LEDA LEME TALIB
Projetos de Pesquisa
Unidades Organizacionais
Instituto de Psiquiatria, Hospital das Clínicas, Faculdade de Medicina
LIM/27 - Laboratório de Neurociências, Hospital das Clínicas, Faculdade de Medicina
LIM/27 - Laboratório de Neurociências, Hospital das Clínicas, Faculdade de Medicina
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conferenceObject Increased GDNF but not BDNF Plasma Levels in Type II Compared to Type I Bipolar Disorder(2013) ZANETTI, Marcus V.; TEIXEIRA, Antonio L.; CHAIM, Tiffany M.; SOUSA, Rafael T. de; TALIB, Leda L.; GATTAZ, Wagner F.; BUSATTO, Geraldo F.; MACHADO-VIEIRA, RodrigoBackground: The brain-derived neurotrophic factor (BDNF) is a neurotrophin important for synaptic plasticity and neurogenesis, whereas the glial cell-line derived neurotrophic factor (GDNF) modulates the activity of monoaminergic neurons and glial cells. Previous works have suggested that abnormal peripheral levels of these proteins might relate to different mood states in bipolar disorder (BD), but none study so far have evaluated it with regard to potential differences between the types I (BD-I) and II (BD-II) subtypes of the disorder. Methods: Eighteen BD-I and 19 BD-II patients presenting with an acute mood episode (depressive, manic or mixed), and 23 healthy controls were studied. Plasma levels of BDNF and GDNF were measured using enzyme-linked immunosorbent assay (ELISA). Results: BD-II individuals showed significantly increased levels of GDNF compared to both BD-I patients and controls (ANOVA, df=2, F= 5.74, p=0.005; Tukey for post hoc comparisons). When we focused our analysis on the treatment-naïve patients only (14 BD-I and 13 BD-II), this result became even more significant (ANOVA, df=2, F= 7.33, p=0.002). No significant between-groups differences were observed on BDNF levels. Also, no significant correlation was observed between BDNF or GDNF levels and depressive and manic symptoms. Conclusions: BD-II at an acute phase of the illness is associated with increased plasma levels of GDNF. Previous use of mood stabilizer and antipsychotic agents might produce a chronic effect on GDNF production.- Correlation between platelet and brain PLA(2) activity(2013) TALIB, Leda L.; VALENTE, Kette D.; VINCENTIIS, Silvia; GATTAZ, Wagner F.The phospholipase A(2) (PLA(2)) enzymes have been implicated in several neuropsychiatry disorders and activity alterations have been described in brain and platelet. Since brain tissue is not readily available for the measurement of PLA(2) activity, it would be of interest to test directly whether PLA(2) activities in both tissues are correlated. We performed this task assessing PLA(2) activity in platelets and hippocampus collected simultaneously from 19 patients undergoing temporal lobectomy for treatment of refractory epilepsy. Our findings suggest that total PLA(2) activity in platelets may reflect the total activity of the enzyme in the brain (r(s)=0.59, p=0.008). However in our sample no correlations were found between the subgroups of the enzyme in brain and in platelets. This lack of correlations may be due to different effects of drug treatment on the PLA(2) subtypes. In face of the difficulty to obtain brain tissues from living patients, further studies with larger drug-free samples are warranted to clarify whether the use of platelets is a reliable strategy to reflect the subtypes of PLA(2) activity in the brain.
- Antipsychotic drugs decrease iPLA(2) gene expression in schizophrenia(2013) KERR, Daniel Shikanai; TALIB, Leda Leme; YAMAMOTO, Victor Junji; FERREIRA, Aline S.; ZANETTI, Marcus V.; SERPA, Mauricio H.; BUSATTO, Geraldo F.; BILT, Martinus Theodorus Van de; GATTAZ, Wagner Farid
- Decreased Levels of Circulating Adiponectin in Mild Cognitive Impairment and Alzheimer's Disease(2013) TEIXEIRA, Antonio L.; DINIZ, Breno S.; CAMPOS, Alline C.; MIRANDA, Aline S.; ROCHA, Natalia P.; TALIB, Leda L.; GATTAZ, Wagner F.; FORLENZA, Orestes V.Adiponectin, an adipocytokine released by the adipose tissue and has important roles in the metabolic regulation and inflammatory control, may play an important roles in the physiopathology of psychiatric and neurodegenerative disorders. The aim of the present work was to evaluate adiponectin serum levels in patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD) as compared to cognitively healthy elders and to correlate these levels with clinical and cognitive parameters. We further evaluated whether circulating adiponectin levels could predict progression from MCI to Alzheimer's disease upon follow-up. We recruited 157 subjects (41 with AD, 65 with MCI and 51 elderly controls) in the baseline assessment. Follow-up data were available for 54 subjects with MCI and 43 controls in whom we ascertained the conversion to AD and the progression of cognitive impairment. Adiponectin was assayed by sandwich ELISA. Serum levels of adiponectin were significantly lower in MCI and AD as compared to controls (p < 0.001). After controlling for age, educational level and APOE genotype, adiponectin levels remained significantly reduced in these groups (p < 0.001). Circulating adiponectin levels did not predict cognitive decline in the elderly controls (i.e., progression from normal cognition to MCI) or progression to Alzheimer's disease in subjects with MCI. We conclude that lower levels of adiponectin were associated with cognitive dysfunction, though it did not predict additional cognitive decline and conversion to dementia in this cohort of elderly subjects. Decreased adiponectin may be a surrogate marker of the pathological process in AD, linking clinical comorbidities, inflammation and cognitive dysfunction.
