INDEX
INTRODUCTION ... 3 DIAGNOSTIC CLASSIFICATION ... 8 ETIOLOGY ... 12 Genetics ... 13 Hormones ... 14 Serotonin and other neurotransmitters ... 15 Psycho-social factors and stress ... 16 PSYCHIATRIC COMORBIDITY ... 20 Unipolar Depression ... 20 Post-Partum Depression ... 21 Bipolar Disorder ... 21 Anxiety Disorders ... 22 Schizophrenia ... 23 Personality Disorders ... 24 Affective temperaments and Emotional Dysregulation ... 24 TREATMENT ... 28 Non-pharmacological methods ... 29 Treatment of somatic symptoms ... 31 Hormonal treatments ... 32AIM OF THE STUDY ... 36 MATERIALS AND METHODS ... 37 Sample ... 37 Data collection ... 37 Assessing Instruments ... 38 Current and lifetime psychiatric diagnosis ... 38 State-Trait Anxiety Inventory ... 38 Reactivity Intensity Polarity Stability Questionnaire (RIPoST) ... 39 The Daily Record of Severity of Problems ... 39 Statistical Analysis ... 40 RESULTS ... 41 DISCUSSION ... 44 LIMITATIONS ... 47 CONCLUSIONS ... 48 TABLES ... 50 REFERENCES ... 58
INTRODUCTION
The term “premenstrual syndrome” (PMS) is used to describe a variety of physical, cognitive, affective and behavioural symptoms that can occur cyclically in the luteal phase of the menstrual cycle and resolve rapidly in the follicular phase, a few days after the onset of menstruation. Some of the physical symptoms include breast tenderness, bloating, headache, swelling of extremities, fatigue, acne and craving / increased appetite. The most common affective symptoms are irritability, anxiety, tension, emotional lability, crying, anger, confusion, impaired memory skill, sleep disorders, social withdrawal (American Psychiatric 2000, Bulletins--Gynecology 2000) Mild premenstrual symptoms occur in about 70-90% of women in reproductive age (Hylan, Sundell et al. 1999) Among them 20-40% describe those symptoms as annoying to the point of interfering with daily functioning and attribute them to the so-called premenstrual syndrome (PMS)(Mishell 2005) (Dean, Borenstein et al. 2006) (Council, Sciences et al. 1998)
A subset of women who experience symptoms related to PMS includes 3-9% of women who have severe symptoms. These symptoms cause a significant subjective distress or a significant functional impairment, meeting the diagnostic criteria of the DSM-IV-TR (American Psychiatric 2000) for Premenstrual Dysphoric Disorder (PMDD) (Grady-Weliky 2003, Halbreich 2010) Another subset of 19% seems to have sub syndromic Premenstrual Dysphoric Disorder (Freeman, Smith et al. 2002).
Premenstrual Dysphoric Disorder (PMDD) is a syndrome that affects almost 3-9% of the women during the reproductive age and has a significant impact on women’s quality of life.
The PMDD, as defined by APA and assumed by ACOG, is recognized as a more severe and pervasive mood disorder that affects a smaller, although significant, percentage of women. It is difficult to define the prevalence of DDPM in the population due to the strict diagnostic criteria proposed by the DSM, which include prospective recording of symptoms, the exclusion of other psychiatric and physical disorders and the assessment of a functional impairment.
The distress related to the premenstrual symptoms, although they occur in the luteal phase of the menstrual cycle and resolve rapidly in the follicular phase, is relevant (Freeman 2003) and causes a severe social and working impairment, with significantly higher percentages of absenteeism from work and worsening in productivity (Grady-Weliky 2003, Halbreich 2010). Costs related to absences from work must be added to the costs for health care services provided, such as outpatient visits, laboratory tests and radiological examinations (Borenstein, Dean et al. 2003, Borenstein, Chiou et al. 2005, Borenstein, Dean et al. 2007).
The prevalence of PMDD is of 3-9% in the US and Europe, while data from non-Western countries shows percentages ranging from 2% to 50.2%. These results are probably related to cultural variables, strictness of the diagnostic criteria used, the retrospective evaluation of symptoms and the range of the symptom severity defined. Although the symptoms of PMDD are short-lived compared to those of other depressive disorders, their impact on quality of life in the luteal phase is equivalent to that found in Major Depressive Disorder, in Post-Traumatic Stress Disorder and Panic Disorder (Freeman 2003).
The impact of PMDD is affected by the severity of symptoms in the luteal phase, its chronicity and the resulting social and working impairment: women with premenstrual symptoms have significantly higher percentages of absenteeism from work and worse productivity. Costs arising from absence from work must be added to the costs of outpatient visits, laboratory tests and radiological examinations performed (Borenstein, Dean et al. 2003, Borenstein, Chiou et al. 2005, Borenstein, Dean et al. 2007). Although the symptoms can manifest at any time after menarche, the average age of onset is around 20 years old. Women request medical assistance at the average age of 30 years. A gradual worsening of symptoms is reported with the increasing of the age until the beginning of menopause (Steiner and Streiner 2005).
High rates of psychiatric comorbidity have been found in women with PMDD (Steiner, Haskett et al. 1980, Leon, Phelan et al. 1986, Pearlstein, Frank et al. 1990, Jacobsen 1993, Yonkers 1997, Halbreich, Borenstein et al. 2003) (Basoglu, Cetin et al. 2000, Critchlow, Bond et al. 2001, Fornaro, Perugi et al. 2010) especially with major depression and post-partum depression (Halbreich, Borenstein et al. 2003, Halbreich and Kahn 2003, Lee, Yi et al. 2015) (Greene and Dalton 1953, Endicott, Amsterdam et al. 1999, Schatzberg 2004), avoidant personality disorder (Endicott, Amsterdam et al. 1999, De Ronchi, Muro et al. 2000, Schatzberg 2004), bulimia nervosa and binge eating disorder (Leon, Phelan et al. 1986) (Fornaro, Perugi et al. 2010, Nobles, Thomas et al. 2016), Bipolar Disorder and Anxiety disorders (Kim, Czarkowski et al. 2011)
PMDD has been clearly identified as a distinct disorder, with clinical and biological profiles, different from those observed in other mood disorders (Endicott, Amsterdam et al. 1999)
In scientific literature the variability of the prevalence data of this menstrual-related mood disorder depends on the definitions used: the American Psychiatric Association (APA) in accordance with the DSM-IV-TR points out that up to 70% of women suffer from some mild symptoms of the premenstrual syndrome; the American College of Obstetricians and Gynecologists (ACOG) reports that up to 85% of women manifest PMS, defined by the presence of at least one emotional symptom and at least one physical symptom present in three consecutive menstrual cycles, severe enough to interfere with the activities of daily routine.
Sociological researches suggest that current diagnostic criteria could lead to an over diagnosis of PMDD, which may cause a stigmatizing view of women's premenstrual angers/distress (Browne 2015).
Recently, it has been inserted in the Depressive Disorders Section of DSM-5 (Association 2013) as a distinct clinical entity. The diagnostic criteria listed in the DSM-5 include prospective recording of symptoms, the exclusion of other psychiatric and physical disorders and the assessment of a functional impairment. The diagnostic criteria adopted to define the population of women suffering from this menstrual-related mood disorder are
heterogeneous and this variability reflects the different range reported in scientific literature.
Most of the studies regarding the aetiology of PMS have evaluated the role of sex steroids, neurotransmitters and genetics, without drawing a shared consensus on the biological basis of PMDD. Psychosocial factors seem to play a role for the development and maintenance of PMS.
In accordance with the two main biological theories, the pharmacological treatment of premenstrual symptoms targets brain neurotransmitters and steroid hormones. Non-pharmacological methods could be useful for the treatment of milder forms of PMS.
