RESUMO
There is increasing recognition that, in a high percentage of cases, bipolar disorder is a progressive illness. Multiple types of sensitization (or increased reactivity to repetition of the same stimulus) drive illness progression. One of the clearest is that of episode sensitization, where increased numbers of prior episodes are associated with: faster recurrences; more dysfunction; disability; social, educational, and employment deficits; suicide; medical comorbidities; cognitive dysfunction; and an increased incidence of dementia in old age. Repetition of stressors and bouts of substance abuse can also result in sensitization. Each type of sensitization appears to have an epigenetic basis, such that preventing sensitization should minimize the accumulation of adverse epigenetic chemical marks on DNA, histones, and microRNA. New data emphasize the importance of early, consistent intervention after an initial manic episode. The cognitive dysfunction associated with a first episode improves only if there are no further episode recurrences during the next year. A randomized study has also shown that comprehensive multimodal prophylactic intervention for 2 years leads to improvements in illness course extending over a total of 6 years. Intensive treatment of the earliest stages of bipolar disorder can thus exert lasting positive effects on the course of illness.
Assuntos
Humanos , Transtorno Bipolar/prevenção & controle , Transtorno Bipolar/epidemiologia , Transtornos Relacionados ao Uso de Substâncias , Recidiva , Comorbidade , Progressão da DoençaRESUMO
There is increasing recognition that, in a high percentage of cases, bipolar disorder is a progressive illness. Multiple types of sensitization (or increased reactivity to repetition of the same stimulus) drive illness progression. One of the clearest is that of episode sensitization, where increased numbers of prior episodes are associated with: faster recurrences; more dysfunction; disability; social, educational, and employment deficits; suicide; medical comorbidities; cognitive dysfunction; and an increased incidence of dementia in old age. Repetition of stressors and bouts of substance abuse can also result in sensitization. Each type of sensitization appears to have an epigenetic basis, such that preventing sensitization should minimize the accumulation of adverse epigenetic chemical marks on DNA, histones, and microRNA. New data emphasize the importance of early, consistent intervention after an initial manic episode. The cognitive dysfunction associated with a first episode improves only if there are no further episode recurrences during the next year. A randomized study has also shown that comprehensive multimodal prophylactic intervention for 2 years leads to improvements in illness course extending over a total of 6 years. Intensive treatment of the earliest stages of bipolar disorder can thus exert lasting positive effects on the course of illness.
Assuntos
Transtorno Bipolar , Transtornos Relacionados ao Uso de Substâncias , Transtorno Bipolar/epidemiologia , Transtorno Bipolar/prevenção & controle , Comorbidade , Progressão da Doença , Humanos , RecidivaRESUMO
INTRODUCTION: Creativity is a complex human ability influenced by affective and cognitive components but little is known about its underlying neurobiology. Bipolar Disorder (BD) is highly prevalent among creative individuals. Brain-derived neurotrophic factor (BDNF) is the most widely distributed neurotrophic factor, and has been implicated in the pathophysiology of BD. In contrast to the better functioning of the BDNF polymorphism (Val(66)Met) Val allele, the Met allele decreases BDNF transport and has been associated with worsened performance on several cognitive domains in euthymic BD subjects and controls. We hypothesized that the Val allele is associated with increased creativity in bipolar disorder. MATERIALS AND METHODS: Sixty-six subjects with BD (41 in manic and 25 in depressive episodes) and 78 healthy volunteers were genotyped for BDNF Val(66)Met and tested for creativity using the Barrow Welsh Art Scale (BWAS) and neuropsychological tests. RESULTS: Manic patients with the Val allele (Met-) had higher BWAS scores than Met+ carriers. This relationship was not observed among patients in depressive episodes or among control subjects. BDNF Met allele status showed no association with cognitive function in any of the groups. CONCLUSION: As postulated, these findings suggest that the better functioning allele of BDNF may selectively facilitate creative thinking in subjects with manic episodes, but not in controls or depressives. Further studies exploring the role of BDNF in the neurobiology of creativity in BD and in euthymic phases are warranted.
Assuntos
Transtorno Bipolar/genética , Fator Neurotrófico Derivado do Encéfalo/genética , Criatividade , Adolescente , Adulto , Alelos , Transtorno Bipolar/fisiopatologia , Transtorno Bipolar/psicologia , Feminino , Genótipo , Humanos , Masculino , Adulto JovemRESUMO
INTRODUCTION: Creativity is a complex construct involving affective and cognitive components. Bipolar Disorder (BD) has been associated with creativity and is characterized by a wide range of affective and cognitive symptoms. Although studies of creativity in BD have tended to focus on creativity as a trait variable in medicated euthymic patients, it probably fluctuates during symptomatic states of BD. Since creativity is known to involve key affective and cognitive components, it is plausible to speculate that cognitive deficits and symptoms present in symptomatic BD could interfere with creativity. MATERIAL AND METHODS: Sixty-seven BD type I patients medication free, age 18-35 years and experiencing a maniac, mixed, or depressive episodes, were assessed for creativity, executive functioning, and intelligence. RESULTS: Manic and mixed state patients had higher creativity scores than depressive individuals. Creativity was influenced by executive function measures only in manic patients. Intelligence did not influence creativity for any of the mood episode types. CONCLUSION: We propose that creativity in BD might be linked to the putative hyperdopaminergic state of mania and be dependent on intact executive function. Future studies should further explore the role of dopaminergic mechanisms in creativity in BD.
