Brain-derived neurotrophic factor serum levels before and after treatment for acute mania.

Accumulating evidence suggests that reduced levels of brain-derived neurotrophic factor (BDNF) in acute mood episodes may play an important role in the pathophysiology of bipolar disorder (BD). In order to assess changes in BDNF serum levels in BD patients before and after treatment for acute mania, ten bipolar patients were prospectively examined at inpatient unit admission and discharge. Diagnoses were made using the Structured Clinical Interview for DSM-IV, SCID-I. Serum BDNF levels were measured by sandwich ELISA. The results showed that BDNF levels were decreased in BD patients during mania when compared to controls (p=0.013) but this difference was no longer significant after treatment (p=0.126). A sharp increase in BDNF levels was found after treatment of the episode of acute mania (p=0.010). These findings suggest that the changes in BDNF serum levels may be associated with treatment response in acute mania. Further studies designed to validate the use of BDNF as a marker of treatment response in bipolar disorder are warranted.

Brain-derived neurotrophic factor gene val66met polymorphism and executive functioning in patients with bipolar disorder.

OBJECTIVE: In the present study, we investigate the association between the val66met polymorphism of the brain-derived neurotrophic factor (BNDF) and the performance on the Wisconsin Card Sorting Test in a sample of Caucasian Brazilian patients with bipolar disorder. METHOD: Sixty-four patients with bipolar disorder were assessed and their performance on the Wisconsin Card Sorting Test was compared with the allele frequency and genotype of the val66met polymorphism of the brain-derived neurotrophic factor. RESULTS: The percentage of non-perseverative errors was significantly higher among patients with the val/val genotype. There was no association between (BNDF) genotype frequency and other Wisconsin Card Sorting Test domains. CONCLUSION: Our results did not replicate previous descriptions of an association between a worse cognitive performance and the presence of the met allele of the val66met brain-derived neurotrophic factor gene polymorphism.

Allostatic load in bipolar disorder: implications for pathophysiology and treatment.

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.

Polypharmacy and suicide attempts in bipolar disorder.

OBJECTIVE: The aim of this study was to assess the association between suicide attempts and the use of multiple drugs in patients with bipolar disorder. METHOD: One hundred sixty-nine bipolar disorder outpatients diagnosed using the DSM-IV Structured Clinical Interview were included. Demographic and socioeconomic data, number of medications currently in use, history of suicide attempts, number of years undiagnosed, age of onset and current psychiatric co-morbidities were assessed using a structured questionnaire and DSM-IV criteria. The main outcome measure was the number of psychotropic drugs currently in use. RESULTS: Approximately half of all patients (48.5%) presented a history of suicide attempt; 84% were using more than one medication, and 19% were using more than three drugs. The most frequent combinations of drugs used by these patients were: lithium + valproate (17%); lithium + antipsychotics (10%); lithium + valproate + antipsychotics (9%); and antidepressants + any drug (6%). The number of suicide attempts was associated with the use of multiple drugs. CONCLUSIONS: Our findings support the notion that the use of combination therapy in bipolar disorder may be related to severity of the BD, such as number of suicide attempts.

Serum concentrations of brain-derived neurotrophic factor and mental disorders in imprisoned women.

OBJECTIVE: Mental disorders and early trauma are highly prevalent in female inmates. Brain-derived neurotrophic factor (BDNF) plays an important role in learning, memory processes, and mood regulation. The aim of this study was to evaluate the relationship between serum BDNF levels and mental disorders among imprisoned women as compared with age- and education-matched controls. METHODS: A consecutively recruited sample of 18 female prisoners with mental disorders was assessed for sociodemographic, criminal, and clinical variables using standardized instruments, the Mini International Neuropsychiatric Interview Plus (MINI Plus), and serum BDNF levels. RESULTS: High rates of childhood sexual abuse and posttraumatic stress disorder (PTSD) were found in the group of forensic patients. Serum BDNF levels in the forensic group did not differ from those of healthy controls, and were significantly higher when compared with those of women with mental disorders hospitalized in a general hospital. CONCLUSION: Elevated serum BDNF levels were found in imprisoned women. The results of this study may suggest neurobiological mechanisms similar to those seen in previous clinical and preclinical studies showing the involvement of BDNF in the pathophysiology of PTSD.

