Yes / A global response to Covid‐19 pandemic has triggered issues related to stress and social restrictions; thus, mental health is seen as a particular area of concern for social well‐being for both policymakers and corporate regulators/companies. Given that mental health intersects with most, if not all, of the 17 sustainable development goals (SDGs), this research brought to light issues surrounding employment of people with mental disabilities (PWMDs) and the financial merits of employing them. An online survey was administered to PWMDs to elicit what possible flexible opportunities could enable them to gain or stay at work. Interviews were also conducted with human resource managers and financial managers. Our results show that there are currently no flexible working opportunities available for PWMDs, which could enable them work effectively to improve both self and general economic growth.

Bakgrund: Patienter med bipolär sjukdom drabbas i högre grad än övriga befolkningen av metabolt syndrom och metabol kartläggning med tillhörande hälsosamtal genomförs för att minska denna risk. Syfte: Syftet med studien var att belysa erfarenheter hos patienter med bipolär sjukdom beträffande hälsosamtal och dess betydelse för välbefinnandet i samband med metabol kartläggning. Metod: Studien genomfördes som en intervjustudie med 8 respondenter och materialet bearbetades genom kvalitativ innehållsanalys. Resultat: Resultatet visar att hälsosamtal i samband med metabol kartläggning skapar trygghet på olika sätt där den fysiska och psykiska hälsan beaktas samtidigt vilket får betydelse för välbefinnandet. Det är betydelsefullt att de egna behoven tillgodoses och medvetenhet och kunskap om livsstilens betydelse för hälsan finns hos patienterna. Två tema framträdde genom analysen: De individuella behoven uppmärksammas och kunskap ger ökad medvetenhet. Slutsats: Fokus bör inriktas på att stärka tryggheten som hälsosamtal i samband med metabol kartläggning medför samt beakta varje enskild patients behov och egen kunskap för att med respekt kunna främja och stärka hälsoprocessen mot välbefinnande. Den breda kunskap som patienterna besitter bör litas till för att tillsammans kunna arbeta mot en mer hälsosam livsstil och på så sätt främja både det fysiska och psykiska välbefinnandet. / Background: Individuals with bipolar disorder are more likely than others to be affected by metabolic syndrome which is why monitoring for metabolic anomalies and health conversations is part of treatment and can reduce the risk. Purpose: The purpose of this study was to shed light on experiences of the health conversation and its meaning for the wellbeing for individuals with bipolar disorder as part of the metabolic monitoring. Method: The study was conducted as a qualitative study with 8 individuals taking part in interviews and qualitative content analysis was used to process the data. Results: The results show that health conversations as part of metabolic monitoring can provide a sense of security taking into account both the physical and mental health which proves to be meaningful to the sense of wellbeing. To accommodate individual needs proves to be important and meaningful and individuals with bipolar disorder have both awareness and knowledge concerning the importance of a healthy lifestyle. Two themes emerged from the analysis: Highlighting individual needs and Knowledge increases awareness. Conclusion: Focus should be on strengthening the sense of security contributed by metabolic monitoring and health conversations and taking into account the needs and knowledge of each individual and with respect encourage and strengthen the experience of health and wellbeing. We need to put trust into the patients’ ability and knowledge and work together towards a healthier lifestyle thus supporting both the physical and mental wellbeing.

