Major depressive disorder (MDD) is a leading cause of disability worldwide, with a lifetime prevalence rate of approximately 20%. Inadequate pharmacological treatment methods for MDD are a significant debilitating factor. Patient estimates suggest that the treatment resistance rate for pharmacological interventions is over 30%. Postmortem analyses of human tissue of individuals diagnosed with MDD have shown an increase in Poly (ADP-ribose) polymerase 1 (PARP-1) mRNA gene expression in prefrontal cortical white matter when compared to psychiatrically normal brain tissue. In order to further investigate this issue, the present study used the social defeat stress/chronic unpredictable stress (SDS + CUS) rodent model of depression to induce a state of chronic psychological distress. Rats were treated with either the PARP-inhibitor, 3-aminobenzamide (3-AB); a common selective serotonin reuptake inhibitor (SSRI) fluoxetine (FLX), or saline. During the stress manipulation we conducted the sucrose preference test, results revealed that saline-treated rats which had undergone SDS + CUS showed significant reductions in sucrose preference compared to all other groups. In addition, a social interaction test was conducted one day after the stress manipulation, and saline-treated stressed animals demonstrated less social interaction compared to all other groups, indicating the stress manipulation was effective. Neurobiological assays were conducted to examine PARP expression, microglial morphology, and proinflammatory cytokine expression. Though we expected to find a decrease, results from immunofluorescence studies of tissue sections revealed an elevation of PARP-1 protein expression in prefrontal cortical gray matter in the FLX/Stress group compared with SAL/Stress group. Microglial morphological changes indicated that the SAL/Stress group had significantly more prolate microglia when compared to all other treatment groups, suggesting early activation of microglia, an indicator of neuroinflammation. Increases in IL-1β and TNF-⍺ expression was observed in the hippocampus of the SAL/Stress group when compared to all other treatment groups. Interestingly, IL-6 expression was significantly elevated in the SAL/Stress group when compared to the FLX/Stress group and the CTRL/No stress group but did not significantly differ from the 3-AB/Stress group. This study revealed therapeutic potential of 3-AB for the treatment of stress-related disorders, as well as the neuroinflammatory mechanisms associated with chronic stress.

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De gravida kvinnorna befann sig i en extra sårbar livssituation som visade sig bero på olika faktorer, såsom graviditetsrelaterade faktorer, socioekonomisk utsatthet, svåra livshändelser och hur de upplevde mötet med vården. Sjuksköterskan kan komma att möta dessa kvinnor på vårdcentraler, somatiska och psykiatriska vårdavdelningar, akutmottagningar samt andra vårdinrättningar. Det är viktigt att sjuksköterskan är lyhörd, har ett respektfullt bemötande och vågar fråga hur den gravida kvinnan mår för att kunna möjliggöra tidig intervention och professionell hjälp. / The pregnant women were in a more vulnerable life situation, which was shown to be due to various factors, such as pregnancy-related factors, socio-economic vulnerability, difficult life events, and their encounters with the health care system. A nurse may meet these women at health care centers, somatic and psychiatric facilities, emergency rooms, and other health care facilities. It is essential that the nurse is attentive, has a respectful attitude, and dares to ask how the pregnant woman is doing to enable early intervention and professional help.

Mindfulness-based cognitive therapy (MBCT) is a meditation-based psychotherapeutic intervention suggested to be equally effective as antidepressant medication for preventing depressive relapse. A lot of patients with major depressive disorder (MDD) have preference for psychotherapeutic intervention compared to antidepressant medication, currently being the most common treatment for preventing depressive relapse. The aim of this systematic review was to examine the effectiveness of MBCT compared to antidepressant medication for preventing depressive relapse in individuals with MDD, treatment-resistant depression, or suicidal ideation. After a literature search in the databases Scopus and Web of Science, 16 articles were included in this systematic review. Results were mixed. While two studies demonstrated that MBCT is equally effective as antidepressant medication in preventing depressive relapse, four studies showed evidence of reduced relapse rates after MBCT treatment alone. Further, four studies suggested that MBCT is inferior to antidepressant medication in preventing depressive relapse. Future studies should focus on comparing MBCT alone to specific antidepressant medication in order to further evaluate the effectiveness of MBCT vs antidepressant medication.

