Premenstrual mood changes in affective disorders.

Mood changes during the premenstrual phase have been the focus of considerable research in recent years. Although there has been significant progress in the diagnosis and etiology of major affective disorders, the relation between these disorders and menstrual changes remains controversial. There have been contradictory reports and speculations on women''s susceptibility to psychiatric disorders during the premenstrual phase. We describe three patients with a history of mood swings associated with menstruation in whom major affective disorders developed, necessitating intensive psychiatric treatment or admission to hospital. Among women who manifest menstrual mood changes, manic-depressive illness may develop only in a subgroup with genetic predisposition. In such cases the possibility of postpartum mania or depression should be kept in mind in follow-up.     

Gender differences in depression

Depression is twice as common in women as in men, although some concern has been raised in terms of misdiagnosing depression in men. The incidence of depression in women varies during the life span. The peak incidence during childbearing years appears to be associated with cyclic hormonal changes. Women also present with reproductive -specific mood disorders: pre-menstrual dysphoric disorder (PMDD), depression in pregnancy, postpartal mood disorder (PDD) and perimenopausal depressive disorder. Gender differences were repeatedly observed in response to antidepressant medication. Premenopausal women appear to respond poorly and to show low tolerability to TCAs, but they tend to show greater responsiveness to the SSRIs. In contrast, men and postmenopausal women can respond equally to the TCAs and SSRIs. These differences are contributed to gender differences in pharmacokinetics of antidepressants and to the influence of menstrual cycle. These findings suggest the need for a gender-specific approach to the evaluation and management of depression.     

Oral Contraceptives,Depression, and Libido

Depression, headaches, and libido were rated in 272 women before starting a contraceptive method and at intervals during the first year of use—54 were fitted with an intrauterine device (I.U.D.) and 218 used one of three oral contraceptives. Side effects caused 25% of the oral contraceptive group and 13% of the I.U.D. group to stop the method. Depression, headaches, and loss of libido were the most common reasons for stopping oral contraceptives and breakthrough bleeding was the most common reason for stopping the I.U.D.The group of women who stopped or changed their oral contraceptives during the survey were compared with the group who remained on the same oral contraceptive throughout. The former had higher mean depression and neuroticism scores at the first clinic visit and contained more women with a history of premenstrual weepiness, depression during pregnancy, outpatient psychiatric treatment, and treatment with antidepressants. Changes in the depression, headache, and libido ratings throughout the survey are presented.     

Postpartum depression: Etiology,treatment and consequences for maternal care

This article is part of a Special Issue “Parental Care”. Pregnancy and postpartum are associated with dramatic alterations in steroid and peptide hormones which alter the mothers' hypothalamic pituitary adrenal (HPA) and hypothalamic pituitary gonadal (HPG) axes. Dysregulations in these endocrine axes are related to mood disorders and as such it should not come as a major surprise that pregnancy and the postpartum period can have profound effects on maternal mood. Indeed, pregnancy and postpartum are associated with an increased risk for developing depressive symptoms in women. Postpartum depression affects approximately 10–15% of women and impairs mother–infant interactions that in turn are important for child development. Maternal attachment, sensitivity and parenting style are essential for a healthy maturation of an infant's social, cognitive and behavioral skills and depressed mothers often display less attachment, sensitivity and more harsh or disrupted parenting behaviors, which may contribute to reports of adverse child outcomes in children of depressed mothers. Here we review, in honor of the “father of motherhood”, Jay Rosenblatt, the literature on postnatal depression in the mother and its effect on mother–infant interactions. We will cover clinical and pre-clinical findings highlighting putative neurobiological mechanisms underlying postpartum depression and how they relate to maternal behaviors and infant outcome. We also review animal models that investigate the neurobiology of maternal mood and disrupted maternal care. In particular, we discuss the implications of endogenous and exogenous manipulations of glucocorticoids on maternal care and mood. Lastly we discuss interventions during gestation and postpartum that may improve maternal symptoms and behavior and thus may alter developmental outcome of the offspring.     