Hintergrund: Die Behandlung von Menschen mit psychischen Störungen stellt seit Jahrzehnten ein sowohl bedeutsames Versorgungssegment als auch Forschungsgebiet dar. Die im Gesundheitswesen in den letzten 20 Jahren aufkommende Haltung hin zu einer stärkeren Patientenorientierung rückt Patienten als Nutzer von Leistungen der Gesundheitsversorgung und „Experten in eigener Sache“ in den Mittelpunkt des Geschehens (Coulter & Magee, 2003). Damit wird den expertenbasierten Therapieleitlinien ein wichtiger Akteur, der Betroffene selbst, gegenübergestellt. Die Entwicklung bisheriger Leitlinien fußt auf der Beurteilung der methodischen Studienqualität sowie relevanter Therapieoutcomes, die ausschließlich von Experten vorgenommen wird. Patienteneinschätzungen werden dabei bisweilen nicht integriert, obwohl gerade durch der Einbezug von Präferenzen, Vorstellungen und Wünschen der Patienten eine wesentliche Grundlage für optimale klinische Therapieentscheidungen darstellt (Haynes, Devereaux & Guyatt, 2002). Eine verstärkt patientenorientierte Haltung hätte damit Auswirkungen auf a) die klinische Versorgungspraxis und b) die Forschung. Der Weg einer gleichberechtigten Kommunikation und gemeinsamen Entscheidungsfindung von Behandler und Patient über Behandlungsstrategien und die Auswahl von Therapieoptionen verbessert potentiell Compliance, Selbstmanagement und Zufriedenheit der Patienten. Fragestellungen: Die vorliegende kumulative Promotionsarbeit (drei peer-reviewed Publikationen) setzt den Kerngedanken der Patientenorientierung um, indem Methoden zur patientenorientierten Forschung erprobt, durchgeführt und hinsichtlich ihrer Nützlichkeit diskutiert sowie empirische Erkenntnisse zur Bedeutung von Patientenpräferenzen in der Gesundheitsversorgung beigesteuert werden. Drei Fragestellungen stehen dabei im Fokus: 1) Wie gut lassen sich Conjoint-Analysen zur patientenorientierten Forschung im Rahmen der Versorgung von psychischen Störungen einsetzen (Beitrag I)? 2) Welche Therapieziele sind bipolar Betroffenen in der Behandlung bipolarer Störungen besonders wichtig (Beitrag II)? 3) Kann mithilfe eines komprimierten achtsamkeitsorientierten Verfahrens ein Beitrag zur Verbesserung der Versorgung der Allgemeinbevölkerung sowie zur Überbrückung langer Wartezeiten auf eine ambulante Psychotherapie geleistet werden (Beitrag III)? Methode: Die methodische Umsetzung einer patientenorientierten Forschung wird anhand des Beispiels der Conjoint-Analyse zur Messung von Patientenpräferenzen für spezifische Therapieziele dargestellt. Die inhaltlichen Beiträge setzen sich aus zwei Studien zur Behandlung einer schweren chronischen psychischen Erkrankung (bipolare Störung) und einer Untersuchung zur Förderung der psychischen Gesundheit (Stressbewältigung, Depressivität, Lebensqualität) im Beratungssetting zusammen. Ergebnisse: Die vorliegende Arbeit stellt zum einen mit der Conjoint-Analyse einen innovativen Ansatz zur Messung von Patientenpräferenzen zu Therapiezielen im Rahmen der Versorgung psychischer Störungen dar (patientenorientierte Forschung). Dazu werden bisherige conjoint-analytische Untersuchungen mittels formaler, methodischer und inhaltlicher Merkmale systematisiert und hinsichtlich Nützlichkeit sowie möglichen Grenzen diskutiert. Zum zweiten liefert die Arbeit Erkenntnisse hinsichtlich der von Patienten eingeschätzten Relevanz und Präferenz von Therapiezielen in der Behandlung bipolarer Störungen. Dabei wird ausgewiesen, worin Unterschiede in den Einschätzungen bestehen und diskutiert, welche Relevanz sich für die Versorgung von Menschen mit bipolaren Störungen ergibt. Zum dritten werden Effekte (Verbesserung der Stressbewältigung, Verringerung der Depressivität, Steigerung der Lebensqualität) eines im Rahmen der psychosozialen Beratungsstelle der TU Chemnitz angewandten achtsamkeitsorientierten Stresstrainings (AST) dargestellt. Die mit einer achtsameren Haltung von Trainingsteilnehmern einhergehenden verbesserten Werte bezüglich Stressverarbeitung, Depressivität und Lebensqualität (patientennaher Endpunkt) deuten auf das Potential von AST hin, als niedrigschwelliges Angebot der psychosozialen Beratung bestehende Versorgungsangebote (Überbrückung von Therapiewartezeit) zu ergänzen. AST stellt einen Ansatz zur patientenorientierteren Ausrichtung von Wartezeitüberbrückung dar, da objektiv sehr lange Wartezeiten auf einen Psychotherapieplatz bestehen und Patienten selbst darin Versorgungsbarrieren sehen. Eine Überbrückung würde Patienten entlasten und psychische Gesundheit bereits vor dem Beginn der Psychotherapie stabilisieren. Diskussion: Patientenorientierte Forschung liefert Beiträge zur Ergänzung bisheriger Erkenntnisse in der Versorgung von Menschen mit psychischen Störungen. Die Befunde zeigen, dass Vorstellungen und Wünsche von Betroffenen nicht immer deckungsgleich mit Expertensichtweisen sind und im Rahmen von Prozessen des Shared Decision Makings Beachtung finden sollten, um eine individuell ausgerichtete Behandlung zu erzielen. Die Conjoint-Analyse als methodischer Ansatz zur Messung von Patientenpräferenzen weist sowohl Nutzen (hohe interne Validität der Messungen) als auch Grenzen auf (geringe externe Validität). Um eine möglichst hohe Generalisierbarkeit der Ergebnisse zu gewährleisten, ist notwendig, die untersuchten Zieldimensionen a priori nach klinischer Praxistauglichkeit auszuwählen. Patientenorientierte Forschung ermöglicht eine gemeinschaftlichere Basis sowohl auf Mikro- (Arzt-Patient-Kommunikation) als auch auf Mesoebene (patientennähere Leitlinien).

