A literature search, supplemented by an expert survey and selected reanalyses of existing data from epidemiological studies was performed to determine the prevalence and associated burden of bipolar I and II disorder in EU countries. Only studies using established diagnostic instruments based on DSM-III-R or DSM-IV, or ICD-10 criteria were considered. Fourteen studies from a total of 10 countries were identified. The majority of studies reported 12-month estimates of approximately 1% (range 0.5–1.1%), with little evidence of a gender difference. The cumulative lifetime incidence (two prospective-longitudinal studies) is slightly higher (1.5–2%); and when the wider range of bipolar spectrum disorders is considered estimates increased to approximately 6%. Few studies have reported separate estimates for bipolar I and II disorders. Age of first onset of bipolar disorder is most frequently reported in late adolescence and early adulthood. A high degree of concurrent and sequential comorbidity with other mental disorders and physical illnesses is common. Most studies suggest equally high or even higher levels of impairments and disabilities of bipolar disorders as compared to major depression and schizophrenia. Few data are available on treatment and health care utilization.

We examined prospectively whether mania and hypomania are associated with an elevated risk for suicidality in a community sample of adolescents and young adults. Baseline and four-year follow-up data were used from the Early-Developmental- Stages-of-Psychopathology (EDSP) Study, a prospective longitudinal study of adolescents and young adults in Munich. Suicidal tendencies (ideation/attempts), mania, and hypomania were assessed using the standardized Munich-Composite-International- Diagnostic-Interview. At baseline, mania/hypomania was associated to a different degree with suicidality (Odds ratios [OR] range from 1.9 to 13.7). In the prospective analyses, the risk for subsequent incident suicidal ideation was increased in the presence of prior mania (38.0% vs. 14.1%; OR = 4:4; 95% CI = 1.4–13.5). No associations could be found between prior mania/hypo-mania and incident suicide attempts. The prospective analyses revealed a remarkable relationship between preexisting mania and increased risk for subsequent suicidal ideation.

Bipolar mood disorder has been traditionally researched, explored, and explained from a modernistic, psychiatric perspective. The purpose of this study is to explicate an alternative description for bipolar mood disorder, from a postmodern perspective. The widely accepted psychiatric knowledge focuses on the signs and symptoms of the disorder, pharmacological treatments, and manualised psychotherapies. This thesis shifts the focus from an intrapsychic, deficit perspective towards one which is inclusive of surrounding discourses and patterned relationships. The social constructionist research approach is followed, utilising vignette and thematic analyses for textual deconstruction and reconstruction. In addition to these data analyses, discourses were analysed using the actual text of the co-researchers. This allowed for a thorough explication of the ways in which discourses shape the construct bipolar mood disorder. From these analyses, emergent themes were then distilled and compared to the existing body of literature in the bipolar mood spectrum field of study. Process models were generated to depict the various pertinent aspects of the social construction of bipolar mood disorder. This research has value for the treating professional, allowing for a broader, more inclusive discourse perspective to add to the already established medical model view. Further, this research gives credence to the voice of the person who has been diagnosed with the illness. This research may also contribute to the epistemological debates within modernist and postmodernist paradigms. Key words: Bipolar mood disorder, medical model, pharmacology, mania, depression, psychiatry, psychotherapy, titrating power relations, expert, problem determined systems, belonging, problems of therapy and therapeutic problems, vignette analysis, people as meaning generating beings, context, reflexivity, self-reflection, multiple realities, positivism, social constructionist epistemology, qualitative research, process model. / Psychology / D. Litt. et Phil. (Psychology)

