GABA receptors,progesterone and premenstrual dysphoric disorder

Premenstrual dysphoric disorder (PMDD) is characterized by depression, anxiety and other affective symptoms which recur in the luteal phase of the menstrual cycle. Evidence from animal models of depression and anxiety indicate the importance of neuroactive steroid hormones and the GABA(A) receptor in the etiology and potential treatment of mood disorders. These data are reviewed in the light of human clinical studies and specific animal models of PMDD.     

Prevalence of premenstrual dysphoric disorder in female patients with seasonal affective disorder

BACKGROUND: Both seasonal affective disorder/winter type (SAD) and premenstrual dysphoric disorder (PMDD) are cyclical disorders characterized by so-called atypical depressive symptoms. In the present study we compared the point prevalence rates of PMDD between a sample of premenopausal female patients suffering from SAD and healthy female controls. METHODS: Forty-six female patients with SAD and 46 healthy controls were included in our study. All subjects underwent a semistructured clinical interview according to DSM IV criteria and completed the Seasonal Pattern Assessment Questionnaire. PMDD was diagnosed in a self-rating interview for PMDD according to DSM IV criteria. To verify the diagnosis of PMDD, all patients were followed up in stable summer remission using daily self-rating scales for two full menstrual cycles. RESULTS: Patients with SAD fulfilled significantly more often the diagnostic criteria for PMDD than female healthy controls (46% vs. 2%, respectively; chi-square: P<0.001). CONCLUSIONS: These results provide preliminary evidence for a high point prevalence rate of PMDD in premenopausal females with SAD. CLINICAL IMPLICATIONS: It would be worthwhile to investigate whether an additional diagnosis of PMDD has an impact on the clinical outcome and the response to bright light therapy in female patients with SAD.     

Cognitive-behavioral therapy for premenstrual syndrome and premenstrual dysphoric disorder: a systematic review

We systematically reviewed empirical studies that investigated the use of cognitive-behavioral therapy (CBT) for premenstrual syndrome (PMS) or premenstrual dysphoric disorder (PMDD). Our multi-database search identified seven published empirical reports. Three were identified as randomized controlled trials (RCTs). The methods utilized to investigate therapeutic efficacy of CBT in these studies varied widely from case reports to RCTs with pharmacotherapy comparison groups. Initially we provide a brief overview of CBT and justifications for its potential use to treat PMS/PMDD. Next, we provide critical evaluations of the analyses used in each study focusing on the detection of intervention effects assessed by statistically significant time by group interactions. When possible we calculate effect sizes to elucidate the clinical significance of results. Our review revealed a dearth of evidence providing statistically significant CBT intervention effects. Issues such as overall time investment, latency to treatment effects, and complementary and combined therapies are considered. We present a theoretical argument for applying mindfulness- and acceptance-based CBT interventions to PMS/PMDD and suggest future research in this area. In conclusion, to produce the necessary evidence-base support for PMS/PMDD given the limited empirical evidence reported here, researchers are called on to produce methodologically rigorous investigations of psychosocial interventions for PMS/PMDD.     

Prevalence of premenstrual syndrome and premenstrual dysphoric disorder in Japanese women

Summary To investigate the prevalence and impact of premenstrual symptoms in Japanese women, we developed the PSQ “The Premenstrual Symptoms Questionnaire” for the screening of premenstrual symptoms. The PSQ translates DSM-IV criteria into a rating scale with degrees of severity. One thousand one hundred and eighty-seven Japanese women between the ages of 20 and 49 yrs, who were seen at a clinic for uterine cancer screening, were assessed regarding their premenstrual symptoms using the PSQ. As many as 95% of these women were found to suffer from premenstrual symptoms. The rates of prevalence of moderate to severe PMS and PMDD in Japanese women were 5.3 and 1.2%, respectively, which are lower than those in Western women. Only 5.3% of women with moderate to severe PMS and PMDD were treated. The results of this study suggest that race and ethnicity influence the expression of premenstrual symptoms and that the current state of medical care for Japanese women with moderate to severe PMS and PMDD is not satisfactory.     

Mood, neuropsychological function and cognitions in premenstrual dysphoric disorder.