Despite the association between hippocampal atrophy and a vast array of highly debilitating neurological diseases, such as Alzheimer’s disease and frontotemporal lobar degeneration, tools to accurately and robustly quantify the degeneration of this structure still largely elude us. In this thesis, we firstly evaluate previously-developed hippocampal segmentation methods (FMRIB’s Integrated Registration and Segmentation Tool (FIRST), Freesurfer (FS), and three versions of a Classifier Fusion (CF) technique) on two clinical MR datasets, to gain a better understanding of the modes of success and failure of these techniques, and to use this acquired knowledge for subsequent method improvement (e.g., FIRSTv3). Secondly, a fully automated, novel hippocampal segmentation method is developed, termed Fast Marching for Automated Segmentation of the Hippocampus (FMASH). This combined region-growing and atlas-based approach uses a 3D Sethian Fast Marching (FM) technique to propagate a hippocampal region from an automatically-defined seed point in the MR image. Region growth is dictated by both subject-specific intensity features and a probabilistic shape prior (or atlas). Following method development, FMASH is thoroughly validated on an independent clinical dataset from the Alzheimer’s Disease Neuroimaging Initiative (ADNI), with an investigation of the dependency of such atlas-based approaches on their prior information. In response to our findings, we subsequently present a novel label-warping approach to effectively account for the detrimental effects of using cross-dataset priors in atlas-based segmentation. Finally, a clinical application of MR hippocampal segmentation is presented, with a combined MR-PET analysis of wholefield and subfield hippocampal changes in Alzheimer’s disease and frontotemporal lobar degeneration. This thesis therefore contributes both novel computational tools and valuable knowledge for further neurological investigations in both the academic and the clinical field.

AbstraktTitel: Upplevelser av att leva med en person med bipolär sjukdom - ett familjeperspektiv – En litteraturstudie. Bakgrund: Psykisk ohälsa och sjukdom är idag så vanligt förekommande att det räknas som ett folkhälsoproblem, men det finns fortfarande fördomar och stigmatisering kvar kring bilden av psykisk ohälsa. Ofta är det närstående som vårdar sina psykiskt sjuka anhöriga och sjukvårdspersonal behöver bli bättre på att möta närstående i vården och ta tillvara på deras kompetens och kunskap. Inom psykiatrin har det visat sig att närstående fortfarande kan känna sig utanför och att de upplever sig inte blir sedda av personalen. Det är viktigt att alla parter blir integrerade i vårdarbetet kring den sjuke och att det krävs samarbete mellan närstående och sjukvårdspersonalen. Syfte: Syftet med denna studie var att beskriva upplevelser av att leva med en person med bipolär sjukdom ur ett familjeperspektiv. Metod: Litteraturstudie genomfördes med åtta artiklar, vilka alla hade kvalitativ ansats. Artiklarna valdes ut utifrån ett helikopterperspektiv, granskades och analyserades för att slutligen sammanställas. Resultat: Resultatet presenteras med tre huvudkategorier och nio subkategorier som i stort speglar närståendes upplevelser av att leva med person med bipolär sjukdom. De tre huvudkategorierna är; isolering och frustration, bemötande och stöd samt anpassning och glädje.  Konklusion: Att som närstående vårda sin närstående med bipolär sjukdom kan innebära en stor börda samtidigt som de uttrycker att de vill vara den som vårdar sin närstående. Många uttrycker djup stolthet och kärlek till sin sjuke närstående och de vill finnas där och ställa upp för denne. Negativa konsekvenser för många närstående är att de ofta upplever isolering och ensamhet. Stöd från andra närstående eller vänner ses som värdefullt för att orka med situationen och stöd från sjukvården är viktigt för att kunna stärka närståendes möjligheter att på bästa sätt hantera livssituationen och att familjen får tillgång till lämplig vård och behandling.   