DIAGNOSTIC CLASSIFICATION
In the last years, clinical research has used a broad diagnostic concept of PMS and PMDD, leading to the development of different diagnostic criteria d, consequently, the inclusion of heterogeneous populations.
After being placed in the Appendix of DSM-IV-TR, among the suggested new diagnostic categories, in the DSM-5 the Premenstrual Disphoric Disorder (PMDD) has been inserted in the Depressive Disorders Section (DSM-5 2013). Nevertheless, this is not a new concept: Hippocrates already described some women who complained of several symptoms before menstruation, including suicidal ideation and other distressing symptoms (Simon 1978). In 1931 Frank used the term “premenstrual tension” to describe a group of 15 women with premenstrual symptomatology(Frank 1931), and later Green and Dalton (1953) conceived the “premenstrual syndrome” (Greene and Dalton 1953). The revision of the DSM-III (1987) defined that condition as a “late luteal phase dysphoric disorder” (Steiner 1997, Schatzberg 2004) and placed it in Appendix A, among the proposed diagnostic categories needing further studies. In the DSM-IV (1994) the name changed from “late luteal phase dysphoric disorder” to “premenstrual dysphoric disorder” and was inserted in Appendix B, among Depressive Disorders Not Otherwise Specified.
In 1998 some experts, reviewing data of the literature, concluded that PMDD was a distinct disorder, with clinical and biological profiles, different from those observed in other mood disorders (Endicott, Amsterdam et al. 1999). Therefore, there are some drugs indicated for the treatment of a disorder that has not yet been totally recognised in the 10th
edition of the International Statistic Classification of Diseases (ICD-10 2004): “tension premenstrual syndrome” is included in the gynaecological section and requires only a physical or
emotional symptom of the seven reported. However, the definition of the syndrome is rather vague and does not specify the crucial aspect of the "gravity" of the symptom or the level of functional impairment.
In the upcoming edition of the ICD-11, due to be published in 2017, PMDD appears set for inclusion as a separate disorder (Kurumaji 2013).
In the DSM-IV-TR (2000) the PMDD is still in the Appendix B, among diagnostic categories needing further studies, but the criteria are more accurate: in most menstrual cycles during the past year, five (or more) of the following symptoms were present for most of the time during the last week of the luteal phase, began to remit within a few days after the onset of the follicular phase, and were absent in the week post menses, with at least one of the symptoms being either (1), (2), (3), or (4):
1. Markedly depressed mood, feelings of hopelessness, or self-deprecating thoughts 2. Marked anxiety, tension, feelings of being “keyed up” or “on edge”
3. Marked affective lability (e.g., feeling suddenly sad or tearful or increased sensitivity to rejection)
4. Persistent and marked anger or irritability or increased interpersonal conflicts 5. Decreased interest in usual activities (e.g., work, school, friends, hobbies) 6. Subjective sense of difficulty in concentrating
7. Lethargy, easy fatigability, or marked lack of energy
8. Marked change in appetite, overeating, or specific food cravings 9. Hypersomnia or insomnia
11. Other physical symptoms, such as breast tenderness or swelling, headaches, joint or muscle pain, a sensation of “bloating,” or weight gain
In the DSM-5 there are some additional changes, and diagnostic criteria for Premenstrual Dysphoric Disorder are:
A. In the majority of menstrual cycles, at least five symptoms must be present in the final week before the onset of menses, start to improve within a few days after the onset of menses, and become minimal or absent in the week post menses.
B. One (or more) of the following symptoms must be present:
1. Marked affective lability (e.g., mood swings: feeling suddenly sad or tearful, or increased sensitivity to rejection).
2. Marked irritability or anger or increased interpersonal conflicts.
3. Marked depressed mood, feelings of hopelessness, or self-deprecating thoughts. 4. Marked anxiety, tension, and/or feelings of being keyed up or on edge.
C. One (or more) of the following symptoms must additionally be present, to reach a total of five symptoms when combined with symptoms from Criterion B above.
1. Decreased interest in usual activities (e.g., work, school, friends, hobbies). 2. Subjective difficulty in concentration.
3. Lethargy, easy fatigability, or marked lack of energy.
4. Marked change in appetite, overeating, or specific food cravings. 5. Hypersomnia or insomnia.
7. Physical symptoms such as breast tenderness or swelling, joint or muscle pain, a sensation of “bloating,” or weight gain.
Note: The symptoms in Criteria A-C must have been met for most menstrual cycles that occurred in the preceding year.
D. The symptoms are associated with clinically significant distress or interference with work, school, usual social activities, or relationships with others (e.g., avoidance of social activities; decreased productivity and efficiency at work, school, or home). E. The disturbance is not merely an exacerbation of the symptoms of another disorder,
such as major depressive disorder, panic disorder, persistent depressive disorder (dysthymia), or a personality disorder (although it may co-occur with any of these disorders).
F. Criterion A should be confirmed by prospective daily ratings during at least two symptomatic cycles. (Note: The diagnosis may be made provisionally prior to this confirmation.)
G. The symptoms are not attributable to the physiological effects of a substance (e.g., a drug of abuse, a medication, other treatment) or another medical condition (e.g., hyperthyroidism).
Nevertheless, it should be noted that many women complaining of clinically relevant premenstrual symptoms do not satisfy DSM-5 diagnostic criteria and probably there is still a percentage of women who could benefit from an effective treatment, but who remain excluded from the diagnosis because they do not reach the minimum number of symptoms required by the DSM.
ETIOLOGY
The current consensus regarding the etiology of premenstrual syndrome suggests that it could be the result of a complex interaction between sex steroids and central neurotransmitters (Mortola 1998).
The correlation between post-partum depression and PMDD supports the hypothesis that there may be a subset of women who are vulnerable to depression during specific reproductive cycle events because of a heightened sensitivity to hormonal fluctuations (Soares and Zitek 2008, Lee, Yi et al. 2015). It has been reported that women affected by PMDD are more likely to develop depressive symptoms, after physiological stimuli of estrogens and progesterone, than women without PMDD (Schmidt, Nieman et al. 1998). It has been postulated that this vulnerability might be in part related to serotonin (Steiner and Pearlstein 2000).
Studies about genetics reveal a possible role of a biological vulnerability associated with an increased risk for the development of mood dysregulation. This hypothesis has linked familiarity for mood disorders with a genetic polymorphism in the serotonin transporter promoter gene (5-HTTLPR) (Praschak-Rieder, Willeit et al. 2002).
In general, there is actually a lack of consensus on the biological basis of PMDD, also underlined by the lack of efficacy of selective serotonin reuptake inhibitors in up to 40% of PMDD. For this reason, in the last years, bio-psychosocial theories have gained increasing attention and have suggested the role of psychosocial factors and stress in the development and maintenance of PMS.
Genetics
Family history of PMDD is actually a risk factor for the development of the disease. Studies on twins suggest that the disease may be heritable in 44% to 56% cases and that PMS genes were shared in part with neuroticism and liability to lifetime major depression (Treloar, Heath et al. 2002).
Prospective studies conducted in the last years have confirmed that women with SPM have a family history of seasonal mood disorder or major depression, suggesting that, among genetic factors implied in the pathogenesis of PMDD, serotonin and oestrogens might have a significant role.
