Puerperal Psychosis is the most severe form of postnatal psychiatric illness, and is a psychiatric emergency. Human-based research to find a means of genetically predicting a woman's risk of puerperal psychosis has so far failed to reliably or reproducibly identify candidate genes or pathways, due to problems common within the field of psychiatric genetics, leading to the proposal of using an animal model in the form of Porcine Maternal Infanticide. In this project, the author has aimed to understand the pathophysiology of PMI using NGS technologies in order to 1) extend the validity of PMI as a model for PP; 2) determine future steps for development of the PMI model; and 3) generate insights into the management of PMI (and by extension PP) via prediction and detection of a puerperal trigger. These aims have been pursued via two experiments. In the first, the author has created RNA-Seq libraries from archival RNA, and then performed differential gene expression analysis. The results indicated that RNA-Seq technologies can be used with archival RNA samples, but using such samples introduces the risk of degradation-based bias. The substantial influence of outliers, confounding factors and sample size on the results prevented reliable identification of candidate genes" but provide concrete guidelines development of the Porcine Maternal Infanticide model. In the second, the author has created MBD-Seq libraries from archival tissue, and then performed differential methylation analysis. The results indicated that it is possible to use MBD-Seq technologies with Sus scrofa brain tissue. Once again, the effect of confounding factors and sample size on the results prevented reliable identification of candidate genes, but provide guidance for development of the Porcine Maternal Infanticide model.

O Transtorno Afetivo Bipolar (TAB) é uma condição crônica, caracterizada pela existência de episódios agudos e recorrentes de alteração patológica do humor, que ocasiona grande impacto na vida do paciente, reduzindo seu funcionamento e sua qualidade de vida. O uso de medicamentos consiste em uma realidade necessária ao cotidiano da pessoa com TAB. Este estudo teve como objetivo compreender o significado da terapêutica medicamentosa para a pessoa com TAB, em sua perspectiva e na de seu familiar. Dada a natureza do problema, esta investigação utilizou uma abordagem qualitativa, tendo como referencial metodológico a Teoria Fundamentada nos Dados, à luz do Interacionismo Simbólico. Participaram do estudo 14 pessoas com TAB que estavam em acompanhamento em uma Unidade Ambulatorial de Transtornos do Humor de um hospital universitário e 14 familiares indicados pelas mesmas. A entrevista e observação foram utilizadas como principais estratégias de obtenção de dados. As entrevistas gravadas, após serem transcritas, foram codificadas em três etapas: codificação aberta, codificação axial e codificação seletiva. A análise comparativa dos dados resultou no fenômeno central: ?ESTANDO ENTRE A CRUZ E A ESPADA? em relação à terapêutica medicamentosa. Tal processo foi constituído pela integração entre categorias no modelo de paradigma de Strauss e Corbin, envolvendo a causa desencadeadora do fenômeno, o contexto em que o mesmo está inserido, as condições intervenientes, a estratégia de ação sobre o fenômeno e suas conseqüências. O fenômeno ESTANDO ENTRE A CRUZ E A ESPADA permitiu compreender que, para pessoas com TAB, existe uma situação de ambivalência em relação à terapêutica medicamentosa: no início, não reconhecendo o transtorno e, paralelamente, tomando muitos medicamentos. Como não se percebem doentes, geralmente não identificam motivos para utilizar medicamentos que lhes impõem como realidade conviver com o preconceito e com as perdas e limitações impostas tanto pelos seus efeitos colaterais quanto pelos sintomas do transtorno, sendo freqüente o abandono da terapia medicamentosa. Ao identificar a real necessidade do medicamento, evidenciada pela vivência de crises na ausência do mesmo, as pessoas com TAB percebem-se frente a um dilema entre as duas alternativas de vida em que se constituem a saúde e a doença. Nesse sentido, ao mesmo tempo em que depositam no medicamento o símbolo de sanidade, esse passa a ser a prova concreta e cotidiana de que possuem um transtorno mental e crônico. Este estudo permitiu, assim, compreender os fatores associados e determinantes da realidade vivenciada pelas pessoas com TAB em relação à terapêutica medicamentosa, possibilitando um salto na implementação de estratégias de intervenção nos serviços de saúde direcionadas à qualidade da assistência a esses pacientes / Bipolar Affective Disorder (BAD) is a chronic condition, characterized by the existence of acute and recurring episodes of pathological mood change, which causes a great impact on patients? lives, reduces their functioning and quality of life. Taking medication is a necessary reality in the daily lives of BAD patients. This study aimed to understand the meaning of medication therapy for these patients, according to their perspectives and those of family members. Given the nature of the problem, this research used a qualitative approach, based on Grounded Theory, in the light of Symbolic Interactionism. Study participants were 14 BAD patients who were followed at a Clinical Unit for Mood Disorders of a university hospital and 14 relatives they indicated. Interviews and observation were the main strategies for data collection. The recorded interviews were first transcribed and then coded in three phases: open coding, axial coding and selective coding. Comparative data analysis resulted in the central phenomenon: BEING BETWEEN THE DEVIL AND THE DEEP BLUE SEA with respect to medication therapy. This process was constituted by integrating categories in Strauss and Corbin?s paradigm model, involving the cause that triggered the phenomenon, the context in which it is inserted, intervening conditions, the strategy to act on the phenomenon and its consequences. The phenomenon of BEING BETWEEN THE DEVIL AND THE DEEP BLUE SEA allowed us to understand that, for patients with BAD, there is an ambivalent situation related to medication therapy. This is perceived, at first, by not acknowledging the disorder and, in parallel, by taking many drugs. As patients do not perceive themselves as ill, they generally do not identify, at this moment in the history of the disorder, motives to take drugs that impose the reality of living with prejudice and with the losses and limitations imposed by their collateral effects as well as by the symptoms of the disorders, with frequent abandonment of medication therapy. By identifying the real need for the drug, evidenced by the experience of crises when it is absent, patients with BAD find themselves faced with a dilemma between the two alternatives of life, which are health and disease. In this sense, patients place the symbol of sanity in the medication but, at the same time, it becomes the concrete and daily proof that they have a mental and chronic disorder. This study allowed us to understand associated and determinant factors of the reality BAD patients experience in relation to medication therapy, permitting a leap in the implementation of intervention strategies in health service directed at the quality of care for these patients