Nyckelord: bipolär sjukdom, upplevelse, närstående, erfarenhet, vårdgivare, syskon, föräldrar, kvalitativ, partner, familj, uppfattning / AbstractTitel: Experiences of living with a person with bipolar disorder from a family perspective - A literature review. Background: Psychiatric illness and psychiatric disease is a major part of the public disease and it´s a common health problem today, but there are still existing prejudice and stigmatization towards psychiatric health problems. Today it´s common that relatives has the role of caregivers to the mentally ill person and the mental health professionals has to become more open minded towards the relatives and see their competence and knowledge about their ill family member. Within the psychiatric care relatives often experience a feeling of exclusion from the staff and they also experience that the health caring staff doesn´t take notice of them. It´s important to integrate all concerned into the care of the mentally ill person and interaction between healthcare staff and relatives are of great importance. Aim: The aim of this literature review was to explain how relatives experience living with a person with bipolar disorder from a familyperspective. Methods: The literature review was conducted from eight articles with qualitative approach. They were chosen from a helicopter perspective, examined, analyzed and finally compiled. Results: The result was presented in three main categories and nine subcategories which represents the experiences relatives to a person with bipolar disorder has. The three main categories was; isolation and frustration, treatment and support, adaptation and happiness.     Conclusion: Taking care of a person with bipolar disorde can be a great burden for relatives, but at the same time many relatives mean that they are the ones who want to take care of them. Many relatives express feelings like love and pride to the ill person and they want to be there for them.  Negative consequences  are that they often experience isolation and loneliness. Support from other family members or friends are importent so that they may be able to cope with the situation. Professional support is also of great important to strengthen the relatives to be able to handle their life and their situation and that the family will receive proper care and treatment.  Keywords: “bipolar disorder”, “bipolar disease”, caregiver, relative*, partner, parent, sibling, family, perspective, experience*, perception, qualitative

Objectifs: Les études quantitatives ont documenté l’ampleur des problèmes d’observance en début de psychose et les conséquences cliniques qui en découlent. La compréhension du phénomène demeure toutefois limitée. Notre étude propose d’explorer, à partir de trois perspectives (celles des patients, des proches et des cliniciens), les raisons pour lesquelles les patients en début de psychose acceptent ou refusent les traitements. Méthode: La collecte des données s’est faite à l’aide d’entrevues individuelles semi-structurées auprès de 18 patients d’une clinique spécialisée en psychose débutante classifiés comme étant observants, ambivalents ou non observants, et auprès de 13 de leurs proches, ainsi qu’à l’aide d’un focus group réunissant 8 cliniciens de la clinique. Résultats: L’observance semble s’inscrire dans un processus marqué par une certaine ambivalence pour la plupart des sujets. Cette ambivalence est modulée par: des enjeux identitaires, des enjeux relationnels, la compréhension du diagnostic et la signification du traitement. Conclusion: L’ambivalence et l’inobservance seraient des étapes normales du processus au cours duquel le patient lutte pour reconstruire son identité. La présence d’un lien de confiance permet la résolution progressive de l’ambivalence, facilitant ainsi le processus de réappropriation du traitement par le patient. / Objective: Quantitative studies have documented the extent of compliance issues in early psychosis and the ensuing clinical consequences. However, an in-depth understanding of this phenomenon remains limited. Drawing upon the perspectives of a sample of patients, their families, and clinicians, this study explores why patients suffering from early-stage psychosis accept or refuse treatment. Method: Data collection was conducted using semi-structured individual interviews with 18 patients from a clinic specializing in early psychosis who were identified as compliant, ambivalent or non-compliant. In addition, interviews were conducted with 13 of their family members, as well as a focus group composed of 8 clinicians working at the clinic. Results: For the majority of patients, compliance appeared to evolve according to a process characterized by varying degrees of ambivalence. In particular, identity issues, relational issues, the understanding of the diagnosis, and the meaning of treatment were key to understanding patients’ sense of ambivalence. Conclusion: Ambivalence and non-compliance can be seen as normal stages of a process whereby the patient struggles to rebuild his or her sense of self and constructs their ongoing identity. A relationship of trust may facilitate a gradual resolution of the ambivalence, promoting a patient’s sense of ownership and empowerment in the context of treatment.

