Serum S100B and antioxidant enzymes in bipolar patients.

Bipolar disorder (BD) is a chronic, severe, and highly disabling psychiatric disorder; peripheral markers have been used to assess biochemical alterations associated with BD and/or possibly involved in its pathophysiology. Beyond neuronal commitment, many groups have proposed the involvement of glial activity in psychiatric disorders. Other biochemical markers, particularly associated with oxidative stress, have been studied in BD. In the present study, we evaluated glial involvement and oxidative stress in patients with BD. Glial activity was assessed by measuring serum S100B content; oxidative stress was assessed using serum thiobarbituric acid reactive substances (TBARS) and activities of antioxidant enzymes in BD patients during different episodes of disease. We found a significant increment of serum S100B during episodes of mania and depression, but not in euthymic patients. Superoxide dismutase (SOD) activity, as well the SOD/glutathione peroxidase plus catalase ratio, was also increased in manic and depressed patients. On the other hand, TBARS levels were increased in BD patients regardless of the phase of the disorder. These findings suggest a potential oxidative damage in BD patients. This peripheral oxidative imbalance indicates that systemic changes are taking place during the active phases of the illness. Such changes appear to relate to astrocyte function, as indicated by serum S100B elevation.

Serum neurotrophin-3 is increased during manic and depressive episodes in bipolar disorder.

Accumulating evidence suggest that neural changes and cognitive impairment may accompany the course of bipolar disorder. Such detrimental effects of cumulative mood episodes may be related to changes in neurotrophins that take place during mood episodes but not during euthymic phases. The present study investigated serum neurotrophin-3 (NT-3) levels in patients with bipolar disorder during manic, depressed, and euthymic states, using an enzyme-linked immunosorbent assay (sandwich-ELISA). Serum NT-3 levels were increased in manic (p<0.001) and depressed (p<0.001) BD patients, as compared with euthymic patients and normal controls. These findings suggest that the NT-3 signaling system may play a role in the pathophysiology of BD.

Mismatch between self-reported quality of life and functional assessment in acute mania: a matter of unawareness of illness?

BACKGROUND: Studies addressing self-reported quality of life (QoL) in acute mania are scarce and inconsistent. While it has been suggested that there is some disagreement between objective measures and subjective QoL as reported by acutely manic patients, this issue has not been systematically studied. This study aims to investigate the self-reported QoL in manic, depressed, and euthymic BD subjects, as compared to matched healthy controls. METHODS: One-hundred and twenty type-I bipolar patients (40 manic, 40 depressed, and 40 euthymic) and 40 matched controls were studied. Self-reported QoL was assessed using the World Health Organization's Quality of Life Instrument-Short Version (WHOQOL-BREF). Objective functioning was assessed using the Global Assessment of Functioning (GAF), and depressive and manic symptoms were assessed using the Hamilton Depression Rating Scale-17 items (HDRS) and the Young Mania Rating Scale (YMRS), respectively. RESULTS: Manic patients presented the lowest GAF measures but reported same overall QoL as euthymic patients and controls, and better QoL than depressed patients. Within the manic subgroup, there was a significant inverse correlation between psychological QoL and GAF scores (r=-0.54; p=0.001). LIMITATIONS: The cross-sectional design and the lack of control for potential comorbid conditions are the major limitations of the present study. CONCLUSIONS: Our findings suggest that this mismatch between objective and subjective measures during acute mania may be associated with a lack of insight or awareness of their own illness.

DNA damage in bipolar disorder.

Bipolar disorder (BD) is a prevalent, chronic, severe, and highly disabling psychiatric disorder that is associated with increased morbidity and mortality due to general medical conditions. There is an emerging body of evidence correlating chronic medical conditions with DNA damage. The present study was designed to assess DNA damage in BD patients using the comet assay (CA). Thirty-two bipolar-I outpatients diagnosed using the Structured Clinical Interview for DSM-IV were matched with 32 healthy volunteers. Manic and depressive symptoms were assessed using the Young Mania Rating Scale and the Hamilton Depression Rating Scale, respectively. Peripheral blood samples were collected and a standard protocol for CA preparation and analysis was performed. The present study showed that BD outpatients present an increased frequency of DNA damage relative to controls. The frequency of DNA damage correlated with the severity of symptoms of depression and mania.

