| 1. |
- Alenius, Malin, 1974-
(författare)
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Treatment Response in Psychotic Patients in a Naturalistic Setting : Classification, Genes, Drugs, Insight and Social Networks
- 2009
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Many patients with psychotic symptoms respond poorly to treatment. Various approaches have been made to classify these patients according to treatment response. However, existing classifications have been criticized for various reasons and a new classification system is needed. Further, no satisfactory explanation of the poor treatment response has been apparent. The general aim of this thesis was therefore to develop and validate a new classification method of functional remission in a naturalistic population of patients with psychosis and to utilize this classification to investigate the population from genetic, drug treatment, insight and social network points of view. Data for this cross-sectional study of patients (n=123) attending the Psychosis Outpatient Care clinic in the county of Jönköping, Sweden, were obtained from patient interviews, blood samples and information from patient files. The new classification method CANSEPT, which combines the CAN rating scale (CAN), the UKU side effect rating scale (SE) and the patient’s previous treatment history (PT), showed validity in discriminating the patients and was accepted well by the patients. CANSEPT was used to group the patients in the other studies in this thesis. The results indicated that the gene polymorphism ABCB1 3435T, was related to worse significant social and clinical needs for patients on olanzapine, while the polymorphism DRD2 Taq1 A1 was related to a greater risk of significant side effects; especially if male, or taking strong dopamine D2-receptor antagonistic drugs. Drug treatment factors were also related to treatment response; longer duration of untreated prodromal and early psychosis was seen for patients with current significant social and clinical needs and non-adherence to treatment was associated with worse significant side effects. Worse treatment outcomes also appeared to be associated with smaller social network groups, worse insight into illness, poorer knowledge of warning signs and worse coping strategies. In summary, CANSEPT was shown to be a useful valid, multidimensional tool for classification of treatment response. Gene polymorphisms, duration of untreated illness, non-adherence to treatment, social networks and knowledge should be taken into consideration when investigating inadequate treatment response.
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| 2. |
- Hjärthag, Fredrik, 1973-
(författare)
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Screening Family Burden in Clinical Practice : The development of a new instrument and investigation of its correlates to psychotic disorders
- 2011
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The primary purpose of this thesis is to develop a short and user-friendly instrument for the assessment of family burden caused by psychotic disorders. A secondary purpose is to further investigate variables that might be linked to an increased burden. Of these variables, patients’ reduced functioning will be addressed in more detail. As a final purpose, ratings of disorder-related variables carried out by staff will be compared to similar ratings carried out by relatives. These different purposes are investigated in five studies.In the first study (Paper I) the instrument Burden Inventory for Relatives to persons with Psychotic disturbances (BIRP) is created. This new screening instrument contains ten statements and shows good psychometrical properties for those dimensions that are investigated. In the second study (Paper II) results show that increased family burden can be tied to patients’ impaired functioning as well as to patients’ higher self ratings regarding distress. In the third study (Paper III) different parts of patients’ observable behavioral functioning are investigated and results show that most functional dimensions correlate with family burden. Also staff ratings of function are compared with relatives’ ratings and despite similar patterns in ratings there are differences. In the fourth study (Paper IV) demographic variables are studied and results show that only higher age and fewer contact hours correlate significantly with lower burden. Also, the BIRP instrument shows good stability. In the fifth study (Paper V) correlations with family burden are generally stronger for relatives’ own ratings of illness activity as compared to symptom ratings made by staff. Relatives’ ratings of illness activity do not correlate significantly with staff symptom ratings on all instruments used.The conclusions of this thesis are that the new screening instrument BIRP can be considered a good instrument to use in regular clinical practice in order to measure relatives’ burden in connection to psychotic disorders. Also, the thesis contributes with knowledge about what in the psychotic disorder and which demographic factors might be linked to an increase of family burden. Findings also indicate that it matters who does the rating of a disorder-related variable. Furthermore, in this thesis a theoretical framework for family burden is presented.