Evidências indicam que o estresse psicológico pode desempenhar um papel importante no desencadeamento e evolução do Transtorno Bipolar. Faz-se importante estudar as maneiras como os pacientes lidam com o estresse (Coping). Os objetivos deste estudo foram investigar as relações entre coping e traços de personalidade em bipolares e controles saudáveis; comparar estratégias e estilos de coping e traços de personalidade de pacientes bipolares com controles saudáveis; comparar estratégias de Coping nos pródromos da mania de pacientes bipolares I e II. Foram realizadas entrevistas diagnósticas e confirmada a eutimia dos pacientes resultando no total de 35 bipolares (foram considerados eutímicos pacientes com escore 12 na Escala de Avaliação de Mania de Young e 7 na Escala de Avaliação para Depressão de Hamilton). O grupo de comparação foi constituído por 40 indivíduos saudáveis do ponto de vista psiquiátrico. Foram avaliadas as habilidades de coping (Coping Inventory for Prodromes of Mania, Escala de Modos de Enfrentamento de Problemas e Brief COPE) e os traços de personalidade (Inventário de Personalidade NEO PI-R). As comparações das médias dos escores da escala Coping Inventory for Prodromes of Mania foram realizadas pelo teste Mann-Whitney. As comparações das médias dos escores das estratégias e estilos de coping e dos traços de personalidade foram realizadas por análises multivariadas de covariância. As associações entre estratégias e estilos de coping e traços de personalidade foram realizados pelos modelos de regressão linear múltipla. Os resultados mostraram que os bipolares apresentam mais estratégias e estilos de coping focalizados na emoção do que no problema, altos níveis de Neuroticismo e baixos níveis de Extroversão e Conscienciosidade. Foram encontradas associações positivas entre Neuroticismo e coping focalizado na emoção e negativas entre Neuroticismo e coping focalizado no problema (estratégias). Nos estilos de coping, foram encontradas associações positivas entre coping focalizado no problema e Conscienciosidade e negativas entre Extroversão e coping focalizado no problema. Estes resultados suportam a hipótese de que associações entre traços de personalidade e habilidades de coping desempenham um importante papel na modulação entre estresse e recorrência no Transtorno Bipolar / Evidence indicates that psychological stress may play a key role in triggering the onset and evolution of Bipolar Disorder. Investigations into the ways patients cope with stress are therefore valuable. The aims of this study were to: (i) investigate the relationship between coping and personality traits in bipolar and control subjects;(ii) compare coping strategies and style besides personality traits in bipolar patients against those of healthy controls;(iii) compare coping strategies between bipolar I and II patients in the prodromes of mania. Diagnostic interviews were conducted confirming euthymia among participants and detecting a total of 35 bipolar patients (scores 12 on the Young Mania Assessment Scale and 7 on the Hamilton Depression Rating Scale indicated euthymia). The control group for comparison comprised 40 psychiatrically-healthy individuals. Coping skills (Coping Inventory for Prodromes of Mania, Ways of Coping Checklist and Brief COPE) and personality traits (Personality Inventory NEO PI-R) were assessed. Mean scores on the Coping Inventory for Prodromes of Mania were compared using Mann-Whitneys test. Mean scores for coping strategies and styles as well as personality traits were compared by multivariate covariance analyses. Associations between coping strategies and styles and personality traits were determined by multiple linear regression models. Results showed that bipolar patients made greater use of emotion-focused strategies than problem-focused strategies, exhibited high levels of Neuroticism and low levels of Extroversion and Conscientiousness. Positive associations between Neuroticism and emotion-focused coping, and negative associations between Neuroticism and problem-focused coping (strategies), were found. Regarding coping styles, positive associations were identified between problem-focused coping and Conscientiousness, while negative associations were found between Extroversion and problem-focused coping. These results support the hypothesis that associations between personality traits and coping skills play a key role in the modulation between stress and relapse in Bipolar Disorder

