Serotonin was first discovered in the late 1940s as a vasotonic factor and is now considered a principal neurotransmitter in the nervous system. 5-HT6 receptors are one of the most recently identified members of the serotonin receptor family which consists of seven classes (5-HT1-5-HT7). 5-HT6 receptors are G-protein coupled, positively coupled to an adenylate cyclase second messenger system and are primarily found in the central nervous system (CNS). The exact functional role of 5-HT6 receptors has not been determined, but is implicated to have possible involvement in certain neuropsychiatric disorders and cognition. To investigate the functional role of these receptors, it is useful to identify 5-HT6 selective ligands as pharmacological tools. Our laboratory identified one of the first 5-HT6 receptor antagonists: the arylsulfonamide MS-245 (14a). It has been assumed that a sulfonyl (i.e., SO2) moiety is important for the binding of arylsulfonamides at 5-HT6 receptors. We now have identified benzyl analog 33 (R=H) as a single example of a non-sulfonyl analog that retains affinity. This questions the importance of the SO2 group and whether an aryl moiety or other hydrophobic groups (of equal or greater hydrophibicity) is required for binding. The purpose of the present investigation was to determine if the SO2, and the aryl moieties are required for high affinity binding. N1-Alkylsulfonyl- 78, and N1-benzyl-substituted tryptamines 33 were synthesized and affinities compared with their corresponding N1-benzenesulfonyl-substituted counterparts 31 at h5-HT6 receptors. None of the alkylsulfonyl or benzyl analogs displayed and/or retained the affinity of the simple benzenesulfonyl tryptamine analog (31a) (Ki = 4.1 nM). The results show that an arylsulfonyl group at the tryptamine N1 position is optimal, relative to an alkylsulfonyl group, for 5-HT6 receptor affinity. In a comparative analysis utilizing six pairs of tryptamines, it was found that there was little correspondence (r2 = 0.048) between the 5-HT6 receptor affinities of the examined benzyl and benzenesulfonyl pairs. Current findings indicate that an aryl (or substituted aryl)sulfonyl (rather than benzyl) moiety is optimal for high affinity binding, and further suggest that N1-benzenesulfonyl- and their corresponding N1-benzyltryptamine counterparts bind in a different fashion.

The aim of this study was to examine how parents of children who refuse school experience the treatment they received from the school and from social services in regards to their situation, and what they believe that social services can improve in their work with these families. The study was conducted by qualitative phone interviews with six mothers of children with school refusal behavior. The main results show that the mothers were displeased with the help and treatment the school provided, but overall pleased with the help from social services although they also described room for improvements. The respondents also expressed that they had to struggle to receive help and had to make a lot of efforts themselves. Several suggestions for improvements for social services were mentioned, especially that more knowledge about school refusal and neuropsychiatric disabilities is needed in social services, and that collaboration between schools and social services should be improved. / Syftet med studien var att undersöka hur föräldrar med s.k. hemmasittande barn, det vill säga som varit frånvarande från skolan utan synbar orsak i minst tre veckor, upplever skolans och socialtjänstens agerande gentemot dem samt vad de anser att socialtjänsten eventuellt kan förbättra i arbetet med dessa familjer. Telefonintervjuer med sex mödrar till hemmasittare genomfördes. Resultaten visade på ett missnöje med skolans bemötande och hjälp medan man överlag var nöjda med socialtjänstens bemötande och hjälp även om de ansåg att det fanns utrymme för förbättringar. Ett annat starkt tema var att man ofta upplevde att deras barn inte togs på allvar utan föräldrarna fick kämpa för att få hjälp och lägga ner mycket arbete själva. Flera förbättringar för socialtjänstens arbete föreslogs, främst nämndes att mer kunskap om hemmasittare och neuropsykiatriska funktionsnedsättningar behövs samt att deras samverkan med skolan behöver förbättras.