PMDD and seasonal affective disorder may share genetic vulnerability factors through a polymorphism in the serotonin transporter promoter gene (5-HTTLPR)(Praschak-Rieder, Willeit et al. 2002). The correlation between PMDD and mood disorders seems to increase with higher severity of the premenstrual symptoms. Women with severe premenstrual dysphoria are more likely to develop a future episode of major depression than women with non-severe dysphoria (Manu 2004)
It has been found a link between 5HTTLPR polymorphism and severity of PMDD symptoms (Steiner and Pearlstein 2000). In women affected by PMDD, an allelic variant of estrogen receptor 1 (ESR 1) has been found to be more frequently expressed (Huo, Straub et al. 2007)
In contrast, a recent study found no significant association of Dopamine D3 receptor (DRD3) polymorphism, and Cannabinoid receptor Type 1 (CNR1) polymorphism with PMDD (Yildiz, Vural et al. 2015).
Hormones
The manifestation of PMDD symptoms requires the hormonal fluctuation of the menstrual cycle (Epperson 2013). The timing of clinical manifestations of PMS underlines the main role of the cyclic ovarian activity in the beginning and in the remission of the symptoms. The hormonal hypothesis is supported by the evidence that premenstrual symptoms are absent before puberty, during pregnancy and after menopause.
Several studies have suggested the role of sexual steroids in the development of premenstrual symptoms. The hormonal hypothesis is supported by the evidence that drugs inducing menopause-like state, such as leuprolide, improve premenstrual symptoms (Schmidt, Nieman et al. 1998) The detention of the steroid concentrations in women with PMDD is conditioned by the timing and the method of evaluation. The detection of physiological level of estrogens and progesterone in women with PMDD, lead some authors to suppose an increased vulnerability to physiological changes caused by hormones during the menstrual cycle (Rubinow and Schmidt 1995, Roca, Schmidt et al. 2003) Other authors suppose the women with PMS may suffer from an inadequate production of ovarian neuroactive steroids, especially in the luteal phase, because of the detention of blunted response to the GnRH test (Monteleone, Luisi et al. 2000).
A recent study reports an association between the development of premenstrual symptoms and a specific kinetic profile of the concentration of progesterone (Lovick, Guapo et al. 2017). The effects of progesterone (Schmidt, Nieman et al. 1998) could be mediated by changes in its active metabolite allopregnanolone. The role of allopregnanolone has not been clarified in clinical study also because the concentration in peripheral blood may not
be a correct marker of its central activity (Wang, Seippel et al. 1996, Monteleone, Luisi et al. 2000) (Rapkin, Morgan et al. 1997)
Androgens were also taken into account, especially due to the prominent appearance of signs and symptoms of irritability in the DDPM profile. Some authors have found high levels of testosterone in women with severe premenstrual irritability and a positive result in treating PMDD with androgen antagonists (Eriksson, Sundblad et al. 2000, Steiner and Pearlstein 2000). Although there is still no strong evidence in this regard, other endocrine factors (cortisol, thyroid hormones, prolactin, aldosterone and endorphins) seems to contribute in various ways to the development of PMS and PMDD (Halbreich, Borenstein et al. 2003).
Serotonin and other neurotransmitters
Research has shown an important role of serotonin in the pathophysiology of PMDD. Patients affected by PMDD seem to have lower blood levels of serotonin (Rapkin, Edelmuth et al. 1987) and reduced platelet serotonin transporter activity (Taylor, Mathew et al. 1984) compared with control patients. It has been observed that women with premenstrual dysphoria have lower platelet binding sites for paroxetine compared to control group. (Melke, Westberg et al. 2003).
It has been reported that lower whole blood 5-HT concentrations in the premenstrual phase could be associated with enhanced negative mood due to lower 5-HT concentrations at brain synapses, which may be caused in part by lower estrogen concentration (Kikuchi, Nakatani et al. 2010).
Inhibition of serotoninergic activity has been shown to aggravate symptoms of PMDD: metergoline, a serotonin selective antagonist that blocks serotonin (5-HT) receptors (particularly 5-HT2A and 5-HT2C) provokes a return of symptoms in women with PMDD treated with fluoxetine (Roca, Schmidt et al. 2002).
Some studies have demonstrated the efficacy of serotoninergic agents, such as L-Tryptophane, Buspirone, Fenfluramine (Bancroft, Cook et al. 1991, Yatham 1993, Rasgon, Serra et al. 2001) and low doses of SSRIs (FitzGerald, Malone et al. 1997, Steiner, Korzekwa et al. 1997, Ramos, Hara et al. 2009). These findings could outline a deficiency of serotonin in patients with PMDD (Steiner, Yatham et al. 1999, Cohen, Miner et al. 2002) (Halbreich, Bergeron et al. 2002) (Wyatt, Dimmock et al. 2002, Ravindran, Woods et al. 2007, Eriksson, Ekman et al. 2008, Steiner, Ravindran et al. 2008).
The evidence reported in clinical studies that only 60% of patients respond to treatments with SSRIs suggests that serotonin cannot be considered the main pathogenic factor of PMDD. Some recent studies have explored the possible role of gabaergic and noradrenergic systems, but these data need further confirmation (Backstrom, Haage et al. 2011, Kim, Cho et al. 2011).
Psycho-social factors and stress
There are poor findings suggesting a role of demographic factors in PMDD. Although the symptoms can manifest at any time after menarche, the years of the late twenties through mid-thirties seems to be the most vulnerable time for distressing PMS (Freeman, Rickels et al. 1995). This data could be in part explained by fact that women request medical
assistance at the average age of 30 years. It has been reported a gradual worsening of symptoms with increasing age until the beginning of menopause (Steiner and Streiner 2005). Multiparity seems to be linked to more severe premenstrual symptoms (Freeman, Rickels et al. 1995).
There are conflicting findings about the relationship of school education with the development of PMDD. Women with advanced school education report more severe premenstrual symptoms (Marvan, Diaz-Erosa et al. 1998, Wittchen, Becker et al. 2002, Adewuya, Loto et al. 2008, Ramos, Hara et al. 2009), even though it has been observed an association between PMDD and low levels of school education (Ross and Steiner 2003, Skrzypulec-Plinta, Drosdzol et al. 2010) A recent study in a sample of young, professional, urban women demonstrates a significant association of PMDD with other lifestyle factors, such as sleep, physical activity, total tea/coffee intake, and change in tea/coffee and food intake under stress (Monteleone, Luisi et al. 2000, Mishra, Banwari et al. 2015)Patterns of associations between specific psycho-social factors, in particular regarding body dissatisfaction, and PMS in dependence of menstrual cycle phase have been recently shown in a comparison study (Kleinstauber, Schmelzer et al. 2016)
The occurrence of premenstrual symptoms seems to be also related to cultural variables, such as nationality. The prevalence of PMDD is of 3-9% in the US and Europe, while data from non-Western countries shows percentages ranging from 2% to 50.2%.
Even though socio-cultural factors cannot fully justify the clinical picture of PMS or PMDD, cultural variables seem to influence the manifestation of PMDD. Western women might be "educated" to have negative expectations regarding menstrual cycle (Johnson 1987, Sveinsdottir 1998). Negative expectations, also perpetuated by media, could increase
women's tendency to interpret physiological changes occurring during menstrual cycle as negative physical symptoms or mood instability(Merikangas, Foeldenyi et al. 1993, Chang, Holroyd et al. 1995) (Chrisler and Caplan 2002).