BACKGROUND: Neuropsychological function and cognitive correlates of depression have not previously been examined in a rigorously defined population of patients suffering from premenstrual dysphoric disorder (PMDD). METHOD: MOOD, neuropsychological function and cognition were measured in 10 PMDD patients and 10 age-matched controls in both phases of the menstrual cycle in a random order, counter-balanced design. RESULTS: The BDI was significantly elevated in the luteal phase of PMDD patients only while other cognitive measures showed no significant differences. Working memory was impaired in the luteal phase of the menstrual cycle with no significant differences between PMDD and control subjects. CONCLUSION: Despite the small sample size, these results show that the BDI is sensitive to the mood fluctuations of PMDD patients. An impairment in working memory was also found although this is a general menstrual cycle effect.     

New perspectives on the treatment of premenstrual syndrome and premenstrual dysphoric disorder

Summary Premenstrual dysphoric disorder was discussed by a panel of European researchers. The criteria for diagnosis of the condition, its categorisation as a mental disorder, and its differentiation from depression and premenstrual syndrome are all considered. Data on the treatment of premenstrual dysphoric disorder, using serotonin reuptake inhibitors and other therapies, are reviewed. An algorithm for the treatment of premenstrual dysphoric disorder is proposed.     

Emotion regulation in women with premenstrual dysphoric disorder

Premenstrual dysphoric disorder (PMDD) is a psychiatric disorder that causes serious impairments in the functioning and quality of life of affected women. Until recently, research efforts were somewhat hampered by the lack of formal diagnostic criteria, which have now been codified as a category in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). Better characterization of deficits in socioemotional functioning caused by PMDD may aid in improving treatment efforts. In this investigation, prospective symptom ratings, based on DSM-5 criteria, were used to measure PMDD symptoms in 36 women (18 with PMDD and 18 healthy controls). Two self-report inventories, the Emotion Regulation Questionnaire and the Difficulties in Emotion Regulation Scale, were used to measure ability to regulate emotions, and socioemotional functioning was measured by inventories of social connectedness, perceived stress, and affect. Potential relationships between ability to regulate emotion and PMDD symptom severity, as well as other measures of socioemotional functioning and affective state, were tested. Women with PMDD reported significantly more behavioral impulsivity and greater difficulties in regulating emotion and in socioemotional functioning. Cognitive or behavioral strategies to improve these problems may benefit women with PMDD and help to alleviate distress caused by this disorder.     

Toward a functional neuroanatomy of premenstrual dysphoric disorder

BACKGROUND: Premenstrual dysphoric disorder (PMDD) is a prevalent disorder in the spectrum of affective illness, and is associated with significant morbidity. The neurobiology of this underdiagnosed and undertreated illness is poorly understood. A functional magnetic resonance imaging (fMRI) probe of fronto-limbic function was used to advance understanding of PMDD pathophysiology. METHODS: We applied BOLD fMRI and Statistical Parametric Mapping to study neural response to emotional words in the context of an emotional Go/NoGo inhibitory control task. We examined alterations in this response across the menstrual cycle, in the premenstrual (late luteal) phase and the postmenstrual (late follicular) phase. RESULTS: In the premenstrual (vs. postmenstrual) phase, PMDD subjects, compared with asymptomatic subjects, showed an increased amygdala response to negative vs. neutral stimuli, and a decreased ventral striatum response to positive vs. neutral stimuli. PMDD subjects failed to show the asymptomatic subjects' patterns of increased medial and decreased lateral orbitofrontal cortex (OFC) response to negative vs. neutral stimuli in the premenstrual vs. postmenstrual phase. This decreased premenstrual medial OFC response to negative stimuli in PMDD subjects was further enhanced in the context of behavioral inhibition. LIMITATIONS: Further studies with larger numbers of subjects are needed. CONCLUSIONS: The results support a neurobiological model of enhanced negative emotional processing, diminished positive emotional processing, and diminished top-down control of limbic activity in PMDD during the premenstrual phase. These findings provide a basis for a neurocircuitry model of PMDD, and have implications for studies of mood/emotional regulation across the human menstrual cycle in health and disease.     