Assuntos
Transtorno Bipolar/psicologia , Criatividade , Função Executiva , Adolescente , Adulto , Afeto , Depressão , Transtorno Depressivo/complicações , Transtorno Depressivo/diagnóstico , Transtorno Depressivo/psicologia , Feminino , Humanos , Inteligência , Masculino , Adulto JovemRESUMO
BACKGROUND: Available data regarding posttraumatic stress disorder (PTSD) in bipolar disorder (BD) are scarce and usually from a limited sample size. The present report was carried out using the Brazilian Research Consortium for Bipolar Disorders and aimed to examine whether patients with BD and comorbid PTSD are at an increased risk for worse clinical outcomes. METHODS: A consecutive sample of bipolar I outpatients from two teaching hospitals in Brazil was recruited. Patients were assessed using the Structured Clinical Interview for DSM-IV, Young Mania Rating Scale, 17-item Hamilton Rating Scale for Depression, and quality of life instrument WHOQOL-BREF. Participants were divided into three groups: a. bipolar patients with PTSD, b. bipolar patients exposed to trauma without PTSD, and c. bipolar patients with no trauma exposure. RESULTS: Of the 405 patients who consented to participate, 87.7% completed the survey. All three groups were similar in terms of demographic parameters. The group with comorbid PTSD reported worse quality of life, more rapid cycling, higher rates of suicide attempts, and a lower likelihood of staying recovered. LIMITATIONS: The cross-sectional design excludes the opportunity to examine causal relationships among trauma, PTSD, and BD. CONCLUSIONS: The findings indicate that PTSD causes bipolar patients to have a worse outcome, as assessed by their lower likelihood to recover, elevated proportion of rapid cycling periods, increased risk of suicide attempts, and worse quality of life.
Assuntos
Transtorno Bipolar/epidemiologia , Transtornos de Estresse Pós-Traumáticos/epidemiologia , Adulto , Afeto , Transtorno Bipolar/diagnóstico , Transtorno Bipolar/psicologia , Brasil , Comorbidade , Estudos Transversais , Feminino , Humanos , Acontecimentos que Mudam a Vida , Masculino , Programas de Rastreamento , Pessoa de Meia-Idade , Modelos Psicológicos , Qualidade de Vida/psicologia , Fatores de Risco , Transtornos de Estresse Pós-Traumáticos/diagnóstico , Transtornos de Estresse Pós-Traumáticos/psicologia , Tentativa de Suicídio/psicologia , Tentativa de Suicídio/estatística & dados numéricos , Adulto JovemRESUMO
OBJECTIVE AND METHOD: There is a growing amount of data indicating that alterations in brain-derived neurotrophic factor and increased oxidative stress may play a role in the pathophysiology of bipolar disorder. In light of recent evidence demonstrating that brain-derived neurotrophic factor levels are decreased in situations of increased oxidative stress, we have examined the correlation between serum thiobarbituric acid reactive substances, a measure of lipid peroxidation, and serum brain-derived neurotrophic factor levels in bipolar disorder patients during acute mania and in healthy controls. RESULTS: Serum thiobarbituric acid reactive substances and brain-derived neurotrophic factor levels were negatively correlated in bipolar disorder patients (r = -0.56; p = 0.001), whereas no significant correlation was observed in the control group.. CONCLUSION: These results suggest that alterations in oxidative status may be mechanistically associated with abnormal low levels of brain-derived neurotrophic factor observed in individuals with bipolar disorder.
