Au, Wing Cheong. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2011. / Includes bibliographical references (leaves 114-148). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese; some appendixes in Chinese.

Offspring of parents with bipolar disorder (BD) are at high risk for psychiatric disorders, but mechanisms conferring risk are not well understood. Identifying and understanding factors that increase offspring vulnerability may inform intervention efforts. Three studies examined the following risk factors: (1) obstetric complications (OCs); (2) family functioning; and (3) clinical characteristics of parental BD. Investigations included cross-sectional data from two Massachusetts General Hospital studies of 109 BD parents and 206 offspring. Study 1 examined associations between: (1) maternal lifetime comorbid anxiety and OCs in pregnancy/delivery; (2) OCs and development of offspring psychopathology. Associations emerged between maternal anxiety and OCs. OCs, particularly during delivery, also correlated with offspring anxiety disorders. Path analyses revealed that delivery complications mediated the relationship between maternal and offspring anxiety. Study 2 examined associations between family functioning (cohesion, expressiveness, conflict) and offspring psychopathology, and explored moderation by offspring age and sex. Higher conflict and lower cohesion correlated with offspring internalizing and externalizing symptoms. Lower cohesion correlated with offspring mood disorders. Moderation analyses indicated that the link between cohesion and internalizing symptoms was stronger for younger compared to older children. Also, conflict and mood disorder were associated in younger boys, but not in older boys or in girls. Study 3 classified parents according to BD course presentation using latent class analysis, and examined associations between parental class membership and offspring psychopathology. The best-fitting model yielded three parent groups that were based on 8 illness characteristics. Some notable patterns differentiated classes: Class 1 and 2 parents had earlier illness onset, whereas Class 3 parents had later onset; Class 2 consisted of parents with Bipolar-II Disorder, whereas Class 1 parents had Bipolar-I Disorder. Class differences emerged for offspring anxiety disorders, but only among females. Class 3 parents had girls with fewer anxiety disorders compared to the other classes, with girls of Class 2 parents at greatest risk. Altogether, these studies identify several specific environmental mechanisms that increase psychopathology risk in offspring of BD parents. Such findings have important implications for targeted prevention and intervention.

Underpinned by the Behavioural Approach System (BAS) dysregulation theory of bipolar disorder (BD), five studies were conducted in non-clinical samples to; refine the measurement of state Approach Motivation (AM); measure minor increases in AM; and then finally, to investigate how this relates to attentional biases for emotional stimuli. Study 1 attempted to clarify the phenomenology of state AM and revealed four separable factors that emerged from pooled AM questionnaire items. These structures loosely mapped on hypothesized components of the BAS (Depue & Iacono, 1989) that pertain to; cognitive elements of approach motivation (feeling determined and inspired); an energized, activated state; an affective structure relating to positive mood and outlook; and finally to feelings of excitement. Studies 2 and 3 investigated the validity of the four derived factors and their parent scales against a reward-oriented laboratory induction, a psychophysiological marker of AM, and a test of the discriminative power. The validity results suggested that the most well-established of the scales, the PANAS-PA, slightly outperformed the other measures by showing the greatest response to an AM induction. A second aim was to explore the substructure of a valid measure of mania risk - the hypomanic personality scale (HPS: Eckblad & Chapman, 1986) – in relation to AM responsivity. Unexpectedly, individuals who endorsed unpredictable and changeable moods (mood volatility) displayed elevated sympathetic arousal in response to control task. On this basis, and with a view to exploring the role selective attentional processes as a mediator of AM dysregulation that is relevant to bipolar disorder, study 4 and 5 utilised PANAS-PA to replicate a bi-directional congruency-effect found in the literature between elevations in AM and attentional information-processing biases to reward-related stimuli. Results in general did not support a causal influence of AM on attentional biases, nor did the attempted manipulation of attentional biases affect downstream AM. However, there was evidence that within a stratified sample of participants who reliably responded to the AM and control conditions, those at greater risk to mania exhibited an attentional bias for both positive and negative stimuli, relative those at lower risk to mania.

