Disordered sleep is strongly linked to depression, but reasons for this are not well understood. One possibility is that this link is partially explained by deficits in the emotional processing system. This model is substantiated based on the strong link between sleep and emotions, as well as ties between affect and depression. Therefore, this study tested whether various emotional and non-emotional deficits mediated the link between poor sleep quality and depression. Two hundred undergraduate students were recruited via an online university system. Participants completed self-report scales of depression, sleep quality, emotion recognition, and affective response to pre-tested pleasant or unpleasant stimuli. Mediation models were tested for viable emotion and non-emotion mediators, as well as using other mediators as covariates. The indirect effect for all models was tested using bootstrapping. Only affective response to unpleasant stimuli emerged as a significant mediator of the relationship between sleep quality and depression and accounted for 5% of the variance in that relationship; it remained a mediator after controlling for non-emotion related mediators. Recently, sleep problems have gained attention due to serious consequences for public health, including a strong association with psychological disorders. This study was a first step in testing pathways by which disordered sleep leads to increases in depression symptoms. In our sample, blunted emotional responding to unpleasant images partially accounted for the link seen between sleep and depression. Future research may aim to extend the study of process and pathway-related models, particularly in the realm of emotional responding in the relationship between sleep and depression.

This essay researches current workings of medicine in relation to contested, female diagnoses. This is made by looking at the construction of the new psychological diagnosis Premenstrual Dysphoric Disorder (PMDD) in Swedish media, and relating it to a current trend seen in medicine; to medicalize women’s underperformance. A qualitative content analysis of 19 articles is conducted, showing that PMDD is constructed as; a biomedical fact and individual problem; a serious disease owned by the sufferers; and as something written out of the women’s self-image as a “not me”. These constructions are analysed with a theoretical framework built around the concept biomedicalisation, which we conceptualise as an exertion of biopower that shapes subjects in line with neoliberal ideals. Biopower is a concept from the Foucauldian notion of Governmentality, and describes power working on micro levels, through for example truth discourses, to make individuals understand and work on themselves as biological subjects. Our analysis shows that biopower can be seen to work through the different constructions of PMDD to shape self-managing, healthy subjects that are willing to biomedically change themselves in accordance with an ideological normal, but that this normal differs from that seen in research on other contested female diagnoses. To conclude we suggest that it would be more fruitful to look at biomedicalisation to understand current workings on female contested diagnoses, than to look at the trend on medicalisation of underperformance.

Introduction: Women with bipolar disorder (BD) have higher rates of premenstrual syndrome (PMS) and premenstrual dysphoric disorder (PMDD). The primary goal of this thesis was to examine the neural correlates of bipolar disorder and comorbid PMDD and identify changes in brain structure or function that may mediate emotional and cognitive dysregulation in the late luteal phase. Results: In healthy women with no history of PMDD, absolute levels of estradiol, progesterone, allopregnanolone and dehydroepiandrosterone sulfate (DHEAS) were correlated with patterns of functional coupling in multiple regions associated with emotional and cognitive processes, in the mid-follicular and late luteal menstrual phases. A systematic review of the literature on resting state functional connectivity (Rs-FC) in BD during euthymia highlighted consistent patterns of resting state functional connectivity (Rs-FC) using ICA and SBA; including stability of the default mode network (DMN), salience network (SN) and fronto-parietal network (FPN) relative to controls. Available literature largely failed to control for sex, menstrual cycle phase or menstrual cycle disorders. Thus, we conducted the first fMRI studies to control for menstrual cycle phase in BD. During the mid-follicular phase, we found increased Rs-FC between critical nodes of the default mode and frontoparietal networks in BD compared to controls and increased functional connectivity between the somatosensory cortex and the insular cortex, inferior prefrontal gyrus and frontal orbital cortex in BD compared to controls. Voxel based morphometry analysis showed decreased gray matter in the somatosensory cortex in the same population compared to controls. Finally, women with BD and co-morbid PMDD displayed different patterns of Rs-FC using the right and left hippocampi as seed regions than women with BD without comorbid PMDD and controls with PMDD. Differences in cortical thickness between controls with and without PMDD and with and without BD were also found in regions central to emotional regulation and cognitive processing. Conclusions: Results highlight the influence of sex hormones on Rs-FC and support the need to control for menstrual phase and PMDD diagnosis. Differences in structural and functional connectivity, and the clinical profile of women with BD and those with BD and co-morbid PMDD highlights the impact of PMDD on BD and the need for future research in this area. / Thesis / Doctor of Philosophy (PhD)