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| 3. |
- Jakobsson, Håkan, 1977-
(författare)
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Dutch experts in the early modern Swedish state : Employment strategies and knowledge building, 1560–1670
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This dissertation investigates the role played by Dutch experts in various enterprises and organisations managed or administered by the early modern Swedish state. The work demonstrates how and why Dutch experts were introduced to Sweden, in what manner they were employed by the Swedish state and how their knowledge was utilised in state-controlled organisations. The overall results challenge the impression of an uncomplicated introduction, steered by the state. Instead, the research suggests that the development was multifaceted, where the role and function of state structures, international politics, networks, as well as concepts, including opportunism and pragmatism all played a part in the process which led to the employment of Dutch experts and use of Dutch knowledge. Underlying analytical tools used to demonstrate this include concepts such as collective knowledge, institutional memory, change agents, as well as strategies to minimise uncertainties and knowledge asymmetries in the recruitment process. The investigation consists of four empirical chapters. The first chapter focuses on some of the key Dutch individuals who settled in Sweden during the second half of the sixteenth century. It shows why a Dutch settlement took place, but also how a specific interest in Dutch trade expertise was developed by the Swedish political leadership. The chapter concludes with an analysis of how Dutch expertise was utilised to develop advanced long-distance trade. The second chapter follows the use of Dutch experts in the naval shipbuilding organisation in the first half of the seventeenth century. It shows how an almost complete reliance on Dutch experts and technical knowledge was established during this period. The chapter details how the Dutch introduction and utilisation evolved, when the naval organisation changed from being single-handedly steered by the king, to a situation where it was administered by an independent Admiralty Board. The third chapter investigates the use of Dutch experts in the foreign administration as well as in the administration and management of trade and commercial undertakings. It details how agents and diplomatic networks facilitated exchange and brought knowledge and experts to Sweden. The chapter also challenges an established notion that many of the trade enterprises that were established in Sweden up until the mid-1630s were failures. The results instead demonstrate how successive proposals to develop commercial ventures by Dutch experts created a necessary knowledge base in Swedish society, which in the long run led to the successful formation of advanced commercial enterprises. The final chapter focuses on the establishment of commercial fishing operations. It follows the introduction and growth of a Dutch model for how to develop advanced fishing, and explains why the model only led to a functioning enterprise towards the very end of the period of investigation.
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| 4. |
- Lindström, Anders, 1978-
(författare)
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In-plane Compressive Response of Sandwich Panels
- 2009
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The high specific bending stiffness of sandwich structures can with advantage be used in vehicles to reduce their weight and thereby potentially also their fuel consumption. However, the structure must not only meet the in-service requirements but also provide sufficient protection of the vehicle passengers in a crash situation. The in-plane compressive response of sandwich panels is investigated in this thesis, with the objective to develop a methodology capable of determining if the structural response is likely to be favourable in an energy absorption perspective. Experiments were conducted to identify possible initial failure and collapse modes. The initial failure modes of sandwich panels compressed quasi-statically in the in-plane direction were identified as global buckling, local buckling (wrinkling) and face sheet fracture. Global buckling promotes continued folding of the structure when compressed beyond failure initiation. Face sheet fracture and wrinkling can promote collapse in the form of unstable debond crack growth, stable end-crushing or ductile in-plane shear collapse. Both the unstable debond crack propagation and the stable end-crushing are related to debond crack propagation, whereas the ductile in-plane shear mode is related to microbuckling of the face sheets. The collapse behaviour of sandwich configurations initially failing due to wrinkling or face sheet fracture was investigated, using a finite element model. The model was used to determine if the panels were likely to collapse in unstable debond propagation or in a more stable end-crushing mode, promoting high energy absorption. The collapse behaviour is mainly governed by the relation between the fracture toughness of the core and the bending stiffness and strength of the face sheets. The model was successfully used to design sandwich panels for different collapse behaviour. The proposed method could therefore be used in the design process of sandwich panels subjected to in-plane compressive loads.During a crash situation the accelerations on passengers must be kept below life threatening levels. The extreme peak loads in the structure must therefore be limited. This can be achieved by different kind of triggering features.Panels with either chamfered face sheets or with grooves on the loaded edges were investigated in this thesis. The peak load was reduced with panels incorporating either of the two triggering features. Another positive effect was that the plateau load following failure initiation was increased by the triggers. This clearly illustrates that triggers can be used to promote favourable response in sandwich panels. Vehicles are harmful to the environment not only during in-serve use, but during their entire life-cycle. By use of renewable materials the impact on the environment can be reduced. The in-plane compressive response of bio-based sandwich panels was therefore investigated. Panels with hemp fibre laminates showed potential for high energy absorption and panels with a balsa wood core behaved particular well. The ductile in-plane shear collapse mode of these panels resulted in the highest energy absorption of all investigated sandwich configurations.