Also the use of less restrictive diagnostic criteria that could lead to an over-diagnosis of PMDD may cause a stigmatizing view of women's premenstrual angers/distress (Browne 2015)
Stressful life events seems to play an important role in the etiology of premenstrual symptoms, notably stress related to daily life might be involved in the pathogenesis of PMDD (Woods, Most et al. 1985) (Warner and Bancroft 1990, Fontana and Palfai 1994). Women with premenstrual syndrome show high levels of anxiety (Picone and Kirkby 1990, Christensen, Board et al. 1992) and usually use less effective coping strategies to deal with stress, such as avoidance, rather than other more effective strategies, such as direct action and problem-focused coping. The occurrence of premenstrual symptoms seems to be associated with hyper-control and with the lack of expression of the symptoms of anger (Stout and Steege 1985) It has been reported a lack of association between psycho-social stress and an increased severity of premenstrual symptoms (Blake, Salkovskis et al. 1998). A study evaluating brain activity with EEG registrations, reports data consistent with a diathesis-stress model for women with menstrual-related dysphoria (Accortt, Stewart et al. 2011).
A recent web-based study evaluating the relationship between perceived stress, acculturative stress, and premenstrual symptoms, shows that perceived stress is significantly related to premenstrual symptoms in Korean students. The study also reports a history of sexual abuse as the strongest related factor (Lee and Im 2016). The prevalence of
sexual abuse in the general population of women is 12.4% (MacMillan, Fleming et al. 2001) Sexual abuse seems to be more frequently reported (40%) in patients treated for SPM and psychiatric patients (32%) (Friedman, Hurt et al. 1982) compared to general population (Praschak-Rieder, Willeit et al. 2002). Sexual abuse, and especially sexual abuse in childhood, has lasting effects on psychological and physiological responses to stress. Through the effects on the hypothalamic-pituitary-adrenal axis, sexual abuse may predispose women to psychiatric disorders, including PMDD. A recent study confirmed the association of PMDD with childhood abuse in a Turkish sample and also suggested that emotional abuse and emotional neglect during childhood could be significantly related to PMDD later in life (Soydas, Albayrak et al. 2014)
PSYCHIATRIC COMORBIDITY
Premenstrual dysphoric disorder (PMDD) can occur in comorbidity with other psychiatric disorders, particularly mood and anxiety disorders.
Several published studies and reviews have focused on the lifetime comorbidity of mood disorders and anxiety disorders in women with PMSs. Many reviews which looked only at studies that prospectively diagnosed PMDD, found that the lifetime risk of major depression ranged from 30–70% and that a lifetime diagnosis of an anxiety disorder occurred in 14–16% of patients (Yonkers 1997). Patients with comorbid psychiatric disorders have increased morbidity and often a more treatment resistant course (Olfson, Hansell et al. 1997, De Graaf, Bijl et al. 2002). Premenstrual symptoms are common. It is estimated that up to 80% of menstruating women suffer from some premenstrual symptoms such as mood fluctuations, depression, irritability, and physical symptoms (Pearlstein and Stone 1998).
Unipolar Depression
Few studies have been designed to examine the prevalence of concurrent depression in women with PMDD. In one such study that prospectively diagnosed PMDD, comorbid mood and anxiety disorders were significantly more common in women with PMDD (66%) than in healthy controls (32%) (Fava, Grandi et al. 1992). Among patients at a university gynaecology clinic, 18% of the women who met DSM-IV criteria for PMDD had a concurrent DSM-IV diagnosis of major depression (Alpay and Turhan 2001).The exact nature of the relationship and interaction between PMDD and depression is still uncertain. Both depression and PMDD have been linked to serotonin (5-HT) dysfunction in some
studies. In women with PMDD, whole blood 5-HT levels and platelet uptake of 5-HT are decreased. In addition, PMS is exacerbated by the depletion of tryptophan, the precursor of 5-HT (Menkes, Coates et al. 1994, Steiner and Pearlstein 2000)
Post-Partum Depression
There appears to be a correlation between a history of postpartum depression and current PMDD. Women with increased severity of premenstrual symptoms were more likely to have experienced a past postpartum depression in a study where women rated symptoms recalling their most recent menstrual cycle (Warner, Bancroft et al. 1991). Pearlstein, Frank et al. (1990) noted a high prevalence (29%) of past postpartum depression in their sample of women with PMS (Pearlstein, Frank et al. 1990). Critchlow et al. (2001) reported that 66% of women with PMDD had experienced a postpartum depression compared to no episodes in the control group (Critchlow, Bond et al. 2001).
Bipolar Disorder
The literature on PMDD and comorbid bipolar disorder is sparse. As both disorders are cyclical mood disorders and both seem to be related to an increase in postpartum mood disorders, studying the relationship is important. In the Wittchen study (2002), of the women with PMDD, 5.7% had bipolar I disorder and 4.9% had bipolar II disorder (Wittchen, Becker et al. 2002). In a sample of 180 women with bipolar I disorder, 66% reported mood changes related to their menstrual cycle (Blehar, DePaulo et al. 1998). Only one study has examined the severity of premenstrual symptoms in women with
rapid-cycling bipolar disorder (RCBD), a variant requiring at least four mood episodes in one year. Price and DiMarzio (1986) found that 60% of women with RCBD had severe PMS and, using a retrospective reporting method, these same women were found to have more affective episodes per year (Price, Dimarzio et al. 1986). However, Roy-Byrne et al. (1987) present data on 16 women with bipolar disorder suggesting there is not an increase in PMS in women with bipolar disorder compared to controls using a retrospective methodology to assess PMS symptoms (Roy-Byrne, Hoban et al. 1987). There are case reports of patients who developed manias, which occurred exclusively premenstrually, who were responsive to lithium (Sproule 2002)
Anxiety Disorders
It appears that anxiety disorders occur more commonly in women with PMDD than in controls. Fava, Grandi et al. (1992) found that 59% of the women with PMDD had a concurrent anxiety disorder, with generalized anxiety disorder (GAD) being the most common. In one study of women seeking treatment at a PMS clinic with prospectively confirmed PMS, 25% had a comorbid diagnosis of GAD and 25% had a diagnosis of panic disorder (Facchinetti, Demyttenaere et al. 1992). In addition, 23% of the women had social phobia and 11% had diagnoses with obsessive-compulsive disorder. Although Wittchen et al. (2002) did not find an increase in panic disorder in patients with PMDD compared to controls; they did find a significant increase in specific phobias (31.7% vs. 12.5%) and social phobia (21.1% vs. 6%) (Wittchen, Becker et al. 2002). When taking into account only the studies that gathered PMDD data prospectively, it appears that panic disorder co-occurs in 25% of these samples. Social phobia was concurrent in 19–23% and OCD in 11–
13%. GAD showed the most variation, co-occurring in 4–38% of patients with PMDD. The literature on PMDD and PTSD is very limited. There may be a physiological overlap between PMDD and anxiety disorders. The rate and symptom intensity of CO2-induced panic attacks were similar in subjects with panic disorder and PMDD, while depressed patients had CO2-induced panic attacks at a rate similar to controls (Kent, Papp et al. 2001). Differences in g-aminobutyric (GABA) plasma levels in women with PMDD have been found and serial proton magnetic resonance spectroscopic measurements showed decreased cortical GABA levels during the follicular phase in women with PMDD compared to controls (Halbreich, Shen et al. 1996, Epperson, Haga et al. 2002). Allopregnanolone, a metabolite of progesterone, has been implicated in the regulation of the GABAA receptor and may provide a link between neuro-steroid function and anxiety symptoms (Smith, Gong et al. 1998).
Schizophrenia
Although there have been several case reports of periodic premenstrual psychosis (Gerada and Reveley 1988), there are only two studies that examined prospectively rated premenstrual symptoms in schizophrenia. The authors found an exacerbation of affective and somatic symptoms premenstrually (but not psychotic symptoms), and they concluded that both studies were consistent with the concept that premenstrual symptomatology may be superimposed on a schizophrenic illness.
