Evidence from various sources suggests that schizophrenia may result from altered brain development. The adult olfactory epithelium provides an available 'window' on neuronal development because new neurons are formed there throughout life. This thesis set out to test the neurodevelopmental hypothesis of psychotic disease. Two cell-based models, skin fibroblast and olfactory mucosa culture, were employed to investigate this hypothesis. In order to first demonstrate the utility of olfactory mucosa culture as a model of neurodevelopment, and to allow the candidate to gain proficiency in the culture of this tissue, an investigation of the mitogenic and differentiating properties of insulin-like growth factor-I within this system was undertaken. Insulin-like growth factor-I has multiple effects within the developing nervous system but its role in neurogenesis in the adult nervous system is less clear. The adult olfactory mucosa is a site of continuing neurogenesis that expresses insulin-like growth factor-I, its receptor, and its binding proteins. The action of insulin-like growth factor-I was assayed in several serum-free culture systems combined with bromodeoxyuridine labelling of proliferating cells and immunochemistry for specific cell types. Once proficiency in olfactory mucosa culture was gained, this model was applied to biopsied olfactory mucosa from schizophrenia and bipolar disorder patients in order to test the developmental parameters of adhesion, cell proliferation, and cell death in a neural tissue. It was previously shown that olfactory cultures from individuals with schizophrenia had increased cell proliferation and attached less frequently than cultures from healthy controls suggesting disrupted neurogenesis. An aim of this study was to replicate those observations in individuals with schizophrenia and and extend them to individuals with bipolar disorder. After completion of the cell and tissue culture assays, microarray analysis of these cell-based models was used to reveal gene expression differences present between patients and healthy controls. Microarray analysis is a complicated technique and the limited amounts of RNA that can be extracted from a single nasal biopsy further compounds this issue. In order to obtain enough material for microarray hybridization RNA samples underwent antisense amplification. Therefore, with the aim of allowing the candidate to gain proficiency in both these techniques prior to microarray analysis of olfactory biopsies from patients with schizophrenia and bipolar disorder, a pilot microarray study of cultured skin fibroblasts from schizophrenia patients and healthy controls was performed. The present findings show that insulin-like growth factor-I and its receptor were expressed by globose basal cells (the neuronal precursor), by neurons and by olfactory ensheathing cells, the special glia of the olfactory nerve. Insulin-like growth factor-I reduced the numbers of proliferating neuronal precursors, induced their differentiation into neurons, and promoted morphological differentiation of neurons. In contrast, this growth factor was mitogenic for olfactory ensheathing cells. The evidence suggests that insulin-like growth factor-I is an autocrine/paracrine signal that induces neuronal precursors to differentiate into olfactory sensory neurons and induces olfactory ensheathing cells to proliferate and that olfactory mucosa culture is valuable in modelling neurodevelopmental processes. When the olfactory musoca culture model was applied to patients with psychosis, a two-fold increase in proliferation of neural cells was found in schizophrenia compared to controls and bipolars. In bipolar cultures there was a 3-fold increase in cell death compared to controls and schizophrenia. Microarray analysis of cultured skin fibroblasts revealed differential expression of over 1000 genes between patients and controls. Inspection of the significant data showed alterations to gene expression between groups in the cell cycle, oxidative phosphorylation, TCA cycle and oxidative stress pathways. Gene expression in each of these pathways was predominately decreased in schizophrenia. Quantitative PCR analysis of selected differentially expressed genes involved with cell cycle regulation validated the increased expression of vitamin D receptor, and decreased expression of proliferating cell nuclear antigen and DEAD (Asp-GIu-Ala-Asp) box polypeptide 5 in skin fibroblasts from patients with schizophrenia. Microarray analysis of biopsied olfactory mucosa showed 146 and 139 differentially expressed genes in schizophrenia and bipolar disorder respectively, compared to controls. Consistent with increased mitosis in schizophrenia biopsy cultures three genes that function to positively influence cell cycle had increased expression. In the bipolar disorder group a dysregulation of the phosphatidylinositolsignalling pathway was seen; five genes that either directly function within or interact with this pathway had decreased expression. There is speculation that the therapeutic effect of psychotropic drugs acting upon this pathway in bipolar disorder involves reduction of neuronal cell death. Increased mitosis of neural cells has now been observed in two separate groups of schizophrenic patients indicating a robust finding. The use of fibroblast and olfactory mucosal tissue can be used to study biological and genetic aspects of neurodevelopment in living humans both with and without psychotic disease. Biopsied olfactory mucosa provides benefits over the use of autopsied material for study of psychotic disease because post-mortem duration and agonal factors that lead to tissue, protein and nucleic acid degradation are not an issue. This study provides evidence for a neurodevelopmental aetiology of schizophrenia and bipolar disorder acting at the level of cell cycle control. Subtle changes in the timing of cell cycle regulation could account for the brain pathologies observed in these diseases. Olfactory mucosa culture is a valuable model of neurodevelopmental processes.

