BRENO SATLER DE OLIVEIRA DINIZ
Projetos de Pesquisa
Unidades Organizacionais
8 resultados
Resultados de Busca
Agora exibindo 1 - 8 de 8
- Reduced serum levels of adiponectin in elderly patients with major depression(2012) DINIZ, Breno S.; TEIXEIRA, Antonio L.; CAMPOS, Alline C.; MIRANDA, Aline S.; ROCHA, Natalia P.; TALIB, Leda L.; GATTAZ, Wagner F.; FORLENZA, Orestes V.Recent studies have implicated adiponectin and other adipocytokines in brain function, particularly in processes related to memory and cognition. Blood levels of adiponectin are reduced in patients with primary cognitive disorders, such as Alzheimer's disease and mild cognitive impairment, and in adult patients with major depression. The aim of the present study is to determine serum levels of adiponectin in a sample of elderly patients with major depressive disorder (MOD) as compared to healthy older adults, and to examine the correlations between adiponectin levels and parameters indicative of mood and cognitive state. We recruited fifty-one unmedicated outpatients with late-life depression (LLD) and 47 age-matched controls in this study. The diagnosis of MDD was made according to the DSM-IV criteria, and the severity of depressive episode was determined with the 21-item Hamilton Depression Scale (HORS). Cognitive state was ascertained with the Cambridge Cognitive Test (CAMCOG) and the Mini-Mental State Examination (MMSE). Serum concentrations of adiponectin were determined using a sandwich ELISA method. Serum levels of adiponectin were significantly reduced in individuals with LLD (F = p < 0.001). Adiponectin level remained significantly reduced in after controlling for BMI index, scores on the CAMCOG, MMSE and HDRS and educational level (p < 0.001). Adiponectin levels showed a negative correlation with HORS scores (r = -0.59, p < 0.001) and BMI index (r = -0.42, p < 0.001); and showed a positive correlation with CAMCOG (r = 0.34, p < 0.01) and MMSE scores (r = 0.20, p = 0.05). The availability of circulating adiponectin is reduced in older adults with major depression, with likely implications on cognitive and mood state. Additional studies are required to determine whether this abnormality pertains to the pathophysiology of geriatric depression per se, or is a consequence of the morbid state.
- Circulating Glial-derived neurotrophic factor is reduced in late-life depression(2012) DINIZ, Breno S.; TEIXEIRA, Antonio L.; MIRANDA, Aline S.; TALIB, Leda L.; GATTAZ, Wagner F.; FORLENZA, Orestes V.Background: The Glial Cell-line derived neurotrophic factor (GDNF) is part of the TGF-beta superfamily and is abundantly expressed in the central nervous system. Changes in GDNF homeostasis have been reported in affective disorders. Aim: To assess serum GDNF concentration in elderly subjects with late-life depression, before antidepressant treatment, as compared to healthy elderly controls. Methods: Thirty-four elderly subjects with major depression and 37 age and gender-matched healthy elderly controls were included in this study. Diagnosis of major depression was ascertained by the SCID interview for DSM-IV and the severity of depressive symptoms was assessed by the Hamilton Depression Rating Scale (HDRS-21). Serum GDNF concentration were determined by sandwich ELISA. Results: Patients with major depression showed a significant reduction in GDNF levels as compared to healthy elderly controls (p < 0.001). Also, GDNF level was negatively correlated with HDRS-21 scores (r = -0.343, p = 0.003). Discussion: Our data provide evidence that GDNF may be a state marker of depressive episode in older adults. Changes in the homeostatic control of GDNF production may be a target to development of new antidepressant strategies.