Personality Disorders
Relationship between premenstrual syndromes and personality disorders is less clear. According to one study (Sassoon, Colrain et al. 2011) women with severe PMS had a higher prevalence of personality disorders than asymptomatic women (27% versus 0%), and are more likely to have odd-eccentric, dramatic-erratic, and anxious-fearful personality disorder traits. Obsessive-compulsive personality disorder (OCPD) seems to be the most common character pathology in the PMS group. OCPD, although not necessarily associated with greater severity of premenstrual symptoms, was related to poorer life functioning in women with PMS. The comorbidity of a personality disorder and severe PMS places an additive burden on general life functioning and may have implications for psychiatric treatment or medication given to those with severe premenstrual symptoms.
Affective temperaments and Emotional Dysregulation
Only few studies have been published on the correlations between premenstrual symptoms and affective temperaments. A positive screening for PMDD was associated with a predominant cyclothymic temperament, while an euthymic temperament was associated with a lower likelihood for a positive screening for PMDD (Camara 2016). These data deserve replication in prospective studies. Very few authors pointed out a possible correlation between premenstrual symptoms and emotional dysregulation. (Reuveni 2016) The emotions are multi-faceted processes, which include subjective experience, behavior, and physiology (central and peripheral) (Mauss et al. 2005). Core features of emotion include situational antecedents, attention, appraisal, and multifaceted response tendencies (Werner and Gross 2010, Jazaieri et al. 2013).
The term “Emotional Regulation” refers to a series of strategies aimed at modulating and adjusting unpleasant emotional experiences (John and Gross 2004, Gross 2011). Emotional regulation is a multidimensional construct composed of the following traits: (1) awareness and acceptance of emotions; (2) skills to engage in behaviors aimed at a target; (3) flexible use of appropriate strategies to modulate the context’s intensity and the duration of the emotional response (Pedersen et al. 2014, Dadomo et al. 2016).
Emotion regulation can be defined also as an individual’s ability to modify an emotional state so as to promote adaptive, goal-oriented behaviors (Thompson 1994). It encompasses the processes that allow the individual to select, attend to, and appraise emotionally arousing stimuli, and to do so flexibly. These processes trigger behavioral and physiological responses that can be modulated in line with goals (Shaw et al. 2014).
Defined in this way, emotions are one type of affective response. We conceive of affect as an overarching term that includes emotions, moods, and stress responses (Gross & Thompson 2007, Wessa et al. 2014).
According to Gross & Thompson (2007) regulation of emotions refers to the process of increasing or decreasing current affect. Such a process may occur consciously or unconsciously on a continuum from effortless and automatic (unconscious) to effortful and controlled regulation (conscious).Within their model of emotion regulation, Gross & Thompson (2007), differentiate five types of emotion regulation strategies which can be broadly divided into (1) antecedent-focused strategies, occurring before full-blown emotional responses are elicited (situation selection, situation modification, attentional deployment, and cognitive change), and (2) response-focused strategies, occurring after emotional responses are generated (response modulation).
When the emotional regulation system works properly, individuals are able to modulate their emotional states and functionally direct their behavior. Indeed adopting effective strategies of emotional regulation is considered one of the fundamental aspects of individual adaptation (Dadomo et al. 2016).
On the contrary, ED is that condition in which despite an individual’s best efforts, regulatory attempts are not achieving the individual’s emotion related goal(s) and the individual is unable to make necessary corrections to achieve the emotion related goal(s). ED practically is an impaired ability to regulate unwanted emotional states (Dadomo et al. 2016).
ED arises when these adaptive processes are impaired, leading to behaviour that defeats the individual’s interests. It encompasses emotional expressions and experiences that are excessive in relation to social norms and are context inappropriate, rapid, poorly controlled shifts in emotion (lability) and the anomalous allocation of attention to emotional stimuli (Shaw et al. 2014).
It speaks more globally of “Affective Disturbance” as a disruption in the multi-system response (subjective experience, expressive behaviour, physiology) of emotions, moods, and stress responses. Affective disturbance can refer to either negative affective states (e.g., anxiety or depression) or positive affective states (e.g., euphoria or mania). One prominent cause of affective disturbance may be difficulties with emotion regulation. From this perspective, then, emotion regulation and potential subsequent ED are subordinate to the broader construct of affective disturbance. Further, emotion regulation is neither good or bad, while ED and affective disturbance are by definition considered to be dysfunctional states.
ED (Reimherr et al. 2003), emotional impulsiveness (Barkley and Fischer 2010), mood instability (Gudjonsson et al. 2013) and emotional lability (Sobanski et al. 2010) have been used to refer to similar conceptualizations (Martel 2009, Corbisiero et al. 2013, Skirrow et al. 2009).
TREATMENT
Over the last two decades, the treatment of PMS and PMDD has gained increasing attention.
In clinical practice, two main type of intervention are used to treat PMS and PMDD: one targeting the hypothalamus-pituitary-ovary axis by abolishing fluctuations in gonadal hormone levels (GnRH analogues, estradiol, COCs), the other targeting brain serotonergic synapses by increasing central serotoninergic transmission (SSRI, NSRI)(Borenstein, Dean et al. 2007).
Other therapeutic approaches include non-pharmacological methods, such as cognitive behavioural therapy, relaxation, regular exercise and nutritional supplements (Rapkin 2003) which are not specifically recommended especially in severe forms (Lustyk, Gerrish et al. 2009).
Recently, a retrospective cohort study regarding UK general practice reports that recording of premenstrual syndrome diagnoses has declined substantially over time and preferred prescription treatment has changed from progestogen to selective serotonin reuptake inhibitor (SSRIs) and combined oral contraceptives (COCs) (Sammon, Nazareth et al. 2016).
Since PMDD is an interdisciplinary disorder to, its treatment depends on the prescribing behaviour of psychiatrists as well of gynaecologists.
Psychiatrists are more likely to prescribe an antidepressant as the first-line of treatment for PMDD, while gynaecologists probably prefer hormonal interventions, mostly oral contraceptives, which are widely used. The OC containing drosperinone /etinyl estradiol (YAZ®
Although some clinicians suggest a possible role of surgery (hysterectomy associated with bilateral ovariectomy) in the treatment of severe forms of PMDD (Cronje, Vashisht et al. 2004, Robinson and Ismail 2015), this intervention, for its invasiveness and irreversibility, should be evaluated with extreme caution.
Non-pharmacological methods
Aerobic exercise could be useful for improving premenstrual symptoms: it has been postulated that aerobic exercise boosts endorphin levels (Prior, Vigna et al. 1986).
Women who have high levels of psychological stress could benefit from the use of relaxation techniques. The relaxation response is a physiological response that can decrease basal metabolic rate, lower the blood pressure and slow heart and breathing rates (Goodale, Domar et al. 1990).
Since sleep disturbances are common to women with PMDD, it’s useful to provide information about sleep hygiene (Baker, Kahan et al. 2007), improving sleep management and a regular sleep-wake pattern during menstrual cycle.
Non-pharmacologic treatment also includes dietary regimes: increasing grains, legumes, fruits, vegetables, and water intake is recommended; limiting salt intake may help reduce bloating and fluid retention. Increasing complex carbohydrate intake may be helpful to reduce tension and depression (Jarvis, Lynch et al. 2008), while reducing caffeine, red meat, and alcohol intake is recommended (Rapkin 2003, Stahl, Lei et al. 2008, Daley 2009, Lustyk, Chawla et al. 2009).
(Lustyk, Gerrish et al. 2009), positive results have been reported for cognitive-behavioural psychotherapy (CBT) (Blake, Salkovskis et al. 1998) and more recently for group CBT, with two studies that demonstrate the effectiveness of group CBT in the relief of premenstrual symptoms (Maddineshat, Keyvanloo et al. 2016) and its role in the improvement of health-related quality of life (Izadi-Mazidi, Davoudi et al. 2016).
