Os estudos de alto risco com descendentes de indivíduos portadores de psicoses fornecem uma oportunidade para estudar possíveis características fenotípicas e genéticas que podem estar envolvidas no desenvolvimento destes transtornos. Até o momento as pesquisas sobre a influência da vulnerabilidade genética e o ambiente sobre o comportamento das crianças de risco são escassos e inconclusivos. Objetivo: Revisão dos principais estudos genético-epidemiolólogicos e dos principais achados dos estudos de alto risco para psicose funcional. Revisão dos estudos genético-moleculares dos polimorfismos Ser9Gly (rs6280), VNTRDAT1 (NM_001044.3), Val66Met (rs6265) e 5HTTLPR (- X76753) e estudo de associação destes polimorfismos em mães portadoras de psicose funcional e em seus respectivos filhos. A distribuição destes polimorfismos em quatro características clínicas nos filhos (Síndrome Ansiedade/depressão e Retraimento/depressão do CBCL, atraso escolar e déficit intelectual) foi o objetivo secundário. Métodos: Sujeitos-Mães com esquizofrenia e transtorno afetivo bipolar atendidas no Instituto Psiquiatria do IPq-HCFMUSP e atendidas na Clínica de Ginecologia da mesma Universidade foram convidadas a participar.Para cada mãe, 1 filho foi escolhido, estratificando-se para gênero e idade (6-18 anos). Os entrevistadores eram cegos e aplicaram nas mães SCID (Entrevista Clínica Estruturada para DSM-IV) e GAF (Avaliação Global de Funcionamento) e nas crianças CBCL (Child Behavior Checklist) (Achenbach, 1983) e WASI (Wechsler Abbreviated Scale of Intelligence). Foi avaliado nível socioeconômico baseado em um instrumento utilizado em estudos de populacionais brasileiros (ANEP). As freqüências de polimorfismos da mães foi feita comparando-as segundo o diagnóstico psiquiátrico (Esquizofrenia, Transtorno Afetivo Bipolar e Controles). A análise das características das crianças foi realizado inicialmente segundo o diagnóstico da materno e posteriormente de acordo com possíveis síndromes clínicas que estas crianças apresentaram. A análise de dados foi executada pelo Programa Estatístico SPSS 15.0. Os grupos foram comparados de acordo com características através de Chi-quadrado de Pearson ou do Teste Exato de Fisher, adotando-se valor de significância de 0.05. RESULTADOS: 167 mães (58 com esquizofrenia, 47 com transtorno afetivo bipolar e 62 controles) e seus filhos participaram. Não se observaram diferenças significantes nos alelos e genótipos dos polimorfismos do Ser9Gly, VNTR-DAT1, Val66Met e 5HTTLPR. Houve diferença na freqüência das Síndromes Retraimento/depressão e Ansiedade/depressão no grupo de filhos de mães portadoras de TAB, porém sem associação com os polimorfismos estudados. Uma tendência de associação foi detectada entre homozigose ser9gly e prejuízo mental (p = 0,09) e uma associação entre homozigose 9 e 10 do VNTR-DAT1- (p=0,03) e Síndrome Ansiedade/Depressão nas crianças independente da diagnóstico da materno. CONCLUSÃO: Apesar da limitação do tamanho da amostra, nossos resultados apóiam a viabilidade metodológica dos estudos de risco alto para analise em genética molecular. Futuramente pretende-se explorar os dados encontrados com o aumento da amostra e com a introdução de novas variáveis advindas do segmento desta população. / The high-risk studies involving offspring of parents who developed psychoses provide the opportunity to clarify quantitative trait loci that may underlie liability traits. Until now, the research about the influence of genetic vulnerability and environmental factors on child behavior is scarce and inconclusive. Objective: In this research a review of the findings of previous HR studies in functional psychoses, the analyze polymorphisms distribution of the genes DRD3 (Ser9Gly - rs6280), DAT1 (VNTR-Variable Number of Tandem Repeats - NM_001044.3), BDNF (Val66Metrs6265) and serotonin transporter (5HTTLPR - X76753.2) among functional psychoses women and their offspring and polymorphisms distribution in four clinical characteristics among the offspring (Anxious/Depressed and Withdrawn/Depressed syndromes from CBCL, school delay and low intelligence coefficient) was done. Methods: Outpatient mothers with schizophrenia and bipolar referred from the Psychiatric Institute in Sao Paulo and outpatient mothers referred from the Gynecologic Clinic of the same university. For each mother, one offspring was chosen and stratified by gender and age (6-18 y.o.). Blinded interviewers applied the SCID (Structured Clinical Interview for DSM-IV) and Global Assessment of Functioning Scale (GAF) to the mothers, the Child Behavior Checklist (CBCL) (Achenbach, 1983) and WASI (Wechsler Abbreviated Scale of Intelligence) to the children. Socioeconomic status was evaluated based on a Brazilian standardized instrument used in population studies (ANEP). The polymorphisms distribution among mothers was done comparing the diagnoses (Controls, Bipolar Disorder and Schizophrenia). The analysis of the offspring characteristics was initially done according to mother s diagnosis and later according to likely clinical syndromes these children showed. Data analysis was performed with the Statistical Program for Social Sciences (SPSS - 15.0). The groups were compared according to characteristics using Pearson s Chi-square or Fisher s Exact Test adopting significance value of 0.05. RESULTS: 167 mothers (58 with schizophrenia, 47 with bipolar disorder and 62 controls) participated. No significant difference was observed in the allelic and genotype frequencies in the polymorphisms of the Ser9Gly, VNTR- DAT1, Val66Met- and 5HTTLPR. There was some difference in Anxious/Depressed and Withdrawn/Depressed syndromes frequency in the children from bipolar group, but without association with the polymorphism studied. A tendency of association was detected between homozygosis ser9gly DRD3 and mental impairment (p= 0,09), and an association between homozygosis 9* and 10* of DAT1-VNTR (p=0,03) and Anxious/Depressed in children, regardless of mother s diagnosis. CONCLUSION: Despite of the sample size limitation, our results supported the methodological feasibility of a high-risk study. Hereafter it intends to explore the data found by increasing the sample and introducing new variables from the follow up.

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

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.

Submitted by Geandra Rodrigues (geandrar@gmail.com) on 2018-04-19T13:29:11Z No. of bitstreams: 1 andreluciopintocoelhostroppa.pdf: 19317921 bytes, checksum: f8efcd9a0d197ed526f74c9541ac1634 (MD5) / Approved for entry into archive by Adriana Oliveira (adriana.oliveira@ufjf.edu.br) on 2018-04-19T13:55:45Z (GMT) No. of bitstreams: 1 andreluciopintocoelhostroppa.pdf: 19317921 bytes, checksum: f8efcd9a0d197ed526f74c9541ac1634 (MD5) / Made available in DSpace on 2018-04-19T13:55:45Z (GMT). No. of bitstreams: 1 andreluciopintocoelhostroppa.pdf: 19317921 bytes, checksum: f8efcd9a0d197ed526f74c9541ac1634 (MD5) Previous issue date: 2018-02-08 / Contexto: Apesar do grande número de estudos encontrados na literatura sobre as relações entre religiosidade/espiritualidade e depressão, outros transtornos mentais e doenças físicas, há uma carência de pesquisas acerca do impacto da religiosidade/espiritualidade em pacientes bipolares, notadamente de estudos longitudinais. Objetivos: Investigar as possíveis relações entre diversas dimensões de religiosidade/espiritualidade sobre sintomas de depressão, mania e qualidade de vida em um estudo longitudinal de 24 meses. Métodos: Estudo observacional longitudinal de dois anos acrescido de aspectos qualitativos, com 168 pacientes bipolares ambulatoriais, avaliando dados sócio demográficos, sintomas de mania (Young Mania Rating Scale), depressão (Montgomery–Asberg Depression Rating Scale), religiosidade (Duke Religious Index), coping religioso (Brief RCOPE) e qualidade de vida (World Health Organization Quality of Life–Brief Version). Análises de regressão linear da associação entre indicadores religiosos e variáveis clínicas foram controladas por variáveis sociodemográficas. Resultados: Entre os 158 pacientes reavaliados após dois anos, Coping Religioso Positivo em T1 predisse melhor qualidade de vida em todos os seus quatro domínios: físico (β 10,2; 95%CI; 4,2–16,1), mental (β 13,4; 95%CI; 7,1–19,7), social (β 10,5; 95%CI, 3,6–17,33) e ambiental (β 11,1; 95%CI; 6,2–16,1) em T2, dois anos depois. Coping Religioso Negativo em T1 predisse pior saúde mental (β -28,1; 95%CI; -52,06– -4,2) e ambiental (β -20,4; 95%CI; -39,3– -1,6) em qualidade de vida. Religiosidade Intrínseca em T1 predisse melhor qualidade de vida ambiental (β 9,56; 95%CI; 2,76–16,36) em T2. Coping Religioso Negativo em T1 predisse sintomas maníacos (β 4.1) em T2. Na investigação qualitativa, 88,2% dos sujeitos relataram que sua fé ajudou a lidar com sua doença e o apoio de sua comunidade religiosa em relação ao tratamento foi apontado por 35,3%. Não houve relato de oposição de líderes religiosos ao tratamento. Limitações: Este é um estudo observacional, inferências causais devem ser feitas com cautela. Conclusão: religiosidade/espiritualidade pode influenciar a qualidade de vida de pacientes com transtorno bipolar, mesmo quando em eutimia. Usar religiosidade/espiritualidade (especialmente coping religioso positivo e negativo) em intervenções psicossociais podem contribuir para melhorar a qualidade de vida de pacientes com transtorno bipolar. / Background: Although several studies have examined the relationship between religiosity/spirituality and depression, there is little research examining the effect of religious involvement on the course of bipolar disorder. This study investigated the effects of religious activity and coping behaviors on the course of depression, mania and quality of life in patients with bipolar disorder. Methods: Two-year longitudinal study of 168 outpatients with bipolar disorder. Linear regression was used to examine associations between religious predictors and outcome variables (manic symptoms, depression, and quality of life), controlling for sociodemographic variables. Results: Among the 158 patients reassessed after two years, positive religious coping at T1 (baseline) predicted better quality of life across all four domains: physical (β 10.2, 95%CI, 4.2 - 16.1), mental (β 13.4; 95%CI; 7.1–19.7), social (β 10.5; 95%CI; 3.6–17.33) and environmental (β 11.1; 95%CI; 6.2–16.1) at T2 (2-years later). Negative religious coping at T1 predicted worse mental (β -28.1; 95%CI; -52.06– -4.2) and environmental (β -20.4; 95%CI; -39.3– -1.6) quality of life. Intrinsic religiosity at T1 predicted better environmental quality of life (β 9.56; 95%CI; 2.76–16.36) at T2. Negative religious coping at T1 predicted manic symptoms (β 4.1) at T2. In the qualitative research, 88.2% of the subjects reported that their faith helped to cope with their illness and the support of their religious community regarding the treatment was pointed out by 35.3%, there was no report of opposition of religious leaders to the treatment. Limitations: This is an observational study, causal inferences must be made cautiously. Conclusions: religiosity/spirituality may influence the quality of life of patients with bipolar disorder over time, even among euthymic patients. Targeting religiosity/spirituality (especially positive and negative religious coping) in psychosocial interventions may enhance the quality of recovery in patients with bipolar disorder.

Exploring the cycloid temperament has been attempted throughout the ages by various pioneers in psychiatry, psychology and psychoanalysis. Contemporary psychiatric approaches have estimated that cycloid pathology, most evident as Bipolar Disorder, accounts for more than 1% of the population and is seen as the sixth leading cause of all illnesses. Despite the latter it is remains a desperately understudied area psychologically. Theoretically, BD is known for (1) its complex epidemiology, (2) costly treatment, (3) occupational impairment; (4) its negative interpersonal implications, (5) negative domestic effects, (6) forensic consequences, (7) death due to suicide and accidents, (8) cost in treatment, and finally, and most importantly from a humanistic perspective, (9) BD's diminished quality of life. Given the various realities faced by those suffering from Bipolar disorder the current study aimed at describing, through the use of the Rorschach Comprehensive system (CS), the self and object-representations, as well as the affect experiences of fifty, predominantly Bipolar I inpatients. The patients were selected through opportunity sampling at two provincial psychiatric hospitals in South Africa and included Caucasian, African and Colored respondents. All protocols were administered and scored by trained CS clinicians and re-scored by both the author and supervisor. Fifteen protocols were thereafter randomly assigned to three inter-raters and a high level of inter-rater reliability seemed evident. Given various inherent limitations of the study, that is, (a) a study of limited scope, (b) the heterogeneous nature of the sample and the reliance on opportunity sampling, (c) the small sample size, (d) lack of a control group, and (d) the focus of the study as exploratory-descriptive in nature, basic descriptive statistic were relied upon. Despite the various limitations, the results obtained seemed to hint at the possibility of a Neglected Self, characterised by difficulties in modulating affect in moderation, lack of self-esteem and positive self-regard, difficulties in introspection and self-inspecting behaviour, a general lack of interpersonal comfort and feelings of threat, as well as affectional and representational constriction. The presence of impaired self-regulation and reflection, possible perceptual differences in sensory-affective reactivity and processing, as well as difficulties in representational elaboration and differentiation needs further research and comparison to other psychiatric disorders. Basic therapeutic inferences were also discussed that may support those who treat cycloid patients. / Thesis (PhD)--University of Pretoria, 2012. / Psychology / unrestricted

