This study explored the Object Relations of a sample of 45 subjects who were using alcohol and were diagnosed with co-morbid Depressive or Bipolar disorders and/or Personality disorders. All subjects were receiving treatment at a government psychiatric hospital in South Africa. The similarities and differences in the Object Relations of these individuals were identified. A biographical questionnaire, the Alcohol Use Disorder Test (AUDIT), which was used as a screening measure, and the Bells Object Relations and Reality Testing Inventory (BORRTI) were administered to obtain information from a purposive sample. Descriptive and inferential statistics were used to analyse the results of the assessment measures. Analysis of the BORRTI data indicated a high rate of depressive and personality disorders within this sample. Results of the sub-sample (n=29) whose scores were included in the Pearson’s Correlation Coefficient analysis indicate that higher levels of alcohol consumption result in increased levels of hallucinations and delusions. Other correlations were identified between high levels of alcohol consumption and heightened levels of reality distortions and more uncertainty in the perceptions of these individuals. Significant differences in the scores of the male and female participants were identified. With the female participants, the higher the level of alcohol consumption, the lower the individuals scored in terms of pathological levels of egocentricity, uncertain perceptions, insecure attachments, alienation, social incompetence as well as hallucinations and delusions. Alternatively, in the male sample, higher levels of alcohol consumption result in increased hallucinations and delusions, reality distortions, uncertainty in perceptions, alienation, social incompetence and egocentricity. / Psychology / M.A. (Research Psychology)

This study investigates the connection between different pathophysiological processes in mitochondria and psychopathological symptoms in patients with bipolar disorder. Changes in activity of selected components of the respiratory chain and overall respiratory rate of mitochondria were analyzed in patients with bipolar disorder when compared to healthy controls. Diagnostic scales and questionnaires, high-resolution respirometry, radiochemical and spectroscopic methods were used. 37 patients with a diagnosis of bipolar disorder (F31) and 21 healthy volunteers were involved in the study. Statistical analysis included the methods of parametric and nonparametric analysis, factor analysis, one-way analysis of variance and linear regression analysis. Obtained results revealed that cellular energetics plays a great role in the pathophysiology of bipolar disorder. There was a mild difference between different mitochondrial enzymes activity in patients within manic phases and depressive phases of the disease. Changes in mitochondrial respiration in patients with BD as compared to healthy controls were also shown. Mitochondrial respiration indexes for patients with BD in remission as compared to healthy controls were altered in accordance with the previous phase of the disease. Association between the...

Chronic kidney disease (CKD) patients have compromised health related quality of life (HRQOL) by several reasons. This study aimed to evaluate HRQOL on hemodialysis (HD) and peritoneal dialysis (PD) patients and to identify HRQOL associated factors. Methods: We conducted a transversal study with 215 patients on HD and 58 on PD between July and September 2013, in Sergipe, Brazil. HRQOL was assessed using the Kidney Disease Quality of Life Short Form Instrument- 1.3 (KDQOL-SF), consisting of two cores: specific (KDCS) and generic (RAND-36). Additionally demographic and clinical variables directly related to CKD, factors such as mood, sleep disorders and sexual dysfunction were evaluated through specific instruments. Results: Patients had a mean age of 51 years (SD ± 15.4), mostly men (62%), with low educational (72%) and economic (95%) levels. There was no difference related to HRQOL among dialysis modalities, only PD patients felt more stimulated by caring staff than that on HD (p<0.01). The prevalence of depressive (29%) and anxiety (30%) symptoms, poor quality of sleep (56%), excessive daytime sleepiness (43%) and male (48%) and female (76%) sexual dysfunction were high. Multiple linear regression showed that depressive (R= -0.39 p<0.01, R= -0.48 p<0.01) and anxiety (R = -0.41 