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| 5. |
- Bodén, Robert, 1973-
(författare)
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Prognostic Factors in First-Episode Schizophrenia : Five-year Outcome of Symptoms, Function and Obesity
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Our knowledge of prognostic factors and optimal treatment organisation in schizophrenia is incomplete. The disparity of outcome measures used has been a major obstacle for research. Increasing evidence has shown that schizophrenia is associated with increased cardiovascular mortality, development of obesity and autonomic nervous system imbalance. Assertive community treatment (ACT) has been suggested as a promising direction for organising treatment services for first-episode schizophrenia, but its long-term effect has not been evaluated. One aim of the present thesis was to investigate prognostic factors for 5-year symptomatic and functional outcome and obesity development. A further aim was to evaluate a recently proposed definition of remission and examine the long-term effects of introducing a modified ACT programme (mACT). Thus, we performed a follow-up study of all consecutive first-episode psychosis patients in Uppsala County, Sweden during 1995-2000 (n=144). In the first study we investigated the changes in a broad 5-year outcome of symptoms and function among patients presenting first time ever to psychiatric health care during 3 years before and during 3 years after the implementation of mACT. This change in the psychiatric service, however, was not followed by any long-term clinical benefits. In the second study, we examined the association between remission of eight core schizophrenia symptoms and functional outcome. Remission was strongly associated with having good function and having a higher self-rated satisfaction with life. In the third study, we explored a set of biochemical markers as predictors of weight gain and development of obesity. Haemoglobin, red blood cell count, hematocrit, γ-glutamyltransferase and creatinine were associated with the development of obesity in first-episode schizophrenia. In the fourth and final study, we tested electrocardiographic measures of autonomic imbalance as predictors of symptomatic remission. Higher heart rate and high ST and T-wave amplitudes were related to symptomatic remission, indicating that cardiac autonomic imbalance at baseline may have a prognostic value in first-episode schizophrenia.
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| 6. |
- Ekholm, Birgit, 1956-
(författare)
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Diagnostic Evaluation of Schizophrenia for Genetic Studies
- 2005
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Schizophrenia is one of the most severe mental disorders. Heredity is accepted as a major causative factor. To find molecular mechanisms behind schizophrenia, patient materials with reliable and valid diagnoses must be identified. In order to compare schizophrenia diagnostic procedures for reliability, validity and suitability for genetic studies by evaluation of record information, interview and register diagnostic data and to examine patient materials for linkage or association with molecular genetic markers three patient materials were recruited: sporadic cases, a large pedigree and sib-pairs. Schizophrenia diagnoses based on patient records only, showed good to excellent agreement with diagnoses based on both records and interviews. Register diagnoses generally displayed poor agreement with research diagnoses, but in 94% of patients sometimes registered as schizophrenic psychoses a research diagnosis of these disorders was certified. In the pedigree, analysis suggested linkage to chr 6p23 in a single branch of the pedigree, and a genome scan indicated linkage to the 6q25 region. A genome scan analysis of the sib-pair material was suggestive of linkage to chr 10q25.3-q26.3. In the case-control sample and a meta-analysis there was an association between a dopamine D2 receptor polymorphism (Ser311Cys), on chr 11q22-23, and the disorder. Brain-derived neurotrophic factor gene variants (chr 11p13) were also analysed without any robust significant findings. For patients in long-term treatment for schizophrenia in Sweden, psychiatric record reviews should be valid, reliable and sufficient for assessment of lifetime research diagnosis. Swedish register diagnosis of schizophrenic psychoses has a high positive predictive power in relation to corresponding research diagnoses. For future Swedish studies focusing on a broad definition of schizophrenia, it is sufficient to rely on the register diagnoses of schizophrenic psychosis. There is no major vulnerability gene or locus that is common to the majority of patients with schizophrenia, indicating genetic heterogeneity.
