Text in English / Literature notes an increase in the number of children and adolescents diagnosed with bipolar disorder. Several challenges faced by clinicians who diagnose and treat early-onset bipolar disorder have been discussed with particular emphasis being placed on its pharmacological management. The contributions made by psychologists including psychosocial interventions, have been explored in this regard; however, there still exists a paucity of voices in the field of psychology that discuss the experiences surrounding the management of this disorder. Most studies on early-onset bipolar disorder do not distinguish between childhood and adolescent presentations. Adolescence has been recognized herein, as a distinct developmental and transitional phase and thus, it forms the basis of this inquiry. This qualitative study thus explores clinical psychologists’ experiences ofmanaging adolescents diagnosed with bipolar disorder and will be approached from a social constructionist perspective which was selected as a means of exploring the meanings that individuals attribute to their experiences as they engage with others in their environment. A literature review evaluated the current available literature on juvenile bipolar disorder. Clinical psychologists in private practices were interviewed using semi-structured interviews. The participants were selected using purposive sampling. Two pilot studies were used to pre-test the study. One participant took part in pilot study 1 and one in pilot study 2. Thereafter, four semi-structured interviews were held with four participants who took part in the main study. Themes were drawn from the data and were explored using thematic content analysis. An analysis of the themes revealed several shared experiences in clinical psychologists’ management of juvenile bipolar disorder which were similar to what is reflected in the current available literature on early-onset bipolar disorder. / Psychology / M.A. (Clinical Psychology)

O HCL-32 é um questionário de 32 itens, de auto-aplicação, onde os sintomas são avaliados através de respostas do tipo \"sim\" (presente ou típico) ou \"não\" (não está presente ou atípico). Além disso, o HCL-32 tem 8 seções para avaliar a gravidade e o impacto dos sintomas sobre os diferentes aspectos da vida do paciente. A pontuação é obtida pela soma das respostas positivas para os 32 itens sobre hipomania. A versão original do HCL-32 foi traduzido e adaptado para o português brasileiro. A primeira versão do HCL-32 foi traduzida por nós, revisados por especialistas em transtornos de humor, bem como por um professor de português brasileiro. Foi então retro-traduzida por um professor de inglês americano. Dos indivíduos inicialmente selecionados, foram excluídos 27, 11 devido à presença de comorbidades com abuso de substância, e 16 devido à incapacidade de preencher corretamente o questionário. Assim, nossa amostra final ficou composta por 81 pacientes com TB (37 TBI; 44TBII), 42 com TDM, e 362 sujeitos de uma população não clínica. A consistência interna foi elevada, com um alfa de Cronbach de 0,793 para todo o HCL-32 VB, indicando que os itens do questionário são suficientemente homogêneos. Indivíduos com TB tiveram a maior pontuação no HCL-32 VB. A média de respostas afirmativas foi significativamente diferente de acordo com o diagnóstico. Analisamos a capacidade em diferenciar os diagnósticos através da curva ROC. A área sob a curva foi de 0.702, indicando a boa capacidade da escala para distinguir entre diagnósticos. A melhor combinação de sensibilidade (0.75) e especificidade (0.58) ocorreu com uma pontuação acima de 18. Esta pontuação distinguiu entre pacientes com TB e TDM. Para comparar as propriedades discriminativas do HCL-32 VB e MDQ VB, foram calculadas a sensibilidade e especificidade de ambos os questionários. A HCL-32 VB teve uma sensibilidade de 0.75 e especificidade de 0.58. O MDQ teve sensibilidade de 0.70 e especificidade de 0.58. Assim, a HCL-32 BV apresentou maior sensibilidade, mas a mesma especificidade que o MDQ. A análise fatorial resultou em nove fatores com autovalores > 1, explicando 53,1% da variância total. De acordo com o teste Scree, foi preferida uma solução com três fatores. O primeiro fator, com autovalor de 4,90, explicou 15,3% da variância e foi composto por 10 itens. Essa subescala reflete questões relacionadas com ativação/elação. O segundo fator, com autovalor de 3,48 (10,88% da variância), composto por 11 itens e sua estrutura inclui questões relacionadas com \"irritabilidade / comportamento de risco\". O terceiro fator, com autovalor de 1,56 (4,87% da variância), ficou composto por cinco itens e sua estrutura reflete questões relacionadas com \"desinibição / ativação sexual. Os parâmetros psicométricos de HCL-32 VB sugerem que é um instrumento útil para a detecção de hipomania em pacientes com transtornos de humor. O HCL-32 VB é um questionário rápido de auto-aplicação e de fácil interpretação / The HCL-32 is a 32-item self-administered questionnaire where symptoms are assessed through yes (present or typical) or no (not present or untypical) answers. In addition, the HCL-32 has 8 other sections evaluating the severity and impact of the symptoms on different aspects of patient\'s life. The score is obtained by adding the positive responses to the 32 symptoms of hypomania. The original version of the HCL-32 was translated and adapted to Brazilian Portuguese .The first draft of the Brazilian version was translated by us, reviewed by experts in mood disorders, as well as by a Brazilian-Portuguese teacher. It was then back-translated by an English (American) teacher. Of the individuals initially enrolled, 27 individuals were excluded; 11 due to the presence of comorbidities with substance abuse, and 16 due to inability to properly fill the questionnaires. Accordingly, our final sample comprised of 81 patients with BP (37 BPI; 44 BPII), 42 with MDD, and 362 subjects from a nonclinical population. Internal consistency was high, with a Cronbach\'s alpha of 0.793 for the entire HCL-32 BV, indicating that the items of the questionnaire are sufficiently homogeneous. Individuals with BP had the highest HCL-32 BV scores. The mean number of affirmative responses to the list of symptoms was significantly different according to diagnosis. We analyzed the scale\'s discrimination for BP trough the ROC curve. The area under the curve was 0.702 indicating the good ability of this screening scale. The best combination of sensitivity (0.75) and specificity (0.58) happened with a score above 18. This score discriminates between BP patients and MDD. To compare the discriminative properties of HCL-32 BV and MDQ, we calculated the sensitivity and specificity of both questionnaires. The HCL-32 BV had a sensitivity of 0.75 and specificity of 0.58. The MDQ had sensitivity of 0.70 and specificity of 0.58. Hence, the HCL-32 BV showed higher sensitivity but the same specificity than the MDQ. The factor analysis resulted in 9 factors with eigenvalues > 1, explaining 53.1% of the total variance. According to the Scree test, a 3-factor solution was preferred. The first factor, with an Eigenvalue of 4.90, explained 15.3% of the variance and comprised 10 items . This subscales structure reflects questions related to active/elated symptoms. The second factor, with an Eigenvalue of 3.48 (10.88% of the variance), comprised 11 items and its structure includes questions associated with irritable/risk-taking items. The third factor, with an Eigenvalue of 1.56 (4.87% of variance), comprised 5 itens and its structure reflect questions related to disinhibition/activation sexual. The psychometric parameters of HCL-32 BV suggest it as a useful instrument for the detection of hypomania in patients with mood disorders. HCL-32 BV is a brief, self-administered questionnaire of easy application and interpretation

O HCL-32 é um questionário de 32 itens, de auto-aplicação, onde os sintomas são avaliados através de respostas do tipo \"sim\" (presente ou típico) ou \"não\" (não está presente ou atípico). Além disso, o HCL-32 tem 8 seções para avaliar a gravidade e o impacto dos sintomas sobre os diferentes aspectos da vida do paciente. A pontuação é obtida pela soma das respostas positivas para os 32 itens sobre hipomania. A versão original do HCL-32 foi traduzido e adaptado para o português brasileiro. A primeira versão do HCL-32 foi traduzida por nós, revisados por especialistas em transtornos de humor, bem como por um professor de português brasileiro. Foi então retro-traduzida por um professor de inglês americano. Dos indivíduos inicialmente selecionados, foram excluídos 27, 11 devido à presença de comorbidades com abuso de substância, e 16 devido à incapacidade de preencher corretamente o questionário. Assim, nossa amostra final ficou composta por 81 pacientes com TB (37 TBI; 44TBII), 42 com TDM, e 362 sujeitos de uma população não clínica. A consistência interna foi elevada, com um alfa de Cronbach de 0,793 para todo o HCL-32 VB, indicando que os itens do questionário são suficientemente homogêneos. Indivíduos com TB tiveram a maior pontuação no HCL-32 VB. A média de respostas afirmativas foi significativamente diferente de acordo com o diagnóstico. Analisamos a capacidade em diferenciar os diagnósticos através da curva ROC. A área sob a curva foi de 0.702, indicando a boa capacidade da escala para distinguir entre diagnósticos. A melhor combinação de sensibilidade (0.75) e especificidade (0.58) ocorreu com uma pontuação acima de 18. Esta pontuação distinguiu entre pacientes com TB e TDM. Para comparar as propriedades discriminativas do HCL-32 VB e MDQ VB, foram calculadas a sensibilidade e especificidade de ambos os questionários. A HCL-32 VB teve uma sensibilidade de 0.75 e especificidade de 0.58. O MDQ teve sensibilidade de 0.70 e especificidade de 0.58. Assim, a HCL-32 BV apresentou maior sensibilidade, mas a mesma especificidade que o