Prevalence of premenstrual syndrome and premenstrual dysphoric disorder in Japanese high school students

To determine the prevalence and the impact of premenstrual symptoms among Japanese adolescent girls, a total of 618 high school students were assessed. Of them, 64.6% were found to suffer from premenstrual symptoms, which is lower than that in adult women. On the other hand, the rates of prevalence of moderate to severe PMS and PMDD in girls were higher than those in adult women. Premenstrual symptoms could have significant consequences by interfering with the daily functioning of adolescent girls.     

Gray matter abnormalities in patients with premenstrual dysphoric disorder: an optimized voxel-based morphometry

BackgroundAlthough brain neurochemistry is thought to play a role in the development of premenstrual dysphoric disorder (PMDD), neuroimaging studies of PMDD are sparse. We examined the extent to which gray matter (GM) abnormalities were present in women with PMDD compared to healthy controls.Methods3.0 T magnetic resonance imaging scans of 15 women with PMDD and 15 healthy controls were compared using optimized voxel-based morphometry (VBM) analysis. A regression analysis was used to assess the relationship between GM density and PMDD-symptom severity.ResultsOur results showed significantly increased GM density in the hippocampal cortex and significantly decreased GM density in the parahippocampal cortex among women with PMDD compared to healthy controls. However, these GM abnormalities were not significantly associated with the severity of PMDD.LimitationOur inferences of the relationships between structural alterations and PMDD are drawn from a small sample, which may have increased the likelihood of type I error.ConclusionsGM abnormalities in limbic and paralimbic cortices were found to be associated with the pathophysiology of PMDD. Etiology of PMDD is likely related to emotional processing and self-regulation. Our findings provide a basis of neurobiological model for PMDD.     

Levetiracetam for treatment of premenstrual dysphoric disorder: A pilot,open-label study

Kindling and impaired electroencephalophysiology have been suggested to play a role in the pathophysiology of premenstrual dysphoric disorder (PMDD). Levetiracetam is a novel antiepileptic drug which has shown strong anti-kindling activity in animal models of epilepsy. In this preliminary prospective study we examined the safety and efficacy of levetiracetam for the treatment of PMDD. One hundred twenty-three potential patients were prospectively screened to enroll seven patients into the open-label treatment phase of the study. PMDD was diagnosed per DSM-IV-TR criteria and two consecutive months of prospective ratings of Daily Record of Severity of Problems (DRSP). The Mini International Neuropsychiatric Interview (MINI) was used to exclude any co-morbid conditions. Levetiracetam was started at 250 mg qhs at the end of the first week of the follicular phase. Dosage was gradually increased up to 1,500 mg bid as tolerated or clinically effective. The treatment phase lasted 4 months. Response to treatment was evaluated by Clinical Global Impression (CGI) and DRSP scores. Six out of seven patients experienced a considerable decrease in their DRSP scores with levetiracetam, starting from the first treatment cycle. One patient dropped out of the study due to lack of efficacy after one cycle. Medication was fairly well tolerated. Improvements in food cravings and premenstrual headaches were also noted as unexpected benefits. Anticonvulsant medications, specifically levetiracetam, could be effective in the treatment of PMDD. Future double-blind, placebo controlled, randomized studies are warranted and should include larger number of patients.     

Prevalence and predictors of premenstrual syndrome and premenstrual dysphoric disorder in a population-based sample

The study aimed at assessing the prevalence of premenstrual symptoms and of premenstrual syndrome (PMS) and premenstrual dysphoric disorder (PMDD) in a population-based sample of women of the entire reproductive age range, as well as to analyse predictors of PMS and PMDD in terms of socio-demographic, health status and health behavioural factors. A set of questions on PMS–based on the premenstrual syndrome screening tool developed by Steiner et al., translated into German and piloted—was integrated into the written questionnaire of the 2007 Swiss Health Survey. Weighted prevalence rates and multivariable regression analysis for the outcome variables PMS and PMDD were calculated. A total of 3,913 women aged 15 to 54 years answered the questions on PMS symptoms, and 3,522 of them additionally answered the questions on interference of PMS with life. Ninety one percent of the participants reported at least one symptom, 10.3% had PMS and 3.1% fulfilled the criteria for PMDD. The prevalence of PMS was higher in non-married women, in women aged 35–44 years and in women of the Italian-speaking region of Switzerland. Both PMS and PMDD were strongly associated with poor physical health and psychological distress. Socio-cultural factors seem to determine the prevalence, perception and handling of PMS. Considering the association with poor physical health and high psychological distress, a broader underlying vulnerability in women qualifying for PMDD must be assumed and should be taken into account in clinical management as well as in future research in this field.     