Introdução: Comparados com pacientes bipolares com episódios maníacos/hipomaníacos e depressivos, os que apresentam estados mistos tendem a curso mais grave da doença, início mais precoce, ocorrência mais frequente de sintomas psicóticos, maior risco de suicídio, altas taxas de comorbidade e tempo maior para remissão. Portanto, medidas objetivas de avaliação desses estados são necessárias. Objetivo:Avaliar a concordância entre três pares formados por uma de três escalas de mania (Young Mania Rating Scale (YMRS), Bech-Rafaelsen Mania Scale (BRMS) ou Clinician-Administered Rating Scale for Mania (CARS-M)) e uma de depressão (21-item Hamilton Depression) na avaliação da resposta a estabilizadores do humor em pacientes mistos. Método:Sessenta e oito (n=68) consecutivos pacientes ambulatoriais bipolares Tipo I e II com sintomatologia mista pelo DSM-IV-TR e pelos critérios de Cincinatti foram incluídos nesse estudo aberto de 8 semanas entre 2010 e 2014 foram randomizados para receberem em monoterapia, ácido valproico, carbamazepina ou carbonato de lítio. Resultados: O padrão de resposta (diminuição de, pelo menos, 50% em uma das escalas de mania e na de depressão) foi muito semelhante: 21-HAM-D + YMRS = 22,1%, 21-HAM-D + BRMS = 20,6% e 21-HAM-D + CARS-M = 23,5%; p < 0,368). Os resultados referentes à concordância de resposta revelam valores de kappa bastante altos: 21-HAM-D + YMRS X 21-HAM-D + CARS-M , Kappa = 0,87; 21-HAM-D + YMRS X 21-HAM-D + BRMS, Kappa = 0,78 e 21-HAM-D + CARS-M X 21-HAM-D + BRMS, Kappa = 0,91 (p < 0,001). Conclusões:O presente estudo sugere que qualquer uma das três escalas de mania utilizadas (YMRS, BRMS, CARS-M) pode ser associada à 21-HAM-D na avaliação da resposta em bipolares mistos. / Background: Compared with patients with bipolar disorder who exhibit pure manic/hypomanic or depressive episodes, the presence of mixed mood states is associated with a more severe course of illness, younger age of onset, more frequent ocurrence of psychotic symptoms, major risk of suicide, higher rates of comorbidities and longer time to achieve remission. Therefore, objective avaliation of these states are necessary. Objective: To evaluate the concorccance amog three pairs of three scales (Young Mania Rating Scale (YMRS), Bech-Rafaelsen Mania Scale (BRMS) or Clinician-Administered Rating Scale for Mania (CARS-M)) and a depression scale (21-item Hamilton Depression) in the assessment of response to humor stabizator drugs in mix bipolar patients. Methods: Sixty eight (n=68) consecutive bipolar type I and II outpatients with mixed sitomatology accordint to DSM-IV-TR and Cincinatti Criteria were included in these 8 weeks open-trial, from 2010 through 2014, to, randomly, receive monotherapy valporic acid, carbamazepine or lithium carbonate. Results: The response answer (decrease of, at least 50 %, in one of the mania and depression scales) were very similar: 21-HAM-D + YMRS = 22.1%, 21-HAM-D + BRMS = 20.6% e 21-HAM-D + CARS-M = 23.5%; p < 0,368). The kappa values were : 21-HAM-D + YMRS X 21-HAM-D + CARS-M , Kappa = 0.87; 21-HAM-D + YMRS X 21-HAM-D + BRMS, Kappa = 0.78 e 21-HAM-D + CARS-M X 21-HAM-D + BRMS, Kappa = 0.91 (p < 0,001). Conclusions: The present study suggests that any of the three mania scales used (YMRS, BRMS, CARS-M) may be associated to 21-HAM-D in the assessment of the response o bipolar patients.

Introdução: Comparados com pacientes bipolares com episódios maníacos/hipomaníacos e depressivos, os que apresentam estados mistos tendem a curso mais grave da doença, início mais precoce, ocorrência mais frequente de sintomas psicóticos, maior risco de suicídio, altas taxas de comorbidade e tempo maior para remissão. Portanto, medidas objetivas de avaliação desses estados são necessárias. Objetivo:Avaliar a concordância entre três pares formados por uma de três escalas de mania (Young Mania Rating Scale (YMRS), Bech-Rafaelsen Mania Scale (BRMS) ou Clinician-Administered Rating Scale for Mania (CARS-M)) e uma de depressão (21-item Hamilton Depression) na avaliação da resposta a estabilizadores do humor em pacientes mistos. Método:Sessenta e oito (n=68) consecutivos pacientes ambulatoriais bipolares Tipo I e II com sintomatologia mista pelo DSM-IV-TR e pelos