The purpose of this study was to compare outcomes for patients with Bipolar Disorder or Major Depressive Disorder based on severity of diagnosis. This study also compared psychotherapy providers and therapy modalities on total cost, number of sessions, and dropout. Our data set (N=136,439) came from Cigna, a national health care company. Results showed significant differences by severity of diagnosis. The comparison of providers showed that psychologists had higher costs and session numbers, while the other providers were not significantly different. However, all providers successfully provided low cost treatment on both MDD and BD. There is no support for the idea that one profession is more successful at providing low cost treatment for MDD and BD. Family therapy did significantly better on all outcomes except dropout rate when compared to individual or mixed (individual and family sessions) therapy. It is a low-cost option when treating MDD and BD, regardless of severity.

The new millennia has been characterised by developments in the digital world, creating a new space for social work practice globally. The aim of this research is to explore the online medium as an alternative resource for social work with online groups through an observation and interviews in an online group for Bipolar Disorderin Sweden. The results found that lived experience proved central to all forms of participation and support was seen as a resource to be shared. The implications for social work practice were found on multiple levels with broad areas of influence, such as utilising the online medium as an alternative source of insight, thereby allowing needs assessment, both onindividual and [sub]group level. Accessibility by way of the internet was seen as a catalyser to participation as well as a comprehensive method in creating such communities both locally and internationally through the development of digital social work.