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| 7. |
- Lundmark, Jöns, 1953-
(författare)
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Clinical and Pharmacological Aspects of Selective Serotonin Reuptake Inhibitors in the Treatment of Depression in Old Age
- 2000
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Objective: The aim of the present thesis is to examine the pharmacokinetic and biochemical effects of the selective serotonin reuptake inhibitors (SSRIs) in the elderly.Background: Symptoms of depression are found in up to 15% of the elderly and the prevalence of major depression is reported to be about 3%. At present SSRIs are the pharmacological tools most frequently used for the treatment of depression. Patients in old age account for a relatively higher proportion of SSRI expenditures, although the elderly are seriously underrepresented in pharmacological studies and are increasingly susceptible to adverse drug events.Subjects and Methods: Serum concentrations of the SSRis fluoxetine, paroxetine, and sertraline in the elderly were compared to those in younger patients. Effects of paroxetine on cerebrospinal fiuid (CSF) monoamine concentrations were investigated. Influences of therapeutic drug monitoring (TDM) of citalopram, paroxetine, and sertraline on clinical dosing strategies and antidepressant drug costs during a 6-9-month follow-up were studied in depressed elderly patients. Various individual factors, including age, which may influence serum concentrations of fluoxetine and sertraline were evaluated using population TOM data.Results: lnterindividual serum concentration variations were pronounced irrespective of age. Compared to the variability between subjects, the intraindividual variability of fiuoxetine and sertraline serum concentrations was found to be low. In the elderly, fiuoxetine, paroxetine, and sertraline serum concentrations were higher than in younger patients. In the case of fluoxetine, gross obesity influenced serum concentrations and sertraline serum concentrations were lower in smokers than in non-smokers. In the case of paroxetine, nonlinear pharmacokinetics were observed in some subjects and paroxetine treatment influenced both serotonergic and noradrenergic neurotransmission, as indicated by 5-HIAA and MHPG concentrations in the CSF. TDM-supported SSRI clinical dosing was found to reduce the doses used and efficacy was sustained when observed during an open follow-up.Conclusions: The results reported in the present thesis emphasize the importance of conducting clinical and pharmacological research in the elderly in different phases of drug development. In the postmarketing phase, TOM databases provide important tools for the collection of new pharmacokinetic data from clinical populations and data important for the interpretation of population SS RI serum concentrations. TDM of the SSRis may support individual dose optimization, including assessments of drug compliance.
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| 8. |
- Nilsson, Kent W., 1964-
(författare)
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Gene-Environment Interaction in Adolescent Deviant Behaviour
- 2006
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The overall aim of this thesis was to explore gene-environmental (G*E) interactions in relation to deviant behaviour among 200 Swedish adolescents, with a focus on criminality, alcohol consumption and depressive symptoms. Those behaviours have been extensively investigated in relation to both psychosocial and biological risk factors. The biological markers used were the monoamine oxidase (MAO-A) and serotonin transporter (5-HTTLPR) gene polymorphisms. The main findings indicated a considerable gene-environment interaction in relation to all outcome variables studied. Individuals with the long/short variant of the 5HTTLPR gene, in combination with unfavourable family relations, both consumed more alcohol and had 12-14 times higher risks of being classified as high alcohol consumers. The MAO-A gene showed a G*E interaction related to criminality. Among boys, the short allele predicted an increased risk for criminality, whereas among girls, it was the long allele, if they lived in multi-family houses and/or had been maltreated, assaulted or sexually abused. A G*E interaction in relation to depressive symptoms among both boys and girls was determined. Girls carrying the short 5HTTLPR allele in combination with psychosocial stress, presented elevated depressive symptoms, whereas among boys, the long 5HTTLPR allele was a source of depressive symptoms. In both sexes, there was a G*E interaction of a psychosocial risk index. Girls were more affected by poor family relations and boys by multi-family housing and separated parents. In conclusion, the MAO-A and 5HTTLPR genotypes, in interaction with psychosocial adversity, are related to different deviant behaviours among adolescents. The direct effects of the genotypes needed to be adjusted for the psychosocial factors, whereas the psychosocial factors had direct relation to the outcome measures. There is also an indication of a different pattern in G*E interaction between boys and girls and that different psychosocial factors affect boys and girls differently.