Bipolar disorder is a serious illness affecting approximately 2-4% of the population and is one of the world’s leading causes of disability. In individuals with bipolar disorder, medical comorbidity associated with cardiovascular, respiratory and endocrine disorders is related to increased rates of mortality. Recent updates to multi-system inflammatory related conceptualizations of bipolar disorder focus on the unique power that medical illness and biological processes may play as factors associated with course and outcome in bipolar disorder. The current study examined medical comorbidity and its associations with various demographic and psychological variables in individuals with bipolar disorder, schizophrenia, and major depressive disorder with psychotic features followed for 10 years from their first hospital admission. When compared to an age, gender and race-matched control sample from the population, those with bipolar disorder had significantly higher medical comorbidity across a range of medical diagnoses both at 6 months and 10 years after first hospital admission. Ten years following initial hospitalization, individuals in all three diagnostic groups reported increased rates of diabetes (OR: 2.0 – 3.7), stroke (OR: 4.6 – 7.0) and asthma (OR: 1.9 - 3.1), and individuals with bipolar disorder reported increased rates of cancer (OR = 2.1). A number of psychological and demographic symptoms were examined for their ability to predict the development of medical illness across the assessment interval. Overall rates of medical illness were elevated both early in illness course and 10 years after diagnosis, suggesting that broad sequelae of multi-system inflammation are present early and progress over time.

O Transtorno de Humor Bipolar (THB) acomete até 3% dos adultos e os filhos desses pacientes constituem uma população em risco para o desenvolvimento de transtornos psiquiátricos. No entanto, faltam marcadores que permitam a identificação precoce dos indivíduos que apresentam maior vulnerabilidade para o desenvolvimento de psicopatologia. Estudos preliminares com Ressonância Magnética (RM) indicaram que alterações em substância branca estariam presentes não apenas em pacientes em episódio de alteração de humor, mas também em pacientes eutímicos e em seus familiares saudáveis, sugerindo que tais alterações poderiam constituir um endofenótipo potencial deste transtorno. A Imagem por Tensor de Difusão (Diffusion Tensor Magnetic Resonance Imaging - DT-MRI) é uma aquisição de RM que permite análise mais completa e detalhada das características da substância branca cerebral que a RM tradicional. A investigação de alterações na estrutura cerebral, particularmente de substância branca, de jovens portadores de THB não medicados e familiares saudáveis criteriosamente avaliados pode ajudar a elucidar a neurobiologia subjacente ao THB e, conseqüentemente, a identificar marcadores de vulnerabilidade ao transtorno. Objetivo: Avaliar se havia alterações em substância branca em crianças e adolescentes com THB e crianças e adolescentes filhos saudáveis de portadores de transtorno do humor bipolar quando comparados a controles saudáveis, utilizando a técnica de neuroimagem de DTMRI. Nossas hipóteses eram que jovens com THB e filhos de pacientes com THB, quando comparados a controles saudáveis, apresentariam (i) diminuição da fração de anisotropia (FA) e (ii) essas alterações seriam mais pronunciadas em crianças acometidas por THB do que em crianças saudáveis filhas de pacientes com THB. Métodos: Obtivemos imagens de DT-MRI de boa qualidade de 16 crianças e adolescentes com THB (média de idade ± D.P.= 12,7 ± 2,5 anos), 15 filhos saudáveis de pacientes com THB tipo I (média de idade ± D.P.= 13,5 ± 2,7 anos) e 15 controles saudáveis (média de idade ± D.P.