MDQ. A análise fatorial resultou em nove fatores com autovalores > 1, explicando 53,1% da variância total. De acordo com o teste Scree, foi preferida uma solução com três fatores. O primeiro fator, com autovalor de 4,90, explicou 15,3% da variância e foi composto por 10 itens. Essa subescala reflete questões relacionadas com ativação/elação. O segundo fator, com autovalor de 3,48 (10,88% da variância), composto por 11 itens e sua estrutura inclui questões relacionadas com \"irritabilidade / comportamento de risco\". O terceiro fator, com autovalor de 1,56 (4,87% da variância), ficou composto por cinco itens e sua estrutura reflete questões relacionadas com \"desinibição / ativação sexual. Os parâmetros psicométricos de HCL-32 VB sugerem que é um instrumento útil para a detecção de hipomania em pacientes com transtornos de humor. O HCL-32 VB é um questionário rápido de auto-aplicação e de fácil interpretação / The HCL-32 is a 32-item self-administered questionnaire where symptoms are assessed through yes (present or typical) or no (not present or untypical) answers. In addition, the HCL-32 has 8 other sections evaluating the severity and impact of the symptoms on different aspects of patient\'s life. The score is obtained by adding the positive responses to the 32 symptoms of hypomania. The original version of the HCL-32 was translated and adapted to Brazilian Portuguese .The first draft of the Brazilian version was translated by us, reviewed by experts in mood disorders, as well as by a Brazilian-Portuguese teacher. It was then back-translated by an English (American) teacher. Of the individuals initially enrolled, 27 individuals were excluded; 11 due to the presence of comorbidities with substance abuse, and 16 due to inability to properly fill the questionnaires. Accordingly, our final sample comprised of 81 patients with BP (37 BPI; 44 BPII), 42 with MDD, and 362 subjects from a nonclinical population. Internal consistency was high, with a Cronbach\'s alpha of 0.793 for the entire HCL-32 BV, indicating that the items of the questionnaire are sufficiently homogeneous. Individuals with BP had the highest HCL-32 BV scores. The mean number of affirmative responses to the list of symptoms was significantly different according to diagnosis. We analyzed the scale\'s discrimination for BP trough the ROC curve. The area under the curve was 0.702 indicating the good ability of this screening scale. The best combination of sensitivity (0.75) and specificity (0.58) happened with a score above 18. This score discriminates between BP patients and MDD. To compare the discriminative properties of HCL-32 BV and MDQ, we calculated the sensitivity and specificity of both questionnaires. The HCL-32 BV had a sensitivity of 0.75 and specificity of 0.58. The MDQ had sensitivity of 0.70 and specificity of 0.58. Hence, the HCL-32 BV showed higher sensitivity but the same specificity than the MDQ. The factor analysis resulted in 9 factors with eigenvalues > 1, explaining 53.1% of the total variance. According to the Scree test, a 3-factor solution was preferred. The first factor, with an Eigenvalue of 4.90, explained 15.3% of the variance and comprised 10 items . This subscales structure reflects questions related to active/elated symptoms. The second factor, with an Eigenvalue of 3.48 (10.88% of the variance), comprised 11 items and its structure includes questions associated with irritable/risk-taking items. The third factor, with an Eigenvalue of 1.56 (4.87% of variance), comprised 5 itens and its structure reflect questions related to disinhibition/activation sexual. The psychometric parameters of HCL-32 BV suggest it as a useful instrument for the detection of hypomania in patients with mood disorders. HCL-32 BV is a brief, self-administered questionnaire of easy application and interpretation

Aim: The overall aim was to create knowledge about what it means to live with bipolar disorder from an existential perspective, both for individuals with the diagnosis and for their close relatives.Method: An existential perspective in this context entails that it is explored and described from a lifeworld perspective of individuals who in various ways experience that which is termed as bipolar disorder. The lifeworld phenomenological approach Reflective Lifeworld Research (RLR) was used in the four empirical studies. Meaning-oriented interviews and analysis were conducted following the leading methodological principles of the chosen scientific approach. A synthesis, based on lifeworld hermeneutic existential philosophy, then presents how it is possible to understand the perspective of individuals with bipolar disorder and their close relatives as a coherent whole.Findings and conclusions: A magnitude and complexity of experiencing, which means that life with bipolar disorder is characterized by extra dimensions, specific tension and contradictions, has been elucidated. Knowledge of the meaning of these aspects enables for the