After obtaining baseline ASR, the procedure was repeated when subjects viewed pleasant, neutral and unpleasant pictures. There was a significant group by menstrual cycle phase interaction for baseline ASR magnitude, which can be attributed to the heightened startle magnitude in women with PMDD compared to healthy women during the luteal relative to the follicular phase. The direction and degree to which picture viewing modulated the startle magnitude did not vary by group or menstrual cycle phase. These data suggest that menstrual cycle phase has a powerful modulatory effect on physiologic reactivity in women with PMDD but not in healthy women. Physiologic response to affective stimuli appears to be intact in women with PMDD across the menstrual cycle.
PMCID: PMC2713599  PMID: 17314917
PMDD; startle; menstrual cycle; affect; valence; arousal
20.  Neurosteroids in the context of stress: Implications for depressive disorders 
Pharmacology & therapeutics  2007;116(1):125-139.
Animal models indicate that the neuroactive steroids 3α,5α-THP (allopregnanolone) and 3α,5α-THDOC (allotetrahydroDOC) are stress responsive, serving as homeostatic mechanisms in restoring normal GABAergic and hypothalamic-pituitary-adrenal (HPA) function following stress. While neurosteroid increases to stress are adaptive in the short term, animal models of chronic stress and depression find lower brain and plasma neurosteroid concentrations and alterations in neurosteroid responses to acute stressors. It has been suggested that disruption in this homeostatic mechanism may play a pathogenic role in some psychiatric disorders related to stress. In humans, neurosteroid depletion is consistently documented in patients with current depression and may reflect their greater chronic stress. Women with the depressive disorder, premenstrual dysphoric disorder (PMDD), have greater daily stress and a greater rate of traumatic stress. While results on baseline concentrations of neuroactive steroids in PMDD are mixed, PMDD women have diminished functional sensitivity of GABAA receptors and our laboratory has found blunted allopregnanolone responses to mental stress relative to non-PMDD controls. Similarly, euthymic women with histories of clinical depression, which may represent a large proportion of PMDD women, show more severe dysphoric mood symptoms and blunted allopregnanolone responses to stress versus never-depressed women. It is suggested that failure to mount an appropriate allopregnanolone response to stress may reflect the price of repeated biological adaptations to the increased life stress that is well documented in depressive disorders and altered allopregnanolone stress responsivity may also contribute to the dysregulation seen in HPA axis function in depression.
PMCID: PMC2650267  PMID: 17597217
Neurosteroids; Allopregnanolone; Stress; Premenstrual dysphoric disorder; Depressive disorders
21.  Increased Sensitivity to Light-Induced Melatonin Suppression in Premenstrual Dysphoric Disorder 
Chronobiology international  2010;27(7):1438-1453.
Increased sensitivity to light-induced melatonin suppression characterizes some, but not all, patients with bipolar illness or seasonal affective disorder. The aim of this study was to test the hypothesis that patients with premenstrual dysphoric disorder (PMDD), categorized as a depressive disorder in DSM-IV, have altered sensitivity to 200 lux light during mid-follicular (MF) and late-luteal (LL) menstrual cycle phases compared with normal control (NC) women. As an extension of a pilot study in which we administered 500 lux to 8 PMDD and 5 NC subjects, in the present study we administered 200 lux to 10 PMDD and 13 NC subjects during MF and LL menstrual cycle phases. We admitted subjects to the General Clinical Research Center (GCRC) in dim light (< 50 lux) to dark (during sleep) conditions at 16:00 h where nurses inserted an intravenous catheter at 17:00 h and collected plasma samples for melatonin at 30-min intervals from 18:00 to 10:00 h, including between 00:00 and 01:00 h for baseline values, between 01:30 and 03:00 h during the 200 lux light exposure administered from 01:00-03:00 h, and at 03:30 and 04:00 h after the light exposure. Median % melatonin suppression was significantly greater in PMDD (30.8%) vs. NC (−0.2%) women (p = 0.040), and was significantly greater in PMDD in the MF (30.8%) than in the LL (−0.15%) phase (p = 0.047). Additionally, in the LL (but not the MF) phase, % suppression after 200 lux light was significantly positively correlated with serum estradiol level (p = 0.007) in PMDD patients, but not in NC subjects (p > .05).
PMCID: PMC3038841  PMID: 20795885
light suppression; melatonin; menstrual cycle; depression; women
22.  The prevalence of premenstrual dysphoric disorder in a randomly selected group of urban and rural women 
Psychological medicine  2008;39(1):129-136.
Premenstrual dysphoric disorder (PMDD) was included as a provisional diagnostic category in the appendices of Diagnostic and Statistical Manual of Mental Disorders (DSM)-III-R (then called late luteal phase dysphoric disorder) and remained as an appendix in DSM-IV. Our study aimed to determine the prevalence of PMDD using all four DSM-IV research diagnostic criteria in a representative sample of women of reproductive age in the United States.
Data were collected in the homes of women between the ages of 13 and 55 years in two urban and two rural sites using a random sampling procedure developed by the National Opinion Research Center. Women completed daily symptom questionnaires and provided urine specimens each day for two consecutive ovulatory menstrual cycles (ovulation was estimated for women taking oral contraceptives) and were screened for psychiatric disorders by trained interviewers. Symptoms were counted toward a diagnosis of PMDD if they worsened significantly during the late luteal week during two consecutive ovulatory menstrual cycles, occurred on days in which women reported marked interference with functioning, and were not due to another mental disorder.