critérios de Cincinatti foram incluídos nesse estudo aberto de 8 semanas entre 2010 e 2014 foram randomizados para receberem em monoterapia, ácido valproico, carbamazepina ou carbonato de lítio. Resultados: O padrão de resposta (diminuição de, pelo menos, 50% em uma das escalas de mania e na de depressão) foi muito semelhante: 21-HAM-D + YMRS = 22,1%, 21-HAM-D + BRMS = 20,6% e 21-HAM-D + CARS-M = 23,5%; p < 0,368). Os resultados referentes à concordância de resposta revelam valores de kappa bastante altos: 21-HAM-D + YMRS X 21-HAM-D + CARS-M , Kappa = 0,87; 21-HAM-D + YMRS X 21-HAM-D + BRMS, Kappa = 0,78 e 21-HAM-D + CARS-M X 21-HAM-D + BRMS, Kappa = 0,91 (p < 0,001). Conclusões:O presente estudo sugere que qualquer uma das três escalas de mania utilizadas (YMRS, BRMS, CARS-M) pode ser associada à 21-HAM-D na avaliação da resposta em bipolares mistos. / Background: Compared with patients with bipolar disorder who exhibit pure manic/hypomanic or depressive episodes, the presence of mixed mood states is associated with a more severe course of illness, younger age of onset, more frequent ocurrence of psychotic symptoms, major risk of suicide, higher rates of comorbidities and longer time to achieve remission. Therefore, objective avaliation of these states are necessary. Objective: To evaluate the concorccance amog three pairs of three scales (Young Mania Rating Scale (YMRS), Bech-Rafaelsen Mania Scale (BRMS) or Clinician-Administered Rating Scale for Mania (CARS-M)) and a depression scale (21-item Hamilton Depression) in the assessment of response to humor stabizator drugs in mix bipolar patients. Methods: Sixty eight (n=68) consecutive bipolar type I and II outpatients with mixed sitomatology accordint to DSM-IV-TR and Cincinatti Criteria were included in these 8 weeks open-trial, from 2010 through 2014, to, randomly, receive monotherapy valporic acid, carbamazepine or lithium carbonate. Results: The response answer (decrease of, at least 50 %, in one of the mania and depression scales) were very similar: 21-HAM-D + YMRS = 22.1%, 21-HAM-D + BRMS = 20.6% e 21-HAM-D + CARS-M = 23.5%; p < 0,368). The kappa values were : 21-HAM-D + YMRS X 21-HAM-D + CARS-M , Kappa = 0.87; 21-HAM-D + YMRS X 21-HAM-D + BRMS, Kappa = 0.78 e 21-HAM-D + CARS-M X 21-HAM-D + BRMS, Kappa = 0.91 (p < 0,001). Conclusions: The present study suggests that any of the three mania scales used (YMRS, BRMS, CARS-M) may be associated to 21-HAM-D in the assessment of the response o bipolar patients.

Introdução: Comparados com pacientes bipolares com episódios maníacos/hipomaníacos e depressivos, os que apresentam estados mistos tendem a curso mais grave da doença, início mais precoce, ocorrência mais frequente de sintomas psicóticos, maior risco de suicídio, altas taxas de comorbidade e tempo maior para remissão. Portanto, medidas objetivas de avaliação desses estados são necessárias. Objetivo:Avaliar a concordância entre três pares formados por uma de três escalas de mania (Young Mania Rating Scale (YMRS), Bech-Rafaelsen Mania Scale (BRMS) ou Clinician-Administered Rating Scale for Mania (CARS-M)) e uma de depressão (21-item Hamilton Depression) na avaliação da resposta a estabilizadores do humor em pacientes mistos. Método:Sessenta e oito (n=68) consecutivos pacientes ambulatoriais bipolares Tipo I e II com sintomatologia mista pelo DSM-IV-TR e pelos critérios de Cincinatti foram incluídos nesse estudo aberto de 8 semanas entre 2010 e 2014 foram randomizados para receberem em monoterapia, ácido valproico, carbamazepina ou carbonato de lítio. Resultados: O padrão de resposta (diminuição de, pelo menos, 50% em uma das escalas de mania e na de depressão) foi muito semelhante: 21-HAM-D + YMRS = 22,1%, 21-HAM-D + BRMS = 20,6% e 21-HAM-D + CARS-M = 23,5%; p < 0,368). Os resultados referentes à concordância de resposta revelam valores de kappa bastante altos: 21-HAM-D + YMRS X 21-HAM-D + CARS-M , Kappa = 0,87; 21-HAM-D + YMRS X 21-HAM-D + BRMS, Kappa = 0,78 e 21-HAM-D + CARS-M X 21-HAM-D + BRMS, Kappa = 0,91 (p < 0,001). Conclusões:O presente estudo sugere que qualquer uma das três escalas de mania utilizadas (YMRS, BRMS, CARS-M) pode ser associada à 21-HAM-D na avaliação da resposta em bipolares mistos. / Background: Compared with patients with bipolar disorder who exhibit pure