Arbetsrelaterad psykisk ohälsa orsakar årligen en ansenlig mängd sjukskrivningar. Behovet av allt tidigare åtgärder, som fokuserar på att anpassa arbetskrav med arbetsförmåga samt samhälleliga strukturer som stödjer dessa har framlyfts. En utmaning är den otillräckliga kunskapen om tidiga arbetsplatsnära åtgärder. Arbetsterapi blir oftast inte aktuellt förrän de negativa konsekvenserna av både tillståndet och sjukskrivningen är betydande. Syftet i denna studie var att utforska och beskriva hur personer som drabbats av arbetsrelaterad psykisk ohälsa, men som inte är sjukskrivna, upplever sin arbetsmiljö samt att undersöka hindrande och stödjande faktorer i arbetsmiljön. Metod: Studien genomfördes med en Mixed Methods design. Data samlades in med Work Environment Impact Scale (WEIS). Analys av kvalitativa data kombinerade deduktiv och induktiv ansats. Kvantitativa data analyserades med deskriptiv statistik. Resultatet framlyfte en flerdimensionell och individuellt varierad miljöpåverkan både i och utanför arbetet som bidrog till upplevelsen av nedsatt arbetsförmåga. Detta är implikationer för behovet av att i ett tidigt skede stödja arbetsförmåga ur ett perspektiv som beaktar den drabbade individens vardagliga helhetskontext. Anpassning av arbetssituationen baserad på en analys av faktorer kopplade till individen, arbetet och miljön, behövs i större utsträckning. Arbetsterapeuters metoder och kompetens kan bidra till ökad kunskap om tidiga åtgärder samt till at stödja individer att undvika sjukskrivning. Denna kompetens berikar och kompletterar de arbetssätt som redan är praxis inom företagshälsovård. Arbetsterapeuters expertis borde i tidigare skede och högre grad finnas tillgänglig som stöd vid arbetsrelaterad psykisk ohälsa. / Work related mental disorders continue to cause significant amounts of work absenteeism. The need of matching working conditions to the individuals’ work ability has been emphasized. The lack of knowledge concerning early interventions is though challenging. Occupational therapy is often offered at too late a point when the negative consequences of the sick-leave or the condition already are significant. The aim of this study was two-fold. Firstly, to explore and describe how people affected by work related stress but not on sick leave, experience their working environment. Secondly, to investigate interfering and supporting aspects in the working environment. A Mixed methods design was chosen, and data collected using the Work Environment Impact Scale (WEIS). The qualitative content analysis employed both deductive and inductive approach. Descriptive statistics were used to analyse gradings. The results reflected a multidimensional environmental influence in and outside the work leading to an experience of decreased work ability. The results imply the necessity to early support of work ability embracing the general daily context of the individual affected. Matching the individual and the work to each other, based on an analysis of individual, environmental and work-related factors, should be more common. The methods and the competence occupational therapists possess can contribute to gaining knowledge concerning early interventions and also support individuals to avoid sick leave. This expertise enrichens customary occupational health services practice and should be more commonly provided.