Submitted by Filipe dos Santos (fsantos@pucsp.br) on 2017-04-19T12:01:46Z No. of bitstreams: 1 Jamile Luz Morais.pdf: 2252268 bytes, checksum: 5cb0517617fa94617de137bd01a0aaab (MD5) / Made available in DSpace on 2017-04-19T12:01:46Z (GMT). No. of bitstreams: 1 Jamile Luz Morais.pdf: 2252268 bytes, checksum: 5cb0517617fa94617de137bd01a0aaab (MD5) Previous issue date: 2017-04-07 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / This thesis main objective was to understand, from the Lacanian psychoanalytic perspective, the instrumental use of the bond in the capitalist discourse, taking as a reference the proliferation of subjects that, according to the Diagnostic and Statistical Manual of Mental Disorders (DSM), fall into the category that encompasses the Bipolar Affective Disorder. We seek to build a critique around the diagnostic reason that supports and determines not only the diagnosis of the disorder, but also its increasing trivialization. We start from the idea that the popular discourse in the DSM, in its copulation with the capital, tries to frame the bond foreclosing the subject of desire, thus taking away from them the mere possibility of building a knowledge about their own uneasiness. We conceive the phenomenon of the proliferation of the bipolar disorder diagnostic as a fact in the social field that has impacts on the subject of desire and on the bonds they establish, working with the idea that the said propagation can be understood as a paradigm of the capitalist discourse. We discuss how the bipolar signifier, taken from the pseudoscientific discourse, arises as one of the masks of the subject's suffering in society and how the multiplication of that disorder disguises the scission between subject ($) and knowledge (S2) in the capitalist discourse. The present thesis aimed, above all, to restore not only the importance of the psychiatric clinic in the treatment of what is now called "mental disorders" (especially bipolar disorder), but also how psychoanalysis, addressed to the subject of desire (subject of the unconscious), stands in the context of a discourse dominated by the logic of the DSM. We understand that the diagnosis in psychiatry should be seen as an instrument rather than a goal, lest it will serve as a specialty in the service of standardization and capital, labeling subjects who escape a presumably well-established rule, more than actually work to reinsert these subjects into society / Esta tese teve como objetivo central compreender, a partir da perspectiva psicanalítica lacaniana, o aparelhamento do laço no discurso capitalista, tomando como referência a proliferação de sujeitos que, conforme o Manual Diagnóstico e Estatístico dos Transtornos Mentais (DSM) são enquadrados na categoria que engloba o Transtorno Afetivo Bipolar (TAB). Buscamos tecer uma crítica em torno da razão diagnóstica que sustenta e determina não só o diagnóstico do transtorno, mas também sua crescente banalização. Partimos da ideia segundo a qual o discurso em voga no DSM, em sua copulação com o capital, tenta forjar um enquadramento de laço que foraclui o sujeito do desejo, expropriando-o, assim, da possibilidade de construir um saber acerca do seu próprio mal-estar. Concebemos o fenômeno da proliferação diagnóstica em torno do TAB como um fato no campo do social que, por assim dizer, acarreta impactos sobre o sujeito do desejo e nos laços que estabelece, trabalhando com a tese de que a dita propagação pode ser entendida como um paradigma do discurso capitalista. Discutimos como o significante bipolar, tomado do discurso pseudocientífico, surge como uma das máscaras do sofrimento do sujeito na sociedade e como a multiplicação do referido transtorno mascara a cisão produzida entre o sujeito ($) e o saber (S2) no discurso capitalista. A presente tese visou, antes de tudo, restituir não só a importância da clínica psiquiátrica no tratamento do que hoje se chama “os transtornos mentais” (especialmente em relação ao transtorno bipolar), mas também como a psicanálise, dirigida ao sujeito do desejo (sujeito do inconsciente), insere-se nesse contexto, de um discurso dominado pela lógica do DSM. Entendemos que o diagnóstico em psiquiatria deve ser visto como um instrumento e não como uma meta, pois, se assim for, ele servirá mais como uma especialidade serva de uma normalização e do capital, rotulando sujeitos que fogem a uma regra pretensamente bem estabelecida, do que trabalhando a favor de (re)inserir esses sujeitos na sociedade