manic/hypomanic or depressive episodes, the presence of mixed mood states is associated with a more severe course of illness, younger age of onset, more frequent ocurrence of psychotic symptoms, major risk of suicide, higher rates of comorbidities and longer time to achieve remission. Therefore, objective avaliation of these states are necessary. Objective: To evaluate the concorccance amog three pairs of three scales (Young Mania Rating Scale (YMRS), Bech-Rafaelsen Mania Scale (BRMS) or Clinician-Administered Rating Scale for Mania (CARS-M)) and a depression scale (21-item Hamilton Depression) in the assessment of response to humor stabizator drugs in mix bipolar patients. Methods: Sixty eight (n=68) consecutive bipolar type I and II outpatients with mixed sitomatology accordint to DSM-IV-TR and Cincinatti Criteria were included in these 8 weeks open-trial, from 2010 through 2014, to, randomly, receive monotherapy valporic acid, carbamazepine or lithium carbonate. Results: The response answer (decrease of, at least 50 %, in one of the mania and depression scales) were very similar: 21-HAM-D + YMRS = 22.1%, 21-HAM-D + BRMS = 20.6% e 21-HAM-D + CARS-M = 23.5%; p < 0,368). The kappa values were : 21-HAM-D + YMRS X 21-HAM-D + CARS-M , Kappa = 0.87; 21-HAM-D + YMRS X 21-HAM-D + BRMS, Kappa = 0.78 e 21-HAM-D + CARS-M X 21-HAM-D + BRMS, Kappa = 0.91 (p < 0,001). Conclusions: The present study suggests that any of the three mania scales used (YMRS, BRMS, CARS-M) may be associated to 21-HAM-D in the assessment of the response o bipolar patients.

Submitted by Renata Lopes (renatasil82@gmail.com) on 2017-06-14T12:24:26Z No. of bitstreams: 1 andreluciopintocoelhostroppa.pdf: 17748362 bytes, checksum: 19a0925c34309dbb1712aed625ee5121 (MD5) / Approved for entry into archive by Adriana Oliveira (adriana.oliveira@ufjf.edu.br) on 2017-06-29T12:06:43Z (GMT) No. of bitstreams: 1 andreluciopintocoelhostroppa.pdf: 17748362 bytes, checksum: 19a0925c34309dbb1712aed625ee5121 (MD5) / Made available in DSpace on 2017-06-29T12:06:43Z (GMT). No. of bitstreams: 1 andreluciopintocoelhostroppa.pdf: 17748362 bytes, checksum: 19a0925c34309dbb1712aed625ee5121 (MD5) Previous issue date: 2011-09-14 / Objetivos: Investigar a relação entre Religiosidade/Espiritualidade (R/E) e o estado de humor, qualidade de vida, ocorrência de internações hospitalares e tentativas graves de suicídio entre pacientes bipolares. Métodos: Em um estudo transversal com pacientes bipolares em tratamento ambulatorial (n=168) foram avaliados sintomas de Mania (YMRS) e Depressão (MADRS), Religiosidade (Duke Religious índex), Coping Religioso-Espiritual (Brief RCOPE) e Qualidade de Vida (WHOQOL-BREF). Dados sociodemográficos, número tentativas de suicídio e internações foram obtidos através da entrevista com o indivíduo e análise do prontuário médico. Foram realizadas regressões logísticas e lineares das associações entre os indicadores de R/E e as variáveis clinicas, controlando para variáveis sociodemográficas. Resultados: Referiram alguma filiação religiosa 148 (88,1%) indivíduos. Religiosidade Intrínseca e mais estratégias de Coping Religioso-Espiritual (CRE) positivo associaram-se a menos sintomas depressivos, respectivamente (OR) 0.19, (Cl) 0.06 — 0.57, (p) 0.003 e (OR) 0.25, (Cl) 0.09 — 0.71, (p) 0.01. Qualidade de vida associou-se a Religiosidade Organizacional (B) 0.188, (p) 0.019, Religiosidade Intrínseca (B) 0.306, (p) <0,001 e CRE positivo (B) 0.264, (p) 0.001. CRE negativo associou-se a pior qualidade de vida (B) — 0.253, (p) 0.001. Conclusões: Religiosidade intrínseca e CRE positivo associaram-se a menor ocorrência de depressão e melhor qualidade de vida de forma significativa. Estudos longitudinais serão úteis na investigação de relações causais. / Aims: To investigate the relationship between Religiousness/Spirituality (R/S) and mood, quality of life, hospitalizations and severe suicide attempts among bipolar patients. Methods: In a transversal study among bipolar patients under ambulatory care (n=168), symptoms of Mania (YMRS) and Depression (MADRS), Religiousness (Duke Religious Index), Religious Coping (Brief RCOPE) and Quality of Life (WHOQOL-BREF) were assessed. Socio-demographic data, number of suicide attempts and hospitalizations were obtained through an interview with the individual