En betydande andel individer med bipolär sjukdom upplever kvarvarande, subkliniska symtom mellan egentliga sjukdomsepisoder. Sådana restsymtom är förenade med sänkt livskvalitet och förhöjd risk för återfall i sjukdomsepisoder. Syftet med föreliggande studie var att undersöka huruvida en kort, internetadministrerad behandling är genomförbar och kan ge en minskning av depressiva restsymtom, genom interventioner riktade mot sömn och emotionsreglering. För detta syfte användes en single-subject design med upprepade mätningar (n=4). Studiens resultat visar att behandlingen är genomförbar och att den, för vissa individer, kan ge en minskning av depressiva restsymtom. Vidare forskning kring behandlingen är motiverad. / A significant proportion of persons diagnosed with bipolar disorder experience subclinical, residual symptoms between major episodes. Residual symptoms are associated with poor quality of life and increased risk of relapse. The current study aims at investigating whether a time limited, internet-based treatment targeting disturbed sleep and emotion regulation is feasible and successful in reducing residual depressive symptoms. Pertaining to this purpose, a single-subject design with repeated measures was used (n=4). Results show that the treatment is feasible and, for some individuals, can lead to a decrease in depressive symptoms. Future studies regarding this treatment are warranted.

Bipolär sjukdom är en kronisk sjukdom där personen upplever maniska och depressiva perioder. Under manin får personen en ökad energinivå, tankarna flödar samt omdömet försämras. Depressionen kännetecknas av nedstämdhet och en dyster sinnesstämning. Syftet med denna studie var att beskriva vilka erfarenheter en person har av att leva med bipolär sjukdom. En narrativ analys har använts. Denna bygger på fyra självbiografier. I resultatet framkom det att det kan ta lång tid innan diagnosen ställs och därmed rätt behandling sätts in. Samtidigt är det vanligt att patienterna slutar ta sina mediciner på grund av biverkningar. Personer med bipolär sjukdom känner ofta oro och ångest inför att insjukna i nya maniska eller depressiva perioder. Känslor som oro och ångest kan i kombination med depressiva perioder leda till självskadebeteende. Till exempel att de skär sig. Den som drabbas av bipolär sjukdom kan ha stor nytta av familjen som skyddsnät. Även andra personer som är i en likande situation kan vara ett stort stöd. / Bipolar disorder is a chronic disease where the person experiencing manic and depressive episodes. During mania has the person an increased energy level, the thoughts flow and impaired reviewed. Depression is characterized by sadness and a gloomy mood. The purpose of this study was to describe the experience a person has to live with bipolar disorder. A narrative analysis was used. This is based on four autobiographies. The results showed that it can take a long time before getting diagnosed and therefore the appropriate treatment. While it is common that patients stop taking their medications because of side effects. People with bipolar disorder often feel anxiety before falling ill with manic or depressive episodes. Emotions such as worry and anxiety can be combined with depressive episodes lead to self-injury. For example, they cut themselves. Those who suffer from bipolar disorder can benefit greatly from their family as a safety-net. Even other people who are in a similar situation can be a great support.

The aims of this study were to explore partners' experiences of living with a loved one with bipolar disorder and how they coped with these experiences. Another aim was to explore whether these individuals felt that Counselling Psychologists could play a role with care-giving tasks and their own psychological needs. Five individuals, who were currently living with, or had been living with, a partner with bipolar disorder, volunteered and participated in a semi-structured interview. These interviews were transcribed and analysed using Interpretative Phenomenological Analysis (IPA) as described by Smith, Flowers and Larkin (2009). A table of super-ordinate and sub-ordinate themes was created as a result of this analysis. Partners' experiences are characterised by various phases which partners could move around and between. This was referred to as the 'cycle of changing illness awareness'. This theme adds to the existing literature. As partners moved around and between these phases they experienced different emotions, employed different coping strategies and had experiences of being 'in it together' interchangeably with being 'isolated and alone'. This research concludes that partners' experiences of caring for a loved one with bipolar disorder do not follow a linear, predictable path and as a result, professionals working with caregivers need to be aware of which phases of the 'cycle of changing illness awareness' partners are in when offering interventions. The analysis also suggests that partners cope differently when their loved one is manic and depressed. However, further exploration is still needed.

No description available.