I denna studie är syftet att undersöka hur respondenter från olika verksamheter upplever ansvarsfördelning och samverkan kring elever med en neuropsykiatrisk funktionsnedsättning som har en problematisk skolfrånvaro. Vidare undersöks vilka faktorer som orsakar skolfrånvaro samt hur skolorna konkret arbetar förebyggande för att elever inte ska bli frånvarande från skolan. I Sverige finns 5500 barn som inte går till skolan och som därmed inte når kunskapsmålen. Följden av en problematisk skolfrånvaro kan innebära psykisk ohälsa hos eleven, men även påverka elevens framtid negativt i form av marginalisering och utanförskap. Det empiriska materialet, som har analyserats genom en systemteoretisk ingång, har samlats in genom semistrukturerade intervjuer med verksamma inom skola samt barn- och ungdomspsykiatrin. I resultatet framgår vikten av samverkan och tydliga rutiner kring ansvarsfördelning för att skolor och barn- och ungdomspsykiatrin ska ha möjlighet att arbeta förebyggande kring elever med en neuropsykiatrisk funktionsnedsättning som har en problematisk skolfrånvaro. Resultatet lyfter att trygghet, delaktighet, struktur och relationer är avgörande för att elever ska vilja komma till skolan. Slutsatsen pekar på att det finns strukturella brister i det gemensamma ansvaret mellan skola, vårdinstanser och föräldrar kring barn och unga med en problematisk skolfrånvaro. Den visar även betydelsen av en omgivning eleven kan känna förtroende för. / The purpose of this study is to examine how professionals from different organisations experience collaboration and division of responsibilities when it comes to pupils with a neuropsychiatric disability who have a problematic school absence. Furthermore, the purpose is to examine what causes school absence and how the professionals describe their preventive work towards pupils with the above described difficulties. Sweden has 5500 children absent from school not fulfilling the educational knowledge requirements. A problematic school absence can cause mental illness during the school years but also marginalise the individual in the future. The empirical material has been collected via semi-structured interviews with professionals within school and psychiatric care for children and youth. The result has been analysed using systems theory. The result indicates the importance of collaboration between professions. To enable the preventive work of schools’ and the psychiatric care for children and youth, the need for a clear division of responsibilities is crucial. The result shows that pupils are more likely to be present in school if they feel safe and are given the opportunity to influence. Structure in the school environment and relations are also described as important. The conclusion indicates structural shortcomings in the responsibilities shared between schools, healthcare and parents regarding children with a neuropsychiatric disability who have a problematic school absence. It also shows the importance of creating a surrounding the pupil can trust.

Transmembrane signal transduction by ligand-activated G protein-coupled receptors (GPCRs) controls virtually every aspect of mammalian physiology, and this receptor class is the target of 40-50% of currently marketed pharmaceuticals. In addition to the clinical use of direct GPCR agonists and antagonists, it is now believed that GPCR effectors and regulators may also be viable drug targets with improved therapeutic efficacy and specificity. The prototypic role of Regulator of G protein Signaling (RGS) proteins is inhibition of G protein signaling through acceleration of GTP hydrolysis by GΑ, which promotes re-association of GΑ and GΒΓ subunits with the receptor at the cell membrane. In this way, RGS proteins determine the magnitude and duration of the cellular response to GPCR stimulation. Though RGS protein biochemistry has been well elucidated in vitro, the physiological functions of each RGS family member remain largely unexplored. RGS6 belongs to the R7 subfamily of RGS proteins originally identified in brain. Our acquisition of an RGS6-/- mouse allowed us to survey RGS6 expression in all tissues of the body revealing the greatest expression of RGS6 in brain. Despite robust neural RGS6 expression, little is known regarding functional roles of RGS6 in the brain and spinal cord. In addition, we identified several novel, higher molecular weight RGS6 immunoreactive bands specifically present in the nervous system. The plan of this thesis work was multifaceted. We sought to elucidate novel GPCR signaling cascades modulated by RGS6 in brain while simultaneously characterizing the expression patterns and identity of the novel RGS6 species specifically detected in the nervous system. Considering the large diversity of RGS6 isoforms present in brain, the abundance of potential RGS6 binding partners, and the possibility of discovering new mechanisms involved in RGS6 