<p>Akut hjärt-kärlsjukdom orsakar mer än hälften av alla dödsfall i Sverige. Många patienter med akut hjärtinfarkt uppvisar inte de klassiska symtom som vanligtvis förknippas med sjukdomen utan har en mer atypisk symtombild. Syftet med litteraturstudien var att beskriva vikten av god kunskap och kännedom om den varierande symtombild som kan förekomma vid hjärtinfarkt, sett ur ett omvårdnadsperspektiv. I metoden har 23 vetenskapliga artiklar bearbetats. Resultatet visade att förekomst av atypiska symtom var vanligare hos kvinnor, äldre och diabetiker. Män upplevde framförallt bröstsmärta, smärtutstrålning till armar och svettning. Kvinnor uppvisade bröstsmärta i mindre omfattning men upplevde däremot mer andnöd, rygg- och nacksmärta, besvär från mag-tarmkanalen, trötthet och orkeslöshet. Varningssymtom förekom hos ett stort antal patienter och framförallt hos kvinnor. Patienterna uppfattade och uttryckte sina besvär på olika sätt, vilket påverkade deras beslut att söka vård. Sjuksköterskans roll ansågs vara att informera patienter, speciellt de med högre risk att uppvisa atypiska symtom samt allmänheten om den annorlunda symtombild som kan förekomma. Sjuksköterskor måste ha god kunskap och kännedom om olikheter i symtombild hos olika patientgrupper. De bör vara lyhörda och ha en klinisk blick samt förstå vikten av god framförhållning och beredskap för ett adekvat omhändertagande. I framtiden måste kunskapen utökas och spridas bland allmänheten. Vidare forskning i ämnet är önskvärt ur ett sjuksköterskeperspektiv.</p>

Akut hjärt-kärlsjukdom orsakar mer än hälften av alla dödsfall i Sverige. Många patienter med akut hjärtinfarkt uppvisar inte de klassiska symtom som vanligtvis förknippas med sjukdomen utan har en mer atypisk symtombild. Syftet med litteraturstudien var att beskriva vikten av god kunskap och kännedom om den varierande symtombild som kan förekomma vid hjärtinfarkt, sett ur ett omvårdnadsperspektiv. I metoden har 23 vetenskapliga artiklar bearbetats. Resultatet visade att förekomst av atypiska symtom var vanligare hos kvinnor, äldre och diabetiker. Män upplevde framförallt bröstsmärta, smärtutstrålning till armar och svettning. Kvinnor uppvisade bröstsmärta i mindre omfattning men upplevde däremot mer andnöd, rygg- och nacksmärta, besvär från mag-tarmkanalen, trötthet och orkeslöshet. Varningssymtom förekom hos ett stort antal patienter och framförallt hos kvinnor. Patienterna uppfattade och uttryckte sina besvär på olika sätt, vilket påverkade deras beslut att söka vård. Sjuksköterskans roll ansågs vara att informera patienter, speciellt de med högre risk att uppvisa atypiska symtom samt allmänheten om den annorlunda symtombild som kan förekomma. Sjuksköterskor måste ha god kunskap och kännedom om olikheter i symtombild hos olika patientgrupper. De bör vara lyhörda och ha en klinisk blick samt förstå vikten av god framförhållning och beredskap för ett adekvat omhändertagande. I framtiden måste kunskapen utökas och spridas bland allmänheten. Vidare forskning i ämnet är önskvärt ur ett sjuksköterskeperspektiv.

Parkinson’s Disease (PD) is the second most common neurodegenerative disorder. It is a disease with a broad spectrum of symptoms, both motor and non-motor, but is often only diagnosed when the motor symptoms begin to appear. By this time however, a large amount of the dopaminergic neurons of the substantia nigra pars compacta have already deteriorated. It is therefore of great interest to be able to diagnose the disease earlier on in its progression and perhaps slow down or halt its course. Recent literature has supported the idea that non-motor symptoms begin to appear years, perhaps even decades, before the motor symptoms are visible. This makes them a prime candidate for diagnosing PD earlier on. With the aim of assessing the prevalence of different NMS in prodromal and early Parkinson’s, 19 studies addressing different NMS were analyzed. It was found that NMS are prevalent in both prodromal and early PD. The strongest prodromal predictors for PD were found to be olfactory dysfunction and REM-sleep behavior disorder (RBD).