Early life stress has been found to be a strong predictor of depression severity, with genetic risk factors such as the serotonin transporter promotor (5-HTTLPR) and brain derived neurotrophic factor (BDNF) polymorphisms moderating depression development. Our investigation aims to extend these findings to examine the impact of depression severity, genetic risk factors, and childhood maltreatment on neuronal connectivity changes using tract based spatial statistics (TBSS) and probabilistic tractography. Fifty-five medication-free patients with major depressive disorder (MDD) [x̅ age: 36.4, M/F: 22/33] and 18 controls [x̅ age: 33.2, M/F: 8/10] underwent diffusion tensor imaging scanning, genotyping and completed the Childhood Trauma Questionairre. Corrected TBSS findings revealed trends toward significantly reduced FA in the right anterior internal capsule [p=0.051], fornix [p=0.085] and right anterior corona radiata [p=0.084] in the MDD group. Probabilistic tractography analysis examined fractional anisotropy (FA) in the cingulum bundle, uncinate fasciculus and superior longitudinal fasciculus. Individuals scoring high in depression severity and who experienced severe childhood physical neglect (PN) and emotional neglect (EN) had higher FA in the uncinate [PN: p=0.003, EN: p=0.029] and superior longitudinal fasciculus [PN: p=0.0748], with BDNF and 5-HTTLPR moderating these associations. BDNF polymorphisms also exhibited a stronger impact on uncinate FA in individuals with high depression severity, with val-BDNF exhibiting higher FA than met carriers [p=0.021]. In conclusion, MDD patients exhibit widespread decreases in FA across many neural regions. Furthermore, the impact that depression severity has on FA is considerably influenced by early life neglect. / Thesis / Master of Science (MSc)

A major challenge in the treatment of major depressive disorder (MDD) is relapse, which is defined as the return of depressive symptoms during a period of remission. Relapse rates in MDD are high, with approximately 50% of individuals relapsing following treatment of their first depressive episode, therefore early intervention to prevent relapse is crucial. Evidence suggests that immune dysregulation may be linked to longitudinal changes in depressive severity. However, it is currently unknown whether inflammation can predict future relapse in MDD. The objective of this project was to identify potential immune predictors of relapse in participants that responded to a treatment or a combination of treatments for MDD. A secondary objective was to investigate immune composition in efforts to stratify MDD individuals into more homogenous groups and further explore these groups in relation to clinical symptoms. This project is part of the Wellness Monitoring for Major Depressive Disorder longitudinal study (NCT02934334) of responders to antidepressant treatment conducted at 6 clinical sites across Canada. Montgomery Asberg Depression Rating Scale (MADRS) scores were used to assess depression severity and to categorize participants into ultrastable, unstable, and relapse groups. Plasma immune profiles were generated using the LEGENDplex Human Th Cytokine Panel immunoassay. Principal Component Analysis and Kruskal-Wallis tests of individual immune cytokines did not show differences between ultrastable, unstable, or relapse groups. Principal Component Analysis did reveal two cytokine clusters. Hierarchical Clustering analysis identified three distinct immune biotypes characterized by differing levels of Th cytokines and validated the presence of the cytokine clusters. Neither of these outcomes was predictive of relapse in this cohort. Our findings have shown that immune composition may serve as an important factor in parsing heterogeneity that is observed in this disorder through identification of distinct immune biotypes and highly interconnected cytokine subnetworks in major depression. The potential for immune biotypes for optimizing treatment regimens and relapse prevention necessitates further investigation and replication. / Thesis / Master of Science (MSc)