O transtorno bipolar (TB) é uma doença crônica, altamente incapacitante e sua fisiopatologia não esta bem esclarecida. Apresenta altas taxas de comorbidades clínicas e risco de suicídio trazendo prejuízos e custos significativos para o indivíduo com a doença e para a sociedade. Existem evidências que relacionam o TB à alterações no fator de crescimento semelhante à insulina tipo 1 (IGF- 1) e nos sistemas endócrino e imune. O objetivo deste estudo foi avaliar os níveis séricos de IGF-1 em pacientes bipolares comparados com indivíduos controle e sua relação com a inflamação. Foram selecionados 31 pacientes com TB e 33 controles saudáveis. Foram avaliadas as concentrações séricas de IGF-1, hormônio do crescimento (GH), insulina e fator de necrose tumoral α (TNF-α). Como resultado deste estudo, observamos que os níveis séricos de IGF-1 estavam aumentados em pacientes com TB em relação aos controles (p = 0,001). Não foram observadas diferenças estatisticamente significativas entre os grupos nas dosagens de insulina, GH e TNF- α. Este estudo sugere uma associação entre IGF-1 na fisiopatologia do transtorno bipolar. É possível que este aumento periférico esteja relacionado com um aumento da resistência do IGF- 1 no SNC, reduzindo assim a sua ação neuroprotetora. / Bipolar disorder (BD) is a chronic, highly debilitating and its pathophysiology is not well understood. It offers high rates of clinical comorbidities and suicide risk causing losses and significant costs to the individual with the disease and society. There is evidence that relates to changes in TB-like growth factor type 1 insulin (IGF-1) and the endocrine and immune systems. The aim of this study was to evaluate serum levels of IGF-1 in bipolar patients compared with control subjects and their relationship to inflammation. We selected 31 patients with TB and 33 healthy controls. Serum concentrations of IGF-1, growth hormone, were evaluated (GH), insulin and tumor necrosis factor α (TNF-α). As a result of this study, we observed that serum levels of IGF-1 were increased in TB patients compared to controls (p = 0.001). No statistically significant differences were found between groups in insulin dosages, GH, and TNF-α. This study suggests an association between IGF-1 in the pathophysiology of bipolar disorder. It is possible that this increase is associated with peripheral increased IGF-1 resistance in the CNS, thus reducing its neuroprotective action.

Introdução: A condição de ser um cuidador de um familiar com transtorno mental pode gerar sentimentos de sobrecarga, estresse e depressão. Entretanto, sabe-se que alguns cuidadores consideram esta situação como recompensadora ou satisfatória. A maior parte das pesquisas com esta população aborda esta experiência de forma dicotômica, utilizando instrumentos de avaliação que implicam em aspectos ou positivos ou negativos. Estudos que abordem conceitos mais neutros e abrangentes, como Qualidade de Vida, se fazem necessários. Objetivos: Comparar a qualidade de vida dos cuidadores de indivíduos com transtorno de humor bipolar (THB) com os cuidadores de indivíduos com esquizofrenia (ESQ). Comparar a qualidade de vida destes cuidadores com os escores normativos de qualidade de vida no Brasil. Identificar fatores sociodemográficos e clínicos tanto dos pacientes como dos cuidadores que estivessem associados com a qualidade de vida destes cuidadores. Métodos: Realizou-se um estudo transversal em ambulatórios especializados em transtornos de humor e esquizofrenia do Hospital Psiquiátrico São Pedro. Foram entrevistados 125 cuidadores, 62 de indivíduos com transtorno de humor bipolar e 63 de indivíduos com esquizofrenia. Dados sociodemográficos e clínicos dos cuidadores e dos pacientes foram avaliados. Os questionários WHOQOL-Bref, o SF-36 e o Beck Depression Inventory foram aplicados nos cuidadores para avaliar o desfecho qualidade de vida e a presença de sintomas depressivos, respectivamente. A Escala Impressão Clínica Global foi utilizada para classificar a gravidade da doença do paciente e foi avaliada de 2 formas, pelo médico e pelo familiar. Resultados: Esta pesquisa sugere que cuidadores de esquizofrênicos apresentam escores mais baixos de QV do que cuidadores de indivíduos bipolares, com maiores diferenças nos domínios do WHOQOL-BREF: físico (ESQ média=55,83+19,57 THB média=67,45+21,18) e relações sociais (ESQ média=50,86+25,50 THB média=60,35+23,80); e no SF-36: aspectos físicos (ESQ md=41,14 THB md=65,16) e emocionais (ESQ md=37,83 THB md=58,06) (p<0,05). Os cuidadores desta amostra apresentaram escores menores de QV quando