Health-Related Quality of Life and Mental Disorders in Finland

Quality of life (QoL) and Health-related quality of life (HRQoL) are becoming one of the key outcomes of health care due to increased respect for the subjective valuations and well-being of patients and an increasing part of the ageing population living with chronic, non-fatal conditions. Preference-based HRQoL measures enable estimation of health utility, which can be useful for rational rationing, evidence-based medicine and health policy. This study aimed to compare the individual severity and public health burden of major chronic conditions in Finland, including and focusing on reliably diagnosed psychiatric conditions. The study is based on the Health 2000 survey, a representative general population survey of 8028 Finns aged 30 and over. Depressive, anxiety and alcohol use disorders were diagnosed with the Composite International Diagnostic Interview (M-CIDI). HRQoL was measured with the 15D and the EQ-5D, with 83% response rate. This study found that people with psychiatric disorders had the lowest 15D HRQoL scores at all ages, in comparison to other main groups of chronic conditions. Considering 29 individual conditions, three of the four most severe (on 15D) were psychiatric disorders; the most severe was Parkinson s disease. Of the psychiatric disorders, chronic conditions that have sometimes been considered relatively mild - dysthymia, agoraphobia, generalized anxiety disorder and social phobia - were found to be the most severe. This was explained both by the severity of the impact of these disorders on mental health domains of HRQoL, and also by the fact that decreases were widespread on most dimensions of HRQoL. Considering the public health burden of conditions, musculoskeletal disorders were associated with the largest burden, followed by psychiatric disorders. Psychiatric disorders were associated with the largest burden at younger ages. Of individual conditions, the largest burden found was for depressive disorders, followed by urinary incontinence and arthrosis of the hip and knee. The public health burden increased greatly with age, so the ageing of the Finnish population will mean that the disease burden caused by chronic conditions will increase by a quarter up to year 2040, if morbidity patterns do not change. Investigating alcohol consumption and HRQoL revealed that although abstainers had poorer HRQoL than moderate drinkers, this was mainly due to many abstainers being former drinkers and having the poorest HRQoL. Moderate drinkers did not have significantly better HRQoL than abstainers who were not former drinkers. Psychiatric disorders are associated with a large part of the non-fatal disease burden in Finland. In particular anxiety disorders appear to be more severe and have a larger public health burden than previously thought.

Työkykyarviokokous moniammatillisen työryhmän päätöksentekotilanteena : Tutkimus vuorovaikutuksesta ja potilaan osallisuudesta

Work capacity assessment meeting as a decision-making situation of a multi-professional team a study on interaction and patient participation Multi-professional working has become an increasingly popular method of work in social and health care. The introduction of the viewpoints of several professionals is seen as a way to enhance the openness and quality of decision-making. However, so far relatively few study results are available on the implementation of this method in actual operations. This study examines one work method, a work capacity assessment meeting, along with medical certificates B and their enclosures written by the doctor to the patient after a meeting. After the theoretical and methodological chapter, providing background information, the study describes the structure of the meeting and the medical certificate as a constructive factor. This is followed by a discussion on the manner of assessing the various domains of the patient s functional capacity and the decision-making based on the assessed factors. Next, the study moves on to examine the effect of patient involvements on the conclusions and decisions that professionals make at the meeting. In conclusion, the study looks into how the voices of the professionals and the customer are transferred to the medical certificate. The material of the study consists of 11 meetings recorded on video, of which eight are work capacity assessment meetings and three are rehabilitation examination meetings. The first type of meeting is attended by a patient and a number of professionals, while the latter is attended only by the professionals. All the patients, whose cases are discussed in the work capacity assessment meetings, have a musculoskeletal disorder, while the rehabilitation meetings are related to patients who all also have some additional problem. The study material also consists of seven medical certificates B, written after a work capacity assessment meeting. For the most part, the material has been collected by the conversation analysis method. Moreover, also discourse analysis and a rhetorical approach were used. By using conversation analysis, it is possible to study closely how interaction is built up at the meeting and to examine how the actors implement their institutional assessment tasks in a co-operation that takes its form turn by turn. The four main findings of the study are as follows: firstly, the meeting is structured to a great extent on the basis of the medical certificate form to various phases of the meeting and the headings of the certificate are seen as communicative affordances at the meeting, directed primarily to the professionals that have assessed the patient s work capacity with various tests. The medical certificate is the ethno-method of the doctor acting as the chairman of the meeting that functions in two directions: it constructs the meeting and constitutes the task of the professionals as they produce contents for it. Secondly, the study describes the ways that are used to assess the different domains of the patient s work capacity, how they are described at the meeting and how a decision is taken when the assessment information has been saturated in the opinion of the team. Thirdly, the study brings up ways, with which the patient can influence the conclusions and decisions made by the professionals at the meeting. The study showed that the patient can affect the preconditions of his or her own future and wellbeing. Fourthly, the study describes how the wealth of expressions at the meeting is transferred to the certificate as an argumentative micro-cosmos, where the patient is classified to be recommended for rehabilitation or disability pension. An important finding is also how objective and subjective information and the voices of actors at the meeting are transferred to the statement in a strategic and intentional manner, with an orientation to the decision that will be taken at the insurance institution. The study results can be utilized in the training of professionals and in developing the operations of organisations performing the assessment of the work capacity of people suffering from musculoskeletal disorders.