Huntington’s disease (HD) is an autosomal dominant, progressive neurodegenerative disorder. Invariably fatal, HD is caused by expansion of the CAG repeat region in exon 1 of the Huntingtin gene which creates a toxic protein with an extended polyglutamine tract 1. Silencing mutant Huntingtin messenger RNA (mRNA) is a promising therapeutic approach 2-6. The ideal silencing strategy would reduce mutant Huntingtin while leaving the wild-type mRNA intact. Unfortunately, targeting the disease causing CAG repeat expansion is difficult and risks targeting other CAG repeat containing genes. We examined an alternative strategy, targeting single nucleotide polymorphisms (SNPs) in the Huntingtin mRNA. The feasibility of this approach hinges on the presence of a few common highly heterozygous SNPs which are amenable to SNP-specific targeting. In a population of HD patients from Europe and the United states, forty-eight percent were heterozygous at a single SNP site; one isoform of this SNP is associated with HD. Seventy-five percent of patients are heterozygous at least one of three frequently heterozygous SNPs. Consequently, only five allele-specific siRNAs are required to treat three-quarters of the patients in the European and U.S. patient populations. We have designed and validated siRNAs targeting these SNPs. We also developed artificial microRNAs (miRNAs) targeting Huntingtin SNPs for delivery using recombinant adeno-associated viruses (rAAVs). Both U6 promoter driven and CMV promoter driven miRNAs can discriminate between matched and mismatched targets in cell culture but the U6 promoter driven miRNAs produce the mature miRNA at levels exceeding those of the vast majority of endogenous miRNAs. The U6 promoter driven miRNAs can produce a number of unwanted processing products, most likely due to a combination of overexpression and unintended export of the pri-miRNA from the nucleus. In contrast, CMV-promoter driven miRNAs produce predominantly a single species at levels comparable to endogenous miRNAs. Injection of recombinant self complementary AAV9 viruses carrying polymerase II driven Huntingtin SNP targeting miRNAs into the striatum results in expression of the mature miRNA sequence in the brain and has no significant effect on endogenous miRNAs. Matched, but not mismatched SNP-targeting miRNAs reduce inclusions in a knock-in mouse model of HD. These studies bring us closer to an allele-specific therapy for Huntington’s disease.

This thesis deals with the collection, sorting and by reflecting artistic expressions of a particular child during the school year. The theoretical part contains information obtained from the study of literature concerning the concepts of art education, perception, sensitivity, imagination, creation, communication, portfolio assessment, children's drawing, ontogeny, psychiatric diagnosis, developmental disorders. The empirical part focused on the development of intellectual and social abilities in connection with the development of drawings, a boy with psychiatric diagnosis. The work is processed by the methods of qualitative research. It is a case study with subsequent analysis results of operations,ie his artistic expressions.

Nach Befunden des Bundes-Gesundheitssurveys 1998/99 (Zusatzsurvey „Psychische Störungen“) litten im Jahr der Erhebung 32% (=15,6 Millionen) der erwachsenen deutschen Bevölkerung im Alter von 18–65 unter einer oder mehreren psychischen Störungen. Jeder dritte Betroffene (36%) steht oder stand im Jahr vor der Erhebung wegen der psychischen Störung in Kontakt mit ambulanten oder stationären psychiatrisch/psychotherapeutischen Diensten oder seinem Hausarzt. Der Anteil von Betroffenen, die eine im weitesten Sinne adäquate Therapie nach modernen wissenschaftlichen Kriterien erhalten, kann konservativ auf ca.10% geschätzt werden. Die niedrige Versorgungsquote betrifft dabei nicht alle spezifischen Störungsgruppen in gleichem Ausmaß; niedrige Versorgungsraten ergaben sich insbesondere für somatoforme und Suchterkrankungen. Ferner ergaben sich zum Teil markante regionale Unterschiede (z.B. besonders schlechte Versorgungslage in Regionen, die weder über eine nahe Universität noch über psychotherapeutische Weiterbildungsinstitutionen verfügen).Ungeachtet unterschiedlich weiter oder enger Definitionen des Begriffs Behandlungsbedarf, zeigt sich eine gravierende Unterversorgung von Personen mit psychischen Erkrankungen. Quantitativ bedeutsame Hinweise auf eine Fehl- oder Überversorgung von Betroffenen lassen sich nicht aufzeigen. / Data from the German Health Interview and Examination Survey, Mental Health Supplement (N=4181) reveal that 32% (15,6 million people) of the adult population between 18 and 65 years of age suffer from one or more mental disorders. Among those only 36% receive treatment which also varies in type, duration, and adequacy. The proportion of cases receiving “adequate evidence- based treatments” was estimated to be about 10%.Lowest treatment rates were found for somatoform disorders and substance abuses, highest for psychotic disorders, panic disorder, generalised anxiety disorder, and dysthymia. The data reveal substantial regional differences with regard to treatment rates (e.g. lower rates in regions without universities or institutions offering postgraduate mental health education).The paper concludes that, depending on the diagnosis, a considerable degree of unmet medical needs exist for the majority of people affected by mental disorders. No evidence was found for an excessive supply of health care for the patients suffering from mental disorders or for treatments without an existing clinical need.