p <0.01, R = -0.27 p <0.01) symptoms were independently associated with KDCS and RAND-36. Confirmatory factorial analysis models confirmed the association of mood disorders with low HRQOL. High prevalence of anxiety (30%) and depressive symptoms (29%) were revealed. Conclusion: Patients on HD and PD showed no differences in HRQOL. Mood disorders are independently associated with low HRQOL, with high prevalence of anxiety and depressive symptoms in dialysis patients. / Portadores de doença renal crônica (DRC) possuem comprometimento da qualidade de vida relacionada à saúde (QVRS) por diversas razões. Este estudo objetivou avaliar QVRS de pacientes em hemodiálise (HD) e diálise peritoneal (DP) e identificar fatores a ela associados. Casuística e Método: Estudo transversal realizado entre julho e setembro de 2013 com 215 pacientes em HD e 58 em DP, em Sergipe, Brasil. Avaliou-se a QVRS através do questionário Kidney Disease Quality of Life Instrument- Short Form 1.3 (KDQOL-SF), composto por dois núcleos: específico (KDCS) e genérico (RAND-36). Além de variáveis demográficas e clínicas diretamente relacionadas a DRC, foram avaliados fatores como distúrbios de humor, sono e disfunções sexuais através de instrumentos específicos. Resultados: Os pacientes possuíam em média 51 anos (desvio-padrão±15,4), eram na maioria homens (62%), com níveis educacional (72%) e econômico (95%) baixos. Não se evidenciaram diferenças relacionadas à QVRS entre as modalidades dialíticas, apenas pacientes em DP se sentiram mais estimulados pela equipe cuidadora que os em HD (p<0,01). As prevalências de sintomas depressivos (29%), sintomas ansiosos (30%), baixa qualidade de sono (56%), sonolência diurna excessiva (43%) e disfunções sexuais masculina (48%) e feminina (76%) foram altas. Análise por regressão linear múltipla mostrou que sintomas depressivos (R= -0,39 p<0,01; R= -0,48 p<0,01) e ansiosos (R= -0,41 p<0,01; R= -0,27 p<0,01) foram fatores independentemente associados aos núcleos KDCS e RAND-36. Modelos de análise fatorial corroboraram a associação dos distúrbios de humor com baixa QVRS. Evidenciou-se alta prevalência de sintomas ansiosos (30%) e depressivos (29%). Conclusão: Pacientes em HD e DP não apresentaram diferenças na percepção de QVRS. Os distúrbios de humor foram fatores independentemente associados à baixa QVRS, com alta prevalência de sintomas ansiosos e depressivos em pacientes em diálise.

O Transtorno de Oposição e Desafio (TOD) é definido por um padrão recorrente de comportamento desafiante, desobediente e hostil com início na infância e adolescência e caracteriza-se por uma alta taxa de comorbidades. Estudos longitudinais apontam o TOD na infância como um dos principais preditores de psicopatologia na idade adulta. Uma possível explicação para a grande heterogeneidade de comorbidades e trajetórias longitudinais é de que o diagnóstico de TOD abrange distintas dimensões de sintomas, cada qual com seu desfecho. O primeiro objetivo desta tese foi a validação das distintas dimensões do TOD em uma amostra comunitária Brasileira composta de 2512 sujeitos. Através de análise fatorial confirmatória, demonstramos que o modelo que melhor representa a heterogeneidade do TOD é composto por três dimensões: a dimensão \"argumentative/defiant\" que está associada com transtorno de déficit de atenção/hiperatividade (TDAH); a dimensão \"vindictiveness\" que possui associação com transtorno de conduta (TC); e a dimensão \"angry/irritable mood\" onde predominam as associações com transtornos depressivos e de ansiedade. O objetivo seguinte foi investigar o papel da dimensão irritável na classificação nosológica dos transtornos mentais na infância e adolescência. A apresentação da irritabilidade é um aspecto crucial: irritabilidade crônica caracterizada por baixa tolerância à frustração e frequentes explosões de raiva, que é distinta da apresentação episódica, associada ao diagnóstico Transtorno de Humor Bipolar (TB). \"Severe mood dysregulation\", \"disruptive mood dysregulation disorder\", ou dimensão irritável do TOD são formas distintas de classificar o fenótipo de irritabilidade crônica. Entretanto, independente da classificação utilizada, a alta taxa de comorbidades é invariavelmente o denominador comum em estudos sobre irritabilidade. Neste sentido, examinamos o impacto da irritabilidade como uma dimensão subjacente a vários transtornos. Para tanto, avaliamos o impacto da dimensão irritável do TOD através de vários