= 13,5 ± 2,5 anos). Os diagnósticos foram formulados de acordo com os critérios do DSM-IV, usando as entrevistas Kiddie-SADS-PL (crianças) e Structured Clinical Interview for DSM-IV (adultos). A RM foi realizada em um scanner Philips 3,0 Tesla, com os seguintes parâmetros de aquisição: TR = 6106,0 ms, TE = 65,0ms, FOV = 224x224mm, espessura de corte = 2.0mm, sem gap, matriz de aquisição = 112x112 pixels e 3 médias, resultando em tamanho de voxel isotrópico = 2,0x2,0x2,0mm. As imagens de DTI foram pré-processadas com programas oriundos do FMRIB\'s software library (FSL), de acordo com o pipeline sugerido para o processamento de substância branca com Tract-Based Spatial Statistics (TBSS) e análise estatística com o programa Randomise (ambos integrantes do FSL). Resultados: Os grupos não diferiram em idade, gênero, grau de puberdade ou QI. Valores de FA de pacientes pediátricos com THB foram significativamente menores em relação aos de controles saudáveis (p < 0,05, corrigido para múltiplas comparações) em um cluster de 695 voxels no hemisfério direito que abrange a porção superiora da corona radiata e o corpo do corpo. Não houve diferença significativa entre pacientes com THB e filhos saudáveis de pacientes com THB, ou com filhos saudáveis de pacientes com THB e controles saudáveis. Discussão: Nossos dados corroboram a literatura de diminuição de FA em crianças e adolescentes com THB e avançam em mostrar esta alteração em pacientes não medicados. Mas nossos resultados não apoiam a hipótese de alterações em substância branca como endofenótipo de THB. Estudos de seguimento com amostras maiores e rigorosamente caracterizadas são necessários para se elucidar o papel das alterações em substância branca no THB. / Up to 3% of adults are affected with Bipolar Disorder (BD) and the offspring of these patients constitute a population at risk for the development of psychiatric disorders. Nevertheless, there are still no vulnerability markers to allow the early identification of those who are at greater risk of developing psychopathology among this population. Preliminary data indicate that white matter abnormalities may precede the disease onset and be present even in unaffected relatives - suggesting they could be further explored as an endophenotype for BD. Diffusion Tensor Magnetic Resonance Imaging (DTMRI) is an MRI acquisition that allows a thorough and detailed analysis of brain white matter characteristics. The investigation of white matter alterations in young, nonmedicated, BD patients and healthy relatives may help us understand the underlying neurobiology of BD. Objectives: evaluate white matter alterations in children at-risk and with BD using DT-MRI. Our hypothesis were that BD offspring, compared to healthy controls, would exhibit (i) reduced fractional anisotropy (FA) and (ii) these alterations would be more pronounced in children with BD than in those at-risk. Methods: We successfully scanned 16 BD patients (mean age ± S.D.= 12,7 ± 2,5 years) 15 healthy offspring with at least one parent with BD I diagnosis (mean age ± S.D.= 13,5 ± 2,7 years) and 15 healthy controls (mean age ± S.D.= 13,5 ± 2,5 years) with no history of psychiatric disorder in first-degree relatives. Psychiatric diagnosis were established according to the DSM-IV criteria, using the Kiddie-SADS-PL interview (children) and Structured Clinical Interview for DSM-IV (adults). The MRI was conducted at a 3.0 Tesla Philips scanner. Acquisition: the parameters were TR = 6106,0ms, TE = 65,0ms, FOV= 224x224mm, slice thickness = 2.0mm/no gap, matrix acquisition = 112x112 pixels, 3 averages, resulting in an isotropic voxel = 2,0x2,0x2,0 mm. DT-MRI images were preprocessed according to do FMRIB\'s software library\'s (FSL) pipeline for Tract-Based Spatial Statistics\' (TBSS) and Randomise analyses. Results: Groups did not differ in age, gender or pubertal status. Voxelwise analyses showed significant differences in FA values between BD patients and healthy controls (p < 0,05, FDR corrected for multiple comparisons) in a 695 voxels cluster comprising right corona radiata and corpus callosum . Discussion: This study was the first to evaluate a sample of non-medicated BD children and adolescents with DT-MRI and it corroborates extant literature data of lower FA in BD children compared to healthy controls. Nevertheless, our data do not support white matter alterations as an endophenotype for BD. More studies, with larger and well characterized samples are necessary to advance our understanding of the role of white matter alteration in BD.