Background: When assessing the association between a factor X and a subsequent outcome Y in observational studies, the question that arises is what are the variables to adjust for to reduce bias due to confounding for causal inference on the effect of X on Y. Disregarding such factors is often a source of overestimation because these variables may affect both X and Y. On the other hand, adjustment for such variables can also be a source of underestimation because such variables may be the causal consequence of X and part of the mechanism that leads from X to Y. Methods: In this paper, we present a simple method to compute control variables in the presence of age at onset data on both X and a set of other variables. Using these age at onset data, control variables are computed that adjust only for conditions that occur prior to X. This strategy can be used in prospective as well as in survival analysis. Our method is motivated by an argument based on the counterfactual model of a causal effect. Results: The procedure is exemplified by examining of the relation between panic attack and the subsequent incidence of MDD. Conclusions: The results reveal that the adjustment for all other variables, irrespective of their temporal relation to X, can yield a false negative result (despite unconsidered confounders and other sources of bias).

This article examines the stability of symptoms, syndromes, and diagnoses of specific anxiety and depressive disorders, as well as diagnostic shifts from one syndrome to another over time. Using retrospective and longitudinal prospective data from the baseline and first follow-up investigation (19.7 months later) of the Early Developmental Stages of Psychopathology Study (EDSP), we focus on establishing stability measures for early stages of mental disorders in a community sample of adolescents aged 14 to 17 years at baseline. The results are as follows: (1) Although only about 30% developed a full-blown DSM-IV disorder, psychopathological syndromes are widespread in adolescents: 15% of the population aged 14 to 17 at baseline were not affected by at least some clinically relevant symptoms of mental disorders either throughout their previous life or throughout the follow-up period. (2) The likelihood of staying free of symptoms and threshold disorders during follow-up was highest among subjects who were completely well at baseline. The probability of a positive outcome decreased as a function of severity of baseline diagnostic status. (3) There was a considerable degree of fluctuation not only in the diagnostic status and severity of specific disorders, but also in terms of complete remissions and shifts from one syndrome and disorder to another. (4) Anxiety disorders, overall, slightly differ with regard to the persistence and stability of the diagnostic status from depressive disorders. (5) However, there were remarkable differences between specific types of anxiety and depressive disorders. Consistent with other longitudinal epidemiological studies in the general population, this study finds that the syndromes and diagnoses of mental disorders have a strong tendency to wax and wane over time in this age group.