comparados aos escores normativos de qualidade de vida no Brasil, principalmente nos domínios de aspectos sociais do WHOQOL-BREF e do SF-36 e nos de aspectos emocionais e de saúde mental do SF-36. Quando os grupos de cuidadores foram comparados conforme a gravidade da doença do paciente indicada pelo médico, não houve diferença significativa em nenhum domínio. Entretanto, quando comparados utilizando a gravidade indicada pelo cuidador, houve diferença em quase todos os domínios, com exceção dos domínios físicos. Cuidadores de esquizofrênicos apresentaram maior presença de sintomas depressivos quando comparados com cuidadores de bipolares (66,7% vs. 27,4%) (p<0,001). Na análise de regressão, piores escores de qualidade de vida no cuidador estavam associados ao diagnóstico de esquizofrenia do paciente; gênero feminino, presença de doença clínica e, principalmente, de sintomas depressivos no cuidador. Conclusões: Este estudo demonstrou o prejuízo na QV dos cuidadores de indivíduos com transtorno mental, especialmente na de cuidadores de esquizofrênicos. A elevada prevalência de sintomas depressivos nestes cuidadores é impactante. Estes achados reforçam a relevância da criação e implementação de políticas de saúde que busquem identificar as necessidades específicas destes cuidadores. / Introduction: The condition of being a caregiver of a family member with a mental disorder can generate feelings of burden, stress and depression. However, it is known that some caregivers consider this as satisfactory or rewarding. Most research with this population addresses this experience dichotomously, using assessment tools that imply in aspects or positive or negative. Studies focusing in more neutral and broad concepts such as quality of life are necessary. Objectives: Compare quality of life between caregivers of individuals with bipolar disorder (BD) and caregivers of individuals with schizophrenia (ESQ). Compare quality of life of these caregivers with the normative data of quality of life in Brazil. Identify sociodemographic and clinical factors of patients and caregivers that were associated with quality of life of caregivers. Methods: A cross-sectional study in specialized clinics in mood disorders and schizophrenia at Hospital Psiquiátrico São Pedro. 125 caregivers were interviewed, 62 of individuals with bipolar disorder and 63 of individuals with schizophrenia. Sociodemographic and clinical data of caregivers and patients were evaluated. The WHOQOL-Bref questionnaire, SF-36 and Beck Depression Inventory were applied to the caregivers to assess the outcome quality of life and the presence of depressive symptoms, respectively. The Clinical Global Impression Scale was used to classify the severity of the patient's disease and was evaluated in 2 ways, through the physician and the caregivers. Results: This research suggests that schizophrenic caregivers have lower scores of quality of life than bipolar caregivers, with greater differences in WHOQOL-BREF domains: physical (ESQ mean=55,83+19,57 THB mean=67,45+21,18) and social relations (ESQ mean=50,86 +25,50 THB mean=60,35+23,80); and in SF-36 domains: physical (ESQ md=41,14 THB md=65,16) and emotional aspects (ESQ md=37,83 THB md=58,06) (p <0.05). Caregivers of this sample presented lower quality of life scores when compared to the normative data of quality of life in Brazil, mainly in the domains of social aspects of WHOQOL-BREF and SF-36 and in emotional aspects and mental health of SF-36. When caregivers groups were compared according to the severity of the patient's disease indicated by the physician, there was no significant difference in any domain. However, when compared using the severity indicated by the caregiver, there were differences in almost all domains, except for the physical domains. Caregivers of schizophrenics had more depressive symptoms when compared with bipolar caregivers (66.7% vs. 27.4%) (p <0.001). In the regression model, worse quality of life scores in caregivers were associated with the diagnosis of schizophrenia in patients; female gender, presence of clinical disease and especially of depressive symptoms in the caregiver. Conclusion: This study demonstrated the impairment in quality of life of caregivers of individuals with mental disorders, especially in caregivers of schizophrenics. The high prevalence of depressive symptoms in these caregivers is alarming. These findings reinforce the importance of developing and implementing health policies that seek to identify the specific needs of these caregivers.

