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Biomedical subjects

Flávio Kapczinski

Publications and source records attributed to Flávio Kapczinski.

At least 19 recordsLinked to original sources
PubMed2006

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.

Journal Article↗
PubMed2006

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.

Journal Article↗
PubMed2006

Correlation between drug treatment adherence and lithium treatment attitudes and knowledge by bipolar patients.

BACKGROUND: Non-adherence should always be investigated when there is a failure in bipolar treatments, since it is known that reported non-adherence rates in bipolar disorder treatment for long-term prophylactic pharmacotherapy range from 18% to 52%, with a median prevalence of 44.7%. Several factors are related to the poor adherence and reduction of medication efficiency, such as the different types of bipolar disorder, the presence of side effects, medication interactions, level of patient's knowledge about the disorder and their attitude towards treatment, complexity of medical regimens and the doctor-patient relationship. METHODS: Bipolar disorder outpatients under lithium treatment from the Hospital de Clínicas and Materno Infantil Presidente Vargas of Porto Alegre were recruited. All the patients had bipolar disorder and gave informed consent to participate in a clinical interview (106), answered the Lithium Attitudes Questionnaire (LAQ), Lithium Knowledge Test (LKT), Medication Adherence Rating Scale (MARS) and had plasma and red blood cells lithium measurements to assess their medication adherence and the factors that influenced it. RESULTS: 85.6% of bipolar disorder were adherent to lithium treatment showing plasma lithium between 0.6 and 1.2 mmol/L. There was an inverted correlation between the total LAQ score with plasma and red blood cells, a positive correlation between LKT and MARS with plasma and red blood cell lithium. CONCLUSION: These results confirmed that knowledge level is directly correlated to treatment adherence and patients' attitudes, lower adherence, general opposition to prophylaxis, fear of side effects, denial of therapeutic effectiveness and illness severity.

Adolescent↗
PubMed2006

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.

Adult↗
PubMed2006

Increased oxidative stress and DNA damage in bipolar disorder: a twin-case report.

OBJECTIVE: There is an emerging body of data suggesting that oxidative stress may be associated with the pathophysiology of bipolar disorder (BD). In the present study we investigated the oxidative stress profile in two monozygotic twins during a manic episode. METHODS: Two monozygotic twins diagnosed as currently manic by the Structured Clinical Interview for DSM-IV were studied. Serum thiobarbituric acid reactive substances (TBARS), superoxide dismutase (SOD) and catalase (CAT) were measured as parameters of oxidative stress. DNA damage was assessed using the single cell gel electrophoresis technique (Comet Assay). All biochemical measures were conducted at baseline and after a 6-week treatment. RESULTS: Bipolar twins had higher TBARS, SOD and DNA damage, and lower CAT than the healthy control. TBARS and SOD were normalized after mood stabilization, whereas CAT and DNA damage remained altered at week 6. CONCLUSIONS: These findings support that oxidative stress may play a role in the pathophysiology of BD and that pharmacological treatment may exert antioxidant effects. Studies with larger samples are warranted to further clarify this issue.

Antimanic Agents↗
PubMed2006

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.

Adult↗
PubMed2006

Increased oxidative stress in submitochondrial particles after chronic amphetamine exposure.

Previous studies have suggested that reactive oxygen species (ROS) production may play a role in the pathophysiology of many neuropsychiatric disorders, such as bipolar disorder (BD) and schizophrenia (SCZ). In addition, there is an emerging body of data indicating that BD and SCZ may be associated with mitochondrial dysfunction. We studied the effects of acute and chronic d-amphetamine on ROS production in submitochondrial particles of rat brain. Male Wistar rats were divided in two experimental groups: acute and chronic treatment. In the acute treatment, rats received one single IP injection of d-amphetamine (1, 2 or 4 mg/kg) or saline (control group). In the chronic treatment, rats received one daily IP injection of d-amphetamine (1, 2 or 4 mg/kg) or saline for 7 days. Locomotor activity was assessed with the open field task, and thiobarbituric acid reactive substances (TBARS) and superoxide production were measured in submitochondrial particles of the prefrontal cortex and hippocampus. Both acute and chronic amphetamine treatment increased locomotor behavior. Chronic amphetamine exposure induced a 3- to 6-fold increase of TBARS and a 1.5- to 2-fold increase of superoxide production in submitochondrial particles of prefrontal cortex and hippocampus (P < 0.05). No effects on superoxide or TBARS were observed with acute treatment. These findings suggest that amphetamine-induced mitochondrial ROS generation may be a useful model to investigate the hypothesis of altered brain energy metabolism associated with BD and SCZ. Further studies assessing the effects of mood stabilizers and antipsychotics in preventing mitochondrial oxidative stress are necessary.

Amphetamine↗
PubMed2006

Changes in antioxidant defense enzymes after d-amphetamine exposure: implications as an animal model of mania.