L’interférence résulte du coût attentionnel provoqué par l’activation simultanée de deux processus cognitifs. Ce phénomène est mesuré par le test de Stroop Couleur qui met en jeu une situation de conflit entre deux dimensions en compétition d’un même stimulus. Les aspects émotionnels de l’interférence sont explorés par le test de Stroop Emotionnel qui évalue le coût attentionnel généré par le traitement de stimuli de valence émotionnelle forte en référence à des stimuli neutres. Une augmentation de l’interférence aux tests de Stroop pourrait être une des caractéristiques des troubles schizophréniques et bipolaires où s’observent un déficit d’inhibition et une dérégulation des émotions, anomalies qui sont particulièrement prononcées au cours des phases aiguës. L’exploration comparative de l’interférence permettrait de mieux différencier ou bien de rapprocher ces pathologies dont la distinction nosographique est discutée. Les objectifs de notre travail étaient : (i) comparer l’interférence dans ses aspects cognitifs et émotionnels dans les troubles schizophréniques et bipolaires, (ii) rechercher les corrélats cliniques de l’interférence aux tests de Stroop et (iii) identifier si l’interférence constitue un facteur de vulnérabilité aux troubles en la mesurant chez des apparentés de premier degré.Méthode : Les performances de patients souffrant de schizophrénie paranoïde (N=30) en phase productive et de manie bipolaire (N=30) ont été comparées à l’aide d’un test de Stroop Couleur et d’un test de Stroop Emotionnel. Les patients souffrant de trouble schizo-affectif étaient exclus. Des apparentés de premier degré non atteints de patients schizophrènes (N=30) et bipolaires (N=30) ont ensuite été comparés à chacun des tests. Des groupes de sujets témoins dépourvus de maladie psychiatrique ont été constitués. Une version carte du test de Stroop Emotionnel en langue française adaptée aux troubles schizophréniques et bipolaires a été spécifiquement élaborée pour inclure des mots paranoïdes (i.e. faisant référence aux idées de persécution), dépressifs, maniaques et neutres, appariés pour la longueur, la familiarité et la fréquence lexicale. Résultats : En phase aiguë, l’interférence cognitive et émotionnelle des patients schizophrènes et maniaques était supérieure à celle des témoins dans toutes les conditions. Au Stroop Couleur, l’effet d’interférence était comparable entre les patients schizophrènes et maniaques et n’était pas corrélé à l’intensité de la symptomatologie. Au Stroop Emotionnel, l’effet d’interférence dans les groupes cliniques était d’autant plus important que la valence émotionnelle faisait référence à la psychopathologie du trouble : les résultats ont montré un biais envers les mots paranoïdes chez les patients schizophrènes et un biais envers les mots maniaques comme dépressifs chez les maniaques. Si, dans le groupe de patients schizophrènes, l’amplitude de l’interférence paranoïde était corrélée à l’intensité des symptômes positifs, aucune corrélation n’a été observée entre les biais émotionnels et la symptomatologie dans le groupe des patients maniaques. Les performances des apparentés de premier degré des patients schizophrènes étaient inférieures à celles des témoins au Stroop Couleur, tandis que les apparentés de premier degré des patients maniaques montraient un biais envers les stimuli dépressifs.Conclusion : L’augmentation de l’interférence au test de Stroop Couleur pourrait être un marqueur de vulnérabilité commun aux troubles schizophréniques et bipolaires dont l’expression varie quantitativement avec l’expression phénotypique et la phase de la maladie. Cette anomalie pourrait se manifester de manière plus prononcée dans les troubles schizophréniques que bipolaires. Aucun corrélat clinique spécifique n’a été identifié. L’exploration des substrats cérébraux de l’effet d’interférence a permis d’identifier dans les deux pathologies un dysfonctionnement du cortex cingulaire antérieur (CCA), structure centrale dans la régulation de l’attention. En outre, une implication plus spécifique du cortex préfrontal v / Entral a été montrée dans le trouble bipolaire, témoignant des troubles de la régulation motivationnelle et affective présents dans cette pathologie. Au test de Stroop Emotionnel, les patients souffrant de schizophrénie et de trouble bipolaire présentent