Prevalence, incidence and stability of premenstrual dysphoric disorder in the community

BACKGROUND: Despite an abundance of clinical research on premenstrual and menstrual symptoms, few epidemiological data provide estimates of the prevalence, incidence, co-morbidity, stability and correlates of premenstrual dysphoric disorder (PMDD) in the community. AIMS: To describe the prevalence, incidence, 12 co-morbidity factors and correlates of threshold and subthreshold PMDD in a community sample of young women. METHODS: Findings are based on prospective-longitudinal community survey of 1488 women aged 14-24, who were followed-up over a period of 48 months (follow-up, N = 1,251) as part of the EDSP sample. Diagnostic assessments were based on the Composite International Diagnostic Interview (CIDI) and its 12-month PMDD diagnostic module administered by clinical interviewers. Diagnoses were calculated using DSM-IV algorithms, but daily ratings of symptoms, as required, were not available. RESULTS: The baseline 12-month prevalence of DSM-IV PMDD was 5.8%. Application of the diagnostic exclusion rules with regard to concurrent major depression and dysthymia decreased the rate only slightly (5.3%). An additional 18.6 % were 'near-threshold' cases, mostly because they failed to meet the mandatory impairment criterion. Over the follow-up period only few new PMDD cases were observed: cumulative lifetime incidence was 7.4%. PMDD syndrome was stable across 48 months with < 10% complete remissions among baseline PMDD cases. The 12-month and lifetime co-morbidity rates were high (anxiety disorders 47.4%, mood disorders 22.9%; somatoform 28.4%), only 26.5 % had no other mental disorder. Particularly high odds ratios were found with nicotine dependence and PTSD. In terms of correlates increased rates of 4-weeks impairment days, high use of general health and mental health services, and increased rates of suicide attempts were found. CONCLUSION: In this sample of adolescents and young adults, premenstrual symptoms were widespread. However, DSM-IV PMDD was considerably less prevalent. PMDD is a relatively stable and impairing condition, with high rates of health service utilization, increased suicidality and substantial co-morbidity.     

Posttraumatic stress disorder and trauma characteristics are correlates of premenstrual dysphoric disorder

Posttraumatic stress disorder (PTSD) is often comorbid with premenstrual dysphoric disorder (PMDD) in women; however, it is unclear whether this relationship is driven by the trauma that may lead to PTSD or if PTSD is uniquely associated with PMDD. In this study, we examine trauma and PTSD as independent correlates of PMDD. Researchers conducted a cross-sectional, secondary data analysis of 3,968 female participants (aged 18–40) of the Collaborative Psychiatric Epidemiology Surveys. Women who had a history of trauma with PTSD (odds ratio, OR = 8.14, 95% confidence interval, CI = 3.56–18.58) or a history of trauma without PTSD (OR = 2.84, 95% CI = 1.26–6.42) were significantly more likely than women with no history of trauma to report PMDD. This graded relationship was also observed in association with premenstrual symptoms. Among trauma survivors, PTSD was independently associated with PMDD, although characteristics of participants' trauma history partially accounted for this association. Our study demonstrated that trauma and PTSD were independently associated with PMDD and premenstrual symptoms. Clinicians should be aware that women who present with premenstrual symptomatology complaints may also have a history of trauma and PTSD that needs to be addressed. This pattern of comorbidity may complicate the treatment of both conditions.     