Abstract Hidradenitis suppurativa (HS) is a chronic inflammatory disease of hair follicles, characterized by subcutaneous inflammatory nodules and abscesses, typically on the axillary, genitofemoral, and perianal skin. Symptoms of HS, such as foul-smelling discharge from the inflamed lesions, pain, and disease location in sensitive areas, markedly diminish patients’ quality of life. Smoking and obesity are associated with HS, which also has several common comorbidities. While there is a growing body of evidence of somatic comorbidities in HS, psychiatric comorbidities have received less attention. Furthermore, literature on comorbidities in young patients with HS is scarce, and no systematic evaluation of mortality in HS has yet been undertaken. This study aimed to clarify the associations between HS and mental disorders, to explore both somatic and psychiatric comorbidities of HS in children and adolescents, and to determine the life expectancy and cause-specific risks of death in patients with HS. The study population comprised over 4300 cases with HS diagnosed in Finnish hospitals between 1987 and 2014. Age- and sex-matched patients with psoriasis and melanocytic nevi served as controls. Patient data were obtained from the statutory Finnish Care Register for Health Care. Information on dates and causes of death of the cases and controls were acquired from Statistics Finland. This study showed a heavy psychiatric disease burden in patients with HS. The prevalence rates and risks of all studied psychiatric comorbidities were higher in the HS than in the control groups. This was also evident in children and adolescents with HS, not only in adults. Furthermore, younger patients also had elevated risks for many somatic disorders including inflammatory bowel and joint diseases. Remarkably, the mean age at death in the HS group was only 60.5 years. The most common causes for death in the order of likelihood were: cardiovascular diseases, neoplasms, ‘accidents, suicides or violence’ and alcohol-related diseases. Suicide risk was elevated in women with HS. HS patients should be cautiously monitored for possible somatic and psychiatric comorbidities. It is clear that these patients require effective, comprehensive and multidisciplinary care to improve their quality of life and prevent premature death. / Tiivistelmä Hidradenitis suppurativa (HS) on krooninen tulehduksellinen karvatuppien sairaus, joka heikentää elämänlaatua merkittävästi. Kivuliaat kyhmyt ja paiseet sekä vuotavat käytävät, jotka sijaitsevat useimmiten kainaloissa, nivusissa, genitaalialueella ja pakaravaossa, ovat sen tyypillisimpiä ilmenemismuotoja. HS-potilailla on moninaisia terveysongelmia, joita ovat mm. tupakointi, lihavuus ja suurentunut riski useisiin somaattisiin sairauksiin. Tutkimustieto HS-potilaiden psykiatrisista sairauksista on kuitenkin vähäistä eikä liitännäissairauksista lapsilla ole juuri lainkaan tietoa. Tämän lisäksi HS-potilaiden kuolemansyitä tai eliniänodotetta ei ole perusteellisesti selvitetty. Tällä tutkimuksella haluttiin määrittää psykiatristen sairauksien riski HS-potilailla ja selvittää sekä somaattisten että psykiatristen liitännäissairauksien todennäköisyyttä lapsuudessa ja nuoruudessa. Tarkoituksena oli myös tutkia, mihin sairauksiin HS-potilailla on suurentunut riski kuolla ja minkä ikäisinä he menehtyvät. Terveyden ja hyvinvoinnin laitoksen hoitoilmoitusjärjestelmästä etsittiin tiedot kaikista Suomen sairaaloissa vuosina 1987–2014 diagnosoiduista HS-tapauksisista (N=4381). Liitännäissairauksien tutkimista varten verrokeiksi valittiin psoriaasi- tai luomidiagnoosin saaneet henkilöt, jotka kaltaistettiin iän ja sukupuolen mukaan. Kuolintiedot menehtyneistä tutkimuspotilaista saatiin Tilastokeskukselta. HS-potilailla havaittiin selkeästi suurentunut psykiatristen sairauksien riski niin aikuisena kuin myös jo alle 18 vuoden iässä. Lisäksi monien somaattisten sairauksien, esim. tulehduksellisten suoli- ja nivelsairauksien, riski oli suurentunut lapsuudessa. HS-potilaiden todettiin menehtyvän huomattavan nuorella iällä, sillä heidän keskimääräinen elinikänsä oli vain 60,5 vuotta. Yleisimmät kuolinsyyt olivat sydän- ja verisuonitaudit, kasvaimet, ’onnettomuudet, itsemurhat ja väkivalta’ sekä alkoholiin liittyvät kuolemat. Itsemurhariski havaittiin suurentuneeksi naisilla. Tämän tutkimuksen perusteella HS-potilailla on runsaasti psykiatrisia liitännäissairauksia. Sekä somaattisten että psykiatristen sairauksien riski onkin pidettävä mielessä aina HS-potilaita hoidettaessa. Tehokas, kokonaisvaltainen ja moniammatillinen hoito on tärkeää potilaiden elämänlaadun parantamiseksi ja ennenaikaisen kuoleman ehkäisemiseksi.