The objective of this thesis was to determine the association between exposure to parental BD during childhood and risk of mood disorder. Offspring of one parent with BD completed annual clinical assessments as part of a 16-year prospective cohort study. Clinical data in the parents from Ottawa and Halifax were mapped onto the first decade of their offspring’s life to estimate the timing, duration and severity of exposure to their illness. The duration of parental BD was associated with a 2 to 2.5 fold increased risk of any psychopathology (HR: 1.9, 95%CI: 1.0-4.0), and unipolar depression (HR: 2.6, 95%CI: 0.9-7.5), and a 7 fold increased risk of substance use disorders (HR: 7.1, 95%CI: 1.8-37.0). A longer duration of exposure to parental BD may be an important indicator of mood and non-mood psychopathology risk in offspring. This has implications for early intervention and preventive efforts in high-risk youth.

No description available.

Bipolar disorders and recurrent depressions are two common psychiatric disorders with a life time prevalence of approximately 1% and 8%, respectively. Despite treatment these patients suffer from affective symptoms up to 50% of the time, resulting in lower well-being. The average life length is also reduced with 10-15 years, mainly attributable to suicide and cardiovascular disease. Increased stress is one of many factors that have been shown to be linked to an increased risk for developing affective disorders and some comorbid somatic conditions such as metabolic disturbances and cardiovascular disease. An increased stress level is known to cause hyperactivity of the hypothalamic-pituitary-adrenal-axis (HPA-axis) with increased cortisol secretion. Hyperactivity of the HPA-axis (or hypercortisolism) is one of the most replicated neurobiological finding in depression. In other stress related disorders it has however been shown that prolonged stress over long periods of time can lead to a state of low HPA-axis activity, hypocortisolism. Since persons with recurrent affective disorders such as bipolar disorder and recurrent depression are exposed to a high degree of recurrent and chronic stress it could be expected that in addition to hypercortisolism, a state of hypocortisolism could also develop in these disorders, potentially exerting an influence upon the psychological and somatic wellbeing among these patients. The major aim of this thesis was to evaluate whether hypocortisolism is related to relevant psychiatric and somatic phenotypes in recurrent affective disorders. In bipolar disorder, individuals with hypocortisolism exhibited a higher degree of depression and low quality of life compared to patients with normal HPA-axis activity. In recurrent depression, individuals with hypocortisolism exhibited shorter leukocyte telomere length than patients with normal or high HPA-axis activity, which is an indication of an accelerated aging process. In a sample of both bipolar and recurrent depression patients, hypocortisolism was associated with an increased proportion of obesity, dyslipidemia and metabolic syndrome compared with patients with normal or high HPA-axis activity. Patients with recurrent depression showed a higher occurrence of hypocortisolism than the control sample representative of the general population. Patients with bipolar disorder showed a similar occurrence of hypocortisolism as the control sample. Among bipolar disorder patients with a low degree of lifetime with lithium prophylaxis, there was an inverse correlation between age and HPA-axis activity. In contrast, among patients with a higher degree of lifetime with lithium prophylaxis as well as among the controls, there was no correlation between age and HPA-axis activity. Accordingly, hypocortisolism was most common among older patients with a low degree of lifetime with lithium prophylaxis. In conclusion, hypocortisolism in both recurrent depression and bipolar disorder was associated with multiple clinically-relevant phenotypes. Additionally it was shown for bipolar disorder patients that increasing age was a risk factor for hypocortisolism and that prophylactic lithium treatment was a protective factor. It is argued that the protective effect of lithium towards the HPA-axis is attributable to its mood-stabilizing effect, which in turn reduces the chronic stress level. These results provide new insight into the role of hypocortisolism and chronic stress in recurrent affective disorders warranting further studies and hopefully providing clues to improved treatment strategies.