Communicative and Anticipatory Decision-making Supported by Bayesian Networks

The purpose of this research is to draw up a clear construction of an anticipatory communicative decision-making process and a successful implementation of a Bayesian application that can be used as an anticipatory communicative decision-making support system. This study is a decision-oriented and constructive research project, and it includes examples of simulated situations. As a basis for further methodological discussion about different approaches to management research, in this research, a decision-oriented approach is used, which is based on mathematics and logic, and it is intended to develop problem solving methods. The approach is theoretical and characteristic of normative management science research. Also, the approach of this study is constructive. An essential part of the constructive approach is to tie the problem to its solution with theoretical knowledge. Firstly, the basic definitions and behaviours of an anticipatory management and managerial communication are provided. These descriptions include discussions of the research environment and formed management processes. These issues define and explain the background to further research. Secondly, it is processed to managerial communication and anticipatory decision-making based on preparation, problem solution, and solution search, which are also related to risk management analysis. After that, a solution to the decision-making support application is formed, using four different Bayesian methods, as follows: the Bayesian network, the influence diagram, the qualitative probabilistic network, and the time critical dynamic network. The purpose of the discussion is not to discuss different theories but to explain the theories which are being implemented. Finally, an application of Bayesian networks to the research problem is presented. The usefulness of the prepared model in examining a problem and the represented results of research is shown. The theoretical contribution includes definitions and a model of anticipatory decision-making. The main theoretical contribution of this study has been to develop a process for anticipatory decision-making that includes management with communication, problem-solving, and the improvement of knowledge. The practical contribution includes a Bayesian Decision Support Model, which is based on Bayesian influenced diagrams. The main contributions of this research are two developed processes, one for anticipatory decision-making, and the other to produce a model of a Bayesian network for anticipatory decision-making. In summary, this research contributes to decision-making support by being one of the few publicly available academic descriptions of the anticipatory decision support system, by representing a Bayesian model that is grounded on firm theoretical discussion, by publishing algorithms suitable for decision-making support, and by defining the idea of anticipatory decision-making for a parallel version. Finally, according to the results of research, an analysis of anticipatory management for planned decision-making is presented, which is based on observation of environment, analysis of weak signals, and alternatives to creative problem solving and communication.