Bakgrund: Patienter med psykossjukdom lider ofta av somatisk ohälsa som uttrycker sig i metabolt syndrom. Dåliga levnadsvanor som till exempel dålig kosthållning, inaktivitet, droger etcetera, samt den nödvändiga läkemedelsbehandling är faktorer som bidrar till utvecklandet av metabolt syndrom. Dessa faktorer leder till att denna patientgrupp riskerar att dö upp till 25 år tidigare än den övriga populationen. Syfte: Syftet med studien var att belysa preventiva och lindrande omvårdnadsinterventioner mot metabolt syndrom hos personer som behandlas för psykossjukdomar. Metod: Studien är utformad och genomförd som en allmän litteraturstudie med systematisk ansats. Databassökningen utfördes i Cinahl, Pubmed, Scopus, Psycinfo och Psycarticle. Artiklarna kvalitetsgranskades utifrån Linköpings universitets granskningsmallar och kvalitetsbedömdes utifrån författarnas kvalitetskrav. Resultat: Resultatet bildade tre kategorier; Levnadsvanor, Socialt stöd och Prevention, vilka står i beroende till varandra. Patienternas levnadsvanor är det huvudsakliga fyndet för att lindra och förhindra metabolt syndrom, men för att kunna genomföra livsstilsinterventioner hos patienter med psykos behövs socialt stöd och information. Dessa faktorer utgör även grunden för det preventiva arbetet för att förhindra metabolt syndrom innan det utvecklats. Konklusion: Sammanfattningsvis kan sägas att de preventiva och lindrande åtgärderna mot metabolt syndrom för personer som behandlas för psykossjukdom är att stödja och uppmuntra patienten till en hälsosammare livsstil, innefattande ökad fysisk aktivitet och förbättrad kosthållning. Det åligger även sjuksköterskans arbetsuppgift att individanpassa vården och skapa en personcentrerad vård, skräddarsydd för den enskilde patientens förmågor och behov. Nyckelord: Psykossjukdom, Metabolt syndrom, Omvårdnad, Sjuksköterska. / Background: Patient with psychosis often suffer from somatic illness that is expressed as metabolic syndrome. Bad living habits such as bad diet, inactivity, drugs etcetera is factors that contribute to the development of metabolic syndrome. Also, the necessary drug treatment is important for the development of metabolic syndrome. These factors sets the patient group in a risk to die up to 25 years earlier than the average population. Aim: The purpose of the study was to highlight preventive and mitigating nursing interventions against metabolic syndrome in people treated for psychiatric diseases. Method: This study was designed and implemented as a general literature study with a systematic approach. The database research was performed in Cinahl, Pubmed, Scopus, Psycinfo and Psycarticle. The articles was quality-reviewed by Linköpings University’s review-templates and was quality assessed by the authors quality requirement. Result: The result formed three categories; Lifestyles, Social support and Prevention, which depend on each other. Patients' living habits are the main finding for relieving and preventing metabolic syndrome, but in order to be able to implement lifestyle interventions in patients with psychosis, social support and information are needed. These factors also form the basis for preventive work to prevent metabolic syndrome before it develops. Conclusion: In summary, it can be said that the preventative and alleviate measures against metabolic syndrome for people treated for psychiatric disease are to support and encourage the patient to a healthier lifestyle, including increased physical activity and improved diet. It is also the duty of the nurse to personalize care and create a person-centered care tailored to the individual's abilities and needs. Keywords: Psychotic Disease, Metabolic Syndrome, Nursing, Nurse.

Background: There is earlier research in the field of recovery and from a patient perspective. However, it is relatively unexplored if you look within the specific group of patients who suffers from a psychotic disease, and in a context of what support the patient desire from the nurse in the open psychiatric care unit. Aim: To describe what type of support patient with psychotic disease would like from the nurse, in the open psychiatric care unit. Method: The study´s methodology is qualitative and inductive. The study is built on five interviews from patients in a psychiatric open care unit who suffers from psychotic diseases. The interviews have been analysed based on qualitative content analysis. Result: The result indicates that the patients express a desire that the nurse supports them in four areas to focus on health, to get support with its problems, to be able to tell and someone listens and through time given, be able to get to know the nurse, which is the foundation of comfort and stability. Conclusion: The result responds to the purpose of the study, and the result also reveals that it's a difference in what support´s requested between de two groups of patients, one with the severe mental illness and the other who´s studied -patients who suffers from psychotic disease. The conclusion is made by compare the earlier research with the result from this study. / Bakgrund: Det finns tidigare forskning inom området återhämtning och ur ett patientperspektiv. Det är däremot relativt outforskat om fokus riktas mot gruppen psykossjuka och i en kontext av vad de önskar för stöd av just sjuksköterskan inom ramen för den öppna psykiatrin. Syfte: Att beskriva vad patienter med psykossjukdom i den psykiatriska öppenvården önskar för stöd av sjuksköterskan i sin återhämtning. Metod: Studie bygger på fem intervjuade patienter som har kontakt med ett psykiatriskt öppenvårdsteam specialiserat på psykossjukdomar. Studien genomfördes med en induktiv ansats. Insamlade data analyserades utifrån kvalitativ innehållsanalys. Resultat: Det framkommer att patienterna uttrycker en önskan om att sjuksköterskan ger stöd inom fyra huvudområden; att ha fokus på det friska, att få stöd med sina problem, att få berätta för någon som vill lyssna och att få tid att lära känna sjuksköterskan är grunden till en trygg och god relation. Slutsatser: Resultatet svarar på studiens syfte, utifrån resultatet i förhållande till tidigare forskning kan också slutsatsen dras att det är skillnad i vilket stöd som efterfrågas mellan gruppen ”svårt psykiskt sjuka”, som bakgrunden i huvudsak utgörs av, mot gruppen av psykossjuka personer.