In the final analysis, 1246 women who had had at least one menstrual cycle and were neither naturally nor surgically menopausal nor pregnant were selected. Of the women in the study, 1.3% met criteria for the diagnosis as defined in DSM-IV.
The prevalence of PMDD is considerably lower than DSM-IV estimates and all but one of the estimates obtained from previous studies when all DSM-IV diagnostic criteria are considered. We suggest a new process for diagnosing PMDD based on our findings.
PMCID: PMC2752820  PMID: 18366818
Premenstrual dysphoric disorder; prevalence
23.  Exposure to American culture is associated with Premenstrual Dysphoric Disorder among ethnic minority women 
Journal of affective disorders  2010;130(1-2):334-341.
Ethnic minorities in America will achieve majority by 2042, and due to their younger age distribution, will represent the largest proportion of women at risk for Premenstrual Dysphoric Disorder (PMDD). Research has not addressed ethnic minority women’s vulnerabilities to PMDD. The objective of this study was to examine the relationship between acculturation and PMDD.
An analysis of acculturation and PMDD among 3,856 English-speaking, pre-menopausal Asian, Latina, and Black women from the National Latino and Asian American Survey and the National Survey of American Life.
The lifetime prevalence of PMDD was 3.3%. Nativity status, duration of residence, and age at immigration were significantly associated with PMDD. Foreign-born women (OR=0.38; 95% Confidence Interval (CI)=0.21–0.68)and immigrants arriving to the US after age six (OR=0.33, 95% CI=0.18, 0.62) were less likely to have PMDD, compared to US-born women, and US-born women/immigrants who arrived before age six, respectively. The likelihood of PMDD increased as the duration of residence in the US lengthened.
The diagnosis of PMDD was provisional due to retrospective symptom reporting. Statements of causality could not be made because the study was cross-sectional.
A substantial percentage of ethnic minority women suffer from PMDD in their lifetimes. Exposure to American culture appeared to elevate ethnic minority women’s likelihood for PMDD. The stressors that are associated with ethnic minority life in America—discrimination, poverty, pressures to assimilate, etc.—may contribute to ethnic minority women’s vulnerability to PMDD, and clinicians should be sensitive to the special risks in this population.
PMCID: PMC3068238  PMID: 21055829
Premenstrual Dysphoric Disorder; acculturation; ethnic minority women
24.  Premenstrual Disorders: Prevalence and Associated Factors in a Sample of Iranian Adolescents 
Premenstrual disorders usually refer to Premenstrual Syndrome (PMS) and Premenstrual Dysphoric Disorder (PMDD). This study was designed to find out the frequency of premenstrual disorders and evaluate the associated factors in a sample of Iranian adolescents.
This study was conducted to investigate the frequency of premenstrual disorders (PMS and PMDD) based on Premenstrual Assessment Scale (PAS) and also to determine the association of some demographic and menstrual characteristics with these disorders in adolescent girls.
Patients and Methods
This was a cross sectional study. A sample of adolescent school girls aged between 14 and 19 years were included in the study. Diagnostic assessments were based on Premenstrual Assessment Scale (PAS). The data were analyzed in a descriptive fashion and were compared among subgroups of the study sample. In addition, demographic and menstrual factors associations with premenstrual disorders were assessed.
In all 1379 female students were included in the study. About 99.5 % of the students reported at least one premenstrual symptom. Of these, 66.3% was mild, 31.4% moderate and 2.3% severe. A total of 814 girls (59%) met the diagnostic criteria for premenstrual dysphoric disorder (PMDD). Most frequently reported symptoms were back pain, lethargy, fatigue and anxiety. Early menarche, lower education was associated with higher scores on PAS.
Premenstrual disorders are common in adolescent girls. Preventive and treatment strategies are highly recommended.
PMCID: PMC3918194  PMID: 24578837
Premenstrual Syndrome; Depressive Disorder; Prevalence, Dysmenorrhea
25.  The Relationship between Severity of Premenstrual Syndrome and Psychiatric Symptoms 
Iranian Journal of Psychiatry  2012;7(1):36-40.
Premenstrual syndrome is a common disorder experienced by up to 50% of women during reproductive age. The prevalence of severe form of PMS (PMDD) is 3% to 8 %. Psychiatric disorders in PMS patients have resulted in significant morbidity and in some cases caused resistance to the treatment process.
Material and Method
390 participants (264 with PMS/PMDD, and 126 healthy students of University of Guilan) who completed the demographic questionnaire, daily symptom rating (DSR) and the checklist 90-revised (SCL-90-R) took part in this study. This study was conducted using a cross sectional method.
According to repeated measure variance, the mean scores of psychiatric symptoms (Depression, Anxiety, Aggression, Interpersonal sensitivity) in the PMS group were significantly higher than the healthy group (p< 0/05), and increase in severity of PMS from mild to severe was accompanied by increase in mean score of these subscales. There was a significant difference in mean score of depression, anxiety, aggression and interpersonal sensitivity between the 3rd and the 13th day of the cycle. Significant effect of the DSR grouping (PMS and Healthy group) and time interaction emerged in interpersonal sensitivity and aggression, significant effect on the DSR grouping (Mild, Moderate, Severer) and time interaction demonstrated in interpersonal sensitivity.
Patients with prospective confirmed PMDD seemed to suffer from psychiatric symptoms. Therefore, recognizing co-morbid psychiatric symptoms in patients with PMDD is of prime importance. All healthcare providers should be sensitive to mental status of women with PMS.
PMCID: PMC3395966  PMID: 23056116
Premenstrual syndrome; Psychiatric symptoms; Severity of illness

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