Studies have demonstrated that oxidative stress is associated with amphetamine-induced neurotoxicity, but little is known about the adaptations of antioxidant enzymes in the brain after amphetamine exposure. We studied the effects of acute and chronic amphetamine administration on superoxide dismutase (SOD) and catalase (CAT) activity, in a rodent model of mania. Male Wistar rats received either a single IP injection of D-: amphetamine (1 mg/kg, 2 mg/kg, or 4 mg/kg) or vehicle (acute treatment). In the chronic treatment rats received a daily IP injection of either D-: amphetamine (1 mg/kg, 2 mg/kg, or 4 mg/kg) or vehicle for 7 days. Locomotor behavior was assessed using the open field test. SOD and CAT activities were measured in the prefrontal cortex, hippocampus, and striatum. Acute and to a greater extent chronic amphetamine treatment increased locomotor behavior and affected SOD and CAT activities in the prefrontal cortex, hippocampus and striatum. Our findings suggest that amphetamine exposure is associated with an imbalance between SOD and CAT activity in the prefrontal cortex, hippocampus and striatum.

Amphetamine↗
PubMed2006

Evidence of astrogliosis in rat hippocampus after d-amphetamine exposure.

INTRODUCTION: Psychostimulants such as amphetamine (AMPH) induce manic-like symptoms in humans and studies have suggested that bipolar disorder (BD) may be associated to dopamine dysfunction. Glial fibrillary acidic protein (GFAP) up-regulation is considered a marker of astrogliosis, and it has been associated to behavioral sensitization. PURPOSE: We aimed to investigate the behavioral effects of acute and chronic AMPH on rat locomotion and assess GFAP levels in rat cortex and hippocampus. METHODS: Rats were administered either acute (single dose) or chronic (seven days) d-amphetamine IP injection. Locomotion was assessed with an open-field test and GFAP immunoquantity was measured using ELISA. RESULTS: Chronic, but not acute, administration of AMPH increased GFAP levels in rat hippocampus. No differences were observed in rat cortex. CONCLUSIONS: Repeated exposure to AMPH leads to an astroglial response in the hippocampus of rats.

Analysis of Variance↗
PubMed2006

Effects of mood stabilizers on hippocampus BDNF levels in an animal model of mania.

There is an emerging body of data suggesting that mood disorders are associated with decreased brain-derived neurotrophic factor (BDNF). The present study aims to investigate the effects of the mood stabilizers lithium (Li) and valproate (VPT) in an animal model of bipolar disorder. In the first experiment (acute treatment), rats were administered D-amphetamine (AMPH) or saline for 14 days, and then between day 8 and 14, rats were treated with either Li, VPT or saline. In the second experiment (maintenance treatment), rats were pretreated with Li, VPT or saline, and then between day 8 and 14, rats were administered AMPH or saline. In both experiments, locomotor activity was measured using the open-field test and BDNF levels were measured in rat hippocampus by sandwich-ELISA. Li and VPT reversed AMPH-induced behavioral effects in the open-field test in both experiments. In the first experiment, Li increased BDNF levels in rat hippocampus. In the second experiment, AMPH decreased BDNF levels and Li and VPT increased BDNF levels in rat hippocampus. Our results suggest that the present model fulfills adequate face, construct and predictive validity as an animal model of mania.

Affect↗
PubMed2006

Glial fibrillary acidic protein expression after electroconvulsive shocks in rat brain.

OBJECTIVE: The aim of the present study was to assess the effect of electroconvulsive shock (ECS) in glial fibrillary acidic protein (GFAP) expression in rat brain. METHODS: Rats were given either a single (acute) or a series of eight (chronic) ECS. Brain regions were isolated and levels of glial fibrillary acidic protein (GFAP) in the brain tissue (cortex, hippocampus, and cerebellum) were assessed using an enzyme-linked immunosorbent assay (ELISA). RESULTS: We showed that GFAP expression is reduced in the hippocampus within 48 h and 7 days after acute ECS. GFAP levels are increased in the cerebellum immediately after acute and chronic ECS. No changes were observed in the cortex. CONCLUSIONS: Our findings showed a differential effect of acute and chronic ECS in the astroglial response in the brain of rats.

Analysis of Variance↗
PubMed2006

Acute and chronic electroconvulsive shock in rats: effects on peripheral markers of neuronal injury and glial activity.

Electroconvulsive therapy is considered one of the most effective treatments of major depression, but controversy still exists on whether it may be brain damaging. The aim of this work was to evaluate the cerebrospinal fluid (CSF) levels of neuron specific enolase (NSE), protein S100B and lactate of rats submitted to acute and chronic models of ECS. Rats were submitted to either one shock (acute) or a series of eight shocks, applied one at every 48 h (chronic). CSF samples were collected at 0, 3, 6, 12, 24, 48 and 72 h after the shock in the acute model and at these same time intervals after the last shock in the chronic model. Both models did not produce significant alterations in the levels of NSE. S100B levels were significantly increased at 6 h in the chronic model (p<0.0001). There was a significant increase in the levels of lactate at 0 h in both models (p<0.001). These results support the proposition that ECS does not produce neural damage, and suggest that the alterations in the levels of S100B and lactate may reflect an astrocytic activity of a protective nature.

Animals↗
PubMed2006

Lithium increases nerve growth factor levels in the rat hippocampus in an animal model of mania.