cenários: indivíduos sem diagnóstico, indivíduos com TDAH e sujeitos com transtornos emocionais. Esta 9 investigação foi realizada em duas amostras, uma brasileira constituída por 2.512 sujeitos e uma amostra britânica composta de 7.977 sujeitos. Os resultados demonstram que a irritabilidade está associada ao aumento do prejuízo funcional independente do diagnóstico comórbido concomitante. Seguindo esta linha, investigamos a influência genética na etiologia da irritabilidade. Para tanto, criamos um escore poligênico que incluiu polimorfismos associados à baixa tolerância à frustração, raiva, agressividade reativa e labilidade emocional. O escore poligênico foi altamente preditivo dos níveis de irritabilidade em 350 sujeitos da amostra brasileira. A associação foi específica para irritabilidade e não foi significativa para TDAH, TOD ou medidas contínuas de sintomas. Além disso, a influência genética se manteve mesmo quando fatores ambientais foram incluídos no modelo estatístico. Por fim, quando testada em diferentes ambientes, a influência genética na etiologia da irritabilidade foi mais importante em ambientes de alto risco, sugerindo uma correlação gene-ambiente (rGE). Concluindo, nossos resultados sugerem que a irritabilidade se caracteriza como um traço dimensional subjacente a inúmeros transtornos na infância e adolescência e agregando impacto e prejuízo funcional. Neste sentido, o constructo da irritabilidade se enquadra no conceito do \"Research Domain Criteria\" (RDoC) que propõe o entendimento dos transtornos mentais através de dimensões subjacentes aos diagnósticos clínicos / The Oppositional Defiant Disorder (ODD) is defined as a pattern of disobedient, hostile and defiant behavior beginning in childhood or adolescence and often accompanied by a wide range of comorbidities. Longitudinal studies support ODD as a predictor of psychopathology in adulthood. A potential explanation for such heterogeneity of comorbidities and longitudinal trajectories is that ODD diagnosis encompasses distinct clusters of symptoms, each with its outcome. The first aim of this work was the validation of ODD dimensions in a Brazilian community sample of 2512 subjects. Confirmatory factorial analysis showed that the best model for ODD comprised three dimensions: an \"argumentative/defiant\" dimension, which associates with attention deficit/hyperactivity disorder (ADHD); a \"vindictiveness\" dimension, which associates with conduct disorder (CD); and an \"angry/irritable\" dimension where emotional disorders such as depression and anxiety are the most common associations. The next step was the investigation of the role of the irritable dimension of oppositionality in diagnostic classifications of childhood mental disorders. The pattern of irritability is a crucial point: its chronic presentation as easy annoyance and frequent temper outbursts should be differentiated from the episodic course of irritability associated with the specific diagnosis of Bipolar Disorder (BD). \"Severe mood dysregulation\", \"disruptive mood dysregulation disorder\", and the irritable dimension of oppositionality are different ways to classify the chronic irritability phenotype. However, regardless of the classification, the high rate of comorbidities is invariably the common denominator in studies of irritability. Therefore, we examined the impact of irritability as a dimension cutting across multiple settings: individuals without any diagnosis, subjects with ADHD, and also those with emotional disorders. For that we used two samples, one from Brazil, with 2.512 subjects, and one from the UK, with 7.977 individuals. Results showed that irritability associates with increased functional impairment regardless of concurrent comorbid status. We then investigated the genetic influence on the etiology of irritability. A polygenic score was generated encompassing polymorphisms previously associated with anger, emotional lability and reactive aggression. The polygenic score significantly predicted irritability in 350 subjects in the brazilian sample, yet failed to predict ADHD, ODD, CD and continuous measures of symptoms. Moreover, the association between the polygenic score and irritability remained significant even after taking into account environmental factors. Finally, when stratified across diverse levels of environmental risk, genetic influence upon the etiology of irritability appears to be stronger in high-risk environments. Taken together, our results suggest that irritability is characterized as a dimensional trait that underlies multiple disorders, adding functional impairment. Thus, the construct of irritability fits well within the concept of Research Domain Criteria (RDoC) that suggests that mental disorders should be understood through dimensions underlying diagnostic categories