conferenceObject Human leukocyte antigen genotype in antiepileptics hypersensitivity reactions: a pilot study in Brazilian patients(2013) TANNO, L. K.; KERR, D. S.; YAMAMOTO, V. J.; PRADO, C. M.; TALIB, L. L.; GATTAZ, W. F.; MOTTA, A. A.; KALIL, J. E.- Higher proportion of inactive Gsk3 beta in platelets of elderly patients with bipolar disorder: an effect of treatment?(2013) LADEIRA, Rodolfo Braga; JOAQUIM, Helena Passarelli Giroud; TALIB, Leda Leme; NUNES, Paula Villela; FORLENZA, Orestes VicenteObjective: It has been postulated that mood stabilizers inhibit glycogen synthase kinase 3-beta (Gsk3 beta) activity, mainly through its phosphorylation on serine-9 (Ser9). However, in vivo studies addressing Gsk3 beta activity in patients with bipolar disorder are scarce. Here, we compare Gsk3 beta inactivation (as indicated by Ser9-phosphorylation) in platelets of elderly patients with bipolar disorder undergoing clinical treatment and healthy elderly adults not taking medication. Methods: Platelet samples were obtained from 37 elderly adults (bipolar disorder = 19, controls = 18). Relative changes in Gsk3 beta inactivation was estimated by comparing the ratios of phosphorylated Gsk3 beta to total Gsk3 beta (p-Gsk3 beta Ser9/Gsk3 beta) between the disease and control groups. Results: Phosphorylated-Gsk3 beta (p < 0.001) and the p-Gsk3 beta Ser9/Gsk3 beta ratio (p = 0.006) were elevated in bipolar patients. In the bipolar disorder group, p-Gsk3 beta Ser9/Gsk3 beta was positively correlated with serum lithium levels (r = 0.478, p = 0.039). Conclusions: Gsk3 beta inactivation is higher in this group of elderly adults undergoing treatment for bipolar disorder. However, whether the treatment or the disease causes Gsk3 beta inactivation was confounded by the lack of an unmedicated, bipolar control group and the non-uniform treatment regimens of the bipolar disorder group. Thus, further studies should help distinguish whether Gsk3 beta inactivation is an effect of drug treatment or an intrinsic characteristic of bipolar disorder.
conferenceObject Oxidative Stress Parameters in Recent-Onset Bipolar Disorder and Possible Lithium Antioxidant Effect(2013) SOUSA, Rafael T. de; ZANETTI, Marcus V.; TALIB, Leda L.; GATTAZ, Wagner F.; MACHADO-VIEIRA, RodrigoBackground: Several studies have shown oxidative stress (OxS) and imbalance of antioxidant enzymes in bipolar disorder (BD). Lithium is a gold-standard treatment in BD and showed a role in decreasing OxS. Despite few data available for recent-onset BD, increased antioxidant defenses were found in first episode of bipolar mania. No study, however, evaluated OxS parameters in depression of recent-onset BD and the effects of lithium treatment in OxS in bipolar depression. Methods: BD subjects in a depressive episode (n=25) with no more than 5 years of illness duration were enrolled and treated for 6 weeks with lithium monotherapy, although hypnotics use as needed was allowed. Blood samples were collected at baseline and after 6-week lithium treatment. Healthy controls (n=28) were used for comparison with patients. Tiobarbituric acid reactive substances (TBARS), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activities were measured spectrophotometrically. Results: BD patients had increased CAT (ANCOVA, df=1, 47, F=56.60, p<0.001), enhanced GPx (ANCOVA, df=1, 49, F=12.20, p=0.001) and decreased SOD/CAT ratio (ANCOVA, df=1, 44, F=30.66, p<0.001) compared to healthy controls. Also, no differences in SOD or TBARS between subjects with BD and healthy controls was observed. Regarding lithium treatment effects, BD patients had a decrease in TBARS (Wilcoxon Signed Ranks Test, z=-2.81, p=0.005) levels, with no changes in other parameters. Conclusions: Results suggest that recent-onset BD may have enhanced antioxidant enzymes. Lithium showed efficacy against OxS, confirming its neuroprotective role.- Reduced Serum Nerve Growth Factor in Patients With Late-Life Depression(2013) DINIZ, Breno S.; TEIXEIRA, Antonio L.; MACHADO-VIEIRA, Rodrigo; TALIB, Leda L.; GATTAZ, Wagner F.; FORIENZA, Orestes V.Introduction: Nerve growth factor (NGF) is one of the most abundant neurotrophic factors in the central nervous system and has been involved in several neuropsychiatric disorders. Methods: We recruited 77 age- and gender-matched elderly subjects (38 with late-life depression, 17 with previous major depressive episode, and 22 healthy subjects in the comparison group). Serum concentration of NGF was determined by enzyme-linked immunosorbent assay. Results: NGF levels were significantly reduced in the depressed patients (p = 0.002) as compared with healthy elderly controls. Elderly control subjects with previous depressive episode also showed a significant reduction in NGF levels as compared with controls (p <0.01); NGF levels were similar between patients with current depressive episode and previous depressive episode (p = 0.2). Conclusion: The present findings provide additional evidence to the relevance of reduced neurotrophic support in the pathophysiology of late-life depression. Also, reduced serum NGF level may be a state marker of depression in elderly subjects. (Am J Geriatr Psychiatry 2013; 21:493-496)