Bakgrund: Depressions- och ångestsyndrom är de vanligaste förekommande psykiska sjukdomarna och leder i stor utsträckning till sjukskrivningar. Patientgruppen utgör en stor del av samhället, samt är en vårdsökande grupp som kommer påträffas inom alla instanser av vården. Det finns en stark korrelation mellan ångest och depression samt fysisk sjukdom, vilket innebär att patientgruppen blir allt vanligare förekommande inom vården. För att kunna förbättra vården blir det därför av stor vikt att förstå vård-upplevelsen utifrån patientens perspektiv. Syfte: att beskriva patienters erfarenheter av faktorer som påverkar vården vid depressions och/eller ångestsyndrom. Metod: En litteraturöversikt över elva artiklar med kvalitativ ansats genomfördes. Resultat: Sex huvudkategorier identifierades: copingstrategier som bidragande faktorer, faktorer som patienten upplever främjar vården, faktorer som patienten upplever försvårar vården, stigmatiseringens konsekvenser för vården, attityder till läkemedelsbehandling av depressions- och ångestsyndrom samt hur patientens självbild påverkar vården. Resultatet redovisar att patienters erfarenheter av försvårande faktorer förekom i större utsträckning än främjande. Erfarenheter som framträdde var bristande bemötande, brister i organisationen, okunskap kring sjukdomsbild samt hur stigmatiseringen påverkar patienten och dennes självbild. Erfarenheter av främjande aspekter var familj och anhöriga som stödjande samt deras eller den egna individens tidigare positiva erfarenheter av vården. Slutsats: Personcentrerad vård kan både underlätta vård och öka följsamheten för denna patientgrupp. För att uppnå en god omvårdnad behöver det etableras en förtroendefull och fördomsfri relation mellan sjuksköterska och patient. Med en personcentrerad omvårdnad stärks patientsäkerheten och sjuksköterskan skapar lättare en förtroendefull relation med patienten. / Background: Depressive and anxiety disorder are the most common mental illnesses and largely contribute to sick leave. The patient group constitutes a large part of society and is a care-seeking group that will be encountered in all instances of healthcare. There is a strong correlation between anxiety and depression as well as physical illness, this means that the patient group is becoming increasingly common in healthcare. To improve care, it is therefore of great importance to understand the care-experience from the patient's perspective. Aim: Where to describe patients' experiences of factors that influence care for depressive and/or anxiety disorders. Method: A literature review of eleven articles with a qualitative approach was carried out. Results: Six main categories were identified: coping strategies as contributing factors, factors that the patient perceives as promoting care, factors that the patient perceives as making care more difficult, the consequences of stigma for care, attitudes to drug treatment of depressive and anxiety disorder, and how the patient's self-image affects care. The results report overall on patients' experiences of care where inhibiting factors occur to a greater extent than promoting factors. Experiences that emerged were deficient treatment in healthcare, shortcomings in the organization, unenlightenment about the clinical characteristics of the disease and how the stigma affects the patient and their self-image. Experiences of enablers were family and relatives as motivators as well as their or the individual's own previous positive experiences of care. Conclusion: Person-centred care can both facilitate care and increase adherence for this patient group. To achieve good nursing care a trustful and unprejudiced relationship between the nurse and patient needs to be established. With person-centred nursing care, patient safety is strengthened, and the nurse creates a trusting relationship with the patient more easily.

Rumination, or extensive mind wandering defines one of the key cognitive symptoms of major depressive disorder (MDD). Several symptoms included in the psychiatric disorder have been associated with altered connectivity within the large-scaled system default mode network (DMN). Although it’s well-known that antidepressant treatment, such as selective serotonin reuptake inhibitor (SSRI) and serotonin norepinephrine reuptake inhibitor (SNRI) tend to positively affect symptoms and alterations of MDD, results are inconsistent regarding DMN connectivity pre-and-post treatment. This systematic review aims to compile findings from studies investigating DMN connectivity in MDD patients’ pre-and post SSRI and SNRItreatment, and to find possible correlations with symptomatic improvements. Five articles were included for further analysis after the literature search in MEDLINE ESBSCO and Scopus. Main findings are in alignment with previous research and suggest both hypo-and hyper DMN connectivity at baseline in MDD patients, and connectivity patterns significantly similar to healthy controls following antidepressant treatment. Future research might consider placebo controlled trials for more diverse, and quantified results, and also consider further investigation on both first-line treatments and other promising antidepressants.

This thesis presents research investigating the relationship between, and methods of, measuring circadian rhythms in mood disorders in a population of currently depressed and euthymic individuals with both depression and bipolar disorder. This was first assessed by comparing group differences in subjective sleep and circadian measures with objective sleep and circadian measures. The objective circadian measures involved actigraphy and melatonin profiling. This analysis showed group differences in subjective sleep and circadian parameters compared to controls, however no robust differences between mood groups. Objective melatonin profiling showed a mild agreement with subjective circadian parameters. Next, we studied the external validity of a subjective rating scale measuring biological rhythm disturbance, the Biological Rhythms Interview for Assessment in Neuropsychiatry (BRIAN), against objective measures of sleep and circadian activity rhythmicity. The BRIAN demonstrated some promising external validity, namely correlations with wake after sleep onset (WASO) and sleep efficiency, as well as melatonin levels in each group. These studies provide evidence of the extent to which a self-report may help in assessing parameters of sleep and circadian rhythms in the clinical setting. In doing so, it is expected that the use of subjective ratings will provide insight into the impact of biological rhythms disturbances and mood disorders. Lastly, we conducted an overview of the preclinical and clinical literature investigating the impact of circadian disturbance on cognitive performance. The results from this literature review yielded patterns of rhythmicity in specific parameters in each of the attention, memory, and executive function domains in humans, whereas attention and memory are more of a primary focus in animal studies. However, we also found that there are significant gaps in the understanding of how disturbances in circadian rhythms may influence cognitive function. This review also highlights the importance of cross-species translational validity from a methodological perspective, in order to generate positive clinical results beginning at the preclinical stage in neuropsychiatric disorders. / Thesis / Master of Science (MSc)