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 Distinct Glycogen Synthase Kinase 3 beta and Phospholipase A2 Expression Profiles in Bipolar I and II Disorders(2016) ZANETTI, Marcus V.; MACHADO-VIEIRA, Rodrigo; JOAQUIM, Helena P. G.; CHAIM, Tiffany M.; SERPA, Mauricio H.; SOUSA, Rafael T. de; GATTAZ, Wagner F.; BUSATTO, Geraldo F.; TALIB, Leda L.- Cognitive impairment in late-life bipolar disorder is not associated with Alzheimer's disease pathological signature in the cerebrospinal fluid(2016) FORLENZA, Orestes V.; APRAHAMIAN, Ivan; RADANOVIC, Marcia; TALIB, Leda L.; CAMARGO, Marina Z. A.; STELLA, Florindo; MACHADO-VIEIRA, Rodrigo; GATTAZ, Wagner F.ObjectivesCognitive impairment is a common feature of late-life bipolar disorder (BD). Yet, there is limited information on the biological mechanisms associated with this process. It is uncertain whether cognitively impaired patients with BD may present the Alzheimer's disease (AD) bio-signature in the cerebrospinal fluid (CSF), defined as a combination of low concentrations of the amyloid-beta peptide (A(1-42)) and high concentrations of total tau (T-tau) and tau phosphorylated at threonine 181 (P-tau). In this study, we sought to determine whether cognitive impairment in elderly patients with BD is associated with the AD CSF bio-signature. MethodsSeventy-two participants were enrolled in the study. The test group comprised older adults with BD and mild cognitive impairment (BD-MCI; n=16) and the comparison groups comprised patients with dementia due to AD (n=17), patients with amnestic MCI (aMCI; n=14), and cognitively healthy older adults (control group; n=25). CSF samples were obtained by lumbar puncture and concentrations of A(1-42), T-tau and P-tau were determined. ResultsCSF concentrations of all biomarkers were significantly different in the AD group compared to all other groups, but did not differentiate BD-MCI subjects from aMCI subjects and controls. BD-MCI patients had a non-significant reduction in CSF A(1-42) compared to controls, but this was still higher than in the AD group. Concentrations of T-tau and P-tau in BD-MCI patients were similar to those in controls, and significantly lower than those in AD. ConclusionsCognitively impaired patients with BD do not display the so-called AD bio-signature in the CSF. We therefore hypothesize that cognitive deterioration in BD is not associated with the classical pathophysiological mechanisms observed in AD, i.e., amyloid deposition and hyperphosphorylation of microtubule-associated tau protein.
- Glycogen Synthase Kinase-3 beta: Variation over Time and the Possible Association with Mood and Cognition in Healthy Individuals(2016) MUNKHOLM, Klaus; LENSKJOLD, Toke; JACOBY, Anne Sophie; MISKOWIAK, Kamilla Woznica; VINBERG, Maj; JOAQUIM, Helena Giroud Passarelli; TALIB, Leda Leme; GATTAZ, Wagner Farid; KESSING, Lars VedelEvidence indicates a role for glycogen synthase kinase-3 beta (GSK-3 beta) in the pathophysiology of mood disorders and in cognitive disturbances; however, the natural variation in GSK-3 beta activity over time is unknown. We aimed to investigate GSK-3 beta activity over time and its possible correlation with emotional lability, subjective mood fluctuations and cognitive function in healthy individuals. Thirty-seven healthy subjects were evaluated with neuropsychological tests and blood samples at baseline and 12-week follow-up. Total GSK-3 beta and serine-9-phosphorylated GSK-3 beta in peripheral blood mononuclear cells were quantitated using enzyme immunometric assays. The activity of GSK-3 beta (serine-9-phosphorylated GSK-3 beta/total GSK-3 beta) was lower at baseline compared with follow-up. No significant mean change over time was observed in levels of total GSK-3 beta and serine-9-phosphorylated GSK-3 beta. Exploratory analysis revealed lower activity of GSK-3 beta in spring and summer compared with the fall season. No correlation was observed between GSK-3 beta activity and emotional lability, subjective mood fluctuations or cognitive function. The results suggest that intra- and interindividual variation in GSK-3 beta activity over time could contribute to the heterogeneity of findings in clinical studies. The stability of GSK-3 beta activity and the role of potential moderators of GSK-3 beta activity warrant further investigation. Clinical studies of GSK-3 beta should consider including repeated measures of both cases and healthy individuals. (C) 2016 S. Karger AG, Basel
- cytochrome P450 genotypes are not associated with refractoriness to antipsychotic treatment (vol 168, pg 587, 2015)(2016) BILT, M. T. van de; PRADO, C. M.; OJOPI, E. P. B.; SOUSA, R. T. de; LOCH, A. A.; ZANETTI, M. V.; TALIB, L. L.; GATTAZ, W. F.
- Glycogen synthase kinase-3 in patients with bipolar I disorder: results from a prospective study(2016) JACOBY, Anne S.; MUNKHOLM, Klaus; VINBERG, Maj; JOAQUIM, Helena G. P.; TALIB, Leda L.; GATTAZ, Wagner F.; KESSING, Lars V.ObjectivesThe enzyme glycogen synthase kinase-3 (GSK3) is involved in the mechanisms of action of lithium and may play a role in relation to affective states in bipolar disorder. The objectives of the present study were to compare the activity of GSK-3 (measured as levels of phosphorylated GSK-3 [p-GSK-3]) between patients with bipolar disorder in the euthymic state and healthy control subjects, and to investigate whether GSK-3 activity varies with affective states in patients with bipolar I disorder. MethodsIn a prospective 6-12-month follow-up study, we investigated state-specific, intraindividual alterations in the activity of GSK-3 in 60 patients with bipolar I disorder with an acute severe manic index episode and in subsequent euthymic, depressive and manic states and compared this with repeated measurements in healthy control subjects. Data were analyzed using linear mixed-effects models. ResultsFrom baseline to the end of follow-up, blood samples were drawn from the 60 patients during 181 affective states, comprising 60 manic, 11 mixed, 23 depressive, and 87 states of euthymia. A total of 69 blood samples were drawn from 35 healthy control subjects, with two samples from the same subject taken three months apart. In mixed-model analysis, p-GSK-3 was decreased in the euthymic state of subjects with bipolar disorder compared with healthy control subjects (b=0.63, 95% confidence interval [CI]: 0.42-0.96, P=.03). In addition, p-GSK-3 varied with affective states, being increased in depressive (b=1.68, 95% CI: 1.08-2.62, P=.02) and mixed (b=2.07, 95% CI: 1.12-3.84, P=.02) states but not in mania compared with euthymia. ConclusionsThe activity of GSK-3 is altered in euthymic bipolar disorder compared with healthy control subjects and varies with affective states.