Maternal infection during pregnancy is associated with increased risk of both schizophrenia and autism in offspring. Based on this observation, the maternal immune activation mouse model was developed, in which pregnant rodents are treated with immune-activating agents and the brains and behavior of the adult offspring studied. This model has been found to recapitulate a variety of molecular, cellular, and behavioral abnormalities observed in both schizophrenia and autism. However, despite the abundant evidence provided by these studies that prenatal exposure to inflammation alters brain development and function later in life, the molecular mechanisms by which inflammation mediates these effects remains unclear. It has been suggested that other prenatal risk factors for neuropsychiatric disease may alter brain development, in part, via epigenetic mechanisms such as DNA methylation and histone modification. However, a link between inflammation and epigenetic modification in brain has not been established. Therefore, the focus of my thesis was to examine the effect of inflammation on the histone modification, trimethylated histone H3 lysine 4 (H3K4me3), which has been implicated in both normal brain development and in schizophrenia. In Chapter II, I describe experiments examining the effect of a specific, cytokine, interleukin-6 (IL-6), on H3K4me3 in rat forebrain culture. I show that IL-6 treatment results in altered levels of H3K4me3 at multiple gene promoters, frequently in conjunction with altered mRNA expression levels, and demonstrate that a subset of these alterations appear to be dependent on signaling via the signal transducer and activator of transcription 3 (Stat3) pathway. Furthermore, some of the genes affected by IL-6 also showed altered H3K4me3 levels in autism postmortem brain. Though a direct link still remains to be established, this observation suggests that epigenetic changes observed in neuropsychiatric disease may have been induced by prenatal exposure to inflammation. In Chapter III, I describe in vivo experiments employing the maternal immune activation (MIA) mouse model to examine the effects of prenatal inflammation on H3K4me3 in the brain of the offspring, at both fetal and adult stages. I found that immune activation resulted in increased levels of IL-6 protein in fetal brain, working memory deficits in the adult offspring, and subtle changes in H3K4me3 levels in fetal and adult brain. Taken together, these findings demonstrate that an environmental risk factor for schizophrenia and autism—namely, inflammation—is capable of inducing robust and widespread histone modifications in a model of the central nervous system and smaller changes in vivo. This suggests that prenatal exposure to inflammation in human populations may lead to increased susceptibility for neuropsychiatric disorders, in part, by altering chromatin modifications in developing brain.

Developmental disabilities (DEVDIS) such as attention deficit hyperactivity disorder (ADHD), autism spectrum disorders (ASD), developmental delay (DD), and learning disabilities, affect 14% of US youth, who also experience higher rates of obesity, approximately 19%, than youth without these conditions. Screen time is a risk factor for obesity, though it is not well-studied among youth with developmental disabilities. Youth with developmental disabilities experience challenges with learning, have underdeveloped social skills, and problematic behaviors. These predispositions can often result in peer rejection. The resulting social isolation may make these youth particularly vulnerable to engaging in solitary activities such as screen time. The objectives of this dissertation were to compare screen time rates among youth with developmental disabilities to typically developing youth and to examine the associations between social and family engagement with screen time among youth with developmental disabilities. Data from the 2007 National Survey of Children’s Health (NSCH), a national cross-sectional study that assesses the physical and emotional health of US children (N = 91,642), were used. Youth 6-17 years, with ADHD (n = 7,024), ASD (n = 1,200), DD (n = 3,276), LD (n = 7,482), and without special health care needs (n = 44,461) were studied. Unadjusted analyses found that children with DEVDIS engage in higher rates of screen time than youth without special health care needs. For youth with DEVDIS who were medicated for their ADHD, these associations attenuated. Thus ADHD symptoms, a common comorbidity across developmental disabilities, drove associations between the other developmental disabilities and screen time. Across all developmental disability groups, television in the bedroom was a significant screen time risk factor in both children and adolescents. Among children with ADHD, additional screen time risk factors included lack of caregiver knowledge of the child’s friends and any social engagement outside of the household. Among adolescents with ADHD, additional screen time risk factors included lower frequency that caregiver attends adolescent’s events and sport social engagement. Findings of this dissertation elucidate modifiable screen time risk factors that could potentially be adapted to decrease screen time among youth with developmental disabilities.