Perimenstrual behavior changes among female yellow baboons: Some similarities to premenstrual syndrome (PMS) in women

Although numerous studies have documented changes in the behavior of nonhuman primate females around the time of ovulation, very little attention has been paid to behavior changes around the time of menstruation. Yet such information is obviously relevant to under standing the origins and etiology of the adverse mood and behavior changes experienced premenstrually by many women. Analysis of data obtained during 115 hours of observation on 13 female Amboseli (Kenya) baboons (Papio cynocephalus) during 24 menstrual periods showed that prior to and during the time of menstrual onset, these individuals exhibited distinct changes in their activity budgets, nearest-neighbor distances, and patterns of social interaction. Furthermore, in comparison to females around the time of ovulation, perimenstrual females showed increased rates of agonistic interaction and decreased (but nonzero) rates of sexual interaction with adult males. These premenstrual and perimenstrual behavior changes among female yellow baboons thus show some intriguing similarities to several commonly reported behavioral symptoms of premenstrual syndrome (PMS) in women.     

The dreams of women with and without severe emotional behavioral premenstrual symptoms.

Women with severe premenstrual symptoms, who tend to have more mood changes during the late luteal phase of their cycle than do women with few or no symptoms, often complain of having unpleasant dreams. This study examined whether these women experienced more intense negative dream emotions during the late luteal phase of their cycle compared with women with minimal symptoms. It also examined whether there was a relationship between presleep mood and dream affect. Seventeen women participated in the study (9 with severe symptoms, 8 with minimal symptoms). Analyses of variance revealed an increase in negative dream affect and misfortunes during the late luteal phase (p     

Antidepressants and pregnancy: risks and benefits for the mother and child

Depression, anxiety disorders, anorexia nervosa and bulimia, all indications for antidepressant use, are common disorders in women of childbearing age. Nevertheless, antidepressant use during the gestational period remains a controversial topic. Given that 50 % of pregnancies are unplanned, the safety of antidepressants during the first trimester of pregnancy, a critical period for foetal development, has become a major public health concern. Until now, most studies suggest that physicians may often under-prescribe or discontinue antidepressants at the time of conception and during pregnancy. This may be a consequence of the concern over the safety of these agents in pregnant women and the risks they may pose to the foetus. In fact, recent studies and warnings from Health Canada and the US Food and Drug Administration have reinforced this uncertainty regarding the adverse effects of antidepressant use on the foetus. On the other hand, discontinuation of antidepressant use during pregnancy was also recently associated with maternal relapse of depression and withdrawal symptoms, which is not optimal for the mother and her foetus. Consequently, women who wish to become pregnant and who suffer from psychiatric disorders are faced with the difficult task of deciding whether to continue or discontinue their antidepressant during pregnancy. At this time, it appears important to take into account all evidence-based data to evaluate the risks/benefits of using antidepressants during the gestational period in order to help mothers make the best choice for themselves, and their infants.     

Separation Anxiety,Attachment and Inter-Personal Representations: Disentangling the Role of Oxytocin in the Perinatal Period

In this paper, we aimed to assess cross-sectionally and longitudinally associations between disturbances in maternal early attachment experiences, symptoms of separation anxiety and depression and oxytocin plasma levels. We examined a mediational model that tested the hypothesis that anxious attachment style arising from the mothers’ early bonding experiences with her own parents was associated with high levels of separation anxiety which, via its impact on depression, was associated with reduced levels of oxytocin in the postnatal period. Data is reported on a structured sample of 127 women recruited during pregnancy from a general hospital antenatal clinic and an initial follow up cohort of 57 women who were re-assessed at 3-months post-partum. We found an association between lower oxytocin level in the post partum period and symptoms of separation anxiety and depression during pregnancy, as well as maternal negative interpersonal representations, upbringing attributes and anxious attachment style. Further meditational analysis revealed that the unique association between anxious attachment and depression is mediated by separation anxiety and that depressed mood mediated the relationship between separation anxiety and oxytocin. In conjunction with evidence from the literature suggesting that lower oxytocin level is associated with bonding difficulties, our findings have significant implications for understanding the biological processes underpinning adverse attachment experiences, negative affect state, and mother-to-infant bonding difficulties.     