Manic symptoms and quality of life in bipolar disorder.

This study evaluates the influence of manic symptoms on quality of life in a sample of adult bipolar disorder (BD) patients. This was a cross-sectional study including 125 BD outpatients from a university-based program. All patients were diagnosed using the Structured Clinical Interview for DSM-IV for BD. Manic symptoms and quality of life were assessed using the Young Mania Rating Scale (YMRS) and the World Health Organization Quality of Life Instrument-Short Version (WHOQOL-BREF), respectively. In the unadjusted analysis using linear regression, the score of manic symptoms was inversely associated with scores of quality of life within the social domain of the WHOQOL. In the adjusted analysis, the score of manic symptoms was inversely associated with the social, physical, and psychological domains of the WHOQOL. In a separate analysis at the YMRS items, items 4 (irritability) and 5 (sleep) were associated with lower quality of life.

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.

An open trial of adjunctive escitalopram in bipolar depression.

OBJECTIVE: This study was designed to evaluate the efficacy and safety of a highly potent and selective serotonergic antidepressant, escitalopram, in the treatment of bipolar depression. METHOD: Twenty outpatients with DSM-IV bipolar depression types I and II were enrolled in a 12-week open trial of escitalopram, 10 mg daily, adjunctive to their ongoing mood stabilizer. Assessments were carried out using the Hamilton Rating Scale for Depression (HAM-D), the Young Mania Rating Scale (YMRS), and the Clinical Global Impressions for Severity (CGI-S) and Improvement (CGI-I) scales. The study was conducted from August 2003 to February 2004. RESULTS: Escitalopram was associated with significant improvement as measured by the HAM-D total score, which showed a mean reduction from baseline (mean = 20.9, SD = 4.2) to endpoint (mean = 8.9, SD = 3.6; p < .001) of 12 points. The mean CGI-S score decreased by 3.3 points (baseline: mean = 4.8, SD = 0.7; week 12: mean = 1.5, SD = 0.6; p < .001). Adverse events emerged in 75% of the patients (N = 15), usually of mild-to-moderate severity. Four dropouts took place due to manic switch (N = 1), hypomanic symptoms (N = 2), and hospitalization due to the emergence of suicidal ideation and psychosis (N = 1). CONCLUSION: These findings suggest that escitalopram in association with mood stabilizers may be an effective and reasonably well-tolerated treatment for patients with moderate-to-severe bipolar depression. The switch rate was similar to what is described in the literature for the selective serotonin reuptake inhibitors. Randomized controlled trials of escitalopram in bipolar depression are warranted.

Serum brain-derived neurotrophic factor is decreased in bipolar disorder during depressive and manic episodes.

Genetic and pharmacological studies have suggested that brain-derived neurotrophic factor (BDNF) may be associated with the pathophysiology of bipolar disorder (BD). The present study investigated serum BDNF levels in manic, depressed, euthymic BD patients and in matched healthy controls, using an enzyme-linked immunosorbent assay (sandwich-ELISA). Serum BDNF levels were decreased in manic (p=0.019) and depressed (p=0.027) BD patients, as compared with euthymic patients and controls. Serum BDNF levels were negatively correlated with the severity of manic (r=-0.37, p=0.005) and depressive (r=-0.30, p=0.033) symptoms. These findings further support the hypothesis that the BDNF signaling system may play a role in the pathophysiology of BD.

Increased serum glial cell line-derived neurotrophic factor immunocontent during manic and depressive episodes in individuals with bipolar disorder.