un biais envers les informations relatives à la psychopathologie spécifique de leur trouble. Dans la schizophrénie, le biais envers les informations relatives aux thèmes paranoïdes pourrait être impliqué dans le maintien ou le développement des symptômes productifs ; ce phénomène serait principalement déterminé par des facteurs d’état. Dans le trouble bipolaire, l’interférence émotionnelle pourrait traduire l’impact de l’hyperréactivité émotionnelle sur les processus d’inhibition cognitive ; de nombreux arguments suggèrent que l’interférence émotionnelle constitue un marqueur de vulnérabilité à cette pathologie. / Interference results from the attentional cost caused by the simultaneous activation of two cognitive processes. This phenomenon is measured by the Stroop Colour-Word Test that involves a situation of conflict between two dimensions in competition within the same stimulus. The emotional aspects of interference are explored by the Emotional Stroop Test, which assesses the attentional cost stemming from the processing of emotionally-valenced stimuli in reference to neutral ones. Increased Stroop interference could characterize both schizophrenic and bipolar disorders that share inhibitory deficit and emotional dysregulation, especially during acute phases. The comparative measure of interference would help to better understand the differences between these disorders whose nosographic distinction is discussed. Our objectives were: (i) to compare cognitive and emotional interference between schizophrenic and bipolar disorders, (ii) to seek the clinical correlates of interference and (iii) to identify whether interference is a marker of vulnerability to both disorders by measuring it among unaffected first degree relatives. Methods: Patients suffering from paranoid schizophrenia, acute phase (N=30) and bipolar disorder, manic phase (N=30) were compared while performing a Stroop Colour-Word Test and an Emotional Stroop Test. Patients with schizo-affective disorder were excluded. Unaffected first-degree relatives of schizophrenic (N = 30) and bipolar patients (N = 30) were then compared to each of these tests. Healthy subjects served as controls in both experiment. A French version of the Emotional Stroop Test adapted to schizophrenic and bipolar disorders was previously constructed; it included paranoid (i.e. referring to persecutory delusions), depressive, manic and neutral words matched for length, familiarity and lexical frequency.Results: Schizophrenic and manic patients showed greater cognitive and emotional interference than controls in each condition. There were no significant differences between schizophrenic and manic patients at the Stroop Colour-Word Test and their performances were not correlated with symptoms. At the Emotional Stroop Test, the interference effect in the clinical groups was greater when the emotional valence of the stimuli was related to the specific psychopathology: schizophrenic patients showed a bias towards paranoid words while manic patients showed a bias towards both depressive and manic words. In the schizophrenic group, paranoid interference was correlated with positive symptoms whereas no correlation was found between emotional bias and symptomatology in the manic group. First-degree relatives of schizophrenic patients performed poorly than controls on the Stroop Colour-Word Test while first-degree relatives of bipolar patients showed an emotional bias towards depressive stimuli. Conclusions: Our results suggest that increased Stroop Colour-Word interference is an endophenotype common to schizophrenic and bipolar disorders whose expression quantitatively varies with the phenotypic expression and the clinical phase. No clinical correlate to the interference effect has been identified yet in none of these disorders. However, this abnormality might be more pronounced and associated with schizophrenic disorders. Neuroimaging studies identified cerebral correlates of abnormal interference that were common to schizophrenic and bipolar disorders like the Anterior Cingulate Cortex. A more specific involvement of the ventral prefrontal cortex has been shown in bipolar disorder; this abnormality might be related to the motivational and emotional dysregulation. In schizophrenia, a bias towards paranoid stimuli could be a mechanism involved in the maintenance or the development of the productive symptoms; this phenomenon might be primarily determined by state factors. In bipolar disorder, we suggest that emotional interference represents the impact of emotional hyperreactivity on cognitive inhibition and a marker of vulnerability.

