TIFFANY MOUKBEL CHAIM AVANCINI
Projetos de Pesquisa
Unidades Organizacionais
LIM/21 - Laboratório de Neuroimagem em Psiquiatria, Hospital das Clínicas, Faculdade de Medicina
13 resultados
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conferenceObject Increased GDNF but not BDNF Plasma Levels in Type II Compared to Type I Bipolar Disorder(2013) ZANETTI, Marcus V.; TEIXEIRA, Antonio L.; CHAIM, Tiffany M.; SOUSA, Rafael T. de; TALIB, Leda L.; GATTAZ, Wagner F.; BUSATTO, Geraldo F.; MACHADO-VIEIRA, RodrigoBackground: The brain-derived neurotrophic factor (BDNF) is a neurotrophin important for synaptic plasticity and neurogenesis, whereas the glial cell-line derived neurotrophic factor (GDNF) modulates the activity of monoaminergic neurons and glial cells. Previous works have suggested that abnormal peripheral levels of these proteins might relate to different mood states in bipolar disorder (BD), but none study so far have evaluated it with regard to potential differences between the types I (BD-I) and II (BD-II) subtypes of the disorder. Methods: Eighteen BD-I and 19 BD-II patients presenting with an acute mood episode (depressive, manic or mixed), and 23 healthy controls were studied. Plasma levels of BDNF and GDNF were measured using enzyme-linked immunosorbent assay (ELISA). Results: BD-II individuals showed significantly increased levels of GDNF compared to both BD-I patients and controls (ANOVA, df=2, F= 5.74, p=0.005; Tukey for post hoc comparisons). When we focused our analysis on the treatment-naïve patients only (14 BD-I and 13 BD-II), this result became even more significant (ANOVA, df=2, F= 7.33, p=0.002). No significant between-groups differences were observed on BDNF levels. Also, no significant correlation was observed between BDNF or GDNF levels and depressive and manic symptoms. Conclusions: BD-II at an acute phase of the illness is associated with increased plasma levels of GDNF. Previous use of mood stabilizer and antipsychotic agents might produce a chronic effect on GDNF production.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.- Increased platelet glycogen sysnthase kinase 3beta in first-episode psychosis(2018) JOAQUIM, Helena P. G.; ZANETTI, Marcus V.; SERPA, Mauricio H.; BILT, Martinus T. Van de; SALLET, Paulo C.; CHAIM, Tiffany M.; BUSATTO, Geraldo F.; GATTAZ, Wagner F.; TALIB, Leda L.Past studies have linked intracellular pathways related to psychotic disorders to the GSK3B enzyme. This study aimed to investigate GSK3B protein expression and phosphorylation in drug-naive first-episode psychosis patients (n = 43) at baseline and following symptom remission, and in healthy controls (n = 77). At baseline GSK3B total level was higher in patients (p < 0.001). In schizophrenia spectrum patients (n = 25) GSK3B total and phosphorylated levels were higher than in controls and patients with other non-affective psychotic disorders (n = 18) (p < 0.001; p = 0.027; p = 0.05 respectively). No enzyme changes were found after clinical remission. The implication of this finding for the biology of psychoses warrants further studies to clarify whether increased GSK3B may be useful as a biomarker for psychosis in general, and schizophrenia in particular.