regulation, elucidation of the novel RGS6 molecular species is of paramount importance. Utilizing RGS6-/- mice we identified RGS6 as a critical modulator of two GPCRs in brain. First, by inhibiting the serotonin receptor 1A (5-HT1AR)-adenylyl cyclase (AC) axis, RGS6 functions to promote anxiety- and depression-related behaviors in mice. As a result, RGS6-/- mice exhibit a robust anxiolytic and antidepressant phenotype remarkably similar to that of animals treated chronically with therapeutic doses of selective serotonin reuptake inhibitors (SSRIs). RGS6 also inhibits GABAB receptor (GABABR)-G protein- activated inwardly rectifying potassium (GIRK) channel current in cerebellar granule cells, and loss of RGS6 results in cerebellar ataxia and gait abnormalities reversible by GABABR blockade. Furthermore, evaluation of voluntary alcohol drinking behaviors in WT versus RGS6-/- mice revealed a striking reduction in alcohol intake resulting from RGS6 loss in both acute and chronic alcohol consumption paradigms due, at least in part, to potentiation of GABABR signaling. Thus, RGS6 inhibitors have potential clinical utility in the treatment of mood disorders and alcoholism. We have shown that one novel RGS6 immunoreactive band expressed in the brain and spinal cord is a phospho-protein sensitive to Λ phosphatase-mediated dephosphorylation. Further, new information acquired from PCR amplification of RGS6 mRNA species from human brain cDNA libraries has necessitated substantial revisions to the RGS6 splicing scheme devised by the Fisher laboratory in 2003. To the 36 isoforms generated from two alternate transcription start sites (RGS6L vs. RGS6), the inclusion or exclusion of exons 14 and 17, and variable splicing to one of 7 different 3' terminal exons, we have added the possible insertion of three novel internal exons (A1, A2, A3), a retained intron, and two new 3' terminal exons. As a result, the number of RGS6 mRNAs present in brain could be as many as 248 unique species, an astonishing diversity unprecedented in the RGS protein family.

Abstract The purpose for this essay has been to illuminate some teachers opinions of integration of students with Aspergers syndrom in the compulsory school, then compare it with the statue documents and see similarities and differences. The studie has been of a quality character, based on quality intervjues to get the teachers understanding at a deeper level. The questions in the intervju are based on open questions with purpose not to control the person during the intervju. The most obvious result which was that it appered two perspective of integration of students with Aspergers syndrom. One in the short run and one in the long run. In the long run it was the integration of the individual into the society and in the short run integration in school. For the perspective in the long run, the opinions from the teachers in compulsory school is good corresponding to the statue documents, that the integration is necessary for our democratic and human values that our sociaty are based on. In the short run, during the years when the students are in school, it came out great difficulties to integrate children with Aspergers syndrom. To proceed an integration that works out for the students, the teachers took site from the individual and not from the society. If we do not look at integration from an individual base we are probably not going to succeed to integrate in society. Searchwords: Aspergers syndrom, neuropsychiatric funktional disorders, integration, inclusion, segregation. / Sammanfattning Syftet med min uppsats har varit att belysa några grundskollärares uppfattningar om integrering av elever med Asperger syndrom för att sedan jämföra med styrdokumenten och se om de stämmer överens. Studien har varit av kvalitativ karaktär, baserad på kvalitativa intervjuer för att få lärares uppfattningar på ett djupare plan. Intervjufrågorna baseras på öppna frågor med syfte att inte styra de intervjuade. Det mest framträdande resultatet var att det framkom två perspektiv på integrering av elever med Asperger syndrom. Ett långsiktigt och ett kortsiktigt perspektiv. Det långsiktiga är en integrering av individen i samhället och det kortsiktiga är en integrering i skolan. I det långsiktiga perspektivet så stämmer grundskollärarnas uppfattning väl överens med styrdokumenten, att integrering är nödvändig för att värna våra demokratiska och humanistiska värden som samhället bygger på. I det kortsiktiga perspektivet, elevens skolgång, framkom stora svårigheter vad det gäller att integrera elever med Asperger syndrom. Som utgångspunkt för att få en fungerande integrering av eleven, så utgick lärarna från individen och inte samhället. Om vi inte ser på integration utifrån individen så kommer vi troligtvis inte att lyckas med integrationen i samhället. Sökord: Asperger syndrom, neuropsykiatriska funktionshinder, integration, inkludering, segregation.