Increased depressive-like traits in an animal model of premenstrual irritability

Women are at higher risk of anxiety and mood disorders, especially at transitions across the reproductive life cycle (premenstruum, postpartum, menopause). Premenstrual dysphoric disorder (PMDD) is one of female mood disorders associated with changing ovarian hormone levels. Because anxiety and depression frequently occur in women with PMDD, premenstrual dysphoria might be a manifestation of certain vulnerability traits increasing the risk of those disorders. The present study was conducted to elucidate a potential association between estrous cycle-dependent aggression, the rodent model of "premenstrual irritability" (resident-intruder test), and anxiety (elevated plus maze), depressive-like traits (forced swim test) as well as carbohydrate craving in female Wistar rats. Some aggressive and nonaggressive females were restraint-stressed before testing to determine their sensitivity to stress at different hormonal stages. The results revealed that females expressing the estrous cycle-dependent aggression but not those not expressing cycle-dependent aggression spent longer time immobile and shorter time swimming in the forced swim test at metestrus compared to proestrus phase of the estrous cycle. There was no difference between aggressive and nonaggressive females in anxiety, locomotor activity and sensitivity to restraint stress and sucrose consumption. The present study suggests a common neurobiological background for the estrous cycle-dependent aggression and depressive-like traits in rodents. This phenomenon could potentially aid the elucidation of premenstrual emotional dysfunctions and might be used as an ethological model to study a biochemical and genetic proneness to depression.     

The unique challenges of managing depression in mid-life women

Throughout most of their lives, women are at a greater risk of becoming depressed than men. Some evidence suggests that this heightened risk is associated with increased sensitivity to the hormonal changes that occur across the female reproductive lifecycle. For some women, the peri-menopause and early post-menopausal years may constitute a “window of vulnerability” during which challenging physical and emotional discomforts could result in significant impairment in functioning and poorer quality of life. A number of biological and environmental factors are independent predictors for depression in this population, including the presence of hot flashes, sleep disturbance, history of severe premenstrual syndrome or postpartum blues, ethnicity, history of stressful live events, past history of depression, body mass index and socioeconomic status. This paper explores the current knowledge on the complex associations between mood changes and aging in women. More specifically, the biological aspects of reproductive aging and their impact on mood, psychosocial factors, lifestyle, and overall health are reviewed. In addition, evidence-based hormonal and non-hormonal therapies for the management of depression and other complaints in midlife women are discussed. Ultimately, this article should help clinicians and health professionals to address a challenging clinical scenario: a preventive and effective strategy for the management of depression in the context of the menopausal transition and beyond.     

Live and Non-Live Pregnancy Outcomes among Women with Depression and Anxiety: A Population-Based Study

Background

Women taking antidepressant or anti-anxiety medications during early pregnancy have high risks of non-live pregnancy outcomes, although the contribution of the underlying illnesses to these risks remains unclear. We examined the impacts of antenatal depression and anxiety and of commonly prescribed treatments on the risks of non-live pregnancy outcomes.

Methods

We identified all pregnancies and their outcome (live birth, perinatal death, miscarriage or termination) among women aged 15–45 years between 1990 and 2009 from a large primary care database in the United Kingdom. Women were grouped according to whether they had no history of depression and anxiety, a diagnosis of such illness prior to pregnancy, illness during pregnancy and illness during pregnancy with use of medication (stratified by medication type). Multinomial logistic regression models were used to compare risks of non-live outcomes among these groups, adjusting for major socio-demographic and lifestyle characteristics.

Results

Among 512,574 pregnancies in 331,414 women, those with antenatal drug exposure showed the greatest increased risks for all non-live pregnancy outcomes, relative to those with no history of depression or anxiety, although women with prior (but not currently medicated) illness also showed modest increased risks. Compared with un-medicated antenatal morbidity, there was weak evidence of an excess risk in women taking tricyclic antidepressants, and stronger evidence for other medications.

Conclusions

Women with depression or anxiety have higher risks of miscarriage, perinatal death and decisions to terminate a pregnancy if prescribed psychotropic medication during early pregnancy than if not. Although underlying disease severity could also play a role, avoiding or reducing use of these drugs during early pregnancy may be advisable.     

Smoking is associated with, but does not cause, depressed mood in pregnancy--a mendelian randomization study

Smokers have a higher prevalence of major depressive episodes and depressive symptoms than the general population, but whether this association is causal, or is due to confounding or reverse causation is uncertain because of the problems inherent in some epidemiological studies. Mendelian randomization, in which a genetic variant is used as a surrogate for measuring exposure, is an approach which may be used to better understand this association. We investigated the rs1051730 single nucleotide polymorphism in the nicotine acetylcholine receptor gene cluster (CHRNA5-CHRNA3-CHRNB4), associated with smoking phenotypes, to determine whether women who continued to smoke were also more likely to report a low mood during pregnancy. We found among women who smoked pre-pregnancy, those with the 1051730 T allele smoked more and were less likely to quit smoking during pregnancy, but were also less likely to report high levels of depressed mood at 18 weeks of pregnancy (per allele OR = 0.84, 95%CI 0.72 to 0.99, p = 0.034). The association between genotype and depressed mood was limited to women who were smokers prior to pregnancy, with weak evidence of an interaction between smoking status and genotype (p = 0.07). Our results do not support a causal role of smoking on depressed mood, but are consistent with a self-medication hypothesis, whereby smoking is used to alleviate symptoms of depression. A replication study using multiple genetic variants which influence smoking via different pathways is required to confirm these findings and provide evidence that the genetic variant is reflecting the effect of quitting smoking on depressed mood, and is not directly affecting mood.     