Nutritional supplements are often used in women with premenstrual symptoms: the use of supplements of calcium carbonate in a dosage of 1000-1,200 mg per day for three menstrual cycles during the luteal phase improves premenstrual symptoms and alleviate bloating, pain, affective symptoms, and craving for food; no adverse effects have been observed up to 1500 mg daily, with the exception of urolithiasis. The administration of magnesium in a dosage of 400 mg per day during the luteal phase has been found to improve psychological and somatic symptoms in women with PMS.
Doses of 50-100 mg of vitamin B6 (pyridoxine) per day seems to be useful in treating somatic and affective symptoms and for reducing the intensity of both physical and emotional symptoms. High-dose pyridoxine (B6) has been reported to cause peripheral neuropathy (Freeman, DeRubeis et al. 1996, Wyatt, Dimmock et al. 2000, Ghanbari, Haghollahi et al. 2009). A recent study reports that the treatment with combination of calcium and vitamin B6 leads to a better control of the premenstrual syndrome symptoms (Masoumi, Ataollahi et al. 2016) Supplemental therapy with vitamins D and E seems to be an effective and affordable treatment for PMS (Dadkhah, Ebrahimi et al. 2016). In general, the effectiveness of nutritional supplements in the treatment of women affected by premenstrual symptoms remains uncertain because of a lack of consistent data from scientific studies.
There are insufficient evidences that support the efficacy of botanic products, such as chaste tree and St. John's wort. Chaste berry extract, in a dosage of 30-40 mg per day, inhibits the release of prolactin (PRL) from the anterior pituitary gland. The inhibition of prolactin release raises progesterone levels and helps to balance ovarian estrogen and progesterone production during the menstrual cycle (He, Chen et al. 2009)
St. John's wort inhibits the neural reuptake of serotonin, norepinephrine, dopamine and GABA into presynaptic nerve terminal and increases post-synaptic 5-HT receptor expression (Whelan, Jurgens et al. 2009)
Chaste berry and St. John's wort should not be used in pregnancy and have been associated with potential side effects: chaste berry can cause rash, skin eruptions, urticaria; St. John's wort can cause photosensitization and several pharmacological interactions, due to cytochrome P450 isoenzyme induction (CYP2C9, CYP2D6, CYP3A4).
Treatment of somatic symptoms
The non-steroidal anti-inflammatory drugs (NSAIDs), administered in the luteal phase, are useful in the treatment of premenstrual physical symptoms: mefenamic acid is effective on physical symptoms and in the relief of pain in the breast; naproxen could improve mood changes and headache (Daley 2009). Possible side effects of this class of drugs are nausea, vomiting, stomach pain, skin rash and stomach bleeding.
Bromocriptine and vitamin E seems to be useful in case of mastopathy.
Spironolactone (at a dose of 25 mg/day) appears to be effective with symptoms secondary to fluid retention, such a s breast tenderness and bloating: spironolactone is a
potassium-excretion and sparing potassium and hydrogen ions (Cunningham, Yonkers et al. 2009, Georgantopoulou and Field 2009).
Hormonal treatments
Oral contraceptives (OC) are useful in the treatment of breast tenderness and abdominal pain (Joffe, Cohen et al. 2003, Rapkin 2005, Rapkin 2008) and are recommended for women who want to use these compounds for contraception. One of the main side effects is venous thrombosis. Recent studies confirm the effectiveness of the association of ethinyl estradiol – drospirenone (a derivate of spironolactone) in improving the severity of premenstrual symptoms (Yonkers, Brown et al. 2005, Lee, Yi et al. 2015) (Freeman, Kroll et al. 2001, Pearlstein, Bellew et al. 2005, Breech and Braverman 2010, Kim, Yoo et al. 2015, Takeda, Kondo et al. 2015). A recent controlled trial demonstrates that OCs combined are more effective in the relief of premenstrual symptoms than calcium supplements (Shehata 2016). There is no evidence for the therapeutic effectiveness of only progesterone or progestins (Wyatt, Dimmock et al. 2001) (Ford, Lethaby et al. 2009).
Agonists of gonadotrophin-releasing hormone (for example Leuprolide), which aim to suppress ovulation (Freeman, Sondheimer et al. 1997, Rapkin 2005, Speroff, Kenemans et al. 2005) have been found to be effective in the treatment of PMS / PMDD, especially on the physical and emotional symptoms. If prolonged for more than 6 months, its use has been associated with side effects such as hypo-oestrogenism and osteoporosis (Wyatt, Dimmock et al. 2004)
Inhibition of ovulation can be achieved even using intrauterine system (IUS-Mirena®) (Bahamondes, Valeria Bahamondes et al. 2015)
Also, androgens are used in the treatment of PMS. Danazol, a synthetic steroid analogous to testosterone, has weak androgenic function and inhibits LH and FSH, suppressing the ovarian cycle in most women. Several randomized trials have shown its effectiveness in the treatment of premenstrual symptoms (Daley 2009) If used at low doses (200 mg/day) ovulation and conception are still possible, but Danazol may cause virilization of the fetus, in case of pregnancy. At higher doses (600-800 mg/day), which are required to inhibit ovulation, the risk of weight gain should be considered, and there is an increased risk of side effects, such as hot flushes, vaginal dryness, mood changes, acne and the effect of masculinizing which can severely restrict its use.
5α-reductase inhibitor (Dutasteride) seems to be useful in reducing several core PMDD symptoms, such as irritability, sadness, anxiety, food cravings, and bloating, through the stabilization of allopregnanolone levels from the follicular to the luteal phase of the menstrual cycle by blocking the conversion of progesterone to its CNS active metabolite allopregnanolone (Martinez, Rubinow et al. 2016).
Psychopharmacological approaches
The use of antidepressants has been confirmed as first-choice treatment: fluoxetine, sertraline, paroxetine are approved by the FDA for the treatment of DDPM, and SNRIs (desvenlafaxine) are currently studied in the treatment of hot flushes. Current literature confirms the effectiveness of fluoxetine (in a mean dose of mg) (Cohen, Miner et al. 2002), sertraline (in a mean dose of 110 mg) (Halbreich and Kahn 2003) and paroxetine (in a mean dose of 25 mg) (Cohen, Soares et al. 2004, Steiner, Ravindran et al. 2008). in the relief of
affective and somatic symptoms and in improving overall functioning (Pearlstein and Steiner 2008)
It is not clear whether certain SSRIs are more effective against specific symptoms compared to others. However, clinical experience allows to affirm that fluoxetine could be more effective in treating patients with eating disorder spectrum, instead of paroxetine and sertraline which may offer benefits to women with predominantly anxiety symptoms. Several studies suggest that SSRIs are more effective than placebo in the relief of physical and psychological symptoms of PMDD(Eriksson 1999, Pearlstein, Bachmann et al. 2005, Landen, Nissbrandt et al. 2007) (Cohen, Soares et al. 2004) and a meta-analysis (Stahl, Lei et al. 2008) has confirmed its effectiveness on both continuous and intermittent dose administration during the luteal phase. Other evidences point out that intermittent dosing regimens (Shah, Jones et al. 2008) are less effective than the ongoing regimens (Dimmock, Wyatt et al. 2000). The intermittent administration has certain advantages over the continuous: a lower incidence of withdrawal symptoms and side effects, better acceptance by women for intermittent occurrence of symptoms.