Mood disorders are often linked with concurrent partner relational distress. The present study compared the cost effectiveness of treating mood disorder alone versus when the condition is comorbid with partner relational distress. Cigna, a leading health insurance management company in the US, provided outpatient data. Participants included patients with solely a mood disorder diagnosis (n = 72,712) and those with both a mood disorder and a comorbid partner relational distress diagnosis (n = 113, including 69 females and 44 males). These participants were treated in outpatient settings throughout the US. These numbers are surprisingly low considering the extensive literature showing a strong relationship between mood disorder and partner relational distress. A multivariate general linear model and binary logistic regressions were used to analyze the data. Results indicate that having a mood disorder present with a partner relational distress disorder significantly increased the average cost of care by about $471 per person compared to having solely a mood disorder. For mood disorders alone, there were also differences in cost effectiveness and readmission for mood disorders by professional license type, age, and gender with counselors being the most cost effective and medical doctors being the least (60% more costly). The treatment modality used impacted readmission rates, with family therapy having the lowest (8.54%) and mixed therapy having the highest (33.54%). Due to the small sample size, we were unable to determine the significance of subsequent analyses for comorbid disorders. Clinical implications and future directions for research will be discussed.

Background. A sizable amount of individuals in the community are presented with various kinds of physical and mental health problems which are either undetected, untreated or inadequately treated, due to the limitations on the availability and accessibility of the services in the existing health care system, or to other social and personal reasons. The current study evaluated the effectiveness of a newly developed modality of health-enhancing treatment---the Mindfulness-based Dejian Mind-Body Intervention, as compared to that of a Group Psychoeducational Treatment, in alleviating depressive mood and improving physical health of adult individuals in the community. / Conclusions. Findings of the current study suggest that compared with the Group Psychoeducational Treatment, Dejian Mind-Body Intervention might be more effective in enhancing the emotional and physical health of community individuals presented with moderate to severe depressive mood and/or problems with bowel functioning. / Method. Forty adult volunteers with various degree of depressive mood and physical problems who expressed interest in receiving either Dejian Mind-Body Intervention or Group Psychoeducational Treatment were recruited in the current study. They were matched for gender, age, education and level of depression, and were randomly assigned to either treatment group. / Results. Both the Dejian Mind-Body Intervention and Group Psychoeducation Treatment were effective in bringing about a significant reduction in depressive mood iv among treatment completers. However, differential effectiveness emerged among those presented with moderate to severe depressive mood, where Dejian Mind-Body Intervention resulted in significantly greater treatment-related reduction in depressive mood compared with the Group Psychoeducational Treatment. Besides, Dejian Mind-Body Intervention brought about significant increase in an objective QEEG measure of positive affect, and improvements in physical health (i.e., bowel functioning) that were not evidenced in the Group Psychoeducation Treatment. / Tsui, Jin Ching. / Adviser: Agnes S.Y. Chan. / Source: Dissertation Abstracts International, Volume: 70-06, Section: B, page: 3799. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2008. / Includes bibliographical references (leaves 62-68). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts in English and Chinese. / School code: 1307.