Genetic Mechanisms Underlying Autism Spectrum Disorders

Autism is a childhood-onset developmental disorder characterized by deficits in reciprocal social interaction, verbal and non-verbal communication, and dependence on routines and rituals. It belongs to a spectrum of disorders (autism spectrum disorders, ASDs) which share core symptoms but show considerable variation in severity. The whole spectrum affects 0.6-0.7% of children worldwide, inducing a substantial public health burden and causing suffering to the affected families. Despite having a very high heritability, ASDs have shown exceptional genetic heterogeneity, which has complicated the identification of risk variants and left the etiology largely unknown. However, recent studies suggest that rare, family-specific factors contribute significantly to the genetic basis of ASDs. In this study, we investigated the role of DISC1 (Disrupted-in-schizophrenia-1) in ASDs, and identified association with markers and haplotypes previously associated with psychiatric phenotypes. We identified four polymorphic micro-RNA target sites in the 3 UTR of DISC1, and showed that hsa-miR-559 regulates DISC1 expression in vitro in an allele-specific manner. We also analyzed an extended autism pedigree with genealogical roots in Central Finland reaching back to the 17th century. To take advantage of the beneficial characteristics of population isolates to gene mapping and reduced genetic heterogeneity observed in distantly related individuals, we performed a microsatellite-based genome-wide screen for linkage and linkage disequilibrium in this pedigree. We identified a putative autism susceptibility locus on chromosome 19p13.3 and obtained further support for previously reported loci at 1q23 and 15q11-q13. To follow-up these findings, we extended our study sample from the same sub-isolate and initiated a genome-wide analysis of homozygosity and allelic sharing using high-density SNP markers. We identified a small number of haplotypes shared by different subsets of the genealogically connected cases, along with convergent biological pathways from SNP and gene expression data, which highlighted axon guidance molecules in the pathogenesis of ASDs. In conclusion, the results obtained in this thesis show that multiple distinct genetic variants are responsible for the ASD phenotype even within single pedigrees from an isolated population. We suggest that targeted resequencing of the shared haplotypes, linkage regions, and other susceptibility loci is essential to identify the causal variants. We also report a possible micro-RNA mediated regulatory mechanism, which might partially explain the wide-range neurobiological effects of the DISC1 gene.

Identifying Genetic Risk Factors in Canine Autoimmune Disorders

Autoimmune diseases are more common in dogs than in humans and are already threatening the future of some highly predisposed dog breeds. Susceptibility to autoimmune diseases is controlled by environmental and genetic factors, especially the major histocompatibility complex (MHC) gene region. Dogs show a similar physiology, disease presentation and clinical response as humans, making them an excellent disease model for autoimmune diseases common to both species. The genetic background of canine autoimmune disorders is largely unknown, but recent annotation of the dog genome and subsequent development of new genomic tools offer a unique opportunity to map novel autoimmune genes in various breeds. Many autoimmune disorders show breed-specific enrichment, supporting a strong genetic background. Furthermore, the presence of hundreds of breeds as genetic isolates facilitates gene mapping in complex autoimmune disorders. Identification of novel predisposing genes establishes breeds as models and may reveal novel candidate genes for the corresponding human disorders. Genetic studies will eventually shed light on common biological functions and interactions between genes and the environment. This study aimed to identify genetic risk factors in various autoimmune disorders, including systemic lupus erythematosus (SLE)-related diseases, comprising immune-mediated rheumatic disease (IMRD) and steroid-responsive meningitis arteritis (SMRA) as well as Addison s disease (AD) in Nova Scotia Duck Tolling Retrievers (NSDTRs) and chronic superficial keratitis (CSK) in German Shepherd dogs (GSDs). We used two different approaches to identify genetic risk factors. Firstly, a candidate gene approach was applied to test the potential association of MHC class II, also known as a dog leukocyte antigen (DLA) in canine species. Secondly, a genome-wide association study (GWAS) was performed to identify novel risk loci for SLE-related disease and AD in NSDTRs. We identified DLA risk haplotypes for an IMRD subphenotype of SLE-related disease, AD and CSK, but not in SMRA, and show that the MHC class II gene region is a major genetic risk factor in canine autoimmune diseases. An elevated risk was found for IMRD in dogs that carried the DLA-DRB1*00601/DQA1*005011/DQB1*02001 haplotype (OR = 2.0, 99% CI = 1.03-3.95, p = 0.01) and for ANA-positive IMRD dogs (OR = 2.3, 99% CI = 1.07-5.04, p-value 0.007). We also found that DLA-DRB1*01502/DQA*00601/DQB1*02301 haplotype was significantly associated with AD in NSDTRs (OR = 2.1, CI = 1.0-4.4, P = 0.044) and the DLA-DRB1*01501/DQA1*00601/DQB1*00301 haplotype with the CSK in GSDs (OR=2.67, CI=1.17-6.44, p= 0.02). In addition, we found that homozygosity for the risk haplotype increases the risk for each disease phenotype and that an overall homozygosity for the DLA region predisposes to CSK and AD. Our results have enabled the development of genetic tests to improve breeding practices by avoiding the production of puppies homozygous for risk haplotypes. We also performed the first successful GWAS for a complex disease in dogs. With less than 100 cases and 100 controls, we identified five risk loci for SLE-related disease and AD and found strong candidate genes involved in a novel T-cell activation pathway. We show that an inbred dog population has fewer risk factors, but each of them has a stronger genetic risk. Ongoing studies aim to identify the causative mutations and bring new knowledge to help diagnostics, treatment and understanding of the aetiology of SLE-related diseases.