Homocysteine and other markers of cardiovascular risk during a manic episode in patients with bipolar disorder.

OBJECTIVE: To evaluate serum levels of different biomarkers associated with cardiovascular disease in patients with bipolar disorder (BD). Patients were prospectively evaluated in two separate instances: during acute mania and after remission of manic symptoms. All measurements were compared with those of healthy controls. METHODS: The study included 30 patients with BD and 30 healthy controls, matched for gender and age. Biochemical parameters evaluated included homocysteine (Hcy), folic acid, vitamin B12, ferritin, creatine kinase (CK) and C-reactive protein (CRP). RESULTS: Hcy levels were significantly higher in the BD patients, both during mania and after achieving euthymia. When Hcy was adjusted for body mass index, there was no significant difference between patients and controls. Ferritin was the only marker that showed a significant decrease during mania when compared to both euthymic patients and controls. There were no significant differences for folate, vitamin B12, CK and CRP. CONCLUSIONS: These findings do not show an association between alterations of markers of cardiovascular risk during manic episodes. Further studies are necessary to determine factors and mechanisms associated with cardiovascular risk in patients with BD.

Association study of tryptophan hydroxylase 2 gene polymorphisms in bipolar disorder patients with panic disorder comorbidity.

Frequent comorbidity between panic disorder (PD) and mood disorders has been widely reported in clinical and epidemiological studies and, recently, an increasing attention has been paid to the cooccurrence of PD and bipolar disorder (BD). Several studies have shown that an imbalance of serotonin activity could be related to panic symptoms. Tryptophan hydroxylase 2 (TPH2) are plausible candidates for the association with PD. The aim of this study is to investigate a possible association between TPH2 gene polymorphisms and the PD comorbidity susceptibility.Our sample consisted of 515 patients; 274 patients with BD (subtypes I and II), including 45 patients with lifetime panic disorder comorbidity and 241 controls. These patients were genotyped for eight tagging single nucleotide polymorphisms of the gene of human TPH2. We found significant differences between patients with BD, with panic disorder comorbidity, and controls in the allelic analysis (rs4448731, P=0.0069; rs4565946, P=0.0359; rs4760820, P=0.0079; rs1487275, P=0.0439) and genotypic analysis (rs4448731, P=0.011; rs4760820, P=0.0259). We also identified significant differences between patients with BD, with and without panic disorder comorbidity in the allelic analysis (rs4448731, P=0.004; rs4565946, P=0.011; rs11179000, P=0.031; rs4760820, P=0.018; rs1487275, P=0.038; rs10879357, P=0.023) and genotypic analysis (rs4448731, P=0.004; rs4565946, P=0.010; rs4760820, P=0.023; rs10879357, P=0.052). The haplotype analysis in the group of patients with BD, with and without panic disorder comorbidity, was also significant (rs4448731-rs4565946, P=0.0190; rs4448731-rs4565946, P=0.0220; rs10506645-rs4760820, P=0.0360). Further studies are needed to replicate the positive association that we observed.

Mental disorders in prisons.

PURPOSE OF REVIEW: The existence of people with mental disorders in prisons is a reality found worldwide. The purpose of this article is not only to review the publications on this subject in 2009 but also to stimulate discussions that could contribute to its further scientific study. RECENT FINDINGS: Most studies published in 2009 related to drug use among inmates and its consequences made it clear that this kind of disorder has a closer relationship with the crime than with mental illness. SUMMARY: The existence of the mentally ill in prisons is a complex issue and the studies attempt to analyze aspects such as the type of disorder, sex of criminals, the opposition between incarceration and treatment, policy, harm reduction and stigma. A further study on the variables raised in this work is required, as well as examining others, to the extent that they are relevant to the various socio-economic and cultural realities.