Schizophrenia is a complex and pervasive brain disorder that effects millions of people in the United States. There are three tiers of symptoms associated with the disorder, they include: positive symptoms, negative symptoms and thought disorders. The most common method of treatment for this disorder involves the use of antipsychotic medications, and while these medications have been shown to be effective in treating certain positive symptoms of the disorder, they have a tendency to be less effective in treating the negative cluster of symptoms and the thought disorders that can be highly debilitating for patients. The aim of this review was to determine the level of effectiveness of psychosocial treatments for the disorder, and in particular to look in to Cognitive- Behavioral Therapy (CBT) as an adjunctive method of treatment to be used in conjunction with medication. By performing searches using the PsycInfo, ERIC, EBSCO and Medline databases, the researcher was able to draw the conclusion that while there are some complications and areas of improvement in study construction, CBT can indeed be a helpful method of treatment for many patients. Importantly, CBT tends to be a very flexible treatment that can accommodate many different combinations of symptoms at varying levels or severity and stages of the illness. A discussion of a possible model of treatment that uses CBT was also undertaken to provide readers with a practical example of how this form of treatment can be used. / text

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The research of my thesis focused on the use of transcriptomic open discovery approaches to interrogate the molecular basis of two distinct yet related neurological disorders that are both associated with cognitive decline, Temporal Lobe Epilepsy and Alzheimer’s Disease. Interestingly, a potential role for compromised synaptogenesis early in disease was common to both, as was the direct role that neurons may play in brain inflammatory processes involving glia. Temporal lobe epilepsy (TLE) is a progressive disorder mediated by pathological changes in molecular cascades and hippocampal neural circuit remodeling that results in spontaneous seizures and cognitive dysfunction. Targeting these cascades may provide disease-modifying treatments for TLE patients. Janus Kinase/Signal Transducer and Activator of Transcription (JAK/STAT) inhibitors have emerged as potential disease-modifying therapies; however, a more detailed understanding of the contribution of JAK/STAT signaling to epileptogenesis is required to increase the potential therapeutic efficacy and reduce adverse effects associated with un-targeted JAK/STAT inhibition. With our collaborators, my lab developed a mouse line in which tamoxifen treatment conditionally abolishes STAT3 signaling from forebrain excitatory neurons (nSTAT3KO). Seizure frequency (continuous in vivo electroencephalography) and memory (contextual fear conditioning and motor learning) were analyzed in wildtype (Wt) and nSTAT3KO mice after intrahippocampal kainate (IHKA) injection as a model of TLE. Selective STAT3 KO in excitatory neurons reduced seizure progression and hippocampal memory deficits without reducing the extent of cell death or mossy fiber sprouting induced by IHKA injection. In my thesis, RNA was extracted from harvested hippocampi 24 h after IHKA and libraries were prepared for bulk RNA-sequencing (70–80 million reads/sample) using the NextSeq 500 Illumina system. 3190 genes were differentially expressed in Wt mice injected with KA vs saline (fold change |1.5|, FDR=<0.05). Ingenuity Pathway Analysis (IPA) revealed significant enrichment in 2 overarching sets of pathways: 1) those related to synaptic signaling and 2) those related to inflammation. As expected, many of the IHKA-induced genes were previously associated with epilepsy or seizure disorders (260 for Seizure Disorder, 267 for Epilepsy or Neurodevelopmental Disorder), and Seizure Disorder had the highest activation score in Neurological Disease based on gene expression patterns. Interestingly, a closer analysis of the IHKA-induced gene set revealed an enrichment of STAT3-associated genes (216), most of which were upregulated by IHKA. Compared to the 3190 Differentially Expressed Genes (DEGs) between IHKA and saline-injected Wt mice 24 hours after SE, more than half of these DEGs (1609) were rescued when comparing IHKA-injected nSTAT3KO mice and saline-injected Wt mice, indicating a significant rescue of gene expression when nSTAT3 is absent in excitatory neurons. While nSTAT3 KO influences the expression of genes in many different pathways, including the reversal of genes whose expression was inhibited in pathways of learning and memory by IHKA, the greatest surprise came from the predicted