O curso longitudinal do transtorno bipolar é altamente variável, mas um subconjunto de pacientes parece apresentar uma evolução progressiva associada a alterações cerebrais e comprometimento funcional. Em nosso primeiro artigo, discutimos a teoria da neuroprogressão no transtorno bipolar. Este conceito considera a resposta ao estresse que ocorre nos episódios de humor e déficits no funcionamento e cognição, bem como alterações neuroanatômicas nos estágios tardios da doença. Discutimos também refratariedade ao tratamento que pode ocorrer em alguns casos de transtorno bipolar. Foi executada uma busca na base de dados PubMed para artigos publicados em qualquer idioma até 04 de junho de 2016. Foram encontrados 315 resumos e 87 estudos foram incluídos em nossa revisão. Somos da opinião de que o uso de estratégias farmacológicas específicas e remediação funcional pode ser potencialmente útil em pacientes bipolares em estágios tardios. Novas abordagens analíticas que utilizam dados multimodais têm o potencial para ajudar na identificação de assinaturas de subgrupos de pacientes que irão desenvolver um curso neuroprogressivo. Com base em nossa hipótese de neuroprogressão, decidimos realizar um ensaio clínico randomizado com o antidepressivo tianeptina como tratamento adjuvante para o transtorno bipolar, a fim de melhorar o comprometimento funcional, desfechos clínicos e aumentar os níveis do Brain-Derived Neurothrofic Factor (BDNF). Tianeptina é um fármaco seguro, que atua sobre o sistema glutamatérgico e tem um efeito antidepressivo. Esse estudo teve como objetivo avaliar a eficácia e tolerabilidade da tianeptina como tratamento adjuvante para a depressão bipolar. Foi realizado um ensaio clínico duplo-cego randomizado de manutenção controlado por placebo com tianeptina 37,5 mg/dia. Os participantes (n = 161) tinham uma pontuação na Montgomery Asberg Depression Rating ≥12 no início do ensaio. Após oito semanas de tratamento com tianeptina na fase aberta, aqueles que responderam a tianeptina foram randomizados para o placebo ou tianeptina adjuvante. Os participantes foram recrutados na rede pública de saúde. Tempo para qualquer intervenção foi o desfecho primário do estudo. Mudanças nos sintomas de humor, funcionamento, ritmos biológicos, qualidade de vida, taxas de virada maníaca e níveis séricos de BDNF foram considerados como desfechos secundários. Houve uma diminuição importante nos sintomas depressivos, assim como melhoras no funcionamento, qualidade de vida e pontuações no ritmo biológico durante a fase aberta de tratamento com tianeptina por oito semanas. Durante as 24 semanas do ensaio duplo-cego randomizado e controlado por placebo, não houve diferença em relação ao desfecho primário: tempo para qualquer intervenção. Além disso, não houve diferenças significativas entre os grupos em relação aos sintomas de humor, funcionamento e níveis de BDNF. Tianeptina foi bem tolerada e não foi associada a virada maníaca em comparação com o placebo. Estes achados sugerem que tianeptina é um medicamento seguro e pode ser eficaz no tratamento da depressão bipolar aguda. No entanto, tianeptina não mostrou efeitos benéficos na fase de manutenção. Este é o primeiro ensaio clínico duplo-cego randomizado de manutenção e de longo prazo com antidepressivo no transtorno bipolar. / The longitudinal course of bipolar disorder is highly variable, and a subset of patients seems to present a progressive course associated with brain changes and functional impairment. In our first article, we discussed the theory of neuroprogression in bipolar disorder. This concept considers the systemic stress response that occurs within mood episodes and late-stage deficits in functioning and cognition as well as neuroanatomic changes. We also discuss treatment refractoriness that may take place in some cases of bipolar disorder. We searched PubMed for articles published in any language up to June 4th, 2016. We found 315 abstracts and included 87 studies in our review. We are of the opinion that the use of specific pharmacological strategies and functional remediation may be potentially useful in bipolar patients at late-stages. New analytic approaches using multimodal data hold the potential to help in identifying signatures of subgroups of patients who will develop a neuroprogressive course. Based on our hypothesis of neuroprogression, we decided to perform a randomized clinical trial with tianeptine as adjunctive treatment for bipolar disorder in order to improve functional impairment and increase serum Brain-Derived Neurothrophic Factor BDNF levels. Tianeptine is a safe medication that acts on the glutamatergic system and has an antidepressant effect. The present study aimed at assessing the efficacy and tolerability of tianeptine as an adjunctive treatment for bipolar depression. We performed an enriched maintenance multi-center double-blind randomized controlled trial of tianeptine 37•5mg/day. Participants (n = 161) had a Montgomery Asberg Depression Rating Score ≥12 at trial entry. After eight weeks of open-label tianeptine treatment, those who responded to tianeptine were randomized to adjunctive tianeptine or placebo in addition to usual treatment. Participants were recruited from public health services and through advertisement. Time to any intervention was the primary endpoint of the study. Changes in mood symptoms, functioning, biological rhythms, quality of life, rates of mania switch and serum BDNF assessments were considered as secondary outcomes. There was a robust decrease in depressive symptoms along with improvements in functioning, quality of life and biological rhythms scores during the eight-week open-label tianeptine treatment phase. During the subsequent 24-week double-blind controlled phase, there was no difference regarding the primary outcome: time to intervention. In addition, there were no significant differences between groups in mood symptoms, functioning and BDNF levels. Tianeptine was well tolerated and not associated with mania switch as compared to placebo. These findings suggest that tianeptine is a safe medication and may be effective in the treatment of acute bipolar depression. However, tianeptine did not show beneficial effects in the maintenance phase. This is the first long-term randomized, double-blind maintenance trial of antidepressant augmentation in bipolar disorder.