A meta-analysis (Brown, PM et al. 2009) showed good efficacy for fluvoxamine, citalopram and tricyclic antidepressants (clomipramine). Also SNRIs (venlafaxine, duloxetine) appear to be useful (Ramos, Hara et al. 2009) Both intermittent and continuous administration of buspirone, a 5HT1 agonist, seems to be effective in the treatment of PMS and PMDD (Rickels, Freeman et al. 1989, Daley 2009)
Preliminary data suggest that adjunctive treatment with quetiapine SR may be a useful in addition to selective serotonin reuptake inhibitor therapy in women with PMS/PMDD who have inadequate response to SSRI/SNRIs in reducing symptoms and improving quality of
life (Jackson, Pearson et al. 2015). There is little evidence about the efficacy of levetiracetam, a new anti-epileptic drug with important anti-kindling activity in animal models of epilepsy. The similarity between the diagnostic criteria for the PMDD and for the Interictal Dysphoric Disorder, have led to speculate that PMDD might be associated with an abnormal temporo-limbic circuit, congenital or acquired. The effectiveness of the treatment of PMS and PMDD with antiepileptic drugs may support this hypothesis. In an open-label study (Kayatekin, Sabo et al. 2008), levetiracetam has been shown to be effective in the treatment of PMDD.
AIM OF THE STUDY
Only few studies are focused on the relationships between premenstrual syndromes and emotional dysregulation. The aim of the present study was to evaluate the current prevalence of premenstrual syndromes and the role of emotional dysregulation in its development in a sample of patients with affective disorders. We evaluated the severity and the characteristics of ED by means of the RIPoST, a specific questionnaire exploring different dimension of emotional regulation such as intensity, reactivity, emotionality and stability. To our knowledge, this is the first study on a sample of women with psychiatric diagnosis and Premenstrual Syndromes that evaluate the presence of emotional dysregulation using the RIPoST questionnaire.
MATERIALS AND METHODS
Sample
The current study included 67 women with diagnosis of mood, anxiety or eating disorders according to DSM-IV criteria, recruited at the outpatient clinics of the Psychiatric Unit II of the University of Pisa. The sample was divided in two groups: women with diagnosis of premenstrual syndromes (PMSs) and women without premenstrual syndromes (N-PMSs). Subjects have been recruited from January 2012 through October 2016. The inclusion criteria were: age between 18 and 49 years; presence of a regular menstrual cycle (normal range for a minimum 24-day cycle and a maximum of 35 days); Diagnosis according to DSM-IV-TR criteria for Bipolar Disorder, recurrent depressive disorder, panic disorder or eating disorders; willingness to sign an informed consent to the study and to answer to phone calls during the follow-up period. The exclusion criteria were: amenorrhea; pregnancy; lactation; any general chronic somatic condition; any other serious or chronic mental disorder (such as psychosis), alcoholism or substance abuse during the two years preceding the search; limitations related to Italian communication and no fixed residence.
Data collection
All the women who met the inclusion criteria and who provided written informed consent were enrolled in the study. The Ethics Committee of the University of Pisa approved the study protocol and the assessment procedures. All the women were evaluated at T0, T1 and T2 with a set of questionnaires that included the State-Trait Anxiety Inventory (STAI) to evaluate anxiety symptoms, the RIPoST questionnaire to evaluate the emotional features.
At T0 they were also evaluated with the structured interview for DSM-IV TR (SCID-I) to assess the presence of a current or lifetime psychiatric diagnosis, and were administered the Gynaecological criteria of American College of Obstetricians and Gynaecologist (ACOG) and the Daily Record of Severity of Problems (DRSP) to confirm a diagnosis of premenstrual syndrome and premenstrual dysphoric disorder, respectively. At the baseline (T0), all the subjects completed a socio-demographic questionnaire which included age, educational level, marital and socio-economic status, residence, employment, nationality, parity and clinical report form which included BMI; physical activity; alcohol, coffee and tobacco consumption; age at the menarche; family history of dysmenorrhea or psychiatric disorders.
Assessing Instruments
Current and lifetime psychiatric diagnosis
The assessment of previous and current psychiatric diagnosis according to the criteria of DSM-IV was performed using the Structured Clinical Interview for Axis I Disorders (SCID-I) (First, Spitzer et al. 2012). The interview was administered at the baseline assessment and during the follow-up period when needed for the purpose of the study.
State-Trait Anxiety Inventory
Anxiety symptoms were evaluated using the State-Trait Anxiety Inventory (STAI) (Spielberger 1983). It is a self-reported scale that includes the size of state and trait anxiety.
We evaluate the anxiety state by using the 20 items that explore it, 20 explore trait anxiety. The items are graded according to a 4-point scale with 1= 'Not at all', and 4= Very much'. The total score ranges from 0 to 80, with higher scores indicating a greater likelihood of anxiety symptoms. It has been used in several studies in samples of pregnant women (Barnett and Parker 1986, McMahon, Barnett et al. 2001, Hart and McMahon 2006). For the Italian version of the scale (Pedrabissi 1989). According to the authors’ recommendations, a STAI score > 40 is indicative of significant anxiety symptoms. In our sample, we used only the Trait Anxiety form, examining the temperamental dimension of anxiety.
Reactivity Intensity Polarity Stability Questionnaire (RIPoST)
The RIPoST is a 60-items self-administered questionnaire exploring the emotional dimension in its various components): the RIPoSt is a 60-items self-administered questionnaire exploring the emotional dimension in its various components. The scale is composed of 4 subscales: reactivity, intensity (the usual force), polarity and stability of emotions, each of whom characterized by 15 items. It can be a useful tool for measuring the emotional features and providing an assessment of the degree of emotional dysregulation (Hantouche, Angst et al. 2010).
The Daily Record of Severity of Problems
The Daily Record of Severity of Problems (DRSP), is a daily symptom chart widely used for the diagnosis of PMS and premenstrual dysphoric disorder. Includes 21 items grouped
(depression, anxiety, lability, anger, interest in activities, concentration, lethargy, appetite, sleep, control, and physical symptom). Each item is rated on a scale of 1 (“not at all”) to 6 (“extreme”). We evaluated the potential use of DRSP scores from day one of menses as a screening instrument for PMS by comparing these scores to the standard of two cycles of prospective daily symptom ratings.
All women were screened for PMS using tools based on the ACOG recommendations for diagnosis of PMS and the diagnostic and statistical manual of mental disorders, fourth edition (DSM-IV). ACOG recommendations for a diagnosis of PMS specified that one or more disturbing affective or somatic symptoms must have occurred during the 5 days before menses in each of 3 previous menstrual cycles. These symptoms must be relieved within 4 days of menses onset without recurrence until at least cycle day 13. In addition, a woman who experiences these symptoms must suffer from identifiable dysfunction in social or economic performance (Halbreich, Borenstein et al. 2003).
Statistical Analysis
The statistical analysis was performed using SPSS 20 for Windows. Results were expressed as Mean + Standard deviation and/or percent values (SD). For comparison between the two groups, we used chi-square test for categorical variables and Student’s t-test for continuous variables. The analysis involved many tests of statistical significance, raising the potential of type I and type II errors. Multivariate Backward Logistic regression models were used to identify the predictive value of the variables considered on premenstrual syndromes. Given the sample size and the number of comparisons, we commented as significant differences with a p < 0.05.
RESULTS
The study population included 67 women recruited at the outpatient clinics of the Psychiatric Unit II of the University of Pisa. The mean age of the sample was 33.12 ± 4.0 years. Almost all of women have never been married (56.3%, n=40) or were married or lived with a partner (32.8%, n=22). The majority of women lived in urban (67.6%, n=48) or suburban (51.9%, n=55) areas, almost half of the women (54.9%, n=39) had completed a college education, were employed (45.1%, n=32) and had a medium socio-economic status (92.5%, n=98). The majority of women had never had pregnancy (69.0%, n=49), had only child (87.3%, n=5) or didn’t use contraceptives (74.6%, n=53) (Table 1a). The majority of women didn’t practice physical activity (52.1%, n=37), didn’t use tobaccos (56.3%, n=40), or drank alcohol (52.1%, n=37), but drank coffee (73.2%, n=52) (Table 1b).