Le trouble bipolaire est un trouble de l'humeur récurrent affectant de 1 à 3% de la population adulte à travers le monde et ayant une comorbidité importante avec une hausse du taux de suicides, l'abus de drogues et d'autres troubles médicaux. Ce trouble semble avoir plusieurs liens avec la schizophrénie et une vulnérabilité au trouble est souvent héréditaire dans une famille. Même si les causes biologiques n'ont pas encore été établies, de nombreuses anomalies dans le système limbique sous-cortical et la zone préfrontal ont été observés.Depuis sa découverte il y a plus d'un demi-siècle, une prise de sels de Lithium a été le traitement le plus fiable, mais l'action biochimique du Lithium sur le cerveau et le pourquoi de l'efficacité du traitement reste un mystère. Afin de pouvoir mieux comprendre cet effet, nous avons développé des séquences d'imagerie du Lithium-7 via résonance magnétique à 7 et 17 Tesla afin de pouvoir établir sa distribution et concentration cérébrale. Spécifiquement, j'ai travaillé sur le développement et la validation des méthodes d'acquisition, de reconstruction et de quantification de notre protocole. Ces méthodes ont d'abord été appliqués afin d'étudier la distribution cérébrale du Lithium sur des cerveaux de rats ex-vivo. Ces rats étés traités pendant 28 jours avec du Li2CO3, sacrifiés et leurs têtes fixés avec du PFA. En utilisant une antenne surfacique double canaux 1H/7Li fait maison, une acquisition 7Li Turbo Spin echo et une méthode de remplacement par fantôme pour la quantification, nous avons pu mesurer les cartes de concentration du Lithium. Les concentrations moyennes obtenus dans des régions d’intérêt prédéfinis ont été mesurés afin de les comparer avec les résultats obtenus par spectrométrie de masse.Après cette étude préclinique qui a permis de valider notre approche, un protocole similaire fut créé pour une étude in-vivo 7Li d'imagerie par résonance magnétique chez des patients bipolaires euthymiques sur un scanner 7T. Ces individus ont tous suivis un traitement régulier de Lithium. Pour cette étude, nous avons utilisé une séquence Steady State Free Precession à TE ultra-court et avec un échantillonnage du k-space non-cartésien. Un pipeline de quantification et d'analyse similaire à celle utilisé pour notre étude préclinique fut appliqué pour cette étude, avec l'ajout d'une étape de correction pour les inhomogénéités de B0. Après avoir fait une analyse statistique au niveau de toute la cohorte par régions d'intérêt, il a été observé que l'hippocampe gauche, une part majeur du système limbique associé au trouble bipolaire à de multiples occasions, possède systématiquement une haute concentration de Lithium. Finalement, la méthode de quantification fut modifiée en quantification bi-compartimentale afin de prendre en compte les différences dans les taux de relaxation du Lithium dans le CSF et dans le parenchyme du cerveau. Cette méthode fut appliqué afin de pouvoir quantifier le Lithium à 7T dans un sous-groupe des patients bipolaires et radicalement réduire les différences initialement observés entre les séquences SSFP et bSSFP. / Bipolar disorder is a chronic affective disorder affecting 1 to 3% of the adult population worldwide and has a high level of comorbidity with suicide rates, substance abuse and other harmful conditions. The disorder has possible ties to schizophrenia and has been observed to have a strong genetic component. The exact biological underpinnings have not been firmly established, however abnormalities in limbic subcortical and prefrontal areas have been observed.Ever since its discovery more than half a century ago, a daily intake of Lithium salts has arguably become the most reliable treatment of the disorder, despite us possessing little to no understanding of its biochemical action. In order to shed some light on the effect of Lithium in the brain, we have developed Lithium-7 MR imaging at 7 and 17 Tesla in order to assess its cerebral concentration and distribution. Specifically, I worked on developing and validating several acquisition, reconstruction and quantification methods dedicated to 7Li MRI and MRS. Those methods were first applied to study ex vivo the cerebral distribution of lithium in rats. These rats were pretreated for 28 days with Li2CO3, sacrificed and their head fixated with PFA. Using a home-made 1H/7Li radiofrequency surface coil and a 7Li Turbo Spin echo acquisition and a modified phantom replacement method for quantification, we were able to measure Li concentration maps. Regional Li concentration values were then compared with those obtained with mass spectrometry.After this preclinical proof-of-concept study, an in vivo 7Li MRI protocol was designed to map the cerebral Li concentration in euthymic bipolar subjects at 7T. These individuals all followed a regular lithium treatment. For this study, we chose to use an ultra-short echo-time Steady State Free Precession sequence with non-Cartesian k-space sampling. A quantification and analysis pipeline similar to the one used for our preclinical study was applied for this study, with the addition of a correction step for B0 inhomogeneities. After conducting a statistical analysis at the cohort level, it was assessed that the left hippocampus, a major part of the limbic system that has been associated with BD on multiple occasions, exhibited systematically a high level of lithium. Finally, I developed a quantification method accounting for the different relaxation times of 7Li in the CSF and in the brain parenchyma. This method was applied to image lithium at 7T in a subset of bipolar patients reducing drastically the differences initially observed between the SSFP and bSSFP sequences.