Glial cell line-derived neurotrophic factor (GDNF) is a neurotrophic factor from the transforming growth factor beta family, which plays a role in the development and function of hippocampal cells. Preclinical studies suggest that changes in neurotrophic growth factor systems might be involved in the pathophysiology of mood disorders including bipolar disorder (BD) [E.J. Nestler, M. Barrot, R.J. DiLeone, A.J. Eisch, S.J. Gold, L.M. Monteggia, Neurobiology of depression, Neuron 34 (2002) 13-25]. This is the first study to analyze GDNF immunocontent in BD subjects across different mood states, including mania, depression, and remission (euthymia). Fourty-four bipolar patients (14 depressed, 15 manic, and 15 euthymic) and 14 healthy controls, diagnosed according to the Structural Clinical Interview for DSM-IV were studied. Serum GDNF immunocontent was measured using Western blotting. Serum GDNF immunocontent was increased in manic (F=42.31; p=0.001; one-way ANOVA) and depressed (F=42.31; p=0.004; one-way ANOVA) bipolar patients, but not in euthymic patients as compared with controls. Our results indicate that changes in GDNF immunocontent occur during acute major affective episodes in bipolar subjects. These results further support the role of neurotrophins in the pathophysiology of bipolar disorder. Whether the observed increase in GDNF immunocontent correspond to a pathological or an adaptive response remains to be determined.

Validation of the Portuguese version of the Lithium Attitudes Questionnaire (LAQ) in bipolar patients treated with lithium: cross-over study.

BACKGROUND: Poor adherence to lithium is very common in bipolar patients and it is a frequent cause of recurrence during prophylactic treatment. Several reports suggest that attitudes of bipolar patients interfere with adherence to lithium. The Lithium Attitudes Questionnaire (LAQ) is a brief questionnaire developed as a means of identifying and grouping the problems patients commonly have with taking lithium regularly. The original version is validated in patients, but a validated version in Portuguese is not yet available. METHODS: One-hundred six patients with bipolar disorder (DSM-IV criteria) criteria under lithium treatment for at least one month were assessed using LAQ. LAQ is a brief questionnaire administered under interview conditions, which includes 19 items rating attitudes towards prophylactic lithium treatment. We analysed the internal consistency, concurrent validity, sensitivity and specificity of the Portuguese version of LAQ. RESULTS: The internal consistency, evaluated by Cronbach's alpha was 0.78. The mean total LAQ score was 4.1. Concurrent validity was confirmed by a negative correlation between plasma lithium concentration and total LAQ score (r = -0,198; p = 0.048). We analysed the scale's discriminative capacity revealing a sensitivity of 69% and a specificity of 71% in the identification of negative attitudes of bipolar patients. CONCLUSION: The psychometric assessment of the Portuguese version of LAQ showed good internal consistency, sensitivity and specificity. The results were similar to the original version in relation to attitudes of bipolar patients towards lithium therapy.

Adaptation and validation of the Portuguese version of the Lithium Knowledge Test (LKT) of bipolar patients treated with lithium: cross-over study.

OBJECTIVE: Adherence problems are a common feature among bipolar patients. A recent study showed that lithium knowledge was the main difference between adherent and non adherents bipolar patients. The Lithium Knowledge Test (LKT), a brief questionnaire, was developed as a means of identifying aspects of patients' practical and pharmacological knowledge which are important if therapy is to be safe and effective. The original English version is validated in psychiatric population, but a validated Portuguese one is not yet available. METHODS: One hundred six patients selected were diagnosed with bipolar disorder (I or II) according to DSM-IV criteria and had to be on lithium treatment for at least one month. The LKT was administered on only one occasion. We analysed the internal consistency, concurrent validity, sensitivity and specificity of the LKT for the detection of the knowledge about lithium treatment of bipolar patients. RESULTS: The internal consistency, evaluated by Cronbach's alpha was 0.596. The mean of total score LKT by bipolar patients was 9.0 (SD: 0.75) for men and 8.74 (SD: 0.44) for women. Concurrent validity based on plasma lithium concentration showed a significant correlation between the total LKT score and plasma lithium (r = 0.232; p = 0.020). The sensitivity was 84% and specificity was 81%. CONCLUSION: LKT is a rapid, reliable instrument which appears to be as effective as a lengthier standard interview with a lithium clinic doctor, and which has a high level of acceptability to lithium patients. We found that the psychometric assessment of the Portuguese version of LKT showed good internal consistency, sensitivity and specificity.