Introduction: Sleep and biological rhythms have not been investigated in women with comorbid Bipolar and Premenstrual Dysphoric Disorder in the context of the menstrual cycle. We explored whether menstrual cycle phase causes increased disturbances in sleep, biological rhythms and mood symptoms. Additionally, we explored whether these women have worse illness outcome than women diagnosed with either Bipolar or Premenstrual Dysphoric Disorder, and healthy women. Methods: In this post-hoc analysis, participants were split into four groups: those with a Bipolar and comorbid Premenstrual Dysphoric Disorder diagnosis (n = 17, BDPMDD), those with a Bipolar Disorder diagnosis (n = 16, BD), those with a Premenstrual Dysphoric Disorder diagnosis (n = 19, PMDD), and women with no history of psychiatric diagnosis (n = 25, HC). The primary outcome variable was biological rhythm disruption as measured by the Biological Rhythms Interview and Assessment in Neuropsychiatry (BRIAN). The secondary outcome variables were depressive symptoms (Montgomery-Asberg Depression Scale, MADRS; Hamilton Depression Rating Scale, HAMD), manic symptoms (Young Mania Rating Scale, YMRS), and sleep quality (Pittsburgh Sleep Quality Index, PSQI). All variables were collected at both mid-follicular and late-luteal stages of the menstrual cycle. Results: The BDPMDD group did not have significantly higher disruptions in biological rhythms than the BD or PMDD groups at the luteal phase; however, there were significant disruptions and mood symptoms in comparison to the HC group, especially at the follicular stage, which point to markedly higher disruptions in these areas that seem to persist beyond the symptomatic luteal phase. Conclusion and Future Directions: Women diagnosed with a BD and PMDD comorbidity experience a higher illness burden then women diagnosed with either BD or PMDD. A relatively small sample size, not excluding for participants who were taking medications that affect sleep and relying solely on subjective measures of biological rhythms may explain some of the null results. Future studies should employ objective measures of sleep such as actigraphy to complement subjective measures like the BRIAN, as well as recruit a larger sample of participants. More importantly, more studies surrounding this topic must be done in order to create a robust body of evidence that can be used to compare results across studies and identify specific biological rhythms domains that can be targets for treatment. / Thesis / Master of Science (MSc) / Sleep disruptions are common in women diagnosed with Bipolar Disorder and in those diagnosed with Premenstrual Dysphoric Disorder. Illness burden has been shown to be greater in women diagnosed with a comorbidity of the above disorders in terms of clinical variables such as number of comorbidities, episode relapse, rapid cycling and mixed mood states. This thesis aims to investigate whether women diagnosed with Bipolar and comorbid Premenstrual Dysphoric Disorder have greater biological rhythms disruptions than women diagnosed with either disorder. Biological rhythms will be evaluated at both the follicular and late-luteal stages. The overall goal of this work is to add to the currently scant literature on the clinical presentation of a Bipolar and Premenstrual Dysphoric Disorder comorbidity.

Background. Despite an abundance of clinical research on premenstrual and menstrual symptoms, few epidemiological data provide estimates of the prevalence, incidence, co-morbidity, stability and correlates of premenstrual dysphoric disorder (PMDD) in the community. Aims. To describe the prevalence, incidence, 12 co-morbidity factors and correlates of threshold and subthreshold PMDD in a community sample of young women. Methods. Findings are based on prospective–longitudinal community survey of 1488 women aged 14–24, who were followed-up over a period of 48 months (follow-up, N = 1251) as part of the EDSP sample. Diagnostic assessments were based on the Composite International Diagnostic Interview (CIDI) and its 12-month PMDD diagnostic module administered by clinical interviewers. Diagnoses were calculated using DSM-IV algorithms, but daily ratings of symptoms, as required, were not available. Results. The baseline 12-month prevalence of DSM-IV PMDD was 5·8%. Application of the diagnostic exclusion rules with regard to concurrent major depression and dysthymia decreased the rate only slightly (5·3%). An additional 18·6% were ‘near-threshold’ cases, mostly because they failed to meet the mandatory impairment criterion. Over the follow-up period only few new PMDD cases were observed: cumulative lifetime incidence was 7·4%. PMDD syndrome was stable across 48 months with <10% complete remissions among baseline PMDD cases. The 12-month and lifetime co-morbidity rates were high (anxiety disorders 47·4%, mood disorders 22·9%; somatoform 28·4%), only 26·5% had no other mental disorder. Particularly high odds ratios were found with nicotine dependence and PTSD. In terms of correlates increased rates of 4-weeks impairment days, high use of general health and mental health services, and increased rates of suicide attempts were found. Conclusion. In this sample of adolescents and young adults, premenstrual symptoms were widespread. However, DSM-IV PMDD was considerably less prevalent. PMDD is a relatively stable and impairing condition, with high rates of health service utilization, increased suicidality and substantial co-morbidity.