Serum concentrations of brain-derived neurotrophic factor and mental disorders in imprisoned women

Objective: Mental disorders and early trauma are highly prevalent in female inmates. Brain-derived neurotrophic factor (BDNF) plays an important role in learning, memory processes, and mood regulation. The aim of this study was to evaluate the relationship between serum BDNF levels and mental disorders among imprisoned women as compared with age- and education-matched controls. Methods: A consecutively recruited sample of 18 female prisoners with mental disorders was assessed for sociodemographic, criminal, and clinical variables using standardized instruments, the Mini International Neuropsychiatric Interview Plus (MINI Plus), and serum BDNF levels. Results: High rates of childhood sexual abuse and posttraumatic stress disorder (PTSD) were found in the group of forensic patients. Serum BDNF levels in the forensic group did not differ from those of healthy controls, and were significantly higher when compared with those of women with mental disorders hospitalized in a general hospital. Conclusion: Elevated serum BDNF levels were found in imprisoned women. The results of this study may suggest neurobiological mechanisms similar to those seen in previous clinical and preclinical studies showing the involvement of BDNF in the pathophysiology of PTSD. .

Association of polymorphisms of the tryptophan hydroxylase 2 gene with risk for bipolar disorder or suicidal behavior.

Bipolar disorder (BD) is a severe psychiatric illness characterized by the occurrence of elevated mood alternating with depressive episodes, having a estimated lifetime prevalence of 0.4-1.6% using DSM-IV criteria. Disturbances of the central serotonergic system has been associated with the pathophysiology of affective disorders and suicidal behavior. Tryptophan hydroxylase 2 (TPH2) which is a rate limiting enzyme in the serotonin synthesis is considered an important candidate gene associated with psychiatric disorders. Our sample consisted of 527 subjects (303 diagnosed with bipolar disorder and 224 healthy controls) which were genotyped for eight tagSNPs (rs4448731, rs4565946, rs11179000, rs7955501, rs10506645, rs4760820, rs1487275 and rs10879357) covering the whole gene of the human TPH2. Statistical analyses were performed using UNPHASED version 3.0.12 and Haploview((R)). Single markers, genotype and haplotype association analysis did not show significant genetic association with bipolar disorder or suicidal behavior. Our findings do not support the association between diagnosis of BD or suicidal behavior and TPH2 polymorphisms.

Emotional memory in bipolar disorder.

BACKGROUND: Cognitive impairment has been well documented in bipolar disorder. However, specific aspects of cognition such as emotional memory have not been examined. AIMS: To investigate episodic emotional memory in bipolar disorder, as indicated by performance on an amygdala-related cognitive task. METHOD: Twenty euthymic patients with bipolar disorder and 20 matched controls were recruited. Participants were shown a slide show of an emotionally neutral story, or a closely matched emotionally arousing story. One week later, participants were assessed on a memory-recall test. RESULTS: In contrast with the pattern observed in controls, patients with bipolar disorder had no enhancement of memory for the emotional content of the story (F=14.7, d.f.=1,36, P<0.001). The subjective perception of the emotional impact of the emotional condition was significantly different from that of the neutral condition in controls but not in people with bipolar disorder. CONCLUSIONS: Our data suggest that the physiological pattern of enhanced memory retrieval for emotionally bound information is blunted in bipolar disorder.

Homocysteine and other markers of cardiovascular risk during a manic episode in patients with bipolar disorder

Objective: To evaluate serum levels of different biomarkers associated with cardiovascular disease in patients with bipolar disorder (BD). Patients were prospectively evaluated in two separate instances: during acute mania and after remission of manic symptoms. All measurements were compared with those of healthy controls. Methods: The study included 30 patients with BD and 30 healthy controls, matched for gender and age. Biochemical parameters evaluated included homocysteine (Hcy), folic acid, vitamin B12, ferritin, creatine kinase (CK) and C-reactive protein (CRP). Results: Hcy levels were significantly higher in the BD patients, both during mania and after achieving euthymia. When Hcy was adjusted for body mass index, there was no significant difference between patients and controls. Ferritin was the only marker that showed a significant decrease during mania when compared to both euthymic patients and controls. There were no significant differences for folate, vitamin B12, CK and CRP. Conclusions: These findings do not show an association between alterations of markers of cardiovascular risk during manic episodes. Further studies are necessary to determine factors and mechanisms associated with cardiovascular risk in patients with BD. .

Traumatic life events in bipolar disorder: impact on BDNF levels and psychopathology.