Pretreatment pattern of symptom expression in premenstrual dysphoric disorder

BACKGROUND: Use of intermittent dosing strategies for the treatment of premenstrual dysphoric disorder (PMDD) highlights the need for detailed empirical data on the onset, duration and pattern of symptom expression in women suffering from PMDD. METHOD: Data were analyzed from 276 women who met DSM-IV criteria for PMDD and prospectively charted two menstrual cycles prior to commencing sertraline treatment. The presence and severity of PMDD symptoms were measured using the Daily Record of Severity of Problems (DRSP). RESULTS: The most frequent PMDD symptoms (moderate-to-severe for > or = 3 days) included anger/irritability (76%), anxiety/tension (71%), tired/lethargic (58%), and mood swings (58%). Mean DRSP scores peaked at day -2 (2 days prior to the onset of menses), but the within-patient day of onset of PMDD-level symptoms was highly variable, differing from cycle-to-cycle by > or = 4 days in 45% of women. Similarly, the within-patient duration of PMDD symptoms varied from cycle-to-cycle by 3 or more days in > or = 50% of women. Depending on the criteria used, 1 day after the onset of menstruation, 34-46% of women continued to report moderate to severe symptoms. LIMITATION: Women in this sample were recruited for participation in a treatment study, and the results may not generalize to women with PMDD in the community. CONCLUSION: The results of this analysis found significant within-patient variability in the time-to-onset and offset of PMDD symptoms, as well as their duration. The temporal pattern and high degree of within-patient variability across menstrual cycles of PMDD symptoms may have treatment implications.     

Association between premenstrual dysphoric disorder and perinatal depression: a systematic review

Premenstrual dysphoric disorder (PMDD) affects 1.2 to 5% of women of reproductive age. Besides significant suffering and social, occupational, and interpersonal impairment, it has been suggested that this syndrome is associated with other affective disorders, in different reproductive phases, such as pregnancy and the postpartum period. However, the literature on this association is scarce and presents great variability in terms of adopted methodology and mixed results. To analyze the relationship between PMDD and other affective disorders, aiming to contribute to the clarification of whether PMDD can be considered a risk factor for perinatal depression (PND). Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we conducted a comprehensive literature search in PubMed, EMBASE, CINAHL, PsycINFO databases. Seven original studies were included. Only one study linked PMDD with depression during pregnancy, with evidence of a positive association between PMDD and PND. This and five other studies show a positive relationship between PMDD and postpartum depression (PPD), assessed in periods ranging from 2 to 4 days to 1 year after birth. Only one study found no significant association between PMDD and PPD, assessed at 4 weeks postpartum. There seems to be a positive and significant association between PMDD and the development of perinatal depression, particularly postpartum depression. This review supports the relevance of health professionals systematically evaluating the presence of premenstrual dysphoric disorder, when monitoring women throughout the perinatal period.

     

Comorbid disorders in patients with bipolar disorder and concomitant substance dependence

OBJECTIVE: Substance dependence is common in bipolar disorder and is associated with an increase in Axis I and II comorbidity. Little research has compared the relative rates of comorbidity among bipolar patients with dependence on different substances. METHODS: The Mini International Neuropsychiatric Interview (MINI) was used to assess 166 outpatients involved in one of three clinical trials of medications for bipolar disorder and substance dependence. Patients had concurrent alcohol dependence, cocaine dependence, or both conditions. RESULTS: Generalized anxiety disorder and current depressed mood were significantly more common in bipolar patients with alcohol dependence than bipolar patients with cocaine dependence. Those with cocaine dependence had significantly higher rates of post-traumatic stress disorder and antisocial personality disorder and were more likely to present in a mixed mood state than patients dependent on alcohol. Cocaine ENC dependent patients were more likely than alcohol dependent patients to have Bipolar I relative to Bipolar II. LIMITATIONS: This is a retrospective, cross-sectional data analysis using the MINI for diagnosis. CONCLUSIONS: Cocaine dependence and alcohol dependence were associated with different clinical features and comorbid disorders in bipolar patients. The results may help confirm the validity of integrative models of mood, behavioral, anxiety, and personality disorders. Further studies on the causal relationship between substance dependence and concurrent and lifetime Axis I disorders for patients with bipolar disorders are indicated.     

Diagnostic and therapeutic algorithm for the treatment of premenstrual dysphoric disorder

Many women experience psychological and physical symptoms associated with menstrual cycle. In 3% to 5% of women that meet the criteria for premenstrual dysphoric disorder, the symptoms are severe and impair their social and occupational functioning. Although the etiology of premenstrual dysphoric disorder is unknown, the symptoms of dysphoria, including depression and anxiety, have been associated with serotonergic dysregulation. Selective serotonin reuptake inhibitors, taken only during the symptomatic luteal phase, are considered as first-line therapy for premenstrual dysphoric disorder.