Premenstrual dysphoric disorder (PMDD) is a severe dysphoric form of premenstrual syndrome (PMS) that is included as a diagnosis for further study in the DSM-IV (APA, 2000). A primary aim of the present study was to characterize the co-occurrence of PMDD and major depression, in a sample that spans the entire range of depressive severity. The range included non-depressed controls, women meeting criteria for dysthymia, and women meeting criteria for current Major Depressive Disorder (MDD). Co-occurrence of MDD and PMDD were only statistically significant when considering Lifetime MDD. Resting frontal electroencephalographic (EEG) asymmetry has been hypothesized to tap a diathesis toward depression or other emotion-related psychopathology. Another primary aim was to assess Frontal EEG asymmetry in college women who meet criteria for Pre-Menstrual Dysphoric Disorder (n = 25) and 25 matched controls. Participants were assessed four times in a two week period. Women reporting low premenstrual dysphoric symptomatology exhibited greater relative left frontal activity at rest than did women high in premenstrual dysphoric symptomatology. These results are consistent with a diathesis-stress model for premenstrual dysphoric symptomatology. A secondary aim was to assess whether individuals with PMDD or menstrual related mood variability, but no current diagnosis of depression, have an increased family history of depression. Promising evidence of a relationship between family history of MDD and a likelihood of PMDD was discovered. A trend was found for Spectrum PMDD women: a higher rate of Family History of MDD (36%) than non PMDD women (19.6%). Ideally, resting frontal electroencephalographic (EEG) asymmetry could help us learn more about the etiology of depression and hormonal-related depression specifically, and test whether they may share etiological factors.

Introduction: Premenstrual Dysphoric Disorder (PMDD) is a condition that affects about 2-6% of women of reproductive age. The relation to ovarian steroids is apparent as symptoms are absent during anovulatory cycles. Neuroactive steroids like allopregnanolone have effect in the brain and on brain function and have been proposed to play an important role for the symptomatology of premenstrual symptoms and in the interaction between the GABAA receptor and alcohol. High doses of alcohol elevate allopregnanolone levels both in rats and humans. Allopregnanolone is a positive modulator of the GABAA receptor with sedative, anxiolytic and anticonvulsant effect in both human and animals. Aims: The aim was to investigate if a low dose (100μg) of GnRH agonist (buserelin) is effective for the treatment of PMDD and if allopregnanolone serum levels during treatment are associated to symptom severity. Furthermore, the studies aimed at investigating the effect of a low dose of alcohol upon saccadic eye movements in women with PMDD, and control subjects in different phases of the menstrual cycle, and to evaluate if there was a difference in response to alcohol between men and healthy women. We also wanted to see if this low dose of alcohol could have an effect on serum allopregnanolone levels in women with PMDD and control subjects in the follicular and luteal phases of the menstrual cycle. Methods: The effect of low dose (100μg) of GnRH agonist (buserelin) on premenstrual symptoms was evaluated in a randomized, placebo controlled, double-blinded cross-over trial. 27 PMDD patients were randomized to either GnRH agonist intranasally once a day or placebo for two months before the crossover. The main outcome measure was the daily symptom ratings for mood and physical symptoms made by the patients. In a subgroup of 12 women, grouped as buserelin responders and placebo responders, luteal phase serum progesterone, allopregnanolone, and pregnanolone was measured together with daily ratings for mood and physical symptoms. Alcohol responsiveness was measured in PMDD patients, female control subjects and men by comparing the effect of a low dose (0.2g/kg) of intravenous alcohol or placebo infusion upon saccadic eye movements. Blood samples for measurement of allopregnanolone and cortisol were taken throughout the alcohol/placebo challenges. Results: Low dose GnRH agonist was effective as treatment of premenstrual irritability and depression. Anovulatory cycles were confirmed in 56% of the subjects, particularly in older women. Buserelin as well as placebo responders displayed decreased allopregnanolone and progesterone levels in parallel with symptom improvement. PMDD patients displayed blunted saccadic eye movement response to alcohol infusion, especially in the luteal phase. Control subjects did not change their response to alcohol between cycle phases. We found no difference in saccadic eye movement sensitivity to alcohol between males and females. Allopregnanolone levels significantly decreased in the luteal phase following the alcohol infusion. Conclusions: Low dose GnRH agonist is effective in treatment of premenstrual depression and irritability but is likely to induce anovulation with increasing age. Independent of whether buserelin or placebo treatment was given decreased levels of allopregnanolone appear to be related to symptom improvement. Women with PMDD have altered saccadic eye movement sensitivity in response to alcohol, particularly in the luteal phase. The low dose of alcohol did not induce any difference in saccade measurements between males and females. Low dose of alcohol does not result in increased peripheral levels of allopregnanolone.