The psychiatric diagnosis, evaluated with SCID-I at the baseline is described in Table 2a: the 43.7% (n=31) of subjects reported one psychiatric diagnosis of bipolar disorder, the 62.0% (n=44) one of anxiety disorder. In our sample 15.5% (n=11) of the subjects had a diagnosis of eating disorder, 23,0% (n=17) of depressive disorder and 40.8% (n=29) had psychiatric comorbidity. The 59.2% (42) of women had premenstrual symptoms of different severity: the 15.5% n=11 of the subjects had a diagnosis of PMDD according to DSM IV criteria, while 46.5% n=33 had a diagnosis of PMS according to ACOG criteria.
Regarding psychopharmacological therapies: the 76.1% (n=54) of subjects had at least one drug. In our sample 39,4% (n=28) of the subjects had Mood Stabilizers in therapy; 64,8% (n=46) had Antidepressant; 12,7% (n=9) had benzodiazepines; 18,3% (n=13) had antipsychotics (Table 2b).
We compared two subgroups of patients: the first group with premenstrual syndromes (PMSs) and the second group without premenstrual syndromes (N-PMSs).
Demographic features
PMSs patients had a higher mean age (mean age 34,8 sd=8,05) than N-PMSs patients (mean age 30,13 sd=7,96). Regarding the marital status, the majority of patients in both groups have never been married, respectively 23 (53,5%) PMSs and 17 (70,8%). Regarding residence area, we didn’t found significant differences between the two groups; most of the patients of both groups lived in an urban area: 31 women (72,1%) belonging to PMSs and 17 women (70,8%) belonging to N-PMSs.
Regarding educational level, we didn’t found significant differences between the two groups: most of the patients of both groups had a tertiary educational degree, 27 (62,8%) patients with diagnosis of premenstrual syndromes and 12 (50%) patients without diagnosis of premenstrual syndromes. The majority of patients in both groups had an occupation, respectively 20 (46,5%) women of the PMSs and 17 (70,8%) of the N-PMSs. Regarding the economic status, we didn’t found significant differences between the two groups: most of the patients of both groups had an average economic status (Table 3)
Clinical features
We didn’t found significant differences between the two groups regarding the affective diagnoses: 12 (29,7%) patients of the groups 1 and 5 (21,7%) of the N-PMSs had diagnosis of depressive disorder; 18 (41,9%) patients of the groups 1 and 13 (54,2%) of the N-PMSs had diagnosis of bipolar disorder; 29 (67,4%) patients of the groups 1 and 15 (62,5%) of
N-PMSs had diagnosis of anxiety disorder and 8 (18,6%) patients of the groups 1 and 3 (13,0%) of the N-PMSs had diagnosis of eating disorder. 20 (46,5%) patients of PMSs showed comorbidity among different psychiatric disorders., whereas 9 (37,5%) of N-PMSs showed it. We found significant differences between the two groups regarding the score of STAI-T (p=<0,001), the Emotional Reactivity RIPoST subscale (p=0,012), Negative Emotional Intensity RIPoST subscale (p=<0,001) and Emotional (In)Stability RIPoST subscale (p=0,008). We found significant difference between the two groups regarding recruitment of psichopharmecological treatments: the women of PMSs had a higher use of psychiatric drugs (93,0%, n=40) than N-PMSs (58,3%, n=14) (p=0,001). We didn’t found significant differences between the two groups regarding the family history for psychiatric and premenstrual symptoms (Tab.4)
We didn’t found significant differences between the two groups regarding the physical activity, smoking and alcohol use. Instead, a significant difference has been found regarding the use of coffee: the women with PMSs had a lower use coffee (67,4%, n=29) than women without premenstrual syndromes (95,8%, n=23) (p=0,008). Most women in both groups had no pregnancy, had only one child and did not use contraceptives. (Tab.5) A Multivariate logistic regression analysis was run including having at least PMS as the dependent variable and the variables that were statistically significant to the univariate regression as the independent variables. The analysis revealed that the variables mostly associated with the premenstrual syndromes in order of statistical significance were STAI- total scale (OR:1.08 – IC [1.01-1.16], p=0.022) and Emotional Reactivity RIPoST subscale (OR:1.14 – IC [1.03-1.26], p=0.009) (Table 6).
DISCUSSION
The prevalence of Premenstrual Syndromes and Dysphoric Premenstrual Disease in our sample of women with affective disorders is in line with other studies in general population. In the only study conducted in a psychiatric sample the reported prevalence was higher the that observed in our patents (respectively 47% and 15%). However, literature shows high variability PMS prevalence due to differences in diagnostic procedure and sample selection.
In our study, we also explored the possible relationships between emotional dysregulation and premenstrual syndromes, in a sample of patients with affective disorders, comparing two groups on the basis of the presence or the absence of premenstrual syndromes.
The results confirm the hypothesis of the study: emotional dysregulation is a predictor of premenstrual syndromes. Furthermore, prevalence of premenstrual syndromes is high among patient with psychiatric diagnosis. There are a few studies exploring the relationship between emotional dysregulation and PMSs, and the participants were enrolled from the general population (Reuveni, Dan et al. 2016, Wu, Liang et al. 2016). To the best of our knowledge, this study is the first to report an association between emotional dysregulation and Premenstrual Syndromes in a sample of psychiatric patients.
PMSs patients had a higher mean age than N-PMSs patients and this data results in line with current literature. Current literature shows that PMS prevalence increases with age (Tschudin, Bertea et al. 2010). Regarding marital status, educational and occupational level, economic status and geographic distribution there aren’t significant differences between the two groups. We investigated also about recreational activity (physical activity, alcohol, smoking, coffee) and we found no differences between the two groups regarding alcohol
consumption, physical activity and smoking. We found, though, a significant difference in coffee use: women in PMSs group consumed less coffee than N-PMSs. Data from literature report coffee use as a predisposing factor for premenstrual syndromes in general population (IŞIK, ERGÖL et al. 2016).
This discordance in our findings can probably be explained by the low consumption of coffee in our sample of psychiatric patients having high comorbidity with anxiety (and in particular PMSs group had higher levels of anxiety), who were advised against coffee use, or tend to avoid it due to its effect on anxious symptoms (Cassano and Pancheri 1999). Only nine (20,9%) woman, in PMSs group, and five (20,8%) in N-PMSs were on oral contraceptives, with no difference among the groups. Previous studies have shown that oral contraceptives failed to show high efficacy in treating mood symptoms of PMS, even if they prevent ovulation (Graham and Sherwin 1992). Regarding parity, in our sample there are no differences in the two groups, even if multiparity seems to be linked to more severe premenstrual symptoms (Freeman, Rickels et al. 1995, Hsiao, Hsiao et al. 2004).
We analysed our sample from a psychopathological point of view, finding that psychiatric diagnoses were equally distributed between the two groups. Nevertheless, we found that within the PMSs group anxiety disorder were predominant, consistently with other data from literature (Fava, Grandi et al. 1992, Kim, Gyulai et al. 2004).
In the PMSs group, we found a high prevalence of Bipolar Disorder. We also found high levels of comorbidity (defined as more than one psychiatric diagnoses), in comparison with N-PMSs group.
As regard psychopharmacologic treatments, we found that women with PMSs used more drugs, in particular antidepressant, than women without PMSs (Freeman, Rickels et al.
