ALANA CAROLINE COSTA
Projetos de Pesquisa
Unidades Organizacionais
LIM/27 - Laboratório de Neurociências, Hospital das Clínicas, Faculdade de Medicina
10 resultados
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- Three plasma metabolites in elderly patients differentiate mild cognitive impairment and Alzheimer's disease: a pilot study(2020) COSTA, Alana C.; JOAQUIM, Helena P. G.; FORLENZA, Orestes V.; GATTAZ, Wagner F.; TALIB, Leda L.The metabolomic profile of patients with Alzheimer's disease (AD) and mild cognitive impairment (MCI) may suggest potential diagnostic biomarkers and provide information on the pathophysiology of dementia. Our aim was to quantify plasmatic metabolites of AD patients, MCI and controls. We investigated the metabolomic profile-using the AbsoluteIDQ (R) p180 assay-of 79 older adults with primary cognitive impairment (34 AD and 20 MCI) and 25 healthy elders (controls). A cluster analysis revealed that a combination C12-DC, C12 and PCaaC26:0 could differentiate the patients according to diagnostic. Future studies should combine metabolomic profiles with other biomarkers to identify diagnostic groups.
- Application of Lipidomics in Psychiatry: Plasma-Based Potential Biomarkers in Schizophrenia and Bipolar Disorder(2023) COSTA, Alana C.; RICA, Larissa B.; BILT, Martinus van de; ZANDONADI, Flavia S.; GATTAZ, Wagner F.; TALIB, Leda L.; SUSSULINI, AlessandraIn this study, we obtained a lipidomic profile of plasma samples from drug-naive patients with schizophrenia (SZ) and bipolar disorder (BD) in comparison to healthy controls. The sample cohort consisted of 30 BD and 30 SZ patients and 30 control individuals. An untargeted lipidomics strategy using liquid chromatography coupled with high-resolution mass spectrometry was employed to obtain the lipid profiles. Data were preprocessed, then univariate (t-test) and multivariate (principal component analysis and orthogonal partial least squares discriminant analysis) statistical tools were applied to select differential lipids, which were putatively identified. Afterward, multivariate receiver operating characteristic tests were performed, and metabolic pathway networks were constructed, considering the differential lipids. Our results demonstrate alterations in distinct lipid pathways, especially in glycerophospholipids, sphingolipids and glycerolipids, between SZ and BD patients. The results obtained in this study may serve as a basis for differential diagnosis, which is crucial for effective treatment and improving the quality of life of patients with psychotic disorders.
- Increased PLA(2) activity in individuals at ultra-high risk for psychosis(2021) TALIB, Leda L.; COSTA, Alana C.; JOAQUIM, Helena P. G.; PEREIRA, Cicero A. C.; BILT, Martinus T. van de; LOCH, Alexandre A.; GATTAZ, Wagner F.Phospholipase A(2) is the main enzyme in the metabolism of membrane phospholipids. It comprises a family of enzymes divided into iPLA(2), cPLA(2) and sPLA(2). Studies have reported increased PLA(2) activity in psychotic patients, which suggests an accelerated breakdown of membrane phospholipids. In the present study we investigated whether increased PLA(2) activity is also present in individuals at ultra-high risk (UHR) for psychosis. One-hundred fifty adults were included in this study (85 UHR and 65 controls). UHR was assessed using the ""structured interview for prodromal syndromes"". PLA(2) activity was determined in platelets by a radio-enzymatic assay. We found in UHR individuals increased activities of iPLA(2) (p < 0.001) and cPLA(2) (p = 0.012) as compared to controls. No correlations were found between socio-demographic and clinical parameters and PLA(2) activity. Our findings suggest that increased PLA(2) activities may be useful as a biological risk-marker for psychotic disorders.
- Reduced Annexin A3 in schizophrenia(2020) JOAQUIM, Helena P. G.; COSTA, Alana Caroline; SERPA, Mauricio Henriques; TALIB, Leda L.; GATTAZ, Wagner F.The cellular and molecular mechanisms underlying onset and development of schizophrenia have not yet been completely elucidated, but the association of disturbed neuroplasticity and inflammation has gained particular relevance recently. These mechanisms are linked to annexins functions. ANXA3, particularly, is associated to inflammation and membrane metabolism cascades. The aim was to determine the ANXA3 levels in first-onset drug-naive psychotic patients. We investigated by western blot the protein expression of annexin A3 in platelets of first-onset, drug-naive psychotic patients (diagnoses according to DSM-IV: 28 schizophrenia, 27 bipolar disorder) as compared to 30 age- and gender-matched healthy controls. Annexin A3 level was lower in schizophrenia patients as compared to healthy controls (p < 0.001) and to bipolar patients (p < 0.001). Twenty out of 28 schizophrenic patients had undetectable annexin A3 levels, as compared to none from the bipolar and none from the control subjects. ANXA3 was reduced in drug-naive patients with schizophrenia. ANXA3 affects neuroplasticity, inflammation and apoptosis, as well as it modulates membrane phospholipid metabolism. All these processes have been discussed in regard to the biology of schizophrenia. In face of these data, we feel that further studies with larger samples are warranted to investigate the possible role of reduced ANXA3 as a possible risk marker for schizophrenia.
