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
4 resultados
Resultados de Busca
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- 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
- Glycogen synthase kinase-313 activity and cognitive functioning in patients with bipolar I disorder(2018) MUNKHOLM, Klaus; MISKOWIAK, Kamilla Woznica; JACOBY, Anne Sophie; VINBERG, Maj; TALIB, Leda Leme; GATTAZ, Wagner Farid; KESSING, Lars VedelCognitive deficits are common in patients with bipolar disorder (BD) in remission and may be associated with glycogen synthase kinase-3 (GSK-3) activity, which is inhibited by lithium. GSK-3 may be a relevant treatment target for interventions tailored at cognitive disturbances in BD but the relation between GSK-3 activity, cognition and lithium treatment is unknown. We therefore investigated the possible association between GSK-3 activity and cognition and whether lithium treatment moderates this association in patients with BD. In a prospective 6-12 month follow-up study, GSK- 313 activity in peripheral blood mononuclear cells was measured concurrently with cognitive performance assessed using a comprehensive test battery in 27 patients with BD-I in early and late remission following a manic or mixed episode. The GSK-313 activity, measured as serine-9 phosphorylated GSK-313 (pGSK-3(3) and the GSK-313 ratio (serine-9-pGSK-313 /total GSK-3(3), was negatively associated with sustained attention (p = 0.009 and p = 0.042, respectively), but not with other cognitive domains or global cognition. A crossover interaction between lithium treatment and the GSK activity was observed, indicating that lower pGSK-313 levels (p = 0.015) and GSK ratio (p = 0.010) were associated with better global cognition in lithium users whereas the opposite association was observed in non-lithium treated patients. Findings were not statistically significant after Bonferroni correction. In conclusion, cognitive functioning may be associated with GSK-3 activity in patients with BD-I and lithium treatment may modulate this relationship. Future studies in larger sample sizes are warranted to confirm these associations.
- 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.
- The Alzheimer's Association external quality control program for cerebrospinal fluid biomarkers(2011) MATTSSON, Niklas; ANDREASSON, Ulf; PERSSON, Staffan; ARAI, Hiroyuki; BATISH, Sat Dev; BERNARDINI, Sergio; BOCCHIO-CHIAVETTO, Luisella; BLANKENSTEIN, Marinus A.; CARRILLO, Maria C.; CHALBOT, Sonia; COART, Els; CHIASSERINI, Davide; CUTLER, Neal; DAHLFORS, Gunilla; DULLER, Stefan; FAGAN, Anne M.; FORLENZA, Orestes; FRISONI, Giovanni B.; GALASKO, Douglas; GALIMBERTI, Daniela; HAMPEL, Harald; HANDBERG, Aase; HENEKA, Michael T.; HERSKOVITS, Adrianna Z.; HERUKKA, Sanna-Kaisa; HOLTZMAN, David M.; HUMPEL, Christian; HYMAN, Bradley T.; IQBAL, Khalid; JUCKER, Mathias; KAESER, Stephan A.; KAISER, Elmar; KAPAKI, Elisabeth; KIDD, Daniel; KLIVENYI, Peter; KNUDSEN, Cindy S.; KUMMER, Markus P.; LUI, James; LLADO, Albert; LEWCZUK, Piotr; LI, Qiao-Xin; MARTINS, Ralph; MASTERS, Colin; MCAULIFFE, John; MERCKEN, Marc; MOGHEKAR, Abhay; MOLINUEVO, Jose Luis; MONTINE, Thomas J.; NOWATZKE, William; O'BRIEN, Richard; OTTO, Markus; PARASKEVAS, George P.; PARNETTI, Lucilla; PETERSEN, Ronald C.; PRVULOVIC, David; REUS, Herman P. M. de; RISSMAN, Robert A.; SCARPINI, Elio; STEFANI, Alessandro; SOININEN, Hilkka; SCHROEDER, Johannes; SHAW, Leslie M.; SKINNINGSRUD, Anders; SKROGSTAD, Brith; SPREER, Annette; TALIB, Leda; TEUNISSEN, Charlotte; TROJANOWSKI, John Q.; TUMANI, Hayrettin; UMEK, Robert M.; BROECK, Bianca Van; VANDERSTICHELE, Hugo; VECSEI, Laszlo; VERBEEK, Marcel M.; WINDISCH, Manfred; ZHANG, Jing; ZETTERBERG, Henrik; BLENNOW, KajBackground: The cerebrospinal fluid (CSF) biomarkers amyloid beta (A beta)-42, total-tau (T-tau), and phosphorylated-tau (P-tau) demonstrate good diagnostic accuracy for Alzheimer's disease (AD). However, there are large variations in biomarker measurements between studies, and between and within laboratories. The Alzheimer's Association has initiated a global quality control program to estimate and monitor variability of measurements, quantify batch-to-batch assay variations, and identify sources of variability. In this article, we present the results from the first two rounds of the program. Methods: The program is open for laboratories using commercially available kits for A beta, T-tau, or P-tau. CSF samples (aliquots of pooled CSF) are sent for analysis several times a year from the Clinical Neurochemistry Laboratory at the Molndal campus of the University of Gothenburg, Sweden. Each round consists of three quality control samples. Results: Forty laboratories participated. Twenty-six used INNOTEST enzyme-linked immunosorbent assay kits, 14 used Luminex xMAP with the INNO-BIA AlzBio3 kit (both measure A beta-(1-42), P-tau(181P), and T-tau), and 5 used Mesa Scale Discovery with the A beta triplex (A beta N-42, A beta N-40, and A beta N-38) or T-tau kits. The total coefficients of variation between the laboratories were 13% to 36%. Five laboratories analyzed the samples six times on different occasions. Within-laboratory precisions differed considerably between biomarkers within individual laboratories. Conclusions: Measurements of CSF AD biomarkers show large between-laboratory variability, likely caused by factors related to analytical procedures and the analytical kits. Standardization of laboratory procedures and efforts by kit vendors to increase kit performance might lower variability, and will likely increase the usefulness of CSF AD biomarkers.