Bipolar depression: the importance of being on remission.

OBJECTIVE: The aim of the present study is to compare quality of life among currently depressed, subsyndromal and remitted patients with bipolar disorder (BD) and to assess whether the level of depression correlates with the scores of quality of life in BD patients. METHOD: Sixty bipolar outpatients diagnosed using the Structured Clinical Interview for DSM-IV who met criteria for diagnosis of BD type I, II or not otherwise specified (BD-NOS), and who were not currently on a manic or mixed episode were included. The main variables of interest were quality of life (QOL) assessed using the 26-item World Health Organization QOL instrument (WHOQOL-BREF) and depression assessed using the 17-item Hamilton Depression Rating Scale (HDRS). RESULTS: A linear trend test showed a dose response association between patients' current mood state and all domains of quality of life. Higher quality of life scores were found among remitted patients, followed by subsyndromal patients; depressed patients presented lower scores of quality of life, except for the social domain. The four domains of the WHOQOL scale correlated negatively with the HDRS. CONCLUSIONS: Our findings suggest that bipolar depression and residual symptoms of depression are negatively correlated with QOL in BD patients.

Clinical impact of late diagnose of bipolar disorder.

BACKGROUND: This study assessed the impact of number of years undiagnosed (NYU) on current morbidity in patients with bipolar disorder. LIMITATIONS: The sample size used was rather small, which may make difficult the generalization of our findings to larger datasets. The data about age of onset and age when patients received their diagnosis may present a certain degree of recall error. METHOD: Sixty-five bipolar outpatients diagnosed using the Structured Clinical Interview for DSM were included. The main outcome measurements were quality of life (QOL) assessed using the 26-item World Health Organization QOL instrument (WHOQOL-Bref) and depression assessed using the 17-item Hamilton Depression Rating Scale (HDRS). RESULTS: Age of onset and years of disorder were not correlated with the outcomes assessed. The NYU were associated with higher scores of HDRS (P<0.01), lower scores of QOL within the physical (p<0.01) and psychological (p<0.05) domains of QOL. CONCLUSION: Our findings suggest that the NYU may be an important predictor of the current clinical status of bipolar patients.

[The multidisciplinary team approach to the treatment of bipolar disorder: an overview]. / O papel da equipe multidisciplinar no manejo do paciente bipolar.

Bipolar disorder is a chronic and recurrent disorder, and many factors have been associated with its course and prognosis. Dysfunction in social, professional or family life has been correlated with poor outcomes and increased risk of relapse and recurrence, especially when the patient does not adhere to the treatment regimen. Within the last decade, new treatments, intended to promote better adherence and minimize the risk of morbidity or hospitalization, have been tested. The multidisciplinary team approach attempts to educate patients and their families about such factors. Herein, we evaluate the therapeutic efficacy of this approach in applying the various psychosocial interventions employed in the treatment of bipolar disorder. The objective of this approach is early identification of prodromal symptoms in order to prevent hospitalization and behavioral dysfunction.

Development and application of the mania rating guide (MRG).