persons with the illness and for their close relatives to understand, to put words to, and to communicate how their life is and what they need, which in turn enhances their ability to influence their lives. It also increases the opportunities for professional caregivers to develop care, both in content and organization, so that it can meet the actual needs of those concerned in an adequate way.Living with bipolar disorder means so much more than the usual description with changes between episodes of depression and mania. The diagnosis “bipolar disorder” thus appears to be an inadequate label that only reflects the more obvious and visible dimensions of the illness, while those that characterize life in its entirety remain hidden.The thesis also shows that the importance of the common everyday life of persons with bipolar disorder and their close relatives should be highlighted as the most important factor in a liveable existence. A change in the view of mental health care is thus needed; a change that is characterized by consensus, collaboration and transparent communication between the person with the illness, their close relatives and mental health care. The common goal should be about meeting actual needs, and to strengthen a profound connectedness in order to make everyday life more liveable. / Disputationen sker den 2012-11-16, Sal Myrdal, Hus K, Växjö, kl. 10:30.

This study applies statistical models to mood in patients with bipolar disorder. Three analyses of telemonitored mood data are reported, each corresponding to a journal paper by the author. The first analysis reveals that patients whose sleep varies in quality tend to return mood ratings more sporadically than those with less variable sleep quality. The second analysis finds that forecasting depression with weekly data is not feasible using weekly mood ratings. A third analysis shows that depression time series cannot be distinguished from their linear surrogates, and that nonlinear forecasting methods are no more accurate than linear methods in forecasting mood. An additional contribution is the development of a new k-nearest neighbour forecasting algorithm which is evaluated on the mood data and other time series. Further work is proposed on more frequently sampled data and on system identification. Finally, it is suggested that observational data should be combined with models of brain function, and that more work is needed on theoretical explanations for mental illnesses.

Bipolar disorder is a heritable psychiatric disorder, and several of the genes associated with bipolar disorder and related psychotic disorders are involved in the development and maintenance of white matter in the brain. Patients with bipolar disorder have an increased incidence of white matter hyper-intensities, and quantitative brain imaging studies collectively indicate subtle decreases in white matter density and integrity in bipolar patients. This suggests that genetic vulnerability to psychosis may manifest itself as reduced white matter integrity, and that white matter integrity is an endophenotype of bipolar disorder. This thesis comprises a series of studies designed to test the role of white matter in genetic risk to bipolar disorder by analysis of diffusion tensor imaging (DTI) data in the Bipolar Family Study. Various established analysis methods for DTI, including whole-brain voxel-based statistics, tract-based spatial statistics (TBSS) and probabilistic neighbourhood tractography, were applied with fractional anisotropy (FA) as the outcome measure. Widespread but subtle white matter integrity reductions were found in unaffected relatives of patients with bipolar disorder, whilst more localised reductions were associated with cyclothymic temperament. Next, the relation of white matter to four of the most prominent psychosis candidate genes, NRG1, ErbB4, DISC1 and ZNF804A, was investigated. A core haplotype in NRG1, and three of the four key single nucleotide polymorphisms (SNPs) within it, showed an association with FA in the anterior thalamic radiations and the uncinate fasciculi. For the three SNPs considered in ErbB4, results were inconclusive, but this was consistent with the background literature. Most notable however, was a clear association of a non-synonymous DISC1 SNP, Ser704Cys, with FA extending over most of the white matter in the TBSS and voxel-based analyses. Finally, FA was not associated with a genome-wide supported risk SNP in ZNF804A, a finding which could not be attributed to a lack of statistical power, and which contradicts a strong, but previously untested hypothesis. Whilst the above results need corroboration from independent studies, other studies are needed to address the cellular and molecular basis of these findings. Overall, this work provides strong support for the role of white matter integrity in genetic vulnerability to bipolar disorder and the wider psychosis spectrum and encourages its future use as an endophenotype.

