ALANA CAROLINE COSTA
Projetos de Pesquisa
Unidades Organizacionais
LIM/27 - Laboratório de Neurociências, Hospital das Clínicas, Faculdade de Medicina
12 resultados
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- Increased Brain Lactate During Depressive Episodes and Reversal Effects by Lithium Monotherapy in Drug-Naive Bipolar Disorder A 3-T H-1-MRS Study(2017) MACHADO-VIEIRA, Rodrigo; ZANETTI, Marcus V.; OTADUY, Maria C.; SOUSA, Rafael T. De; SOEIRO-DE-SOUZA, Marcio G.; COSTA, Alana C.; CARVALHO, Andre F.; LEITE, Claudia C.; BUSATTO, Geraldo F.; ZARATE JR., Carlos A.; GATTAZ, Wagner F.Objective: Mitochondrial dysfunction and energy metabolism impairment are key components in the pathophysiology of bipolar disorder (BD) and may involve a shift from aerobic to anaerobic metabolism. Measurement of brain lactate in vivo using protonmagnetic resonance spectroscopy (H-1-MRS) represents an important tool to evaluate mitochondrial and metabolic dysfunction during mood episodes, as well as to monitor treatment response. To date, very few studies have quantified brain lactate in BD. In addition, no study has longitudinally evaluated lactate using H-1-MRS during depressive episodes or its association with mood stabilizer therapy. This study aimed to evaluate cingulate cortex (CC) lactate using 3-T H-1-MRS during acute depressive episodes in BD and the possible effects induced by lithium monotherapy. Methods: Twenty medication-free outpatients with short length of BD (80% drug-naive) in a current major depressive episode were matched with control subjects. Patients were treated for 6 weeks with lithium monotherapy at therapeutic doses in an open-label trial (blood level, 0.48 +/- 0.19 mmol/L). Cingulate cortex lactate was measured before (week 0) and after lithium therapy (week 6) using H-1-MRS. Antidepressant efficacy was assessed with the 21-item Hamilton Depression Rating Scale as the primary outcome. Results: Subjects with BD depression showed a significantly higher CC lactate in comparison to control subjects. Furthermore, a significant decrease in CC lactate was observed after 6 weeks of lithium treatment compared with baseline (P = 0.002). CC Lactate levels was associated with family history of mood disorders and plasma lithium levels. Conclusions: This is the first report of increased CC lactate in patients with bipolar depression and lower levels after lithium monotherapy for 6 weeks. These findings indicate a shift to anaerobic metabolism and a role for lactate as a state marker during mood episodes. Energy and redox dysfunction may represent key targets for lithium's therapeutic actions.
bookPart Proteômica e neuroquímica(2021) JOAQUIM, Helena Passarelli Giroud; COSTA, Alana Caroline; SARNO, Tamires Alves; TALIB, Leda Leme- 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.
bookPart Exames laboratoriais, marcadores genéticos e biomarcadores humorais(2021) TALIB, Leda Leme; PAIS, Marcos Vasconcelos; DINIZ, Breno; BRAM, Jessyka Maria de França; JOAQUIM, Helena Passarelli Giroud; COSTA, Alana Caroline; FORLENZA, Orestes Vicente- Kynurenine is correlated with IL-1 beta in plasma of schizophrenia patients(2018) JOAQUIM, Helena P. G.; COSTA, Alana C.; GATTAZ, Wagner F.; TALIB, Leda LemeThe etiology of schizophrenia is still unclear. It is well-known that pro-inflammatory cytokines are higher in schizophrenia patients since the first episode psychosis comparing to healthy controls. Inflammatory downstream cascades influence different cellular pathways, like the displacement of the tryptophan (TRP) metabolism to the production of kynurenine (KYN) instead of serotonin, which results in the generation of several neuro and immunoactive metabolites. The aim of this study was to determine TRP, KYN and IL-1 beta plasma levels in first-onset schizophrenia (n = 28) and healthy controls (n = 30). The plasmatic levels of TRP and KYN were decreased in schizophrenic patients (p = 0.004 and p = 0.002, respectively), but there was no difference in the ratio of KYN/TRP (p = 0.554) or either in IL-1 beta (p = 0.101). Positive correlation was observed between KYN and IL-1 beta only in the schizophrenia group (r = 0.461, p = 0.021). And, there was also positive correlation between KYN and Positive and Negative Symptoms Scale (PANSS) (r = 0.395, p = 0.037). There is no correlation between the other analytes and other parameters of PANSS. Although our results of KYN have been different than expected and there was no difference in the KYN/TRP ratio, we observed a positive correlation between IL-1 beta and KYN, corroborating findings that pro-inflammatory agents hold up the KYN pathway.
- 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.
- 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.
- Donepezil effects on cholesterol and oxysterol plasma levels of Alzheimer's disease patients(2018) COSTA, Alana C.; JOAQUIM, Helena P. G.; NUNES, Valeria S.; KERR, Daniel S.; FERREIRA, Guilherme S.; FORLENZA, Orestes V.; GATTAZ, Wagner F.; TALIB, Leda LemeCholesterol is an essential component in the structure and function of cell membranes and has been associated with the major pathological signatures of Alzheimer's disease (AD). To maintain brain cholesterol homeostasis, it is converted into 24(S)-hydroxycholesterol (24OHC) which can be driven through the blood-brain barrier. Several studies have already described a decrease in 24OHC and an increase of 27(S)-hydroxycholesterol (27OHC) in AD, as a reflection of disease burden, the loss of metabolically active neurons and the degree of structural atrophy. It is also well known that peripheral cholesterol is altered in AD patients. However, there are no data regarding effects of AD treatment in this cholesterol pathway. Since a study from our group indicated a significant increase in membrane phospholipid metabolism by donepezil, the aim of this study was to evaluate the effect of short- and long-term donepezil treatment on cholesterol and metabolites 24OHC and 27OHC in plasma of AD patients and in healthy volunteers. At baseline, we found a decrease of 24OHC (p = 0.003) in AD patients. Cholesterol levels increased with donepezil treatment (p = 0.04) but no differences were observed regarding 24OHC and 27OHC. However, these results confirm and extend previous studies demonstrating disturbed cholesterol turnover in Alzheimer's disease.