Assuntos
Transtorno Bipolar/fisiopatologia , Fator Neurotrófico Derivado do Encéfalo/sangue , Estresse Oxidativo/fisiologia , Doença Aguda , Biomarcadores/sangue , Transtorno Bipolar/sangue , Estudos de Casos e Controles , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Substâncias Reativas com Ácido Tiobarbitúrico/análiseRESUMO
OBJECTIVE AND METHOD: There is a growing amount of data indicating that alterations in brain-derived neurotrophic factor and increased oxidative stress may play a role in the pathophysiology of bipolar disorder. In light of recent evidence demonstrating that brain-derived neurotrophic factor levels are decreased in situations of increased oxidative stress, we have examined the correlation between serum thiobarbituric acid reactive substances, a measure of lipid peroxidation, and serum brain-derived neurotrophic factor levels in bipolar disorder patients during acute mania and in healthy controls. RESULTS: Serum thiobarbituric acid reactive substances and brain-derived neurotrophic factor levels were negatively correlated in bipolar disorder patients (r = -0.56; p = 0.001), whereas no significant correlation was observed in the control group.. CONCLUSION: These results suggest that alterations in oxidative status may be mechanistically associated with abnormal low levels of brain-derived neurotrophic factor observed in individuals with bipolar disorder.
OBJETIVO E MÉTODO: Existem crescentes evidências indicando que alterações no fator neurotrófico derivado do cérebro e aumento do estresse oxidativo podem estar envolvidos na fisiopatologia do transtorno bipolar. Considerando os achados recentes de que os níveis de fator neurotrófico derivado do cérebro estão diminuídos em situações de aumento de estresse oxidativo, nós testamos a correlação entre os níveis séricos de substâncias reativas do ácido tiobarbitúrico, um índice de peroxidação lipídica, e os níveis séricos de fator neurotrófico derivado do cérebro em pacientes portadores de transtorno bipolar durante mania aguda e em controles saudáveis. RESULTADOS: Os níveis séricos de substâncias reativas do ácido tiobarbitúrico e fator neurotrófico derivado do cérebro apresentaram uma correlação negativa em pacientes bipolares (r = -0,56; p = 0,001), enquanto não houve correlação significativa no grupo controle. CONCLUSÃO: Estes resultados sugerem que alterações de estresse oxidativo podem ser mecanisticamente associadas com níveis reduzidos de BDNF observados em indivíduos com transtorno bipolar.
Assuntos
Feminino , Humanos , Masculino , Transtorno Bipolar/fisiopatologia , Fator Neurotrófico Derivado do Encéfalo/sangue , Estresse Oxidativo/fisiologia , Doença Aguda , Biomarcadores/sangue , Transtorno Bipolar/sangue , Estudos de Casos e Controles , Ensaio de Imunoadsorção Enzimática , Substâncias Reativas com Ácido Tiobarbitúrico/análiseRESUMO
Current literature on the effects of chronic stress in general health converges to the concept of allostatic load (AL). AL is the bodily 'wear and tear' that emerges with sustained allostatic states. In the field of bipolar disorder (BD), AL offers an important clue as to why patients who undergo recurrent mood episodes are clinically perceived as less resilient. In addition, AL helps explaining the cumulative disruptive health effects of intermittent episodes and stressors. Stress- and episode-induced changes in brain regions involved in the emotional circuitry may lead to dysfunctional processing of information, which would render BD patients more vulnerable to subsequent environmental stressors, episodes, and drugs of abuse. Mood stabilizing agents exert opposite effects than chronic stress in neurons, increasing neuroprotective factors what may help to quench the cycle of affective episode recurrence and neural and bodily deterioration. Therefore, AL provides an explanatory link to apparently unrelated findings such as cognitive impairment and higher rates of physical comorbidity and mortality that are observed in the course of BD and further highlight the importance of effective long-term prophylaxis.
Assuntos
Alostase/fisiologia , Transtorno Bipolar/fisiopatologia , Transtorno Bipolar/terapia , Transtorno Bipolar/patologia , Encéfalo/patologia , Encéfalo/fisiopatologia , Ritmo Circadiano , Emoções , Meio Ambiente , HumanosRESUMO
OBJECTIVE: We examined age of onset of bipolar disorder as a potential course-of-illness modifier with the hypothesis that early onset will engender more severe illness. STUDY DESIGN: A total of 480 carefully diagnosed adult outpatients with bipolar disorder (mean age, 42.5 +/- 11.6 years) were retrospectively rated for age of illness onset, time to first pharmacotherapy, and course of illness. Clinicians prospectively rated daily mood fluctuations over 1 year. RESULTS: Of the 480 patients, 14% experienced onset in childhood (12 years or younger); 36% in adolescence (13 to 18 years); 32% in early adulthood (19 to 29 years); and 19% in late adulthood (after 30 years). Childhood-onset bipolar illness was associated with long delays to first treatment, averaging more than 16 years. The patients with childhood or adolescent onset reported more episodes, more comorbidities, and rapid cycling retrospectively; prospectively, they demonstrated more severe mania, depression, and fewer days well. CONCLUSIONS: This study demonstrates that childhood onset of bipolar disorder is common and is associated with long delays to first treatment. Physicians and clinicians should be alert to a possible bipolar diagnosis in children in hopes of shortening the time to initiating treatment and perhaps ameliorating the otherwise adverse course of illness.