Syftet med denna kvalitativa studie var att undersöka hur elever med neuropsykiatriska funktionshinder upplever tiden i grund- och gymnasieskolan. Mina frågeställningar handlade om i vilka sammanhang eleverna upplevde svårigheter kopplade till funktionshindren, på vilka sätt skolan visade förståelse för dessa svårigheter, hur skolan löste de problem som uppstod, vad skolan kunde ha gjort mer samt vilka starka sidor hos eleverna som var betydelsefulla i skolan. Jag intervjuade sex ungdomar i åldrarna 18 - 21 år. Jag använde mig av halvstrukturerade intervjuer. Resultatet, som analyserades ur ett sociokulturellt perspektiv, visade att eleverna upplevde svårigheter i skolan i flera olika sammanhang. Stora klasser och störande ljud i klassrummet förvärrade elevernas koncentrationssvårigheter. Projektarbeten utan strikta ramar och att tvingas redovisa inför klassen utgjorde ett stort hinder för flera av eleverna, medan undervisning på för låg nivå ledde till bristande studiemotivation. Under högstadietiden upplevde eleverna stress och svårigheter att hitta till klassrummen. Annat som medförde problem var bland annat fobier, sömnstörningar och att delta i skolidrotten. Utanförskap och mobbing i elevgrupperna var vanligt förekommande. Även lärare utsatte eleverna för kränkande särbehandling genom utpekande handlingar, skuldbeläggande och bestraffningar. Eleverna upplevde att de oftast möttes av oförståelse och okunskap från skolan. Endast enstaka lärare visade förståelse. Skolans åtgärder sattes oftast in väldigt sent och lösningarna på problemen blev därför kortvariga. Vissa åtgärder gjorde till och med större skada än nytta. Eleverna berättade om sina starka sidor och menade att dessa hjälpte dem genom åren i skolan. Av resultatet framgick att mindre klasser, men också kunskap hos lärarna och förmågan att samtala med eleverna och lyssna på dem, är viktiga medel för att kunna ta tag i problemen på ett tidigt stadium och skapa en skola för alla. / The purpose of this qualitative study was to get knowledge of experiences of the years in compulsory school and upper secondary school by pupils with neuropsychiatric disabilities. The questions dealt with when and where in school the pupils had difficulties connected to their neuropsychiatric disabilities, in what way they were met with understanding for their difficulties, how the school solved the problems, what the school could have done more and what qualities the pupils possessed that helped in school. I interviewed six youngsters in the ages of 18 - 21. I used half-structured interviews. The result was analysed in a sociocultural perspective and showed that the pupils had difficulties in many ways at school. Big classes and noises in the classroom made their concentration difficulties worse. Projects in school without strict directions as well as appearances before the class became huge barriers for some of the pupils, while teaching at a too low level led to a lack of motivation. In upper level of compulsory school the pupils felt stress and difficulties in finding classrooms. Some other problems were phobias, insomnia and participating in school gymnastics. Bullying and exclusion from fellowship was usual. Even teachers were insulting the pupils by indicating them as outsiders, blaming them for their difficulties and punishing them. The pupils experienced that they were mostly met with misunderstanding and a lack of knowledge from the school. Just a few teachers were sympathetic. The school mostly took measures very late and the solutions therefore became short-lived. Some of the measures made the problems even worse. The pupils told me about their strong sides that helped them through school. The result showed that smaller classes as well as teachers knowledge and ability to converse and listen to the pupils are important instruments to be able to face the problems in an early phase and create a school for all kinds of minds.