In this article we present the development and application of the Mania Rating Guide (MRG), a semi-structured interview. This guide was created in order to assist the filling of three mania Scales: Mania Rating Scale, Bech-Rafaelsen Mania Scale and Clinician-Administered Rating Scale for Mania. The MRG consists of twenty-one Psychopathological Dimensions, that correspond to the Items of the original Scales, and are structured in Questions. The guide was applied to fifteen manic patients admitted in the Psychiatric Unit of the Clinical Hospital of Porto Alegre. A psychiatrist interviewed them using the MRG, and the interviews were videotaped. Afterwards, three independent raters scored the Mania scales based on the films. The impression of the raters was that the MRG allows not only to easily score all the Items of the Scales but also to cover the wide spectrum of the symptomatological presentation of a manic syndrome.

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.

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.

Pilot-project of implantation of pharmaceutical care close to the program of bipolar mood disorder of the Hospital of Clinics of Porto Alegre / Projecto-piloto de implantação da assistência farmacêutica junto ao programa de transtorno de humor bipolar do Hospital das Clínicas de Porto Alegre

The Bipolar Mood Disorder is characterized by the alternation of depressive crises with episodes of mania or euphoria, having these patients 15 to 35 times more chances of suicide, as compared with people without this disorder. The pharmacotherapy is fundamental for this disease, aiming to decrease the frequency of episodes and disease severity. In these patients, the polypharmacy has recently increased and one of the main difficulties is the adherence to treatment. The objective of this study was to contribute for the improvement of bipolar patients health conditions, developing their respective pharmacotherapeutic follow-up. Twenty eight adult bipolar patients who were participants of a specialized clinic within a tertiary hospital in Porto Alegre have been randomly selected, and the Dader Method of pharmacotherapeutic follow-up has been applied. The more common clinical comorbidities were: hypertension (50 percent), obesity (46.43 percent), and hypothyroidism (36.29 percent). The bipolar patients are more susceptible to clinical comorbidities, and many of them could be due to pharmacotherapy. Only 1.43 percent of patients presented Drug Related Problems, being all of them resolved along the study. It was also observed that 32.14 percent of evaluated patients presented low adherence to treatment, and between these patients, 55.56 percent passed to have good adherence after pharmacotherapeutic follow-up. The pharmacotherapeutic follow-up is fundamental for the improvement of patient's health. New studies, with higher number of patients and longer duration, are necessary to evaluate the percentage of patients that could be beneficiary of Pharmaceutical Care.

O Transtorno do Humor Bipolar é caracterizando pela alternância de crises depressivas com episódios de mania ou euforia, tendo estes pacientes 15-35 vezes mais chances de suicídio em comparação com pessoas sem este transtorno. A farmacoterapia é fundamental, visando diminuir a freqüência dos episódios e a gravidade da doença. Nestes pacientes, a polifarmácia tem aumentado ultimamente e uma das maiores dificuldades é a adesão ao tratamento. O objetivo do estudo foi contribuir para a melhoria das condições de saúde de pacientes bipolares, realizando o acompanhamento farmacoterapêutico dos mesmos. Foram selecionados aleatoriamente 28 pacientes bipolares adultos, participantes de um ambulatório especializado de um hospital terciário em Porto Alegre e aplicado o Método Dáder de acompanhamento farmacoterapêutico. As co-morbidades clínicas mais comuns foram: hipertensão (50 por cento), obesidade (46,43 por cento) e hipotiroidismo (39,29 por cento). Os pacientes bipolares são mais suscetíveis a co-morbidades clínicas e muitas destas podem ser devidas a farmacoterapia. Apenas 1,43 por cento dos pacientes apresentavam Problemas Relacionados a Medicamentos, sendo todos solucionados no decorrer do estudo. Também se observou que 32,14 por cento dos pacientes avaliados apresentavam baixa adesão ao tratamento e entre estes, 55,56 por cento passaram a ter boa adesão após o acompanhamento farmacoterapêutico. É fundamental para a melhoria da saúde do paciente o acompanhamento farmacoterapêutico. Novos estudos, com maior número de pacientes e maior duração, são necessários para avaliar o percentual de pacientes que poderão ser beneficiados pela Atenção Farmacêutica.