Background. Emerging evidence suggests that youth with attention deficit/hyperactivity disorder (ADHD) may engage in sub-optimal health behaviors including high levels of screen time, low physical activity participation, and consumption of poor diets. These are independent risk factors for adverse health outcomes, and health-related behavior patterns established in childhood can track into adulthood. Thus, identifying and addressing dietary and physical activity habits in sub-populations of youth have important implications for health over the lifespan. The specific aims of this dissertation were to: (1) compare screen time between youth with and without ADHD and to assess its relationship to ADHD symptomatology; (2) compare participation in physical activity (PA) between adolescents with and without ADHD and to assess the relationship of PA participation to ADHD symptomatology; and (3) evaluate the association of diet quality and dietary patterns to ADHD symptomatology among youth ages 8-15 years. Methods. The aforementioned outcomes of interest were analyzed using data from the continuous National Health and Nutrition Examination Survey (NHANES) 2001-2004. These waves of NHANES included a structured DSM-IV-based interview administered to parents that identified youth with ADHD and also yielded symptom counts for hyperactivity/impulsivity and inattention. Screen time and physical activity data were obtained from questionnaires that queried the amount of time spent watching television, playing videos, or using the computer outside of school time, and also surveyed the types, frequency, and duration of PA in which youth participated. Diet quality and dietary patterns, which included consumption of sugar-sweetened beverages (SSBs), total calorie intake, and eating frequency, were obtained by a 24-hour dietary recall using the Automated Multiple Pass Method of interviewing. Linear and logistic regression models adjusted for sociodemographic factors and anxiety/depression were employed to address the specific aims. Results. The findings suggest that youth with ADHD are at the same, if not higher, risk for engaging in suboptimal health behaviors. Overall, youth participating in NHANES engaged in excessive amounts of screen time, failed to acquire sufficient physical activity, and consumed diets of poor quality. However, our findings suggest that ADHD symptomatology places youth at higher risk for sedentary behavior and poor diet quality. Relative to screen time, youth with ADHD showed a trend toward increased screen time, as did youth who took medication. ADHD symptoms were also associated with over two hours of daily TV viewing and overall increased screen time, and this was particularly true for children ages 8-11 years. Relative to physical activity, the outcomes did not differ between youth with and without ADHD, but the majority of youth did not meet the recommended guidelines of 60 minutes or more of moderate-to-vigorous PA each day. Diet quality was poor across the population of youth who participated in NHANES, and hyperactive/impulsive symptoms were associated with an even greater decrease in diet quality in both children and adolescents. In males, the presence of hyperactive/impulsive symptoms was associated with a decrease in diet quality, whereas in females, inattentive symptoms accounted for a decrease in diet quality. No differences in the other dietary patterns (i.e., SSB consumption, total energy intake, and eating frequency) were observed. Conclusions. The diagnosis of ADHD and/or its symptoms are associated with less-than-recommended levels of screen time and poor diet quality, though youth in general were found to be engaging in suboptimal sedentary, physical activity, and dietary behaviors. The mechanisms for why youth with ADHD may have increased vulnerability to poorer health behaviors are not yet well understood. The findings from this dissertation support the need for ongoing efforts to address lifestyle factors among the nation’s youth generally, but may also stimulate new hypotheses about the needs of youth with ADHD from both public health and clinical perspectives, and encourage research on the implications of ADHD symptomatology on health-related behaviors and lifestyle factors.