regulatory control over microglial function. nSTAT3KO mice displayed the greatest number of rescued DEGs compared to IHKA-injected WT mice in pathways that regulate inflammation and ion transport, and while inflammation was an expected response to IHKA, we were surprised to find evidence for its rescue in nSTAT3 KO mice. We also interrogated the expression of the Alzheimer’s disease genome as modeled using a rat model (TgF344-AD ) of familial AD that allows for behavioral and molecular characterization of AD, and expresses an endogenous pathogenic form of tau in addition to Abeta oligomers and plaques. AD is a neuropsychiatric disorder characterized initially by short term memory loss and disorientation, followed by declining cognitive functioning, and eventually, death. Widespread failure of 99% of AD drugs that make it to clinical trials has led to renewed interest in early signatures of disease in hopes of altering disease trajectory through early intervention. Key to such efforts is capturing a molecular window into AD at its earliest stages. The TgF344-AD rat shows overt pathology (including Aβ plaques, frank neuronal loss, and endogenous tau pathology) at 16 and 26 mo, but only to a very limited extent at 6 mo (Towne, 2013). Thus, in my thesis research, we set out to uncover any cell-type specific transcriptomic alterations that may be present in advance of major behavioral deficits or appearance of pathology, given that a strong body of literature suggests a long pre-symptomatic stage of illness in which subtle abnormalities may be present. 10x Genomics’ v3 gene expression assays were used to perform snRNA-seq on freshly dissected hippocampi from 6 mos, 9 mos and 19 mos littermate pairs of Tg and Wt rats (n=16 for 6 months and 9 months, with 8 for 19 months). ~2000 cells/subject were collected, and cDNA libraries were sequenced to a depth of ~120k reads/nuclei. Interestingly, data analysis revealed wide-scale gene changes in dentate granule cells (DGCs) and non-DGC excitatory neurons (Excit Ns) at 6 mos, suggestive of a significant decrease in synaptogenesis in Tg vs their Wt littermates, as well as small increases in cholesterol biosynthesis in the Tg rats in these cell types. By 9 months, some differentially expressed genes were observed across genotype in classes of glial cells, but the strongest impact on gene expression could still be seen in Excit Ns and DGCs, which continued to display evidence of decreased synaptogenesis, though to a lesser extent than at 6 mos. Interestingly, 9 mos Tg rats displayed an even stronger upregulation in genes related to cholesterol biosynthesis than 6 mos for both DGCs and Excit Ns. At 19 months, cholesterol and steroid biosynthesis were amongst the top biological pathways enriched for in Excit Ns and Inhibitory neurons of the Tg, to an even greater extent than changes in synaptogenesis. Altogether, our results suggest the transcriptional basis for a profound suppression of synapse formation or maintenance during early stages of illness in the TgF344-AD rat model, as well as abnormalities in neuronal cholesterol biosynthesis. Given that cholesterol is a key component of plasma membranes and lipid rafts, structures needed for the generation of new synapses and the stability of their receptor populations, it may be that deficiencies in the available cholesterol of Tg neuronal cells is leading to the impaired synaptogenesis in these cell types. Future work will focus on identifying whether these transcriptional alterations can be detected at even earlier time points, whether they are prescient for changes at the membrane in vivo that are correlated with memory impairment, and whether they are related to the alterations in the genome seen in our acquired epilepsy models, suggesting a common theme for the brain’s genomic response to injury of the hippocampus. / 2025-02-12T00:00:00Z

While many studies of risk factors for psychosis focus on positive symptoms, such as subthreshold levels of hallucinations and delusions, fewer studies have examined negative symptoms in the early course of the schizophrenia or other psychotic disorders. This relative lack of focus on the role of negative symptoms is problematic, given findings that negative symptoms, such as a loss of motivation and pleasure (MAP), are associated with a more persistent and impairing course of psychosis, and tend to appear earlier in the development of psychotic symptoms. Psychotic disorders, which afflict approximately 3-5% of the population, tend to emerge in late adolescence/early adulthood and are among the most debilitating and costly of mental disorders. The current project explored three areas of negative symptoms in young adults who demonstrated a range of psychotic-like experiences (PLEs). First, a review