Mental Disorders among Burn Patients

ABSTRACT Mental disorders and suicide attempts among acute burn patients were investigated in a collaborative research project between National Institute for Health and Welfare and Departments of Psychiatry and Plastic surgery in University of Helsinki in Finland. This project was realized in two parts. The first cohort of burn patients consisted of all burn patients admitted to the Helsinki Burn Centre during 1989 97. In this retrospective cohort, 5.7% (N=46) of the total of 811 burn patients had attempted suicide. The burn severity of suicide attempters was markedly higher than in the other burn patients. Suicide attempters were more often unemployed or on disability pension and had psychiatric history before the injury. The second sample was a prospective cohort of all acute consecutive burn patients admitted to the Helsinki Burn Centre during 18 months in 2006- 2007. All subjects (N=107) of the cohort were interviewed with the Structured Clinical Interview for DSM-IV for Axis I and II mental disorders (SCID-I and SCID-II) at baseline and then 86 % of all (N=92) with SCID-I at the end of six-month follow-up. Most (61%) patients had at least one lifetime mental disorder before burn; 47 % substance-related, 10% psychotic and 23% personality disorders. The overall prevalence of Axis I mental disorders increased significantly from the month prior to burn to acute care but decreased significantly from acute care to six months. However, more than one half (55%) of the cohort suffered from some mental disorder during follow-up. Less than one half of the burn patients with estimated need for psychiatric care received psychiatric care. Burn severity independently and strongly predicted risk for mental disorders during follow-up and pre-burn psychiatric history, severe burns and estimated need for psychiatric care significantly predicted psychiatric care received. The proportion of patients with self-inflicted burns is not high but mental disorders are common among burn patients. Mental disorders may predispose to burns. After burn injury, more than half of the patients suffer from mental disorders and a strong relationship exists between burn severity and some post-burn mental disorders. A minority of the patients with unequivocal need for psychiatric care actually receive it. Psychiatric consultations and care follow mainly the course of acute burn treatment.

Cognitive Functioning in Alcohol and Other Substance Use Disorders in Young Adulthood : A Genetic Epidemiological Study