- A radioenzymatic assay to identify three groups of phospholipase A(2) in platelets(2012) TALIB, Leda L.; DINIZ, Breno S.; ZAINAGHI, Isis A.; FORLENZA, Orestes V.; GATTAZ, Wagner F.Phospholipases A(2) (PLA(2)) are key enzymes in membrane metabolism. The release of fatty acids and lysophospholipids by PLA(2) activates several intra-cellular second messenger cascades that regulate a wide variety of physiological responses. The aim of the present study is to describe a radioenzymatic assay to determine the activity of three main PLA(2) subtypes in platelets, namely extracellular calcium-dependent PLA(2) (sPLA(2)) and intracellular calcium-dependent (cPLA(2)) and calcium-independent PLA(2) (iPLA(2)). The differentiation of these distinct PLA(2) subtypes was based on the enzyme substrate preference (arachdonic acid or palmitoyl acid) and calcium concentration. Our results indicate that this new assay is feasible, precise and specific to measure the activity of the aforementioned subtypes of PLA(2). Therefore, this protocol can be used to investigate modifications of PLA(2) homeostasis in distinct biological models addressing the pathophysiology of many medical and neuropsychiatric disorders such as schizophrenia and Alzheimer's disease.
- Reduced platelet amyloid precursor protein ratio (APP ratio) predicts conversion from mild cognitive impairment to Alzheimer's disease(2012) ZAINAGHI, Isis A.; TALIB, Leda L.; DINIZ, Breno S.; GATTAZ, Wagner F.; FORLENZA, Orestes V.Studies have shown that platelet APP ratio (representing the percentage of 120-130 kDa to 110 kDa isoforms of the amyloid precursor protein) is reduced in patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD). In the present study, we sought to determine if baseline APP ratio predicts the conversion from MCI to AD dementia after 4 years of longitudinal assessment. Fifty-five older adults with varying degrees of cognitive impairment (34 with MCI and 21 with AD) were assessed at baseline and after 4 years. MCI patients were re-classified according to the conversion status upon follow-up: 25 individuals retained the diagnostic status of MCI and were considered as stable cases (MCI-MCI); conversely, in nine cases the diagnosis of dementia due to AD was ascertained. The APP ratio (APPr) was determined by the Western blot method in samples of platelets collected at baseline. We found a significant reduction of APPr in MCI patients who converted to dementia upon follow-up. These individuals had baseline APPr values similar to those of demented AD patients. The overall accuracy of APPr to identify subjects with MCI who will progress to AD was 0.74 +/- A 0.10, p = 0.05. The cut-off of 1.12 yielded a sensitivity of 75 % and a specificity of 75 %. Platelet APPr may be a surrogate marker of the disease process in AD, with potential implications for the assessment of abnormalities in the APP metabolism in patients with and at risk for dementia. However, diagnostic accuracy was relatively low. Therefore, studies in larger samples are needed to determine whether APPr may warrant its use as a biomarker to support the early diagnosis of AD.
conferenceObject Circulating Nerve Growth Factor in elderly subjects: state marker of depression?(2012) DINIZ, Breno S.; TEIXEIRA, Antonio L.; TALIB, Leda L.; GATTAZ, Wagner F.; FORLENZA, Orestes V.- Long-term sertraline treatment increases expression and decreases phosphorylation of glycogen synthase kinase-3B in platelets of patients with late-life major depression(2012) JOAQUIM, Helena P. G.; TALIB, Leda L.; FORLENZA, Orestes V.; DINIZ, Breno S.; GATTAZ, Wagner F.Background: Abnormal regulation of glycogen synthase kinase 3-beta (GSK3B) activity has been implicated in the pathophysiology of mood disorders. Many pharmacological agents, including antidepressants, can modulate GSK3B. The aim of the present study was to investigate the effect of short-and long-term sertraline treatment on the expression and phosphorylation of GSK3B in platelets of patients with late-life major depression. Methods: Thirty-nine unmedicated elderly adults with major depressive disorder (MOD) were initially included in this study. The comparison group comprised 18 age-matched, healthy individuals. The expression of total and Ser-9 phosphorylated GSK3B (pGSK3B) was determined by Enzyme Immunometric Assay (EIA) in platelets of patients and controls at baseline, and after 3 and 12 months of sertraline treatments for patients only. During this period, patients were continuously treated with therapeutic doses of sertraline. GSK3B activity was indirectly estimated by calculating the proportion of inactive (phosphorylated) forms (pGSK3B) in relation to the total expression of the enzyme (i.e.. GSK3B ratio). Results: Depressed patients had significantly higher levels of pGSK3B as compared to controls (p < 0.001). Within the MDD group, after 3 months of sertraline treatment no significant changes were observed in GSK3B expression and phosphorylation state, as compared to baseline levels. However, after 12 months of treatment we found a significant increase in the expression of total GSK3B (p = 0.05), in the absence of any significant changes in pGSK3B (p = 0.12), leading to a significant reduction in GSK3B ratio (p = 0.001). Conclusions: Our findings indicate that GSK3B expression was upregulated by the continuous treatment with sertraline, along with an increment in the proportion of active forms of the enzyme. This is compatible with an increase in overall GSK3B activity, which may have been induced by the long-term treatment of late-life depression with sertraline.