Family and twin studies have shown a heritable component to seasonal affective disorder (SAD). While a few studies have examined individual genetic variants in SAD, many methodological issues exist in the current literature. First, most studies combined major depression (MDD) and bipolar (BD) cases in the genetic analysis of SAD. This makes it difficult to differentiate the effect from MDD and BD. Second, most studies adopted a candidate gene approach and used fairly small sample sizes. This does not allow for testing across a wide variety of genes, and it yields less robust P-values. Third, healthy controls have been used, but not case comparisons, which makes it difficult to differentiate the effects of seasonality from that of the primary illness (MDD and BD). To overcome these issues, seasonal MDD and BD cases were separated into two different studies in this thesis; sample sizes for both studies are the largest in the current SAD molecular genetics literature; GWAS was used to test for potential risk loci in a hypothesis-free fashion; case comparisons were incorporated to exclude potential genetic contributions related generally to the primary diseases themselves (MDD and BD). For MDD, we performed a GWAS with 562 seasonal MDD cases and 1,225 comparison cases with non-seasonal MDD. Subjects were drawn from two iterations of the Genetics of Recurrent Early Onset Depression (GenRED) study. Seasonal cases were those whose depressive episodes typically started in fall or winter. A mega-analysis of the two GWAS datasets was done using SNPTEST. We found that two single nucleotide polymorphisms (SNPs), rs149882931 and rs77073398, on chromosome 16p12.1 were associated with seasonal depression, at a genome-wide significant level (OR= 1.66, P= 3.59 x 10-8 and OR=1.62, 4.76 x 10-8, respectively). Since SAD is more prevalent in females, a female-specific analysis was carried out. The two variants were more significant in this analysis: P=2.18x10-9 (OR=1.89) and P=2.79x10-9 (OR=1.82), respectively, and a significant sex-by-SNP interaction was observed. These SNPs are located in a conserved intergenic region between the genes HS3ST4 and C16orf82. The protein product of HS3ST4 modifies the side chains of heparan sulfate proteoglycans. We therefore tested the hypothesis that the heparan sulfate biosynthesis pathway would be enriched in nominally significant SNPs using the SNP ratio test, and found evidence for such enrichment (P=0.008, SNP ratio test, P=0.027, SKAT). For BD, the GWAS analysis of 818 seasonal BD cases and 1,515 healthy controls showed that BD-S is most strongly associated with two SNPs within the ZBTB20 genes. BD subjects were drawn from NIMH Bipolar Genetics Study (BIGS), and seasonal cases were defined as those with depressive episodes starting in fall or winter. An association study was carried out with SNPTEST, and we found two single nucleotide polymorphisms (SNPs) in the intronic region of ZBTB20 gene to be associated with BD-S (rs7646282, OR=2.34, P= 7.23 x 10-8 and rs139459337, OR=2.37, 8.05 x 10-8). A similar case-only study was carried out with 818 BD-S cases and 1239 cases without seasonal depressive symptoms (non-BDS), though no SNP was found to be significantly associated in this analysis. rs7646282 is the strongest SNP in cis-association with ZBTB20 gene expression, and ZBTB20 has been shown to affect the neural development of the hippocampus, a brain region implicated in the pathophysiology of BD. Finally, we sought to determine whether there is a role for circadian rhythm genes in BD susceptibility. In this study, we used a discovery set of 189 exome-sequenced BD patients and 105 healthy controls to look for circadian genes associated with BD. We found the DRD2 gene to be the circadian gene most strongly associated with BD. Among the rare damaging variants in the DRD2 gene, the S311C variant was the predominant SNP. To test whether this variant segregates in family members with BD, we genotyped the family members of probands from the discovery sample. This data was used for a linkage and family-based association study. Even though the linkage analysis was only very weakly positive, the family-based association study showed significant segregation of the variant in family members with BD (P< 0.05). To follow up on this finding, we further genotyped 2,185 unrelated BD cases and 1,982 healthy controls. We found no support for the S311C variant in this replication dataset. Sub-phenotype study of psychotic features and mood-incongruence also did not show significant association. Meta-analysis with 2,994 BD cases and 3,661 controls, however, revealed no association between the S311C variant and BD.

For over a century, there have been suggestions of a link between what is currently called bipolar disorder and cardiovascular mortality. In the contemporary epidemiological literature, this risk has been confirmed and approximates twice that expected based on age and gender. To date, however, this information has come primarily from clinical samples, which carry considerable risk of selection bias. The studies contained in this dissertation sought to assess this relationship using methods less vulnerable to selection bias and to determine the role that course of illness and treatments for illness may play in the development of vascular disease. In a nationally representative sample, we confirmed a link between mood disorders and vascular disease, which was particularly pronounced in women with bipolar disorder. In subsequent studies, a dose-response relationship between the duration of clinically significant hypomanic or manic symptoms and both cardiovascular mortality and endothelial function was seen. While medication exposure did not appear related to mortality or endothelial function, first generation antipsychotics were associated with arterial stiffness, an effect apparently mediated by elevations in blood pressure. In cross-sectional samples, our data suggests that vasculopathy is not present early in the course of bipolar disorder although is much greater than expected later in the course of illness. This dissertation purports that vasculopathy develops over the long-term course of bipolar disorder, is proportional to symptom burden, and is influenced by health behaviors and treatments. These findings may provide opportunities for clinicians and those afflicted to intervene to address this excess risk of vascular morbidity and mortality.