Although psychological research into manic experiences is increasing, it remains an underresearched phenomenon. In particular, there is a dearth of qualitative research exploring these experiences in a clinical sample of people diagnosed with Bipolar Disorder. This study examined six participants’ experiences of mania using Interpretative Phenomenological Analysis. Through semi-structured interviews, the participants provided detailed accounts of how they made sense of and experienced their manic states. Three master themes were described: “A mixed relationship with mania,” “A separate and controlled self”, and “The struggle to be different.” The first master theme explored the participants’ mixed and ambivalent relationship with their manic experiences. These were viewed as both alluring and dangerous, but overall the perceived costs had outweighed the benefits, for all but one of the participants. Most participants described losses in relation to giving up their manic experiences, as well as losses related to the destructive consequences of their episodes. The second master theme examined perceptions of mania as a separate, uncontrollable phenomenon, over which they had little influence. It was hypothesised that these explanations served to relieve these participants from underlying negative emotions, such as guilt, regret, shame and selfstigma. The third master theme described how manic experiences had represented struggles to be different. These included a struggle against society; a struggle to experience a preferred self; and a struggle to access very unique experiences or abilities. A number of issues were discussed in relation to the above themes. These included positive and conflicting appraisals of high moods; loss; entrapment and helplessness; ambivalence; negative moral emotions and a preferred manic identity. A range of therapeutic approaches were suggested as potentially helpful for some of these issues. These included Motivational Interviewing, Narrative, Constructivist and Compassion therapies. Additionally, the findings of the study provided support for existing therapies for Bipolar Disorder; particularly Cognitive-Behavioural Therapy (CBT) and Interpersonal & Social Rhythm Therapy (IPSRT).

Major depressive disorder (MDD) and bipolar disorder (BD) are psychiatric diseases that affect behavior and impair cognition. A gene important to these disorders is the brain derived neurotrophic factor (BDNF) which is involved in processes controlling neuroplasticity. Previous studies have suggested that BDNF expression levels have to be finely regulated for normal mental health and cognition. This study therefore aimed to identify cis-regulatory elements that regulate BDNF promoter IV (BP4), which plays a role in mood and cognition, and investigated how polymorphisms in these cis-regulatory elements might alter BP4 activity contributing to MDD and BD. BP4-LacZ transgenic mice and primary neuron cultures were used to show that BP4 was active in the hippocampus, cortex and amygdala and responded to PKC, KCl and Wnt signaling activation. Using comparative genomics, two highly conserved regions were identified, BE5.1 and BE5.2, which contain the rs10767664 and rs12273363 polymorphisms respectively. Reporter gene assays in primary cultures derived from these brain structures showed that BE5.1 and BE5.2 were responsible for “filtering” or “gating” the effects of different combination of activated signal transduction pathways on BP4. Thus, BE5.1 increased BP4 response to forskolin in cortical cultures while abolishing BP4 response to PMA in hippocampal cultures. Similarly, BE5.2 permitted BP4 response to KCl and combined forskolin and PMA treatment, but not individual forskolin and PMA treatment nor LiCl in cortical cultures. Significantly, the minor allele of rs12273363, which has been associated with MDD and BD susceptibility, acted as a more potent repressor of BP4 response to neuron depolarization by KCl and PKA/PKC activation in different primary cultures. The possible relevance of these findings to the role of altered BDNF expression in MDD and BD are discussed.