Alcohol and other substance use disorders (SUDs) result in great costs and suffering for individuals and families and constitute a notable public health burden. A multitude of factors, ranging from biological to societal, are associated with elevated risk of SUDs, but at the level of individuals, one of the best predictors is a family history of SUDs. Genetically informative twin and family studies have consistently indicated this familial risk to be mainly genetic. In addition, behavioral and temperamental factors such as early initiation of substance use and aggressiveness are associated with the development of SUDs. These familial, behavioral and temperamental risk factors often co-occur, but their relative importance is not well known. People with SUDs have also been found to differ from healthy controls in various domains of cognitive functioning, with poorer verbal ability being among the most consistent findings. However, representative population-based samples have rarely been used in neuropsychological studies of SUDs. In addition, both SUDs and cognitive abilities are influenced by genetic factors, but whether the co-variation of these traits might be partly explained by overlapping genetic influences has not been studied. Problematic substance use also often co-occurs with low educational level, but it is not known whether these outcomes share part of their underlying genetic influences. In addition, educational level may moderate the genetic etiology of alcohol problems, but gene-environment interactions between these phenomena have also not been widely studied. The incidence of SUDs peaks in young adulthood rendering epidemiological studies in this age group informative. This thesis investigated cognitive functioning and other correlates of SUDs in young adulthood in two representative population-based samples of young Finnish adults, one of which consisted of monozygotic and dizygotic twin pairs enabling genetically informative analyses. Using data from the population-based Mental Health in Early Adulthood in Finland (MEAF) study (n=605), the lifetime prevalence of DSM-IV any substance dependence or abuse among persons aged 21—35 years was found to be approximately 14%, with a majority of the diagnoses being alcohol use disorders. Several correlates representing the domains of behavioral and affective factors, parental factors, early initiation of substance use, and educational factors were individually associated with SUDs. The associations between behavioral and affective factors (attention or behavior problems at school, aggression, anxiousness) and SUDs were found to be largely independent of factors from other domains, whereas daily smoking and low education were still associated with SUDs after adjustment for behavioral and affective factors. Using a wide array of neuropsychological tests in the MEAF sample and in a subsample (n=602) of the population-based FinnTwin16 (FT16) study, consistent evidence of poorer verbal cognitive ability related to SUDs was found. In addition, participants with SUDs performed worse than those without disorders in a task assessing psychomotor processing speed in the MEAF sample, whereas no evidence of more specific cognitive deficits was found in either sample. Biometrical structural equation models of the twin data suggested that both alcohol problems and verbal ability had moderate heritabilities (0.54—0.72), and that their covariation could be explained by correlated genetic influences (genetic correlations -0.20 to -0.31). The relationship between educational level and alcohol problems, studied in the full epidemiological FT16 sample (n=4,858), was found to reflect both genetic correlation and gene-environment interaction. The co-occurrence of low education and alcohol problems was influenced by overlapping genetic factors. In addition, higher educational level was associated with increased relative importance of genetic influences on alcohol problems, whereas environmental influences played a more important role in young adults with lower education. In conclusion, SUDs, especially alcohol abuse and dependence, are common among young Finnish adults. Behavioral and affective factors are robustly related to SUDs independently of many other factors, and compared to healthy peers, young adults who have had SUDs during their life exhibit significantly poorer verbal cognitive ability, and possibly less efficient psychomotor processing. Genetic differences between individuals explain a notable proportion of individual differences in risk of alcohol dependence, verbal ability, and educational level, and the co-occurrence of alcohol problems with poorer verbal cognition and low education is influenced by shared genetic backgrounds. Finally, various environmental factors related to educational level in young adulthood moderate the relative importance of genetic factors influencing the risk of alcohol problems, possibly reflecting differences in social control mechanisms related to educational level.

Functional limitations and quality of life in schizophrenia and other psychotic disorders