Normal children acquire the necessary social habits without being consciously aware of this, they learn instinctively. (Author’s translation from Swedish to English) (Asperger & Frith, 1998, s. 21)   This essay is about people who do not learn to socialize, the social habits, instinctively but through conscious learning. We have interviewed three adults with the diagnosis of Asperger syndrome with the aim to let them tell us about what it means to have a neuropsychiatric disability. We will briefly describe how the Asperger syndrome is described in the literature and what facilities are offered within the Swedish health care system. A diagnosis refer to a deviation from what is assumed to be the normal, therefore we will put forward theories concerning the norm of normality and normativity. We have tried through a theoretical discussion to deepen our understanding of identity formation and found the following arguments are reliable individual identity is shaped by three sub-aspects of identity; the identity of biological, psychological identity and social identity. Based on these theoretical arguments, a reasoning regarding how this affects what people with Asperger syndrome will and can tell us about when they talk about how they perceive their life before and after they have been diagnosed. Our intention is to critically discuss how identity formation is affected and how normality are handled and experienced by a group people with this diagnosis. / Normala barn tillägnar sig nödvändiga sociala vanor utan att vara medvetet uppmärksamma på detta, de lär sig instinktivt. (Asperger & Frith, 1998, s. 21) Denna uppsats handlar om människor som inte lär sig sociala vanor instinktivt utan att säger sig att göra det genom medveten intellektuell inlärning. I den här uppsatsen har vi intervjuat tre vuxna med diagnosen Asperger syndrom för att kunna belysa vad det kan innebära att ha en neuropsykiatrisk funktionsnedsättning. Vi kommer kortfattat att beskriva hur Asperger syndrom beskrivs i litteraturen och vilka hjälpmedel som erbjuds inom svensk sjukvård. En diagnos refererar till en avvikelse från vad som antas vara normalt och därför kommer vi att resonera kring det normala och normativitet. Varje individ skapar sig en identitet och i den här studien har vi utgått från förklaringar baserade på tre delaspekter; biologisk, psykologisk och social identitet. Vi har också sökt teoretiska resonemang för att fördjupa förståelsen kring identitetskapande. Med utgångspunkt i dessa teoretiska resonemang har vi resonerat kring hur detta kan påverka vad människor med Asperger syndrom berättar om när de talar om hur de upplever sitt liv före och efter att de har fått diagnosen. Vår avsikt är att kritiskt resonera kring hur identitetskapande påverkas och hur normalitet kan hanteras och upplevas av några människor med denna diagnos.  Studien har resulterat i ett resonemang kring hur diagnosen kan förstås dels som en förutsättning för att få de hjälpmedel dessa människor behöver för att leva ett normalt liv, dels vad just normalitet innebär och hur detta kan förstås påverka dessa människor utifrån de tre normativa aspekterna för identitetskapande. Vi menar att det är viktigt att kritiskt förhålla sig till vad som betraktas som normalt. Vidare att det behövs en förståelse för vad denna normalitet innebär och upplevs som av människor som avviker eller inte uppfyller de normativa kraven i det samhälle som de lever i.