Bakgrund: Bipolär sjukdom är en kronisk sjukdom som medför lidande för individen. Sjukdomen kännetecknas av återkommande maniska och depressiva perioder. Den påverkar individens livsvärld och hens upplevelse av sin hälsa. Sjuksköterskan har en betydande roll i att stödja dessa patienter. Syfte: Syftet är att beskriva patienters upplevelser av att leva med bipolär sjukdom. Metod: En kvalitativ metod användes och baserades på sex självbiografier som analyserades med innebördsanalys. Resultat: I resultatet framkom fem teman. Dessa är: upplevelsen av att leva i becksvart mörker och det klaraste ljus, att uppleva skam, upplevelsen av att förlora kontrollen över sitt liv, att uppleva rädsla samt betydelsen av trygghet och stöd för att minska ensamheten. Diskussion: Personer med bipolär sjukdom upplever både hälsa och ohälsa beroende på vart i sjukdomen de befinner sig. Familjen och samhället har en inverkan på hur individen upplever sin tillvaro. Med stöd från en sjuksköterska kan personerna delvis kontrollera sin sjukdom. Deras verklighet förändras ständigt och stöd från sjuksköterskan är betydelsefullt. Konklusion: Personer med bipolär sjukdom upplever starka känslor som påverkar deras liv. För att personerna ska känna sig sedda och bekräftade måste sjuksköterskan visa öppenhet inför individens unika livsvärld. / Background: Bipolar disorder is a chronic disease that entails suffering for the individual. The disease characterized by recurrent manic and depressive episodes. It affects the individual's lifeworld and his or her's health experience. The nurse has a significant role to support these patients. Aim: The aim is to describe patients' experiences of living with bipolar disorder. Method: A qualitative method was used and was based on six autobiographies analyzed with meaning analysis. Results: The results showed five themes. These are: the experience of living in the pitch-black darkness and the clearest light, the experience of shame, the experience of losing control of their life, the experience of fear and the sense of safty and support to reduce loneliness. Discussion: People with bipolar disorder experience both health and illness, depending on their current state of disease. The family and society have an impact on how the individual experience their existence. With support from a nurse the person can achieve control of the disease. Their reality is constantly changing and support from a nurse is important. Conclusion: People with bipolar disorder experience strong emotions that affect their lives. For people to feel seen and recognized the nurse must show candidness to the individual's unique lifeworld.

Aim: The overall aim was to create knowledge about what it means to live with bipolar disorder from an existential perspective, both for individuals with the diagnosis and for their close relatives. Method: An existential perspective in this context entails that it is explored and described from a lifeworld perspective of individuals who in various ways experience that which is termed as bipolar disorder. The lifeworld phenomenological approach Reflective Lifeworld Research (RLR) was used in the four empirical studies. Meaning-oriented interviews and analysis were conducted following the leading methodological principles of the chosen scientific approach. A synthesis, based on lifeworld hermeneutic existential philosophy, then presents how it is possible to understand the perspective of individuals with bipolar disorder and their close relatives as a coherent whole. Findings and conclusions: A magnitude and complexity of experiencing, which means that life with bipolar disorder is characterized by extra dimensions, specific tension and contradictions, has been elucidated. Knowledge of the meaning of these aspects enables for the persons with the illness and for their close relatives to understand, to put words to, and to communicate how their life is and what they need, which in turn enhances their ability to influence their lives. It also increases the opportunities for professional caregivers to develop care, both in content and organization, so that it can meet the actual needs of those concerned in an adequate way. Living with bipolar disorder means so much more than the usual description with changes between episodes of depression and mania. The diagnosis “bipolar disorder” thus appears to be an inadequate label that only reflects the more obvious and visible dimensions of the illness, while those that characterize life in its entirety remain hidden. The thesis also shows that the importance of the common everyday life of persons with bipolar disorder and their close relatives should be highlighted as the most important factor in a liveable existence. A change in the view of mental health care is thus needed; a change that is characterized by consensus, collaboration and transparent communication between the person with the illness, their close relatives and mental health care. The common goal should be about meeting actual needs, and to strengthen a profound connectedness in order to make everyday life more liveable.