Background: Current screening recommendations for early detection of lithium-associated hyperparathyroidism propose an exclusive measurement of serum albumin-adjusted calcium (Aac) concentration as a single first step. However, longitudinal data in patients with recurrent affective disorders suggest that increases in serum intact parathyroid hormone (iPTH) levels in lithium-treated patients may not necessarily be accompanied by a parallel increase in the concentration of Aac. If true, patients with an isolated increase in iPTH concentration above the reference range might be missed following current screening recommendations. Therefore, this study set out to examine key parameters of calcium metabolism, including iPTH and 25-hydroxycholecalciferol concentrations in patients with bipolar disorder that was or was not managed with lithium. Methods: Sixty patients with bipolar disorder according to DSM-IV were enrolled, 30 of whom had received long-term lithium treatment (lithium group), whereas the other 30 patients were on psychopharmacological treatment not including lithium (non-lithium group) at the time of the study. Owing to exclusion criteria (e.g., lithium < 6 months, laboratory results indicative of secondary hyperparathyroidism), 23 bipolar patients composed the final lithium group, whereas 28 patients remained in the non-lithium group for statistical analyses. Results: Patients in the lithium group showed a significantly higher concentration of iPTH compared to the non-lithium group (p < 0.05). Similarly, Aac concentrations were significantly increased in the lithium group compared to the non-lithium group (p < 0.05). However, in a multivariate linear regression model, group affiliation only predicted iPTH concentration (p < 0.05). In line with this, none of the four patients in the lithium group with an iPTH concentration above the reference range had an Aac concentration above the reference range. Discussion: This study suggests that the biochemical characteristics between primary hyperparathyroidism and lithium-induced hyperparathyroidism differ substantially with regard to regulation of calcium homeostasis. As such, current screening practice does not reliably detect iPTH concentrations above the reference range. Therefore, further research is needed to elucidate the consequences of an isolated iPTH concentration above the reference range in order to develop the most appropriate screening tools for hyperparathyroidism in lithium-treated patients with bipolar disorder.

Introduction: The late menopausal transition is a time of increased risk of depression in the general population. Nonetheless, mood course during the late menopausal transition in women with bipolar disorder in relatively unknown. Methods: Mood state data in 519 reproductive age women (5989 clinic visits), 116 late menopausal transition (perimenopausal) women (2046 visits), and 133 postmenopausal women (1,437 visits) with bipolar disorder who were receiving optimized naturalistic treatment in the multisite STEP-BD study over an average of 19.8±15.5 months were analyzed for proportion of clinic visits with syndromal depression, mood elevation and euthymia between the three groups. History of postpartum and perimenstrual mood exacerbation as well as hormone therapy use were evaluated as potential predictors of mood. Results: No significant difference in the proportion of clinic visits with syndromal depression was found between reproductive age (18.1%), perimenopausal (18.1%) and postmenopausal (19.3%) women. Reproductive age women had significantly greater proportion of visits with syndromal mood elevation (5.3%) compared to perimenopausal (4.1%, Z=2.1, p2(3, N = 9960) = 19.8, p Conclusions: While proportion of clinic visits with syndromal depression did not differ among the three reproductive groups, thirteen women who had recorded transition from perimenopause to postmenopause showed significantly greater depression than reproductive age, perimenopausal or postmenopausal women. Proportion of visits with euthymia or with syndromal mood elevation decreased from reproductive age to perimenopausal to postmenopausal women. Reported history of mood exacerbation during times of hormonal fluctuation, or current use of hormone therapy, was not significantly associated with depression during the perimenopause. Limitations include women excluded due to absence of menstrual data. Future studies should include hormonal assessments.