BACKGROUND: There is evidence that vulnerability to depression and anxiety disorders is markedly increased by traumatic life events. While childhood abuse has been reported to be associated with poorer outcomes in bipolar disorder, little is known about the neurobiological basis underlying this association. The aim of this study was to ascertain whether bipolar patients who were exposed to a traumatic event or events (TE) have lower brain-derived neurotrophic factor (BDNF) levels and more severe psychopathology as indicated by increased comorbidity and other clinical features when compared to those who were not exposed to TE. METHODS: One-hundred and sixty-three consecutively recruited bipolar outpatients were assessed by Structured Clinical Interview for DSM-IV (SCID) and standard protocol in order to evaluation psychopathology and clinical features. The reported TE was assessed using DSM-IV stem criteria for trauma (as defined by A1 and A2 criteria for trauma for post-traumatic stress disorder). Subjects were divided into 2 groups according to presence or absence of lifetime TE. The levels of BDNF, comorbidity and other clinical features were compared between groups. RESULTS: After adjusting for confounders, results indicated that bipolar patients with a history of TE have alcohol abuse/dependence (p < 0.001), anxiety comorbidity, and lower levels of serum BDNF (p < 0.01) compared to those without a history of TE. There was no difference between the 2 groups in age of onset, presence of psychosis, other substance abuse and dependence, rapid cycling or suicide attempts. CONCLUSIONS: Our findings suggest that TE are associated with significantly increased prevalence of alcohol and anxiety comorbidity as well as lower BDNF levels in bipolar patients. It is possible that a decrease in BDNF levels may account for increased comorbidity, but further prospective studies are required to confirm this.

Anxiety comorbidity and quality of life in bipolar disorder patients.

OBJECTIVE: To assess the impact of anxiety comorbidity on the quality of life of patients with bipolar disorder (BD). METHODS: We undertook a cross-Sectional survey of 162 BD outpatients interviewed with the Structured Clinical Interview for DSM-IV. The primary outcome measure was quality of life, assessed with the 26-item WHO Quality of Life Instrument (WHOQOL-BREF). RESULTS: Anxiety comorbidity in BD patients was associated with lower scores in all domains of quality of life. The impact of anxiety comorbidity on the psychological domain of the WHOQOL-BREF was kept, even when the current level of depression was added to the model as a confounding factor. Current anxiety comorbidity was also associated with lifetime alcohol abuse and dependence, rapid cycling, lifetime psychosis, number of suicide attempts, and a lower score in the Global Assessment of Functioning measure. CONCLUSION: Our findings suggest that anxiety comorbidity in BD patients is related to lower quality of life, particularly on the psychological domain. BD-anxiety comorbidity may be associated with such markers of illness severity as number of suicide attempts, rapid cycling, lifetime alcohol abuse, and psychosis. The recognition and treatment of anxiety comorbidity may help patients with BD to relieve their psychological pain and improve their overall quality of life.

Brain-derived neurotrophic factor gene val66met polymorphism and executive functioning in patients with bipolar disorder / Polimorfismo do gene do fator neurotrófico derivado do cérebro val66met e função executiva em pacientes com transtorno bipolar

OBJECTIVE: In the present study, we investigate the association between the val66met polymorphism of the brain-derived neurotrophic factor (BNDF) and the performance on the Wisconsin Card Sorting Test in a sample of Caucasian Brazilian patients with bipolar disorder. METHOD: Sixty-four patients with bipolar disorder were assessed and their performance on the Wisconsin Card Sorting Test was compared with the allele frequency and genotype of the val66met polymorphism of the brain-derived neurotrophic factor. RESULTS: The percentage of non-perseverative errors was significantly higher among patients with the val/val genotype. There was no association between (BNDF) genotype frequency and other Wisconsin Card Sorting Test domains. CONCLUSION: Our results did not replicate previous descriptions of an association between a worse cognitive performance and the presence of the met allele of the val66met brain-derived neurotrophic factor gene polymorphism.

OBJETIVO: O presente estudo tem por objetivo investigar a associação entre o polimorfismo val66met do gene do fator neurotrófico derivado do cérebro (BDNF) e o desempenho cognitivo no Teste Wisconsin de Classificação de Cartas em uma amostra de pacientes bipolares brasileiros caucasianos. MÉTODO: Sessenta e quatro pacientes com transtorno bipolar foram avaliados em relação a sua cognição por meio do Teste Wisconsin de Classificação de Cartas que foi comparada com a freqüência alélica e genotípica do polimorfismo val66met do gene do fator neurotrófico derivado do cérebro. RESULTADOS: O percentual de erros não-perseverativos foi significativamente maior nos indivíduos com genótipo val/val. Não foi encontrada diferença significativa entre a freqüência genotípica do polimorfismo do BDNF e os outros domínios do Teste Wisconsin de Classificação de Cartas. CONCLUSÃO: O estudo do polimorfismo val66met em relação ao desempenho executivo em pacientes bipolares caucasianos de uma amostra brasileira não reproduziu achados anteriores que sugeriam um pior desempenho em indivíduos portadores do alelo met.