Psychosocial and psychological interventions for prevention of postnatal depression: systematic review

Objective To assess the effects of psychosocial and psychological interventions compared with usual antepartum, intrapartum, or postpartum care on the risk of postnatal depression.Data sources Medline, Embase, CINAHL, Cochrane central register of controlled trials, Cochrane pregnancy and childbirth group trials register, Cochrane depression, anxiety, and neurosis trials register, secondary references and review articles, and experts in the field.Study selection All published and unpublished randomised controlled trials of preventive psychosocial or psychological interventions in which the primary or secondary aim was a reduction in the risk of postnatal depression. All trials recruited pregnant women or new mothers less than six weeks postpartum. Eligible studies were abstracted, assessed for methodological quality, and pooled with relative risk for categorical data and weighted mean difference for continuous data.Results Fifteen trials with 7697 women were included. Although there was no overall statistically significant effect on the prevention of postnatal depression in the meta-analysis of all types of interventions (15 trials, n = 7697; relative risk 0.81, 95% confidence interval 0.65 to 1.02), these results suggest a potential reduction in postnatal depression. The only intervention to have a clear preventive effect was intensive postpartum support provided by a health professional (0.68, 0.55 to 0.84). Identifying women “at risk” assisted in the prevention of postnatal depression (0.67, 0.51 to 0.89). Interventions with only a postnatal component were more beneficial (0.76, 0.58 to 0.98) than interventions that incorporated an antenatal component. In addition, individually based interventions were more effective (0.76, 0.59 to 1.00) than group based interventions (1.03, 0.65 to 1.63).Conclusions Diverse psychosocial or psychological interventions do not significantly reduce the number of women who develop postnatal depression. The most promising intervention is the provision of intensive, professionally based postpartum support.     

Progesterone,fluid, and electrolytes in premenstrual syndrome.

Changes in mood, plasma progesterone concentration, urinary volume, sodium excretion, sodium:potassium ratio, and body weight during the menstrual cycle were determined in 18 women with premenstrual syndrome and 10 symptomless (control group) women. Plasma progesterone concentration was higher in the women with symptoms during the postovulatory phase of the cycle, and the peak progesterone concentration appeared earlier. The changes in progesterone concentration were accompanied by a natriuresis and diuresis that fell towards preovulatory values in the premenstrual phase. Sodium retention was not confined to any definite period. Mood symptoms occurred after the changes in progesterone and electrolyte concentrations. Progesterone deficiency is probably not the cause of premenstrual syndrome. Thus treatment with progesterone is probably illogical unless a deficiency is detected. Treatment should be aimed at preventing the natriuretic effect of progesterone in the postovulatory phase and the sodium-retaining and water-retaining effects of aldosterone in the premenstrual phase.     

Early lactation performance in primiparous and multiparous women in relation to different maternity home practices. A randomised trial in St. Petersburg

Background

Research in the field of psychoneuroimmunology (PNI) has revealed that depression is associated with inflammation manifested by increased levels of proinflammatory cytokines.

Discussion

The old paradigm described inflammation as simply one of many risk factors for depression. The new paradigm is based on more recent research that has indicated that physical and psychological stressors increase inflammation. These recent studies constitute an important shift in the depression paradigm: inflammation is not simply a risk factor; it is the risk factor that underlies all the others. Moreover, inflammation explains why psychosocial, behavioral and physical risk factors increase the risk of depression. This is true for depression in general and for postpartum depression in particular. Puerperal women are especially vulnerable to these effects because their levels of proinflammatory cytokines significantly increase during the last trimester of pregnancy – a time when they are also at high risk for depression. Moreover, common experiences of new motherhood, such as sleep disturbance, postpartum pain, and past or current psychological trauma, act as stressors that cause proinflammatory cytokine levels to rise. Breastfeeding has a protective effect on maternal mental health because it attenuates stress and modulates the inflammatory response. However, breastfeeding difficulties, such as nipple pain, can increase the risk of depression and must be addressed promptly.