and analysis of medical records. Logistical and linear regressions of the association between the Religious indicators and clinical variables were carried out, controlling for socio-demographic variables. Results: 148 individuals mentioned some kind of religious affiliation (88.1%). Intrinsic Religiousness (IR) and Positive Religious Coping (RC) strategies associated to less depressive symptoms [respectively odds ratio (OR) = 0.19, 95% confidence interval (Cl) = 0.06 - 0.57, p=0.003 and OR= 0.25; Cl = 0.09 - 0.71, p=0.01]. Quality of life inversely associated with negative RC ([3= - 0.253, p=0.001) and directly associated with Organizational Religiousness (13= 0.188, p=0.019), Intrinsic Religiousness (13= 0.306, =p <0,001) and positive RC (13- 0.264, p= 0.001). Conclusions: Intrinsic Religiousness and positive RC are strongly associated with less depressive symptoms and better quality of life. Negative RC associated to worse quality of life. Religiousness is a relevant aspect which must be taken into consideration by physicians when assessing and guiding

One of the key features of bipolar disorder (BD) is risky and impulsive decision-making, behaviours theorised to arise from dysregulation in a biobehavioural system governing approach of rewards. However the neural mechanisms of this conceptual model have not been well specified, and there remains a gap between this model and key clinical phenomena such as mixed episodes. This thesis takes a neuroeconomics and reinforcement learning approach to characterise the neural mechanisms of motivational decision-making in BD. A review of the neurobiological evidence for reward dysregulation in BD (Chapter 1) arrives at a model in which striatal hypersensitivity is exacerbated by reduced dorsolateral prefrontal cortical (dlPFC) control. This model is tested by four studies using electrophysiology, source analysis and functional neuroimaging. Chapters 3 and 4 employ EEG to explore how hypomanic traits modulate motivational processing in contexts requiring learning and trade-offs between risk and between immediate and delayed reward. In Chapter 3, high trait hypomania was associated with impaired loss learning and a neural evaluation of rewards and losses more favourably, relative to low hypomania. This “rose-tinted” bias may reinforce risky behaviours that pay off and reduce learning from aversive repercussions. Chapter 4 reports an attentional bias towards immediate reward which may drive a steeper delay discounting trajectory and an inability to delay gratification. In Chapters 5 and 6 simultaneous electrophysiological and functional neuroimaging was utilised to characterise spatial and temporal perturbations to the mesocorticolimbic reward network in a clinical sample of BD. Patients showed a poorer ventromedial prefrontal cortical representation of the objective value of outcomes as well as a heightened striatal reward response. The latter finding was related to decreased dlPFC activation, which also interacted with residual manic symptoms. This is interpreted in terms of reduced top-down executive control that is exacerbated by residual manic symptoms, suggesting a potential mechanism underlying relapse and extremely high levels of reward-seeking seen during mania. EEG source imaging localised differences during reward outcome evaluation to early sensory-attentional (N1), reward evaluation (FRN) and cognitive (P300) stages of processing. For rewards, patients exhibited greater activity in precuneus, frontal eye fields (N1) and ventral anterior cingulate (FRN), consistent with an attentional bias to reward that drives hyperactivity in reward circuitry. Collectively the results provide evidence of reward dysfunction from behavioural measures and two neuroimaging modalities. The results support a model in which a core hypersensitivity to reward and a “rose-tinted” evaluation bias act to 1) potentiate the impact of rewarding outcomes and 2) attenuate aversive ones maintains a distorted representation of objective likelihood and value associated with actions. This is exacerbated by reduced prefrontal control – which may be particularly associated with mania – highlighting a potential target for novel pharmacological and psychological interventions.

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