There is substantial evidence of the decreased functional capacity, especially everyday functioning, of people with psychotic disorder in clinical settings, but little research about it in the general population. The aim of the present study was to provide information on the magnitude of functional capacity problems in persons with psychotic disorder compared with the general population. It estimated the prevalence and severity of limitations in vision, mobility, everyday functioning and quality of life of persons with psychotic disorder in the Finnish population and determined the factors affecting them. This study is based on the Health 2000 Survey, which is a nationally representative survey of 8028 Finns aged 30 and older. The psychotic diagnoses of the participants were assessed in the Psychoses of Finland survey, a substudy of Health 2000. The everyday functioning of people with schizophrenia is studied widely, but one important factor, mobility has been neglected. Persons with schizophrenia and other non-affective psychotic disorders, but not affective psychoses had a significantly increased risk of having both self-reported and test-based mobility limitations as well as weak handgrip strength. Schizophrenia was associated independently with mobility limitations even after controlling for lifestyle-related factors and chronic medical conditions. Another significant factor associated with problems in everyday functioning in participants with schizophrenia was reduced visual acuity. Their vision was examined significantly less often during the five years before the visual acuity measurement than the general population. In general, persons with schizophrenia and other non-affective psychotic disorder had significantly more limitations in everyday functioning, deficits in verbal fluency and in memory than the general population. More severe negative symptoms, depression, older age, verbal memory deficits, worse expressive speech and reduced distance vision were associated with limitations in everyday functioning. Of all the psychotic disorders, schizoaffective disorder was associated with the largest losses of quality of life, and bipolar I disorder with equal or smaller losses than schizophrenia. However, the subjective loss of qualify of life associated with psychotic disorders may be smaller than objective disability, which warrants attention. Depressive symptoms were the most important determinant of poor quality of life in all psychotic disorders. In conclusion, subjects with psychotic disorders need regular somatic health monitoring. Also, health care workers should evaluate the overall quality of life and depression of subjects with psychotic disorders in order to provide them with the basic necessities of life.

Molecular diagnosis of developmental disorders

ABSTRACT Idiopathic developmental disorders (DDs) affect ~1% of the population worldwide. This being a considerable amount, efforts are being made to elucidate the disease mechanisms. One or several genetic factors cause 30-40% of DDs, and only 10% are caused by environmental factors. The remaining 50% of DD patients go undiagnosed, mostly due to a lack of diagnostic techniques. The cause in most undiagnosed cases is though to be a genetic factor or a combination of genetic and environmental factors. Despite the surge of new technologies entering the market, their implementation into diagnostic laboratories is hampered by costs, lack of information about the expected diagnostic yield, and the wide range of selection. This study evaluates new microarray methods in diagnosing idiopathic DDs, providing information about their added diagnostic value. Study I analysed 150 patients by array comparative genomic hybridization (array CGH, 44K and 244K), with a subsequent 18% diagnostic yield. These results are supported by other studies, indicating an enourmous added diagnostic value of array CGH, compared with conventional cytogenetic analysis. Nevertheless, 80% of the patients remained undiagnosed in Study I. In an effort to diagnose more patients, in Study IV the resolution was increased from 8.9 Kb of the 244K CGH array to 0.7 Kb, by using a single-nucleotide polymorphism (SNP) array. However, no additional pathogenic changes were detected in the 35 patients assessed, and thus, for diagnostic purposes, an array platform with ca 9 Kb resolution appears adequate. The recent vast increase in reports of detected aberrations and associated phenotypes has enabled characterization of several new syndromes first based on a common aberration and thereafter by delineation of common clinical characteristics. In Study II, a familial deletion at 9q22.2q22.32 with variable penetrance was described. Despite several reports of aberrations in the adjacent area at 9q associated with Gorlin syndrome, the patients in this family had a unique phenotype and did not present with the syndrome. In Study III, a familial duplication of chromosome 6p22.2 was described. The duplication caused increased expression of an important enzyme of the γ-aminobutyric acid (GABA) degradation pathway, causing oxidative stress of the brain, and thus, very likely, the mild mental retardation of these patients. These two case studies attempted to pinpoint candidate genes and to resolve the pathogenic mechanism causing the clinical characteristics of the patients. Presenting rare genetic and clinical findings to the international science and medical community enables interpretation of similar findings in other patients. The added value of molecular karyotyping in patients with idiopathic DD is evident. As a first line of testing, arrays with a median resolution of at least 9 Kb should be considered and further characterization of detected aberrations undertaken when possible. Diagnostic whole-exome sequencing may be the best option for patients who remain undiagnosed after high-resolution array analysis.