Bakgrund Att leva med de psykiska sjukdomarna schizofreni eller bipolärt syndrom innebär stora utmaningar i det dagliga livet, då det sociala livet är inskränkt och stigmatiserade uppfattningar leder till en känsla av diskriminering och ytterligare utanförskap för denna patientgrupp. Symtomen behandlas i första hand farmakologiskt, men det räcker inte med enbart läkemedel för att personen ska uppnå god psykisk hälsa. Alla individer har rätt till adekvat och personcentrerad omvårdnad för att öka välbefinnandet och livskvaliteten, vilket i sin tur påverkar det psykiska måendet. Syfte Syftet med studien var att beskriva hur omvårdnad kan främja den psykiska hälsan hos personer med schizofreni eller bipolärt syndrom. Metod Det utfördes en icke-systematisk litteraturöversikt, där totalt 16 vetenskapliga originalartiklar utgör grunden till resultatet. Sökning av relevant litteratur har gjorts i databaserna PubMed, CINAHL och PsycINFO. Genom tydliga inklusions- och exklusionskriterier har artiklarna granskats och valts ut för resultatet. Med hjälp av tematisk analys av artiklarnas innehåll har följande sex kategorier utarbetats: den terapeutiska alliansen, copingstrategier för ökad livskvalitet, ökad självkänsla, stigmatisering av patienter med schizofreni och bipolärt syndrom, samarbete mellan olika vårdgivare samt hälso- och sjukvårdens kunskap i ämnet. Resultat Resultatet tyder på att byggandet av en terapeutisk allians mellan sjuksköterskan och patienten är grunden till personcentrerad vård. Personer med schizofreni eller bipolärt syndrom måste hitta strategier för att hantera sina sjukdomsepisoder med stöd från sjuksköterskan. Detta leder till ökat välmående och främjar den psykiska hälsan. Individanpassad omvårdnad baseras på utbildning och kunskap, samt ett samarbete mellan olika vårdgivare. Slutsats                                                                                             Som legitimerad sjuksköterska är det viktigt att inneha kunskap om bemötande av personer med schizofreni eller bipolärt syndrom för att kunna ge adekvat omvårdnad och stödja utsatta patientgrupper till god hälsa och ökad livskvalitet. Detta innefattar att främja empowerment hos patientgruppen för att ge möjlighet till önskvärd egenvård. / Background Living with the mental illnesses schizophrenia or bipolar disorder involves major challenges in daily life, as social life is restricted, and stigmatized perceptions lead to feelings of discrimination and further exclusion for this patient group. The symptoms are primarily treated pharmacologically, but medication alone is not enough for each person to achieve satisfactory mental health. All individuals have the right to adequate and person-centered care to increase well-being and quality of life, which affects the mental state. Aim The purpose of the study was to describe how nursing care can promote mental health for individuals with schizophrenia or bipolar disorder. Method A non-systematic literature review was accomplished, where a total of 16 Scientific original articles form the basis for the result. Searches of relevant literature were performed in the databases PubMed, CINAHL and PsycINFO. Through precise inclusion and exclusion criteria, the articles have been carefully reviewed and selected for the result. Using a thematic analysis for the content of the articles, the following six categories were developed: the therapeutic alliance, coping strategies for increased quality of life, increased self-esteem, stigmatization of patients with schizophrenia and bipolar disorder, collaborative care and health care knowledge within the subject. Results The results indicate that the establishing of a therapeutic alliance between the nurse and the patient is the basis for person-centered care. People with schizophrenia or bipolar disorder need to find strategies for managing their episodes of illness with the support of the nurse. This leads to increased well-being and promotes mental health. Individualized nursing is based on education and knowledge, as well as a collaboration between different care providers. Conclusions As a licensed nurse, it is important to possess knowledge about treating individuals with schizophrenia or bipolar disorder, in order to provide adequate care and support vulnerable patient groups to good health and increased quality of life. This includes promoting the empowerment of the patient group to provide the opportunity for desirable self-care.