INTRODUÇÃO: O transtorno afetivo bipolar (TAB) e o transtorno obsessivocompulsivo (TOC) estão entre as dez condições médicas mais incapacitantes. No entanto, suas bases neurobiológicas são ainda desconhecidas. Os estudos postmortem podem dar uma boa contribuição para o entendimento da fisiopatologia desses transtornos, pois permitem a comparação das alterações celulares, citoarquitetônicas e moleculares com as manifestações clínicas, além de auxiliarem numa melhor compreensão dos achados dos estudos de neuroimagem. OBJETIVOS: Comparar a densidade neuronal, volume e número total de neurônios do córtex orbitofrontal (COF) e suas sub-regiões: antero-medial (AM), médio-orbitofrontal (MO) e antero-lateral (AL) entre casos psiquiátricos e controles; Verificar se há diferenças de densidade neuronal, volume e número total de neurônios do COF entre os casos de TAB e casos de TOC e controles. MÉTODOS E CASUÍSTICA: 17 encéfalos de indivíduos acima de 50 anos foram coletados, diagnosticados e submetidos a análises estereológicas, sendo três indivíduos acometidos por TAB, sete indivíduos acometidos por TOC e sete controles saudáveis pareados por idade, gênero e hemisfério cerebral analisado. Um hemisfério foi fixado por perfusão com formalina 20% e processado para estudos neuroestereológicos, enquanto o outro teve as 45 regiões de interesse dissecadas e congeladas a -80ºC para futuros estudos moleculares. RESULTADOS: O COF e suas sub-regiões apresentaram menor densidade neuronal no grupo total de casos vs. controles (p < 0,05). No entanto, não houve diferença em relação ao volume. A subregião MO apresentou um número menor de neurônios nos casos que em controles (p < 0,05). Curiosamente, na análise de densidade neuronal das camadas corticais, apenas a camada IV não apresentou diferença estatisticamente significante entre casos e controles. CONCLUSÕES: Nossos achados mostram que alterações no COF podem estar envolvidas com a fisiopatologia do TOC ou TAB, e indicam que podem haver interações entre elas e, além disso, concordam com estudos de imagem funcional e de atividades cerebrais na região MO que nos faz refletir que além de uma perda neuronal, há também uma hipoativação e uma redução funcional. Estudos com um número maior de amostras e com diferenciação celular poderão trazer novas contribuições para o entendimento da fisiopatologia desses transtornos neuropsiquiátricos / INTRODUCTION: Bipolar disorder (BD) and obsessive compulsive disorder (OCD) are within the ten medical condition promoving incapacity worldwide. To date, their neuropathological substrates are yet to be disclosed. Postmortem studies designed to estimate cytoarchitectonic and molecular changes for clinical and imaging correlation, have the potencial to undercover pathophysiological aspects of these conditions. OBJECTIVE: Objective: To compare neuronal density, volume and total neuron number of orbitofrontal cortex (OFC) as a whole and divided by sub-regions: anteromedial (AM), medio-orbitofrontal (MO) and antero-lateral (AL) among BD, OCD and matched controls. METHODS: We used 17 postmortem brains sourced from the Psy- BBBABSG. All the subject were older than 50 years and were classified based on clinical evaluation in BD, OCD and healthy control. Subjects were matched by age, gender and brain hemisphere. One hemisphere were perfusion fixed with 20% formalin and used for neuroestereological studies. The second hemisphere had ROIs dissected and snap frozen for future molecular studies. OUTCOMES: Neuron density in OFC and the sub-regions were decreased in cases vs. controls (p < 0,05). This result was observed in cortical layers analyses with exception of layer IV. We did not observed significant changes in volume. The MO sub-region had reduced total neuron number in cases than in controls (p < 0,05). CONCLUSION: Ours results suggest that OFC changes may be part of BD and OCD pathogenesis. These results go in line with functional imaging findings. Further studies with a higher number of cases and adressing specific neuron types are needed

Mesmo quando adequadamente medicados pacientes com transtorno bipolar (TB) apresentam elevadas taxas de recaída, considerável sintomatologia residual e prejuízo funcional. Intervenções psicoterápicas têm sido propostas com intuito de aumentar o período de remissão e reduzir sintomas de humor, porém os achados iniciais ainda são controversos e pouco se sabe sobre a eficácia de tais intervenções em desfechos funcionais. Ao mesmo tempo diversos estudos apontam para um prejuízo cognitivo entre uma parcela significativa destes pacientes que perdura mesmo na fase eutímica. A Neuropsicologia clínica oferece instrumentos para quantificar este prejuízo e melhor compreender os achados de ensaios clínicos em psicoterapia no TB. Diversos autores desenvolveram intervenções de reabilitação