- Plasmatic endocannabinoids are decreased in subjects with ultra-high risk of psychosis(2022) JOAQUIM, Helena P. G.; COSTA, Alana C.; PEREIRA, Cicero A. C.; TALIB, Leda L.; V, Martinus M. Bilt; LOCH, Alexandre A.; GATTAZ, Wagner F.The onset of frank psychosis is usually preceded by a prodromal phase characterized by attenuated psychotic symptoms. Currently, research on schizophrenia prodromal phase (ultra-high risk for psychosis [UHR]) has focused on the risk of developing psychosis, on the transition to full blown psychosis and on its prediction. Neurobiological differences between UHR individuals who fully recover (remitters) versus those who show persistent/progressive prodromal symptoms (nonremitters) have been little explored. The endocannabinoid system constitutes a neuromodulatory system that plays a major role in brain development, synaptic plasticity, emotional behaviours and cognition. It comprises two cannabinoid receptors (CB1/CB2), two endocannabinoid ligands, arachidonylethanolamide (AEA) and 2-arachidonoylglycerol (2AG) along with their inactivation enzymes. Despite much evidence that the endocannabinoid system is imbalanced during psychosis, very little is known about it in UHR. Therefore, we aimed to quantify the plasma endocannabinoid levels in UHR and healthy controls (HC) and verify if these metabolites could differentiate between remitters and nonremitters. Circulating concentrations of AEA (p = .003) and 2AG (p < .001) were lower in UHR when compared with HC, with no difference between remitters and nonremitters. Regarding clinical evolution, it was observed that out of 91 UHRs initially considered, 16 had psychiatric complaints (3 years of follow-up). Considering those subjects, there were weak correlations between clinical parameters and plasma concentrations of endocannabinoids. Our results suggest that the endocannabinoids are imbalanced before frank psychosis and that changes can be seen in plasma of UHR individuals. These molecules proved to be potential biomarkers to identify individuals in the prodromal phase of psychosis.
- Decreased plasmatic spermidine and increased spermine in mild cognitive impairment and Alzheimer's disease patients(2019) JOAQUIM, Helena P. G.; COSTA, Alana C.; FORLENZA, Orestes V.; GATTAZ, Wagner E.; TALIB, Leda L.Background: Current evidence suggests that upregulation of polyamines system plays a role both in cognitive deficit and synaptic loss observed in Alzheimer's disease (AD). Objective: The aim of this study was to determine the plasmatic concentration of polyamines in mild cognitive impairment (MCI) and AD patients in comparison with healthy controls (HC). Methods: Plasmatic polyamines were quantified using the AbsoluteIDQ (R) p1130 and liquid chromatography coupled to tandem mass spectrometry (LC/MS-MS). Results: The study group comprised 34 AD patients, 20 MCI and 25 HC. All individuals were followed for 4 years. During this period 8 amnestic MCI patients (40% of the MCI sample at baseline) converted to AD. Spermidine level was lower in both patient groups (AD; MCI) compared to HC (p = 0.007). Plasma levels of spermine were higher in the MCI group (p < 0.001), but decreased in the sub-sample of MCI patients who converted to AD (p = 0.043). No statistically significant differences were found in ornithine and putrescine levels (p = 0.056 and p = 0.126, respectively). Discussion: Our results suggest dynamic changes in the expression of polyamines in the MCI-AD continuum.
- COX-2 pathway is upregulated in ultra-high risk individuals for psychosis(2022) PEREIRA, Cicero A. C.; COSTA, Alana C.; JOAQUIM, Helena P. G.; TALIB, Leda L.; BILT, Martinus T. van de; LOCH, Alexandre A.; GATTAZ, Wagner F.Background The identification of Ultra-High Risk (UHR) individuals is thought to be useful for early intervention to improve psychosis outcomes. However, transition rates vary widely, and there is an effort to make these criteria more specific and accurate. Neuroinflammation has been discussed in the pathophysiology of psychosis. The metabolism of eicosanoids is a key process in inflammatory states. Therefore, we investigated whether the study of the inflammatory COX-2 pathway through the quantification of the eicosanoid levels can be a useful approach for the characterisation of UHR individuals. Methods One hundred and twenty-two individuals were included in this study (67 UHR and 55 controls) based on performance on the Prodromal Questionnaire. UHR status was assessed by Structured Interview for Prodromal Syndromes (SIPS). We determined the levels of Prostaglandin F-2 alpha (PGF(2 alpha)), Prostaglandin E-2 (PGE(2)), and Thromboxane B-2 (TxB(2)) in plasma using ELISA assays. Results Concentrations of PGE(2) and TxB(2) were increased in UHR compared to controls (p = 0.01 and p < 0.05, respectively). PGE(2) and PGF(2 alpha) levels were correlated to negative symptoms (p < 0.01 and p < 0.05), whereas TxB(2) correlated with positive symptoms (p = 0.05) as assessed by the SIPS. Conclusions Our findings suggest that overactivation of the COX-2 pathway may be related to an increased risk for psychosis. However, our data do not allow us to draw conclusions related to the cause-effect mechanisms. Future studies should determine whether the levels of the eicosanoids have a predictive value for the transition of UHR to frank psychosis.