- Increased platelet GSK3B activity in patients with mild cognitive impairment and Alzheimer's disease(2011) FORLENZA, Orestes V.; TORRES, Carolina A.; TALIB, Leda L.; PAULA, Vanessa J. de; JOAQUIM, Helena P. G.; DINIZ, Breno S.; GATTAZ, Wagner F.The disruption of glycogen synthase kinase 3-beta (GSK3B) homeostasis has implications in the pathophysiology of neuropsychiatric disorders, namely Alzheimer's disease (AD). GSK3B activity is increased within the AD brain, favoring the hyperphosphorylation of microtubule-associated protein Tau and the formation of neurofibrillary tangles. Such abnormality has also been detected in leukocytes of patients with cognitive disorders. The aim of the present study was to determine the expression of total and phosphorylated GSK3B at protein level in platelets of older adults with varying degrees of cognitive impairment, and to compare GSK3B activity in patients with AD, mild cognitive impairment (MCI) and healthy controls. Sixty-nine older adults were included (24 patients with mild to moderate AD, 22 patients with amnestic MCI and 23 elderly controls). The expression of platelet GSK3B (total- and Ser-9 phosphorylated GSK3B) was determined by Western blot. GSK3B activity was indirectly assessed by means of the proportion between phospho-GSK3B to total GSK3B (GSK3B ratio), the former representing the inactive form of the enzyme. Ser-9 phosphorylated GSK3B was significantly reduced in patients with MCI and AD as compared to controls (p = 0.04). Platelet GSK3B ratio was significantly decreased in patients with MCI and AD (p = 0.04), and positively correlated with scores on memory tests (r = 0.298, p = 0.01). In conclusion, we corroborate previous evidence of increased GSK activity in peripheral tissues of patients with MCI and AD, and further propose that platelet GSK may be an alternative peripheral biomarker of this abnormality, provided samples are adequately handled in order to preclude platelet activation.
- Disease-modifying properties of long-term lithium treatment for amnestic mild cognitive impairment: randomised controlled trial(2011) FORLENZA, Orestes V.; DINIZ, Breno S.; RADANOVIC, Marcia; SANTOS, Franklin S.; TALIB, Leda L.; GATTAZ, Wagner F.Background Two recent clinical studies support the feasibility of trials to evaluate the disease-modifying properties of lithium in Alzheimer's disease, although no benefits were obtained from short-term treatment. Aims To evaluate the effect of long-term lithium treatment on cognitive and biological outcomes in people with amnestic mild cognitive impairment (aMCI). Method Forty-five participants with aMCI were randomised to receive lithium (0.25-0.5mmol/l) (n=24) or placebo (n = 21) in a 12-month, double-blind trial. Primary outcome measures were the modification of cognitive and functional test scores, and concentrations of cerebrospinal fluid (CSF) biomarkers (amyloid-beta peptide (A beta(42)), total tau (T-tau), phosphorylated-tau) (P-tau). Trial registration: NCT01055392. Results Lithium treatment was associated with a significant decrease in CSF concentrations of P-tau (P=0.03) and better perform-ance on the cognitive subscale of the Alzheimer's Disease Assessment Scale and in attention tasks. Overall tolerability of lithium was good and the adherence rate was 91%. Conclusions The present data support the notion that lithium has disease-modifying properties with potential clinical implications in the prevention of Alzheimer's disease.