cognitiva a fim de melhorar tanto o prejuízo cognitivo e funcional bem como diminuir sintomatologia depressiva, porém os achados até o momento não apresentam evidência de uma eficácia robusta. Dessa forma, novas intervenções psicoterápicas se mostram necessárias. Desenvolvemos um novo protocolo de psicoterapia em grupo baseado na experiência prévia do grupo que objetiva prevenir novos episódios e melhorar a performance cognitiva e funcionalidade dos pacientes com TB. Metodologia: Foram incluídos 60 pacientes neste ensaio clínico cego controlado randomizado com portadores de TB tipo I ou II que se encontravam em uso de tratamento farmacológico padrão. O grupo controle foi mantido apenas em uso de tratamento padrão e o grupo experimental, além desse participou de 12 sessões semanais desta nova intervenção chamada de Reabilitação Cognitivo Comportamental (RCC). Inicialmente todos participantes eram avaliados para presença de episódios de humor, funcionalidade e desempenho cognitivo o que foi repetido após 12 semanas e nove meses do início da fase interventiva, totalizando 12 meses de seguimento. Resultados: Ao todo 39 pacientes fora incluídos nas análises finais e 21 foram excluídos, não havendo diferença entre os grupos para as perdas de indivíduos. Trinta e nove pacientes foram randomizados sendo que 20 participaram das sessões de RCC e 19 mantidos sobre tratamento padrão e todos participaram das reavaliações após o fim das 12 semanas de tratamento, porém o período de 12 meses não foi atingido por todos os participantes e, assim são apresentados os resultados parciais do pós-tratamento. Não houve diferença entre os grupos para tempo até novo episódio de humor bem como nas escalas de funcionalidade e de qualidade de vida. O grupo de RCC melhorou seu desempenho no reconhecimento total de emoções e reduziu seu tempo de reação. Conclusão: A nova intervenção proposta não foi eficaz na prevenção de novos episódios de humor no transtorno bipolar embora pareça melhorar de forma específica alguns domínios cognitivos comumente reportados como prejudicados no TB / Even when correctly medicated patients with bipolar disorder (BD) continue to present high rates of relapse, considerable residual symptomatology and functional impairment. Psychotherapeutic interventions have been proposed aiming to increase the remission period and reduce mood symptoms, however initial results are still controversial and little is known about the effectiveness of such interventions in functional outcomes. At the same time, several studies point to cognitive impairment among a significant portion of these patients that lasts even in the euthymic phase. Clinical Neuropsychology offers tools to quantify this impairment and to better understand the findings of clinical trials in psychotherapy in BD. Authors have developed cognitive rehabilitation interventions to improve both cognitive and functional impairment as well as reduce depressive symptoms, but the findings so far have not provided evidence of robust efficacy. Thus, new psychotherapeutic interventions are needed. We developed a new protocol in group psychotherapy based on previous experience of the group aiming at preventing new episodes and improving cognitive performance and functionality of patients with TB. Method: Sixty patients were included in this randomized controlled clinical trial with type I or II TB patients who were using standard pharmacological treatment. The control group was maintained only on standard treatment and the experimental group, in addition to this, participated in 12 weekly sessions of this new intervention called Cognitive Behavioral Rehabilitation (RCC). Initially all participants were evaluated for episodes of mood, functionality and cognitive performance, which was repeated after 12 weeks and nine months after the beginning of the intervention phase, totaling 12 months of follow-up. Results: A total of 39 patients were included in the final analysis and 21 were excluded, with no difference between groups for the loss of individuals. Thirty-nine patients were randomized, 20 of which participated in RCC sessions and 19 maintained on treatment as usual and all participated in the re-evaluations after the end of the12-week treatment, but the 12-month period has not been reached by all participants and therefore we present the preliminary results of the post-treatment. There was no difference between groups for time to new mood episode as well as for functional and quality of life scales. The RCC group improved their performance in total recognition of emotions and reduced their reaction time. Conclusion: The new proposed intervention was not effective in preventing new mood episodes in bipolar disorder although it seems to improve in a specific way some cognitive domains commonly reported as impaired in TB