Pharmacological studies suggest that neurotrophins may play a role in the effects of lithium and valproate on mood regulation. In this study, we tested the hypotheses that lithium and valproate would reverse and prevent the behavioral and biochemical effects of amphetamine, using a rat model of mania. In the reversal treatment, male Wistar rats were first administered D-amphetamine or saline for 14 days, and then, between days 8-14, rats were treated with lithium, valproate or saline. In the prevention treatment, rats were pretreated with lithium, valproate or saline, and then, between days 8-14, rats were administered D-amphetamine or saline. Locomotor behavior was assessed using the open-field task and hippocampal nerve growth factor levels were determined by enzyme-linked immunosorbent assay. Both lithium and valproate reversed and prevented D-amphetamine-induced hyperactivity. Lithium increased nerve growth factor content in rat hippocampus in both experiments, but this effect was blocked with the co-administration of D-amphetamine. No significant effects on nerve growth factor levels were observed with valproate or D-amphetamine alone. These findings suggest that nerve growth factor may play a role in the neurotrophic effects of lithium but do not support the hypotheses that the nerve growth factor/TrkA pathway is involved in the pathophysiology of bipolar disorder.

Amphetamine↗
PubMed2006

Increased oxidative stress after repeated amphetamine exposure: possible relevance as a model of mania.

BACKGROUND: Acute mania can be modeled in animals using D-amphetamine (AMPH). Acute AMPH injections are associated with monoamine depletion, loss of neurofilaments and neurite degeneration. However, the precise mechanisms underlying AMPH-induced neurotoxicity are still unclear. Several studies have demonstrated that oxidative stress may play a role in the behavioral and neurochemical changes observed after AMPH administration. METHODS: The effects of a single and repeated injections (seven daily injections) of AMPH administered intraperitonially on locomotion and the production of lipid and protein oxidative markers in rat cortex, striatum and hippocampus were assessed. Locomotion was assessed in an open-field task and markers of oxidative stress were assessed in brain tissue. RESULTS: Both single and repeated injections of AMPH increased protein carbonyl formation in rat brain. Repeated exposure to AMPH induced an additional increase in thiobarbituric acid reactive species in brain tissue. CONCLUSIONS: Longer periods of exposure to AMPH were associated with increased oxidative stress in rat brain. This adds to the notion that repeated manic episodes may be associated with greater brain damage and, therefore, poorer outcomes.

Animals↗
PubMed2006

Effects of lithium and valproate on amphetamine-induced oxidative stress generation in an animal model of mania.

OBJECTIVE: Previous studies have suggested that oxidative stress may play a role in the pathophysiology of bipolar disorder (BD). Moreover, recent studies indicate that lithium and valproate exert neuroprotective effects against oxidative stress. We studied the effects of the mood stabilizers lithium and valproate on amphetamine-induced oxidative stress in an animal model of mania. METHODS: In the first model (reversal treatment), adult male Wistar rats received d-amphetamine or saline for 14 days, and between the 8th and 14th days, they were treated with lithium, valproate or saline. In the second model (prevention treatment), rats were pretreated with lithium, valproate or saline, and between the 8th and 14th days, they received d-amphetamine or saline. We assessed locomotor activity with the open-field task. We measured thiobarbituric acid reactive substances (TBARS) and protein carbonyl formation, as parameters of oxidative stress, and superoxide dismutase (SOD) and catalase (CAT), the major antioxidant enzymes, in the prefrontal cortex and hippocampus. RESULTS: Lithium and valproate reversed (reversal treatment model) and prevented (prevention treatment model) amphetamine-induced hyperactivity and reversed and prevented amphetamine-induced TBARS formation in both experiments. However, the co-administration of lithium or valproate with amphetamine increased lipid peroxidation, depending on the brain region and treatment regimen. No changes in protein carbonyl formation were observed. SOD activity varied with different treatment regimens, and CAT activity increased when the index of lipid peroxidation was more robust. CONCLUSION: Our findings suggest that lithium and valproate exert protective effects against amphetamine-induced oxidative stress in vivo, further supporting the hypothesis that oxidative stress may be associated with the pathophysiology of BD.

Animals↗
PubMed2005

The efficacy of antidepressants for generalized anxiety disorder: a systematic review and meta-analysis.

OBJECTIVE: To investigate the efficacy and acceptability of antidepressants in the treatment of generalized anxiety disorder. METHODS: All randomized controlled trials assessing the use of antidepressants in generalized anxiety disorder up to may 2002 were included. Non randomized trials and those that included patients with both generalized anxiety disorder and another Axis I co-morbidity were excluded. Relative risks, weighted mean difference and number needed to treat were estimated. People who died or dropped out were regarded as having had no improvement. RESULTS: Antidepressants (imipramine, venlafaxine and paroxetine) were found to be superior to placebo in treating generalized anxiety disorder. The calculated number needed to treat for antidepressants in generalized anxiety disorder was 5.15. Dropout rates did not differ between antidepressants and placebo. CONCLUSION: The available evidence suggests that antidepressants would probably be a reasonable treatment for generalized anxiety disorder patients in the clinical context.

Antidepressive Agents↗