Conclusion

PNI research suggests two goals for the prevention and treatment of postpartum depression: reducing maternal stress and reducing inflammation. Breastfeeding and exercise reduce maternal stress and are protective of maternal mood. In addition, most current treatments for depression are anti-inflammatory. These include long-chain omega-3 fatty acids, cognitive therapy, St. John's wort, and conventional antidepressants.     

Prenatal Exposure to Maternal Depressed Mood and the MTHFR C677T Variant Affect SLC6A4 Methylation in Infants at Birth

Background

Prenatal and early postnatal exposure to maternal depression may “program” childhood behavior via epigenetic processes such as DNA methylation. Methylenetetrahydro-folate reductase (MTHFR) is an important enzyme in the generation of methyl groups for DNA methylation. The common MTHFR C677T variant is associated with depression in men and non-pregnant women, and with global changes in DNA methylation. This study investigated the effect of maternal MTHFR C677T genotype on antenatal maternal mood, and their impact on the gene-specific methylation in pregnant women and their newborn infants. The methylation status of SLC6A4, which encodes the transmembrane serotonin transporter, and BDNF, which encodes brain derived neurotrophic factor, were assessed because of their potential role in behaviour.

Methods/Principal Findings

Depressed mood was assessed by the Edinburgh Postnatal Depression Scale (EPDS) and the Hamilton Rating Scale for Depression (HAM-D) in women (n = 82, all taking folate) during the 2^nd and 3^rd trimesters of pregnancy. The methylation status of SLC6A4 and BDNF were assessed in 3rd trimester maternal peripheral leukocytes and in umbilical cord leukocytes collected from their infants at birth. Women with the MTHFR 677TT genotype had greater 2^nd trimester depressed mood (p<0.05). Increased 2^nd trimester maternal depressed mood (EPDS scores) was associated with decreased maternal and infant SLC6A4 promoter methylation (p<0.05), but had no effect on BDNF promoter methylation.

Conclusions

These findings show that the MTHFR C677T variant is associated with greater depressed mood during pregnancy. We further showed that prenatal exposure to maternal depressed mood affects gene-specific DNA methylation patterns. These findings support the concept that alterations in epigenetic processes may contribute to developmental programming of behaviour by maternal depression.     

Mood and anxiety disorders in women with PCOS

Women with polycystic ovary syndrome have gynecologic, reproductive and metabolic co-morbidities that span their entire lifespan. More recently a higher risk of mood and anxiety disorders has been reported in women with PCOS. Women with PCOS have higher depression scores and a higher risk of depression independent of BMI. Although clinical features of hyperandrogenism affect health related quality of life, the association between hirsutism, acne, body image and depression is currently unclear. Similarly there is limited data on the association between variables such as biochemical hyperandrogenism or infertility and depression. Women with PCOS are also at risk for symptoms of generalized anxiety disorder. There is insufficient data examining the risk of other anxiety disorders such as social phobia, obsessive compulsive disorders and panic disorder. In a number of patients some of these disorders coexist increasing the health burden. These data underscore the need to screen all women with PCOS for mood and anxiety disorders and adequately treat women who are diagnosed with these conditions.     

Progesterone and the premenstrual syndrome: a double blind crossover trial.

A double blind, randomised, crossover trial of oral micronised progesterone (two months) and placebo (two months) was conducted to determine whether progesterone alleviated premenstrual complaints. Twenty three women were interviewed premenstrually before treatment and in each month of treatment. They completed Moos''s menstrual distress questionnaire, Beck et al''s depression inventory, Spielberger et al''s state anxiety inventory, the mood adjective checklist, and a daily symptom record. Analyses of data found an overall beneficial effect of being treated for all variables except restlessness, positive moods, and interest in sex. Maximum improvement occurred in the first month of treatment with progesterone. Nevertheless, an appreciably beneficial effect of progesterone over placebo for mood and some physical symptoms was identifiable after both one and two months of treatment. Further studies are needed to determine the optimum duration of treatment.     

Finding the intracellular signaling pathways affected by mood disorder treatments

Postmortem and brain imaging studies have revealed structural changes and cell loss in cortico-limbic regions of the brain in bipolar disorder and major depression. Consistent with these findings, mood stabilizers such as lithium ion and valproic acid, which are used to treat bipolar disorder, as well as antidepressants and electroconvulsive therapy have recently been shown to activate interconnected intracellular signaling pathways that promote neurogenesis and synaptic plasticity. These insights should assist in understanding the pathophysiology of severe mood disorders as well as aid in the development of more effective treatments.