Personer med en neuropsykiatrisk funktionsnedsättning kan ha olika svårigheter som påverkar de dagliga aktiviteterna i vardagen. Aktivitetsbalans är ett begrepp som ofta används inom arbetsterapi och beskriver en individs uppfattning av att ha en tillfredsställande mängd av aktiviteter och rätt variation mellan olika aktiviteter. Det förekommer inga studier om aktivitetsbalans kopplat till personer med en neuropsykiatrisk funktionsnedsättning vad författarna har noterat. Syftet med examensarbetet var att beskriva den självskattade aktivitetsbalansen hos vuxna personer med en neuropsykiatrisk funktionsnedsättning. Den metod som användes var en kvantitativ icke – experimentell tvärsnittsstudie. Totalt deltog 55 personer i åldrarna 18-65 år. Rekryteringen skedde via bekvämlighetsurval. Data insamlades med hjälp av en enkät som innehöll instrumentet Occupational Balance Questionnarie (OBQ) samt några bakgrundsvariabler. För sammanställning av insamlad data har deskriptiv och använts. Resultatet visade att respondenterna skattade sin aktivitetsbalans lågt. Det förekom ingen signifikant skillnad i aktivitetsbalansen i förhållande till bakgrundsvariablerna kön, ålder, boendesituation, hemmaboende barn eller lönearbete. Resultatet visar att det finns ett ökat behov av arbetsterapi för att hjälpa personer med neuropsykiatriska funktionsnedsättningar att strukturera sin vardag. Då resultaten inte kan generaliseras till en större population, rekommenderar författarna ytterligare forskning kring aktivitetsbalans hos vuxna personer med en neuropsykiatrisk funktionsnedsättning. / Persons with neuropsychiatric disabilities can experience difficulties that can have significant impact on the activities of daily life. Occupational balance is a frequently used concept in occupational therapy, describing an individual’s perception of having the satisfactory amount of occupation and the right variation between occupations. There are currently no studies addressing the occupational balance rates in adults with neuropsychiatric disabilities. The aim of this study was to describe the self-reported occupational balance in adults with neuropsychiatric disabilities. This quantitative non- experimental cross-sectional study comprised a convenience sampling of 55 participants (age range 18-65 years). Data were collected from a self-rating questionnaire that contained the instrument Occupational Balance Questionnaire (OBQ) and some background variables. Descriptive statistics were used to compile the results. The results show that the participants rated their activity balance as low. Moreover no significant difference was found in the occupational balance when normalized to: gender, age, housing, child dependency and employment. These results imply that an increased utilization of occupational therapy might be beneficial for people with neuropsychiatric disabilities. The authors conclude that further research is required to more fully evaluate the rate of occupational balance in adults with a neuropsychiatric disability.

Correlations between neuropsychiatric symptoms and beta-amyloid (Aβ) burden in specific brain regions in living Alzheimer’s disease (AD) patients remain to be elucidated. Ten mild AD patients underwent MR and [11C]SB-13 PET imaging. Neuropsychiatric symptoms were quantified with the Neuropsychiatric Inventory (NPI). NPI-depression/dysphoria, -apathy, -agitation/aggression, -anxiety, and -appetite/eating disorders scores were hypothesized to correlate with Aβ burden in particular brain regions. Pearson’s correlation coefficient revealed that depression/dysphoria scores positively correlated (p<0.05) with standardized uptake values (SUVs) from left medial temporal lobe (r=0.67), and agitation/aggression correlated with SUVs from bilateral anterior cingulate (right, r=0.71; left, r=0.78), temporal (right, r=0.71; left, r=0.75), parietal (right, r=0.77; left, r=0.81), and dorsolateral prefrontal cortex (right, r=0.74; left, r=0.73). However, NPI scores did not significantly correlate with better estimates of Aβ burden that use the cerebellum as reference region. Overall, our results confirm the lack of association between Aβ burden and neuropsychiatric symptoms reported in autopsy studies.

Correlations between neuropsychiatric symptoms and beta-amyloid (Aβ) burden in specific brain regions in living Alzheimer’s disease (AD) patients remain to be elucidated. Ten mild AD patients underwent MR and [11C]SB-13 PET imaging. Neuropsychiatric symptoms were quantified with the Neuropsychiatric Inventory (NPI). NPI-depression/dysphoria, -apathy, -agitation/aggression, -anxiety, and -appetite/eating disorders scores were hypothesized to correlate with Aβ burden in particular brain regions. Pearson’s correlation coefficient revealed that depression/dysphoria scores positively correlated (p<0.05) with standardized uptake values (SUVs) from left medial temporal lobe (r=0.67), and agitation/aggression correlated with SUVs from bilateral anterior cingulate (right, r=0.71; left, r=0.78), temporal (right, r=0.71; left, r=0.75), parietal (right, r=0.77; left, r=0.81), and dorsolateral prefrontal cortex (right, r=0.74; left, r=0.73). However, NPI scores did not significantly correlate with better estimates of Aβ burden that use the cerebellum as reference region. Overall, our results confirm the lack of association between Aβ burden and neuropsychiatric symptoms reported in autopsy studies.