Background: Exercise is recommended as a non-pharmacological intervention for individuals with a bipolar disorder diagnosis (BDD). Although physical activity can be beneficial for reducing depressive symptoms, there is preliminary evidence that high-intensity exercise can exacerbate (hypo)mania-related symptoms. Risks associated with other forms of exercise remain unknown. Method: To investigate the potential risks and benefits of low-intensity exercise, non-clinical participants were asked to either copy repetitive movements (n = 20), copy variable movements (n = 20) or watch variable movements (n = 21), following approach motivation induction. Hypomania-like symptoms, positive affect and approach motivation were measured pre-, during and post-task. Trait behavioural activation system (BAS) sensitivity was measured as a moderating factor. Results: There were no group differences in symptom change over time. BAS sensitivity did not moderate this relationship. Limitations: A predominantly student population with low average trait BAS sensitivity was studied. The reliability and validity of the approach motivation induction, mania measure and physical activity task are uncertain. Conclusions: It is unclear whether different types of low-intensity exercise are of risk or benefit for individuals prone to (hypo)mania. This area requires further investigation.

Background: Psychiatric diseases such as bipolar disorder, major depressive disorder (MDD)and schizophrenia are chronic ailments that severely affect daily function and quality of life. A relationship between elevated levels of proinflammatory cytokines and these disorders hasbeen suggested in several studies. Lithium is used as a treatment in bipolar disorder, and as anadjunctive treatment in MDD and schizophrenia. Despite the extensive use of lithium, it’smechanism of action is not fully understood. One of the proposed hypotheses of lithium’smechanism of action is reduction in the levels of proinflammatory cytokines. Aim: The aim of this systematic literature review is to describe the effects of lithium onproinflammatory cytokines (IL-1, IL-6, INF- γ, TNF) in bipolar disorder, MDD andschizophrenia. Methods: The study was conducted through a search in the electronic database PubMed.Using the PICOS format, inclusion and exclusion criteria were specified. Search words andfilters were combined using both Medical Subject Headings (MeSH) terms and free textsearch words. The search initially resulted in 105 articles and through inclusion and exclusioncriteria full-text articles were estimated for eligibility. Risk of bias was estimated using theCochrane Handbook. Results: A total of 10 eligible articlets were included in this study. Nine out of 10 articlesinvestigated bipolar patients, and one article investigated patients with MDD. No article investigated patients with schizophrenia. Four out of 9 articles regarding bipolar patientsreported a significant decrease in some proinflammatory cytokines after lithiumtreatment, 4 articles reported a significant increase, and one article reported no change in theproinflammatory cytokines. In two well conducted studies where bipolar disorder wasinvestigated, lithium had differential effects, namely decreasing proinflammatory cytokines inlithium responders compared to lithium non-responders. No significant change inproinflammatory cytokine levels after lithium treatment were found in the article studyingMDD patients. Conclusions: The results indicated that lithium may have different effects depending onwhich specific cytokine was studied and on the specific characteristics of the studiedpopulation. Therefore, the outcomes of our review cannot unequivocally answer whetherlithium acts by increasing or decreasing proinflammatory cytokines, or both depending on theexperimental conditions. Further research is needed to fully elucidate the relationship betweenlithium and proinflammatory cytokines in bipolar disorder, MDD and schizophrenia.