Evidências sugerem o envolvimento de um estado de inflamação crônica de baixo grau na fisiopatologia do transtorno bipolar (TB). Os estudos apresentados nesta tese tiveram como objetivo explorar o papel da inflamação crônica nos mecanismos fisiopatológicos do TB através da avaliação dos níveis séricos de proteína C-reativa (PCR). A PCR é um marcador de inflamação sistêmica comumente utilizado na prática clínica, sendo considerado fator de risco para várias patologias, incluindo câncer e doença cardiovascular. O primeiro artigo, através de um estudo de meta-análise, teve como objetivo avaliar o tamanho de efeito da associação entre níveis de PCR em pacientes bipolares nas diferentes fases de humor (n=730) comparado a indivíduos controles (n=888). Pacientes bipolares apresentaram níveis de PCR significativamente elevados em comparação ao grupo controle, com moderado tamanho de efeito (effect size, ES = 0.39; 95% IC, 0.24 – 0.55; P < 0.0001). Níveis de PCR foram significativamente maiores em pacientes maníacos (ES = 0.73; 95% IC, 0.44 – 1.02; P < 0.001) e em eutímicos (ES = 0.26; 95% IC, 0.01 – 0.51; P = 0.04). O segundo artigo se propôs a revisar dados da literatura relacionados a biomarcadores periféricos potencialmente implicados na progressão do TB. Pacientes em diferentes estágios do TB apresentaram níveis alterados de marcadores de estresse oxidativo, neurotrofinas e de inflamação, incluindo a PCR, o que reforça a hipótese da inflamação crônica exercer um papel importante na fisiopatologia do TB. Em seguida, considerando a abordagem multidimensional no TB, o terceiro artigo avaliou a reatividade emocional como uma dimensão relevante para caracterizar pacientes bipolares apresentando sintomas subclínicos de humor durante a fase de remissão (N=613). Apesar de todos pacientes estarem em remissão, a maioria deles (68%) apresentou reatividade emocional anormal (hipo ou hiper-reatividade emocional). Esse estudo avaliou, também, o funcionamento psicossocial nesses pacientes e os níveis de PCR ultra-sensível como um possível marcador objetivo de hiper-reatividade emocional no TB. Os pacientes com hiper-reatividade emocional, em comparação aos pacientes com hipo- ou normal reatividade emocional, apresentaram prejuízo cognitivo e níveis de PCR significativamente mais elevados (P < 0.001). Esses resultados provêm de um estudo transversal e, portanto, conclusões sobre causalidade dessas associações não podem ser inferidas, já que outros fatores, além dos níveis de PCR, podem também contribuir para o estado inflamatório crônico observado nesses pacientes. Em suma, os resultados desta tese sugerem que a inflamação crônica de baixo grau, evidenciada pelas alterações nos níveis de PCR, parece estar implicada na fisiopatologia e na progressão do TB. Novas intervenções terapêuticas com alvo em mecanismos inflamatórios e na modulação dos níveis de PCR devem ser priorizados em estudos futuros. / Evidence suggests that chronic low-grade inflammation appears to be involved in the pathophysiology of bipolar disorder (BD). The studies presented in this thesis aimed at exploring the role of chronic inflammation in the BD pathophysiological mechanisms by assessing serum levels of C-reactive protein (CRP). CRP is a marker of low-grade inflammation widely used in clinical practice, and a risk factor for cardiovascular and malignant diseases. The first article, a meta-analysis, aimed at evaluating the effect size of the association between CRP levels in bipolar patients (n=730) compared to healthy subjects (n=888). Overall, CRP levels were significantly elevated in patients with BD versus controls (effect size, ES = 0.39; 95% CI, 0.24 to 0.55; P < .0001). CRP levels were significantly higher in manic (ES = 0.73; 95% CI, 0.44 to 1.02; P < 0.001) and euthymic (ES = 0.26; 95% CI, 0.01 to 0.51; P = 0.04). The second paper aimed at reviewing the scientific literature regarding peripheral biomarkers potentially implicated in the progression of BD. Bipolar patients within different disease’s stages presented altered levels of oxidative stress, neurotrophins and inflammatory markers, including PCR. These findings reinforce the hypothesis of the potential role of the chronic inflammation in BD pathophysiology. Regarding the multidimensional approach in BD, the third article assessed emotional reactivity as a major dimension for better characterizing remitted bipolar patients with subthreshold mood symptoms (N=613). Although all patients were in remission, most of them (68%) showed abnormal emotional reactivity (hipo- or hyper-reactivity). In addition, this study assessed the psychosocial functioning in these patients as well as the levels of high-sensitivty PCR (hsCRP) as an objective marker of emotional hyper-reactivity in BD. Patients with emotional hyper-reactivity had higher levels of PCR and cognitive impairment compared to patients with emotional hypo or normal emotional reactivity (P < 0.001). This was a crosssectional study of emotional reactivity, hsCRP levels and functional status in remitted bipolar patients, and no conclusions regarding the causality of these associations can be substantiated. Others factors could also be contributing to the chronic inflammatory state in these patients. In conclusion, the results of this thesis suggest that low-grade chronic inflammation, as evidenced by alteration in CRP levels, may be implicated in the pathophysiology as well as in the BD progression. Novel therapeutic interventions targeting inflammatory mechanisms and the modulation of CRP levels should be prioritized in future studies.