La leucémie lymphoblastique aiguë (LLA) est le cancer le plus fréquent chez les enfants. Malgré le fait que plus de 80% des enfants atteints de LLA sont aujourd'hui guéris de leur maladie, ce succès a toutefois un prix élevé, car l’exposition aux médicaments cytotoxique et/ou à l’irradiation pendant une période vulnérable du développement de l’enfant peut entraîner des conséquences à long terme. En effet, environ 60% des enfants ayant survécu à une LLA devront vivre avec des problèmes de santé liés au traitement, également appelés effets indésirables tardifs (late-adverse effects, LAEs). Parmi ces derniers, on notera des problèmes métaboliques, l’ostéoporose, une altération des fonctions cognitives ou cardiaques, ainsi que la dépression et l’anxiété. Si certains survivants ne présentent aucune de ces complications, d'autres peuvent en avoir plusieurs. Différents facteurs peuvent contribuer à cette variabilité, notamment le traitement reçu, les caractéristiques de la maladie, les habitudes de vie et, surtout, la constitution génétique du patient. Ce projet s'est concentré sur les biomarqueurs génétiques permettant d'identifier les individus les plus susceptibles de souffrir de LAEs. Récemment, une étude exhaustive (évaluations cliniques, psychosociales et biochimiques) s’est déroulée au CHU Sainte-Justine pour caractériser chacune de ces morbidités chez 250 survivants de la LLA de l'enfant (cohorte PETALE). De plus, on a obtenu le profil génétique de chaque participant. Nous avons utilisé cet ensemble de données et des outils statistiques et bio-informatiques pour réaliser des études d'association comparant la fréquence des variants génétiques chez les survivants ayant développé ou non des LAEs; en particulier, les complications cardiovasculaires et neurocognitives, ainsi que les troubles de l'humeur tels que l'anxiété et la dépression. D'autres facteurs de risque tels que les caractéristiques de traitement et/ou de la leucémie ont été pris en compte lors de l'analyse pour dériver les meilleurs prédicteurs génétiques. Ainsi, en utilisant l'approche des gènes candidats, nous avons identifié les variants communs des gènes MTR, PPARA, ABCC3, CALML5, CACNB2 et PCDHB10 qui étaient associés à des déficits de performance des tests neurocognitifs, tandis que les variants des gènes SLCO1B1 et EPHA5 étaient associés à l'anxiété et à la dépression. Deux variants, rs1805087 dans le gène MTR et rs58225473 dans le gène CACNB2 sont particulièrement intéressants, car ces associations ont été validées dans la cohorte de réplication SJLIFE (St. Jude Children's Research Hospital, Memphis, USA). Les analyses d'association ont été complémentées par une étude d'association à l'échelle de l'exome, qui a identifié plusieurs gènes supplémentaires comme des modulateurs potentiels du risque de développer des complications neurocognitives liées au traitement (gènes AK8 et ZNF382), ainsi que l'anxiété et la dépression (gènes PTPRZ1, MUC16, TNRC6C-AS1, APOL2, C6orf165, EXO5, CYP2W1 et PCMTD1). Le variant rs61732180 du gène ZNF382 a ensuite été validé dans la cohorte de réplication SJLIFE. Également, nous avons effectué des analyses d’association concernant les complications cardiaques liées au traitement qui ont identifié plusieurs nouveaux marqueurs associés à ces complications dans les gènes TTN, NOS1, ABCG2, CBR1, ABCC5, AKR1C3, NOD2 et ZNF267. De plus, nous avons résumé les connaissances actuelles sur les marqueurs pharmacogénomiques qui ont été associés aux effets de cardiotoxicités, induites par les anthracyclines, qui affectent les patients atteints de cancer pédiatrique. Nous avons également inclus un aperçu de l'applicabilité des résultats rapportés, notamment ceux qui ont été validés dans la cohorte PETALE. Par ailleurs, nous nous sommes intéressés aux complications qui surviennent après une greffe de cellules souches hématopoïétiques. Nous avons appliqué des approches bio-informatiques et statistiques similaires pour obtenir un profil plus complet de la composante génétique derrière ces complications potentiellement mortelles. Ainsi, une étude d'association à l'échelle de l'exome a été réalisée dans une cohorte de patients pédiatriques subissant une greffe de cellules souches hématopoïétiques après un régime de conditionnement contenant du busulfan. Nous avons identifié de nouvelles variations génétiques conférant un risque plus élevé de syndrome d'obstruction sinusoïdale (notamment dans les gènes UGT2B10, BHLHE22, et KIAA1715) et de maladie aiguë du greffon contre l'hôte (dans les gènes ERC1, PLEK, NOP9 et SPRED1), qui pourraient être utiles pour des stratégies personnalisées de prévention et de traitement. Ces travaux contribuent à la compréhension de l'influence des facteurs génétiques sur