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| 9. |
- Nordström, Annika, 1956-
(författare)
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Violent offenders with schizophrenia : quantitative and qualitative studies focusing on the family of origin
- 2004
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The focus of the thesis is on violent offenders with schizophrenia and their relatives. The aims were to explore incidence of violent crimes, the extent to which family members were victims, to investigate individual background factors among violent offenders, and to identify psychotic symptoms and triggering factors associated with fatal violence. In addition, parents were interviewed to build an understanding of their experiences and emotional reactions. One study examined all 369 male individuals who had committed a violent crime (assault, homicide or attempt to any of these crimes), who in a pre-trial forensic psychiatric evaluation (FPE) during 1992-2000 were diagnosed with schizophrenia, and who were referred to forensic psychiatric treatment. Although the majority of the 615 victims was unacquainted to the offenders, family members or male acquainted were most at risk of being severely injured or killed as victims. Background factors were studied for the 207 Swedish offenders who for their first time were subjects of a FPE during the study period. There were indications that those offenders who targeted family members had an earlier onset and more severe course of their mental illness. During the study period, 48 offenders committed homicides. Of the 52 victims, 83% were family members or acquainted to the offender. Those who killed a family member had more often delusions and/or hallucinations, were less often intoxicated, had to a lesser extent committed a previous violent crime and they were younger at the time of the homicide. Parents, who were interviewed, were very emotionally involved in their adult sons, although they were not living together. Ignorance regarding the diagnosis of their son and his criminality negatively influenced the contacts, both between parent and son and between parent and professionals in psychiatry. However, the referral to forensic psychiatric treatment gave the parents hope for a positive development.
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| 10. |
- Salmi, Peter, 1965-
(författare)
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Clozapine as a dopamine D₁ receptor agonist
- 1998
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Objectives'. The present study had two major objectives; [1] to examine the specific role of dopamine D, and DM receptors in body temperature regulation in rats, and [2] to examine in vivo dopamine D, and Dm receptor agonist/antagonist properties of clozapine by use of core temperature measurements.Methods'. Body temperature homeostasis is known to be regulated via a number of neurotransmitters, including dopamine, noradrenaline, serotonin and acetylcholine. Thus, core temperature measurements have been used to investigate in vivo actions of clozapine as an agonist/antagonist at various receptor subtypes of these neurotransmitters.Results'. A new finding in the present series of experiments was the observation that the selective dopamine D1 receptor agonists A 68930 and dihydrexidine produce hypothermia in rats. This effect is distinct from hypothermia produced by the dopamine Dj, receptor agonists quinpirole and 7-OH-DPAT. Thus, these dopamine D, and DM receptor agonists interact in an additive, rather than a synergistic or antagoniste, manner, suggesting specific and independent roles of dopamine D, and DM receptors involved in body temperature regulation in rats. The dopamine D, or Dm receptor agonist-induced hypothermia could not be antagonized by the administration of clozapine (0.6 mg kg-1). At higher doses (2.5-10.0 mg kg“1), clozapine produced hypothermia that could be antagonized by selective dopamine D,, but not DM, receptor antagonists, suggesting dopamine Dt receptor agonist properties of clozapine at receptors involved in temperature regulation in rats. As expected, in this core temperature model clozapine displayed properties as a 5-HT2A and a, adrenergic receptor antagonist. In the present model, there were no, or much weaker, effects of clozapine as an agonist/antagonist at 5-HT1A, or, adrenergic or muscarinic receptors.Conclusions'. The present study shows that clozapine displays in vivo properties as a dopamine D, receptor agonist. The effects of clozapine, and known dopamine D, receptor ligands, in Parkinsons disease and in schizophrenia, are in agreement with the notion that intrinsic efficacy of clozapine at brain dopamine D, receptors may contribute to its atypical clinical profile as an antipsychotic agent.
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