Alterações em estruturas específicas do SNC, em particular, no sistema fronto-límbico, assim como a diminuição das células neuronais e gliais parece estar envolvida com a fisiopatologia do Transtorno do Humor Bipolar (THB). A glia exerce um importante papel no SNC, entre os quais, a produção de neurotrofinas, em especial, o Fator de Crescimento Neurotrófico derivado de Células da Glia (GDNF). Um marcado aumento dos níveis séricos de GDNF em pacientes deprimidos (F= 42.31; p=0.004; one-way ANOVA) e maníacos (F= 42.31; p=0.001; one-way ANOVA) foi demonstrado neste estudo, sugerindo um possível envolvimento desta neurotrofina com o THB. Por outro lado, alterações nos fatores neurotróficos afetam os mecanismos de plasticidade sináptica, podendo contribuir para as deficiências cognitivas apresentadas pelos pacientes. Deficiências cognitivas, em especial, as falhas de memória são descritas, as quais influenciam a funcionalidade destes indivíduos, principalmente a nível ocupacional e social. As altas taxas de disfuncionalidade apresentadas pelos pacientes e a falta de padronização dos instrumentos usados nos estudos para avaliar funcionalidade, nos levaram ao desenvolvimento de uma escala. A Escala Breve de Funcionalidade (FAST) é um instrumento de rápida e fácil aplicação desenvolvida para usar em psiquiatria, em especial, paciente com THB. A FAST avalia objetivamente seis áreas específicas da funcionalidade, tais como autonomia, trabalho, cognição, relacionamentos interpessoais, finanças e lazer. A validação da escala foi realizada através de testes psicométricos, tais como: consistência interna (alfa de Cronbach’s igual a 0.909), validade concorrente comparada com a GAF (r=-0.903; p<0.001), test-retest (0.98; p<0.01), validade em detectar diferenças entre episódios agudos (maníacos: 40.44±9.15 e deprimidos 43.21±13.34) e períodos de remissão (18.55±13.19; F=35.43; p<0.001) e análise fatorial. Os resultados obtidos foram muito positivos, tornando o instrumento válido e prontamente disponível para o uso na prática clínica e investigação. Palavras-chave: transtorno do humor bipolar, GDNF, glia, neurotrofinas, funcionalidade, disfuncionalidade, escalas de funcionalidade. / Alterations in specific structures of CNS, in particular, fronto-lymbic system, and a reduction of neurons and glial cells appear to be involved in the pathophysiology of bipolar disorder. Glial cells have an important role in the CNS, for example, the production of neurotrophins, especially, Glial Cell Line-derived Neurotrophic Factor (GDNF). In this study, we showed a marked increased in the serum levels of GDNF in depressive (F= 42.31; p=0.004; one-way ANOVA) and manic bipolar patients (F= 42.31; p=0.001; one-way ANOVA), which suggested that GDNF could be involved in the physiopathology of bipolar disorder. On the other hand, alterations in the neurotrophic factors hinder synaptic plasticity mechanisms, may result in cognitive impairment in bipolar patients. In particular, memory difficulties have been reported here, and these difficulties influence occupational and social functioning in these subjects. High rates of functional impairment showed by bipolar patients and a lack of standardization of the instruments available to assess functioning in the studies motivated us to development the scale. The Functioning Assessment Short test (FAST) is a rapid instrument and easy to apply developed to use in psychiatry, especially, bipolar patients. It assesses six specific domains of functioning, such as autonomy, occupational functioning, cognitive functioning, financial issues and leisure time. The validation of FAST was performed by psychometric tests such as internal consistency (Cronbach’s alpha: 0.909), concurrent validity compared to the GAF (r=-0.903; p<0.001), validity as a discriminative measure to detect the difference between euthymic (18.55; F=23.59; p<0.001) and acute patients (manic: 38.50; depressive: 42.38; mixed: 43.21), factorial analysis and test-retest reliability (0.953; p<0.01). The FAST scale showed strong psychometric properties and it is now available for use in both clinical practice and investigation settings.