Polypharmacy and suicide attempts in bipolar disorder

OBJECTIVE: The aim of this study was to assess the association between suicide attempts and the use of multiple drugs in patients with bipolar disorder. METHOD: One hundred sixty-nine bipolar disorder outpatients diagnosed using the DSM-IV Structured Clinical Interview were included. Demographic and socioeconomic data, number of medications currently in use, history of suicide attempts, number of years undiagnosed, age of onset and current psychiatric co-morbidities were assessed using a structured questionnaire and DSM-IV criteria. The main outcome measure was the number of psychotropic drugs currently in use. RESULTS: Approximately half of all patients (48.5 percent) presented a history of suicide attempt; 84 percent were using more than one medication, and 19 percent were using more than three drugs. The most frequent combinations of drugs used by these patients were: lithium + valproate (17 percent); lithium + antipsychotics (10 percent); lithium + valproate + antipsychotics (9 percent); and antidepressants + any drug (6 percent). The number of suicide attempts was associated with the use of multiple drugs. CONCLUSIONS: Our findings support the notion that the use of combination therapy in bipolar disorder may be related to severity of the BD, such as number of suicide attempts.

OBJETIVO: O objetivo deste trabalho foi verificar associação entre tentativas de suicídio e uso de múltiplas drogas em pacientes com transtorno do humor bipolar. MÉTODO: Cento e sessenta e nove pacientes ambulatoriais com transtorno do humor bipolar, diagnosticados pela entrevista clínica estruturada do DSM-IV, foram incluídos. Dados demográficos e socioeconômicos, número de medicações em uso, história de tentativas de suicídio, número de anos sem diagnóstico, idade de início e comorbidades psiquiátricas foram avaliados através de um questionário estruturado e pelos critérios do DSM-IV. A principal medida de desfecho foi o número de medicamentos psicotrópicos usados correntemente. RESULTADOS: Cerca de metade dos pacientes (48,5 por cento) apresentou uma história de tentativas de suicídio; 84 por cento estavam usando mais do que uma medicação e 19 por cento estavam usando mais do que três medicações. As combinações de fármacos mais utilizadas por estes pacientes foram: lítio + valproato (17 por cento); lítio + antipsicóticos (10 por cento); lítio + valproato + antipsicóticos (9 por cento); e antidepressivos + outros fármacos (6 por cento). O número de tentativas de suicídio mostrou-se associado ao uso de polifarmácia, na análise ajustada. CONCLUSÕES: Nossos resultados sugerem que a polifarmácia em pacientes bipolares pode estar relacionada a indicadores de gravidade, como número de tentativas de suicídio.

Tratamento farmacológico do transtorno bipolar: as evidências de ensaios clínicos randomizados / Pharmacological treatment of bipolar disorder: evidence from randomized clinical trials

O presente artigo é uma síntese das evidências provenientes de ensaios clínicos randomizados sobre o tratamento do transtorno bipolar. A metodologia para a busca do material disponível é descrita, e os resultados são apresentados. Com o melhor nível de evidência disponível, ou seja, revisões sistemáticas de mais de um ensaio clínico randomizado ou pelo menos um ensaio clínico randomizado, temos as seguintes recomendações: 1) a mania aguda pode ser tratada com Lítio, Valproato, Carbamazepina, e antipsicóticos; 2) a depressão bipolar pode ser tratada com antidepressivos (com risco aumentado de virada para mania), com lamotrigina e a associação fluoxetina/olanzapina e 3) a manutenção do transtorno bipolar pode ser realizada com o lítio, valproato, carbamazepina, olanzapina e lamotrigina (quando o objetivo for a profilaxia da depressão bipolar). A não existência de ensaios clínicos publicados não significa que determinadas intervenções não sejam úteis.