of the literature pertaining to negative symptoms across the span of psychosis was conducted. Second, we tested whether experiential negative symptoms – specifically MAP deficits – were associated with increases in PLEs, including those that are experienced as distressing (PLEDs). Third, we examined the potential influence of episodic memory performance factors on the relationship between MAP symptoms and PLEs/PLEDs. Collectively, this project highlights the importance of including negative symptoms (i.e., MAP deficits) and/or cognitive performance (i.e., associative/relational learning/memory) outcomes when evaluating people with PLEs/PLEDs to identify those who may be at greater risk for developing a psychotic disorder. / Psychology

Prodromes of schizophrenia or prodromes of psychosis are a relatively new and expanding field of interest in psychiatric research. They are seen by some researchers as the initial symptom of having schizophrenia and have become a crucial topic in early psychosis research and intervention. In this thesis current psychiatric research publications were analysed and eleven prospectively psychotic patients were interviewed. The research publications analysed were applyed on the information given by the patients, and the analysis showed that it was easy to find prodromes or prodrome-like phenomena in all the collected interviews. In addition a second analysis was performed on the material, a phenomenological psychological analysis, showing a more subject-oriented dimension of the interviews. This led to a further aim, analysing what explanations could be given of these phenomena. There are probably many possibilities of getting the diagnosis of schizophrenia, but the examples in this study show that long-term abuse, often sexual actually can trigger psychiatric conditions corresponding to the definition of “prodromes of schizophrenia” according to some psychiatric publications as well as “schizophrenia” according to DSM and ICD. This means that trauma and/or neglect proved to be a likely partial causal condition of the prodrome- like phenomena or schizophrenia to occur. However, trauma has not been shown to be a necessary condition for the occurrence of prodrome-like phenomena or schizophrenia. In the discussion of the results some consequences deriving from using different interpretations and explanations of the phenomena are analysed, for example using the prodromes of psychosis for the assessments of a coming psychosis, especially schizophrenia. I emphasize, because of the results of the phenomenological case analyses, the value of several dimensions of understanding prodrome-like phenomena as well as schizophrenia and schizophrenia-like conditions, especially as early as the initial phase. / Prodromalfasen till schizofreni är ett relativt nytt begrepp och det utgör ett expanderande intresseområde för psykiatrisk forskning. Förändringar i prodromalfasen ses av vissa forskare som de första tecknen på schizofreni, och dessa fenomen har kommit i fokus speciellt vad gäller tidig upptäckt och intervention inom schizofreniforskning. I denna avhandling analyseras åtskilliga psykiatriska texter som behandlar prodromalfasens fenomen. I den empiriska studien har elva personer, som senare utvecklat psykotiska symtom, intervjuats.  Två etablerade listor på prodromalfenomen testades på det empiriska materialet. Resultaten av den analysen visade att de gick att finna prodromalliknande fenomen hos alla intervjuade patienter. En andra fenomenologisk och mer subjektorienterad analys av det empiriska materialet genomfördes parallellt. Resultaten av de två analyserna ledde till ett tredje fokus för avhandlingen, nämligen frågan om möjliga kausalförklaringar till de prodromalliknande fenomenen. Det finns förmodligen många orsaker till att en person uppvisar symtom som överensstämmer med diagnosen schizofreni. Exemplen i denna studie visar dock att långvariga, ofta sexuella, övergrepp kan leda till psykiatriska tillstånd som överensstämmer med fenomen i prodromalfasen och med själva diagnosen schizofreni enligt kriterierna i DSM-IV och ICD-10. Avhandlingens huvudhypotes är således att svåra trauman utgör delorsaker både till prodromalliknande fenomen liksom till tillstånd som diagnosticerats som schizofreni. Avhandlingens resultat ger dock ingen anledning att anta att trauman utgör nödvändiga betingelser för schizofreni. I avhandlingens resultatdiskussion lyfter författaren fram några viktiga konsekvenser av olika definitioner av begreppen prodromalfenomen och schizofreni bl a vad avser förslag till terapeutiska interventioner. Mot bakgrund av resultaten från den fenomenologiska analysen understryks vikten av en bred förståelse av prodromalliknande fenomen liksom av fenomen som diagnosticeras som schizofreni.