- Plasma Metabolite Profiles in First Episode Psychosis: Exploring Symptoms Heterogeneity/Severity in Schizophrenia and Bipolar Disorder Cohorts(2020) JOAQUIM, Helena P. G.; COSTA, Alana C.; TALIB, Leda L.; DETHLOFF, Frederik; SERPA, Mauricio H.; ZANETTI, Marcus V.; BILT, Martinus van de; TURCK, Christoph W.Introduction The first symptoms of psychosis are frequently shared amongst several neuropsychiatry disorders, which makes the differentiation by clinical diagnosis challenging. Early recognition of symptoms is important in the management of psychosis. Therefore, the implementation of molecular biomarkers will be crucial for transforming the currently used diagnostic and therapeutic approach, improving insights into the underlying biological processes and clinical management. Objectives To define a set of metabolites that supports diagnosis or prognosis of schizophrenia (SCZ) and bipolar disorder (BD) at first onset psychosis. Methods Plasma samples from 55 drug-naive patients, 28 SCZ and 27 BD, and 42 healthy controls (HC). All participants underwent a seminaturalistic treatment regimen, clinically evaluated on a weekly basis until achieving clinical remission. All clinical or sociodemographic aspects considered for this study were equivalent between the groups at first-onset psychosis time point. The plasma samples were analyzed by untargeted liquid chromatography-tandem mass spectrometry (LC-MS/MS) using reversed-phase and hydrophilic interaction chromatography. The acquired molecular features were analyzed with MetaboAnalyst. Results We identified two patient groups with different metabolite profiles. Both groups are composed of SCZ and BD patients. We found differences between these two groups regarding general symptoms of PANSS score after remission (p = 0.008), and the improvement of general symptoms (delta of the score at remission minus the baseline) (-0.50 vs. -0.33, p = 0.019). Conclusion Our results suggest that plasma metabolite profiles cluster clinical remission phenotypes based on PANSS general psychopathology scores.
- Plasma metabolites in first episode psychoses(2019) COSTA, Alana C.; JOAQUIM, Helena P. G.; TALIB, Leda L.; SERPA, Mauricio H.; ZANETTI, Marcus V.; GATTAZ, Wagner F.
- Plasma lipids metabolism in mild cognitive impairment and Alzheimer's disease(2019) COSTA, Alana C.; JOAQUIM, Helena P. G.; FORLENZA, Orestes; TALIB, Leda L.; GATTAZ, Wagner F.Objectives: Expression of phospholipids and related molecules could provide panels of multiple biomarkers searching for the signature of Alzheimer's disease (AD). The aim of the present study was to quantify ten phospholipids and simultaneously determine phospholipase A(2) (PLA(2)) activity in blood of mild cognitive impairment (MCI) and AD patients. Methods: Thirty-four AD, 20 MCI and 25 controls were enrolled. The phospholipids where analysed using the AbsoluteIDQp180 Kit. PLA(2) activities were accessed in platelets by a radio-enzymatic assay. Results: The study failed to fix the ten phospholipids as a panel to predict AD; the levels of PCaaC36:6, PCaaC40:6 and C16:1-OH were lower in MCI than in controls (P = 0.041, P = 0.012, P = 0.044 respectively). PCaaC40:2 levels were lower in MCI than in AD (P = 0.041). The converters MCI-AD showed at baseline lower levels of PCaaC40:2 (P = 0.050) and PCaaC40:6 (P = 0.037) than controls. iPLA(2) activity was reduced in AD and MCI than in controls (P < 0.001). We found positive correlation in the control group between PCaaC38:6 and tPLA(2) (r = 0.680; P = 0.001) and sPLA(2) (r = 0.601; P = 0.004); PCaaC40:1 and iPLA(2) (r = 0.503; P = 0.020); PCaaC40:6 and tPLA(2) (r = 0.532; P = 0.013) and sPLA(2) (r = 0.523; P = 0.015). Conclusions: Lipids metabolites in plasma might indirectly indicate changes in neuronal membrane and this deregulation can outline the transition between healthy and diseased brains.