Contexto: O Transtorno Bipolar (TB) freqüentemente está associado a um curso crônico e altamente incapacitante, com comprometimento das funções cognitivas e sociais. O prejuízo funcional no TB pode estar associado a um prejuízo nos processos de tomada de decisão. Ainda que o déficit cognitivo esteja bem documentado no TB, a avaliação de funções cognitivas específicas como a tomada de decisão econômica e a punição altruística ainda não foram bem estudadas. Nesse contexto, o Jogo do Ultimato (JU) é um teste único na avaliação da cognição social por compreender a avaliação da punição altruística, a qual é um importante mecanismo de adaptação social, funcional e do comportamento econômico. Objetivos: Avaliar o padrão de respostas ao JU e o comportamento de punição altruística em uma amostra de pacientes com TB e em controles sadios, além dos fatores clínicos e sociodemográficos associados aos diferentes padrões de resposta ao jogo. Métodos: Vinte e oito pacientes com diagnóstico de TB, eutímicos, e vinte e oito controles saudáveis foram avaliados utilizando o JU em um estudo comparativo. Todos os participantes do estudo fizeram o papel de respondedores no JU, recebendo ofertas injustas previamente estabelecidas. Os sintomas depressivos e maníacos foram avaliados através da Escala de Avaliação da Depressão de Hamilton de 17 itens (HAMD) e da Escala de Avaliação de Mania de Young (YMRS), respectivamente, devendo ser igual ou menor que 8 pontos. A história de traumas na infância foi avaliada pelo Questionário de Traumas na Infância (CTQ), e a impulsividade foi avaliada pela Escala de Impulsividade de Barratt (BIS). Resultados: Não houve diferença significativa na idade e no gênero entre os grupos. A taxa de rejeição das ofertas injustas do JU foi diferente entre pacientes e controles (53% nos pacientes e 28% nos controles). A história de traumas na infância estava relacionada à maior aceitação de ofertas injustas em pacientes (p=0,038), mas não em controles (p=0,691). Com o objetivo de avaliar a interação entre os dois grupos, o padrão de resposta no JU e a história de traumas na infância, uma análise log-linear foi realizada, mostrando uma interação estatisticamente significativa entre as três variáveis (p=0,038). Conclusão: As maiores taxas de rejeição ao JU indicam maior uso do mecanismo de punição altruística no TB, quando comparado aos controles. Por outro lado, a coexistência de TB com trauma na infância está associado a um menor uso do comportamento de punição altruística em comparação ao TB sem trauma na infância. , A flexibilidade de uso da punição altruística parece ser um importante mecanismo adaptativo segundo estudos prévios em população saudável. Dessa forma, os resultados sugerem que tanto o maior uso da punição altruística (maior taxa de rejeição no JU) no TB quanto a inibição de seu uso, que parece associado ao trauma, podem explicar em parte a dificuldade de adaptação social destes pacientes e seu comportamento econômico. / Introduction: Bipolar Disorder is frequently associated to cronic and disabling course, with impairment of social and cognitive functions. Functional impairment can be related to decision-making process impairment. Although cognitive deficits in Bipolar Disorder are well documented, assessment of specific cognitive functions such as economic decision making and altruistic punishment have not been well studied. In this context, the Ultimatum Game is a unique test in the study of social cognition by the assessment of altruistic punishment, which is an important mechanism of social adaptation, functioning and economic behavior. Objective: To compare Ultimatum Game responses and the altruistic punishment behavior between individuals with Bipolar Disorder and healthy controls and assess its associated factors. Methods: Twenty-eight euthymic Bipolar Disorder patients and an equal number of healthy controls were evaluated using the Ultimatum Game paradigm in a comparative design study. The entire sample acted as responders in the Ultimatum Game, receiving previously fixed unfair offers. Depressive and manic symptoms were determined by Hamilton Depression Rating Scale - 17 items and the Young Mania Rating Scale, respectively, and they must be 8 points or lesser. A childhood trauma history was recorded using Childhood Trauma Questionnaire, and impulsivity was evaluated by the Barratt Impulsiveness Scale. Results: There were no significant differences in age and gender between groups. The rate of rejection of unfair offers in Ultimatum Game was significantly different between groups (53% in Bipolar Disorder patients and 28% in healthy controls). History of childhood trauma was correlated with unfair offer acceptance in Bipolar Disorder (p=0.038), but not in controls (p=0.691). In order to explore the interaction between the two groups, the pattern of response in Ultimatum Game and the history of childhood trauma, a log linear analysis was carried out and showed a statistically significant interaction (p=0.038). Conclusion: The highest rates of Ultimatum Game rejections indicate greater use of altruistic punishment mechanism in Bipolar Disorder compared to controls. Besides, childhood trauma in Bipolar Disorder is associated with greater acceptance of the Ultimatum Game offers, indicating less use of altruistic punishment in comparison with Bipolar Disorder patients without childhood trauma. The appropriate use of altruistic punishment seems to be an important social adaptive mechanism, as previously reported by non-clinical population studies. Thus, results suggest that both the greater use of altruistic punishment (higher rate of Ultimatum Game rejections) in Bipolar Disorder and the inhibition of its use, which seems related to trauma, may explain in part difficulties in social adaptation and economic behavior of these patients.