Bakgrund: PMDS är en relativt okänd diagnos. Det är en progression av Premenstruellt syndrom (PMS) men allvarligare och är ibland invalidiserande för den som lider utav det. Prevalensen av PMDS är cirka fem procent av alla fertila kvinnor. Syfte: Syftet var att undersöka hur kvinnor med diagnosen PMDS upplevde hur det är att leva med diagnosen, vilken behandling de provat samt bemötandet som de fått i kontakt med vården. Metod: För att kunna besvara syftet så valdes en kvalitativ studie i form av intervjuer. Detta för att få en utökad förståelse kring PMDS och vad sjukdomen innebär. Intervjuerna var semistrukturerade och sju kvinnor inkluderades i studien. Inklusionskriterierna för denna studie var kvinnor med diagnosen PMDS som har varit i kontakt med sjukvården och blivit diagnostiserade med sjukdomen. Intervjuerna analyserades med hjälp av innehållsanalys enligt Graneheim och Lundman (2004). Resultat: PMDS tycks fortfarande vara en relativt okänd diagnos inom sjukvården och en del av informanterna var inte nöjda med vården de mottagit medan andra haft tur och hittat rätt väg på en gång. Det är en svår diagnos att leva med som inkräktar på såväl vardagsliv som arbetsliv och alla mänskliga relationer. Informanterna anser att en utökad förståelse och hjälp från vården skulle underlätta deras leverne. Slutsats: Mer kunskap krävs inom både vården och för samhället i stort då detta är en allvarlig diagnos som behöver upptäckas i tid så dessa kvinnor kan få rätt hjälp. Det är livsavgörande att kvinnor med diagnosen PMDS får de verktyg de behöver för att kunna leva ett fullvärdigt liv. / Background: PMDD is a relatively unknown diagnosis. There is a progression of Premenstrual Syndrome (PMS), but serious and sometimes debilitating for the sufferer out of it. The prevalence of PMDD is about five percent of all women of childbearing potential. Purpose: The purpose of this study was to examine how women diagnosed with PMDD experienced how it is to live with the diagnosis, the treatment they have tried, and the response they got in contact with health services. Method: A qualitative survey based on interviews was made in order to comprehend the diagnosis PMDS and its symptoms. Seven women participated in semi-structured interviews. The terms and conditions in this survey included women diagnosed with PMDS by and in contact with the health care system. The interviews were analyzed in accordance to Graneheim and Lundman’s content analysis. Results: The result indicated that PMDS is a relatively unknown condition within the health care system. Some of the informants were not pleased with the treatment given. Others received efficient treatment straight away. PMDS is burdensome to live with and it affects working life as well as social relations in common life. Conclusion: Acquaintance, both within the health care system and the society as a whole, is crucial for women diagnosed with PMDS. PMDS is a serious diagnosis which has to be discovered early in order to give these women efficient treatment. It is essential that women diagnosed with PMDS get efficient tools to handle their diagnosis in order to live vital lives.