le risque de développer des complications liées au traitement, tant au cours du traitement qu'à long terme. De plus, les marqueurs génétiques signalés ainsi que d'autres facteurs de risque connus peuvent conduire à des modèles de prédiction identifiant les patients à risque accru de ces complications. / Acute lymphoblastic leukemia (ALL) is the most common cancer in children. Even though more than 80% of children with ALL are now cured of their disease, this success comes at a high price as exposure to cytotoxic drugs and/or radiation during a vulnerable period of child development may have long-term consequences. In fact, approximately 60% of children who survive ALL will have to live with treatment-related health problems, also called late-adverse effects (LAEs). These include metabolic problems, osteoporosis, impaired cardiac or cognitive functions, as well as depression and anxiety. While some survivors do not have any of these complications, others may have more than one. Different factors can contribute to this variability, in particular, the treatment received, the characteristics of the disease, the lifestyle, and, above all, the genetic makeup of the patient. This project focused on genetic biomarkers capable of identifying the individuals most likely to suffer from LAEs. Recently, an exhaustive study (clinical, psychosocial, and biochemical evaluations) took place at Sainte-Justine University Health Center (Montreal, Canada), with the goal to characterize each of these morbidities in 250 survivors of childhood ALL (PETALE cohort). In addition, the genetic profile of each participant was obtained, and we used statistical and bioinformatics tools to perform association studies on this dataset in order to compare the frequency of genetic variants in survivors with or without LAEs. We evaluated cardiovascular and neurocognitive complications, as well as mood disorders such as anxiety and depression. Other risk factors, such as treatment and/or leukemia characteristics were also considered during the analysis to derive the best genetic predictors. Thus, using the candidate gene approach, we identified common variants in the MTR, PPARA, ABCC3, CALML5, CACNB2, and PCDHB10 genes that were associated with deficits in neurocognitive tests performance, whereas variants in the SLCO1B1 and EPHA5 genes were associated with anxiety and depression. Two variants, rs1805087 in the MTR gene and rs58225473 in the CACNB2 gene, are of particular interest since these associations were validated in an independent SJLIFE replication cohort (St. Jude Children's Research Hospital, Memphis, USA). The association analyses were complemented by an exome-wide association study, which identified several additional genes as potential modulators of the risk of developing treatment-related neurocognitive complications (genes AK8 and ZNF382), as well as anxiety and depression (genes PTPRZ1, MUC16, TNRC6C-AS1, APOL2, C6orf165, EXO5, CYP2W1, and PCMTD1). Variant rs61732180 in the ZNF382 gene was further validated in the replication SJLIFE cohort. To a great extent, we performed association analyses regarding treatment-related cardiac complications which identified several novel markers associated with these toxicities in the TTN, NOS1, ABCG2, CBR1, ABCC5, AKR1C3, NOD2, and ZNF267 genes in survivors of childhood ALL. In addition, we summarized the current knowledge on pharmacogenomic markers related to anthracycline-induced cardiotoxicity affecting pediatric cancer patients. We also included a brief overview of the applicability of reported findings to the PETALE cohort, validating several of them. Besides, we were interested in the complications that arise after a hematopoietic stem cell transplantation. We applied similar bioinformatics and statistical approaches to gain a more complete insight into the genetic component behind these life-threatening complications. Thus, an exome-wide association study was performed in a cohort of pediatric patients undergoing hematopoietic stem cell transplantation following a conditioning regimen containing busulfan. Our results identified new genetic variations conferring a higher risk of sinusoidal obstruction syndrome (notably in the UGT2B10, BHLHE22, and KIAA1715 genes) and acute graft-versus-host disease (ERC1, PLEK, NOP9, and SPRED1 genes), which could be useful for personalized prevention and treatment strategies. This work contributes to the understanding of the influence of genetic factors on the risk of developing treatment-related complications, both during treatment and in the long term. Furthermore, the reported genetic markers along with other known risk factors can lead to prediction models identifying patients at increased risk for these complications.