Bakgrund: Bipolär sjukdom karaktäriseras av att sinnestillståndet pendlar mellan höga och låga stämningslägen. De växlande sjukdomsepisoderna bidrar till en komplex livssituation för patienten. Patientens symtombild står som grund för diagnostisering av bipolär sjukdom och behandling inriktas främst på farmakologisk behandling och även psykoterapi vid behov. Utöver det beskrivna krävs ett gott samarbete mellan anhöriga, patient och vårdpersonal. Detta är väsentligt för att patienten ska erhålla ett adekvat stöd och samtidigt öka förutsättningarna för god följsamhet av sin behandling. Syfte: Syftet var att belysa patienters upplevelser av att leva med bipolär sjukdom. Metod: Denna uppsats är en litteraturöversikt och elva vetenskapliga artiklar med kvalitativ metod har analyserats. Resultat: Utifrån analysen skapades fem huvudteman med tillhörande underteman. Fem huvudteman formades: Det sociala sammanhanget, Identitet och förlorad kontroll, Upplevelsen av sjukdomssymtom, Att bli stigmatiserad och Att medicinera- En ambivalent upplevelse. Resultatet visar att patienter upplevde bristande kunskap från omgivningen gällande bipolär sjukdom vilket ledde till isolering och en känsla av identitetsförlust hos patienterna. Diskussion: Bipolär sjukdom kräver i många fall ett starkt socialt nätverk för att patienten ska få stöd i sin hantering av sjukdomen och omgivningen kan bidra med både positiva och negativa upplevelser för patienten. För att patienten ska erhålla ett adekvat stöd krävs det vid bipolär sjukdom kunskap och förståelse från omgivningen samt vårdpersonal. Phil Barkers omvårdnadsteori belyser samarbete med anhöriga och evidensbaseradeverktyg, som fokuserar på patientens berättelse, som avgörande komponenter i patientens omvårdnadsprocess. / Background: Bipolar disease is characterized by a state of mind that commutes between high and low mood swings. The variating episodes contribute to a complex life situation for the patient. The patient’s symptoms are used for diagnosing bipolar disorder and treatment is primarily pharmacological treatment and psychotherapy commonly used when needed. Furthermore good cooperation between relatives, patients and healthcare professionals are required. This is essential so that the patient can receive adequate support and also increase presumptions for good compliance with treatment.  Aim: The purpose was to illustrate patients’ experiences of living with bipolar disorder. Method: This essay is a literature review and eleven scientific articles with qualitative method have been analyzed.   Results: Based on the analysis, five main themes were created with associated subtheme. Five main themes emerged: The social context, Identity and loss of control, The experience of disease symptoms, Becoming stigmatized and Being medicated- An ambivalent experience. The result shows that patients experienced insufficient knowledge from the environment regarding bipolar disorder which has led to isolation and a sense of identity loss in patients.  Discussion: Bipolar disorder requires in many cases a strong social network in order for the patients to receive support in their management of the disease and the environment can contribute with both positive and negative experiences for the patient. In order for the patient to receive adequate support, bipolar disorder requires knowledge and understanding from the environment as well as healthcare professionals. Phil Barker's Nursing Theory illustrates collaboration with relatives and evidence-based tools, that focus on the patient's story, as crucial parts of the patient's nursing process.

This thesis explores the lived experience of those with Bipolar Disorder type I or type II condition. The aim is to delineate how individuals cope following the diagnosis of this chronic, recurrent mental illness. Twenty participants were interviewed in depth, producing 18 hours of recordings and 480 pages of transcript. Narrative data were thematically analysed to reveal themes common to the process of adaptation. The exploratory framework identified key elements of the lived experience of bipolar disorder, including: the phenomenology of highs and lows, the role of anxiety in triggering episodes, reactions to diagnosis, and issues with prescribed medications. Analyses highlighted how difficult it is for individuals to reconcile themselves to the symptoms and consequences of the illness, and also illustrated the extent of subjective distress and reduced quality of life incurred. The psychosocial burden, particularly the difficulties developing a sense of authenticity and coherent identity, and having to adjust life goals, were examined in detail. Negative coping behaviours, specifically the use of alcohol and drugs, as well as the influence of shame and guilt on peoples??? coping repertoires were also explored. Finally, the importance of psychosocial interventions, collaborative health care strategies and necessity for long-term, follow-up care were emphasised.

The extensive suffering related to a complex life situation with bipolar disorder and the reported difference between care needs and the needs that are actually met implicates that there are still questions about management of life with bipolar disorder that need to be answered. The present study therefore aims to describe the meaning of the conditions that enable a good life with bipolar disorder. Ten persons, six women and four men, (aged 30 – 61), diagnosed with bipolar disorder were interviewed. A reflective lifeworld perspective based on phenomenological philosophy was used. The findings present the essential meaning of the conditions that enable a good life with bipolar disorder as a dependence that empowers, which is further described by its constituents: “turning the course of life”, “protecting oneself from running out of energy”, “being needed”, “being oneself through reliable others”, “personal landmarks for navigating through life”. A voluntary chosen dependence, as described in the present study, is a new approach of care that enables a good life with bipolar disorder, while enhancing own power, freedom and control. The conditions that enable a good life with bipolar disorder are more than separate supporting measures. Therefore a holistic perspective is preferable while providing care for individuals with bipolar disorder.