Background: Premenstrual dysphoric disorder (PMDD) affects 3–8% of women in fertile ages. Combined oral contraceptives (OCs) are widely used and some users experience adverse mood effects. The cyclicity of PMDD symptoms coincides with increased endogenous levels of allopregnanolone after ovulation. Allopregnanolone enhances the effect of γ-aminobutyric acid (GABA) on the GABAA receptor, the principal inhibitory transmitter system in the brain. The sensitivity to other GABAA receptor agonists than allopregnanolone (i.e. benzodiazepines, alcohol and the 5 β epimer to allopregnanolone, pregnanolone) has been reported to depend on menstrual cycle phase and/or PMDD diagnosis. Isoallopregnanolone, the 3 β epimer to allopregnanolone, has previously been used to verify specific allopregnanolone GABAA receptor effects. Saccadic eye velocity (SEV) is a sensitive and objective measurement of GABAA receptor function. Aims: To study the pharmacological effects, and any effect on gonadotropin release, of intravenous allopregnanolone in healthy women. A second aim was to explore whether allopregnanolone sensitivity differs over the menstrual cycle or during OC use in healthy women, and thirdly in PMDD patients. Methods: Ten women were challenged with a cumulative dose of intravenous allopregnanolone in the follicular phase of the menstrual cycle. The effect on FSH and LH was compared to women exposed to isoallopregnanolone. A single dose of allopregnanolone was administered once in the follicular phase and once in the luteal phase in another ten healthy women and in ten PMDD patients, and additionally in ten women using OCs. Repeated measurements of SEV, subjectively rated sedation and serum concentrations after allopregnanolone injections were performed in all studies. Results: Allopregnanolone dose-dependently reduced SEV and increased subjectively rated sedation. Healthy women had a decreased SEV response in the luteal phase compared to the follicular phase. By contrast, PMDD patients had a decreased SEV response and subjectively rated sedation response to allopregnanolone in the follicular phase compared to the luteal phase. There was no difference in the SEV response to allopregnanolone between women using oral contraceptives and healthy naturally cycling women. Allopregnanolone decreased serum levels of FSH and LH whereas isoallopregnanolone did not affect FSH and LH levels. Conclusion: Intravenous allopregnanolone was safely given and produced a sedative response in terms of SEV and subjectively rated sedation in women. The sensitivity to allopregnanolone was associated with menstrual cycle phase, but in the opposite direction in healthy women compared to PMDD patients. The results suggest mechanisms of physiological tolerance to allopregnanolone across the menstrual cycle in healthy women and support that PMDD patients have a disturbed GABAA receptor function. In addition, one of our studies suggests that allopregnanolone might be involved in the mechanism behind hypothalamic amenorrhea.

Background. Despite an abundance of clinical research on premenstrual and menstrual symptoms, few epidemiological data provide estimates of the prevalence, incidence, co-morbidity, stability and correlates of premenstrual dysphoric disorder (PMDD) in the community. Aims. To describe the prevalence, incidence, 12 co-morbidity factors and correlates of threshold and subthreshold PMDD in a community sample of young women. Methods. Findings are based on prospective–longitudinal community survey of 1488 women aged 14–24, who were followed-up over a period of 48 months (follow-up, N = 1251) as part of the EDSP sample. Diagnostic assessments were based on the Composite International Diagnostic Interview (CIDI) and its 12-month PMDD diagnostic module administered by clinical interviewers. Diagnoses were calculated using DSM-IV algorithms, but daily ratings of symptoms, as required, were not available. Results. The baseline 12-month prevalence of DSM-IV PMDD was 5·8%. Application of the diagnostic exclusion rules with regard to concurrent major depression and dysthymia decreased the rate only slightly (5·3%). An additional 18·6% were ‘near-threshold’ cases, mostly because they failed to meet the mandatory impairment criterion. Over the follow-up period only few new PMDD cases were observed: cumulative lifetime incidence was 7·4%. PMDD syndrome was stable across 48 months with <10% complete remissions among baseline PMDD cases. The 12-month and lifetime co-morbidity rates were high (anxiety disorders 47·4%, mood disorders 22·9%; somatoform 28·4%), only 26·5% had no other mental disorder. Particularly high odds ratios were found with nicotine dependence and PTSD. In terms of correlates increased rates of 4-weeks impairment days, high use of general health and mental health services, and increased rates of suicide attempts were found. Conclusion. In this sample of adolescents and young adults, premenstrual symptoms were widespread. However, DSM-IV PMDD was considerably less prevalent. PMDD is a relatively stable and impairing condition, with high rates of health service utilization, increased suicidality and substantial co-morbidity.