Introdução: O desempenho neurocognitivo é considerado como potencial endofenótipo do transtorno bipolar. As baterias de avaliação totalmente informatizadas representam uma alternativa interessante aos testes neuropsicológicos tradicionais porque oferecem vantagens como correção e armazenagem automatizada dos dados, redução do tempo de aplicação e diminuição da interferência subjetiva do aplicador. No Brasil ainda é raro o número de baterias totalmente computadorizadas disponíveis para uso em pesquisa, portanto, o objetivo deste trabalho foi verificar a aplicabilidade da Bateria Computadorizada da Universidade da Pensilvânia em uma amostra de adultos com Transtorno Bipolar. Métodos: Avaliamos o desempenho da Bateria Neurocognitiva Computadorizada da Universidade da Pensilvânia contra uma Bateria Neurocognitiva Tradicional em uma amostra de 30 pacientes com Transtorno Bipolar eutímicos versus 27 controles saudáveis pareados por idade, gênero e educação parental. Resultados: Os pacientes apresentaram desempenho pior do que controles saudáveis no controle inibitório/controle executivo, velocidade de processamento e tarefas de aprendizagem visuoespacial da Bateria Neurocognitiva Tradicional, enquanto que nenhuma diferença significativa foi observada com a Bateria Neurocognitiva Computadorizada da Universidade da Pensilvânia. Dentro do grupo de pacientes, os sintomas afetivos subclínicos se correlacionaram inversamente com a flexibilidade mental na Bateria Neurocgnitiva Tradicional e, com a memória operacional e o raciocínio visuoespacial na Bateria Neurocognitiva Computadorizada da Universidade da Pensilvânia. Paralelamente, os desempenhos dessas tarefas estão diretamente correlacionados com o funcionamento sócio-ocupacional. Limitações: O tamanho modesto da amostra e o fato de que estudamos um grupo misto de pacientes com Transtorno Bipolar tipo I e tipo II podem ter aumentado o risco de erros estatísticos de tipo II. Conclusões: Os resultados desta investigação preliminar sugerem que os testes tradicionais com uma bateria neuropsicológica abrangente proporcionam maior sensibilidade para detectar diferenças entre grupos. No entanto, as tarefas da Bateria Neurocognitiva Computadorizada da Universidade da Pensilvânia correlacionaram-se com variáveis clínicas específicas no grupo de pacientes, fornecendo informações adicionais relevantes que não foram detectadas com a Bateria Neurocognitiva Tradicional. Assim, a seleção de testes adequada dependeria das funções cognitivas específicas que se pretende analisar e da questão sob investigação / Background: Neurocognitive performance is considered a potential endophenotype of bipolar disorder (BD) and fully computerized batteries represent an interesting alternative to traditional neuropsychological testing because they offer advantages such as automated correction and storage of data, reduction of application time and decrease of the applicator\'s subjective interference. In Brazil, the number of fully computerized batteries available for research use is still rare, so the purpose of this study was to verify the applicability of the Computerized Neurocognitive Battery of the University of Pennsylvania in a sample of adults with Bipolar Disorder. Methods: We assessed the performance of the Computerized Neurocognitive Battery of the University of Pennsylvania against a Traditional Neurocognitve Battery in a sample of 30 euthymic bipolar disorder patients versus 27 healthy controls matched for age, gender and parental education. Results: The patients performed worse than healthy controls in executive control/ response inhibition, processing speed and visuospatial learning tasks of the Traditional Neurocognitve Battery, while no significant differences were observed with the Computerized Neurocognitive Battery of the University of Pennsylvania. Within the Bipolar Disorder group, subclinical affective symptoms inversely correlated with mental flexibility in the Traditional Neurocognitve Battery, and with working memory and visuospatial reasoning in the Computerized Neurocognitive Battery of the University of Pennsylvania. Concurrently, performances on these tasks directly correlated with social/ occupational functioning. Limitations: The modest sample size and the fact that we studied a mixed group of patients with type I and type II Bipolar Disorder might have increased the risk of type II statistical errors. Conclusions: The results of this preliminary investigation suggest that traditional testing with a comprehensive neuropsychological battery affords better sensitivity to detect between-group differences. Nevertheless, Computerized Neurocognitive Battery of the University of Pennsylvania tasks correlated with specific clinical variables in the Bipolar Disorder group, providing relevant additional information that was not detected with the Traditional Neurocognitve Battery. Thus, adequate test selection would depend on the specific neurocognitive functions to be analyzed and the question under investigation