L’évaluation de biomarqueurs et de thérapies innovantes pour la maladie d’Alzheimer (MA) souffre de la mauvaise compréhension des phases initiales de la maladie mais également du manque de modèles animaux pertinents et proches de la physiopathologie humaine. La majorité des modèles rongeurs disponibles reproduisent en seulement quelques mois les lésions classiques de la MA telles que les plaques amyloïdes et les dégénérescences neurofibrillaires (DNF), alors que leur apparition prend des années chez l’Homme. L’objectif de mon travail de doctorat a été de développer une nouvelle stratégie de modélisation des phases précoces de la MA sans surexpression majeure de transgène. Pour cela, nous avons utilisé le co-transfert des gènes humains APPSL et PS1M146L à l’aide de vecteurs viraux dans l’hippocampe de souris et de rats de 8 semaines. Nous avons caractérisé ces modèles et montré une production de peptides, comme le betaCTF ou l’abeta?42 issus du clivage de l’APP, similaire à ce que l’on observe dans l’hippocampe de patients atteints de la MA. Nous avons également montré une hyperphosphorylation de Tau et une défaillance synaptique caractérisée par une diminution des niveaux de PSD-95 et GLT-1 ainsi que par une augmentation du courant tonique glutamatergique. Ces modifications ont enfin été associées à des défauts comportementaux. Mes résultats suggèrent que de nombreux évènements apparaissent bien avant la formation des plaques amyloïdes ou des DNFs et conduisent à une perturbation de la synapse et à l’apparition précoce de défauts comportementaux. Nous disposons donc d’outils relevants quant à la compréhension des premiers stades de la MA qui permettront à la fois de tester de nouveaux composés médicaments sur ces modèles à large fenêtre thérapeutique, et de découvrir de nouveaux biomarqueurs précoces dans le plasma et le liquide cérébro-spinal. / Evaluation of biomarkers and new innovative therapies for Alzheimer's disease (AD) suffers from a misunderstanding of early phases and lack of appropriate animal models close to the human physiopathology. Most available rodent models reproduce hallmarks of AD such as amyloid plaques and neurofibrillary tangles in a few months, while it takes many years to be achieved in human. My PhD work consisted to develop a new modelling strategy of AD early phases without major overexpression of transgenes. To do so, we used gene transfer of human APPSL and PS1M146L using viral vectors injection in the hippocampus of 8 weeks old mice and rats. We characterized these models and showed peptides production, such as betaCTF and abeta42 from APP processing, similar to what is observed in AD patients hippocampi. We also highlighted a hyperphosphorylation of Tau followed by a synaptic failure characterized by a decrease of PSD-95 and GLT-1 levels and by an increase of the tonic current mediated by glutamate. These changes have been finally associated with behavioral deficits. My results suggest that many events appear well before the formation of amyloid plaques or tangles and lead to the disruption of the synapse and the early onset of behavioral defects. Thus, we now have relevant tools to understand the early stages of AD, which will allow us to test new drug compounds on these models with a wide therapeutic window and discover new early biomarkers in plasma and cerebrospinal fluid.

Background: Parkinson’s disease (PD) is a common, progressive neurodegenerative disorder, recognized by the motor symptoms of bradykinesia, tremor, rigidity, and postural impairment. At clinical onset, extensive amounts of dopaminergic neurons have already been lost. The duration of this prodromal phase is uncertain, and it is thought to include predominantly non-motor symptoms. The progressive nature and the symptoms of PD are disabling and reduces the quality of life. Among patients affected in working age, early cessation of employment is common, and such socioeconomic consequences of PD may contribute to an impaired quality of life. The aims of this thesis were to investigate the life situation for people affected by PD in working age, with attention to factors of importance for quality of life and working situation, and to evaluate long-term associations between potential prodromal signs and the later development of PD.Methods: We used a postal survey to investigate the self-perceived life situation among working-aged individuals with PD compared to matched controls, with a specific attention to socioeconomic consequences of disease (paper I). To investigate risk markers preceding the diagnosis of PD (paper II-IV), we used data from nationwide registers. Study II was performed as a cohort study, based on the Swedish Military Service Conscription Register, and study III-IV were performed as nested case-control studies based on a cohort comprising all Swedish citizens aged ≥50 years in 2005.Results: In the survey study (paper I), 38% of the PD participants and 9% of the controls were dissatisfied with life as a whole, and the working situation was an independent risk factor for dissatisfaction with life. In total, 59% of the PD participants had reduced working hours or stopped working due to PD, and many PD participants struggled to cope with their work demands. Support from employer was associated with a higher likelihood to remain employed.We found that low muscle strength in young adulthood, (paper II) and depression (paper III) were associated with an increased risk of PD over follow-up times of more than 2 decades, and that patients with PD were at increased risk of fall-related injuries, hip fractures in particular, a decade or more before the PD diagnosis (paper IV). For depression and fall-related injuries, the association with PD was clearly time-dependent, strongest in the last years before the diagnosis of PD.Conclusions: The results suggest that the prodromal phase of PD may last for more than 2 decades and include also motor symptoms. The consequences of PD include a reduced quality of life associated with the working situation. Employer’s support appear to be particularly important for a successful vocational rehabilitation.