- Lithium increases platelet serine-9 phosphorylated GSK-3 beta levels in drug-free bipolar disorder during depressive episodes(2015) SOUSA, Rafael T. de; ZANETTI, Marcus V.; TALIB, Leda L.; SERPA, Mauricio H.; CHAIM, Tiffany M.; CARVALHO, Andre F.; BRUNONI, Andre R.; BUSATTO, Geraldo F.; GATTAZ, Wagner E.; MACHADO-VIEIRA, RodrigoBackground: Glycogen synthase kinase-3 beta (GSK3 beta) is an intracellular enzyme directly implicated in several neural processes relevant to bipolar disorder (BD) pathophysiology. GSK3 beta is also an important target for lithium and antidepressants. When phosphorylated at serine-9, GSK3 beta becomes inactive. Few studies evaluated serine-9 phosphorylated GSK3 beta(phospho-GSK3 beta) levels in BD subjects in vivo and no study has assessed it specifically in bipolar depression. Also, the effect of lithium monotherapy on GSK3 beta has never been studied in humans. Methods: In 27 patients with bipolar depression, total GSK3 beta and phospho-GSK3 beta were assessed in platelets by enzyme immunometric assay. Subjects were evaluated before and after 6 weeks of lithium treatment at therapeutic levels. Healthy subjects (n = 22) were used as a control group. Results: No differences in phospho-GSK3 beta or total GSK3 beta were observed when comparing drug-free BD subjects in depression and healthy controls. Baseline HAM-D scores were not correlated with phospho GSK3 beta and total GSK3 beta levels. From baseline to endpoint, lithium treatment inactivated GSK3 beta by significantly increasing phospho-GSK3 beta levels (p = 0.010). Clinical improvement (baseline HAM-D endpoint HAM-D) negatively correlated with the increase in phospho-GSK3 beta (p = 0.03). Conclusion: The present results show that lithium inactivates platelet GSK3 beta in BD during mood episodes. No direct association with pathophysiology of BD was observed. Further studies are needed to clarify the role of GSK3 beta as a key biomarker in BD and its association with treatment response as well as the relevance of GSK3 beta in other neuropsychiatric disorders and as a new therapeutic target per se.
- Elevated neurotrophin-3 and neurotrophin 4/5 levels in unmedicated bipolar depression and the effects of lithium(2015) LOCH, Alexandre A.; ZANETTI, Marcus V.; SOUSA, Rafael T. de; CHAIM, Tiffany M.; SERPA, Mauricio H.; GATTAZ, Wagner F.; TEIXEIRA, Antonio L.; MACHADO-VIEIRA, RodrigoBackground: Bipolar disorder (BD) has been associated with diverse abnormalities in neural plasticity and cellular resilience. Neurotrophin-3 (NT-3) and neurotrophin-4/5 (NT-4/5) support synaptic neuronal survival and differentiation. NT-3 and NT-4/5 levels were found to be altered in BD, potentially representing a physiological response against cellular stress. However, the use of psychopharmacological agents and heterogeneous mood states may constitute important biases in such studies. Thus, we aimed to assess NT-3 and NT-4/5 levels in medication-free BD type I or II individuals in a current depressive episode, before and after 6weeks of lithium monotherapy and matched with healthy controls. Methods: Twenty-three patients with BD type I or II during a depressive episode and 28 healthy controls were studied. Patients were required to have a 21-item Hamilton Depression Rating Scale score >= 18 and had not undergone any psychopharmacological treatment for at least 6 weeks prior to study entry. Patients were treated with lithium for 6 weeks and plasma NT-3 and NT-4/5 levels were determined at baseline and end point using ELISA method. Results: Baseline plasma levels of both NT-3 and NT-4/5 were significantly increased in acutely depressed BD subjects in comparison to healthy controls (p = 0.040 and 0.039, respectively). The NT-3 and NT-4/5 levels did not significantly change after lithium treatment. NT-3 and NT-4/5 levels were positively correlated to illness duration in BD (p = 0.032 and 0.034, respectively). Conclusion: Our findings suggest that NT-3 and NT-4/5 levels are increased in the depressive phase of BD, which seems directly associated with illness duration. The increased levels of NT-3 and NT-4/5 may underlie a biological response to cellular stress associated with the course of BD.
conferenceObject Neuroanatomical Pattern Classification in Unmedicated First-Episode Psychosis: Influence of Different Imaging Feature Selection(2012) SERPA, Mauricio H.; ZANETTI, Marcus V.; VAROL, Erdem; CHAIM, Tiffany M.; GAONKAR, Bilwaj; DOSHI, Jimit; BILT, Martinus T. van de; SALLET, Paulo C.; GATTAZ, Wagner F.; BUSATTO, Geraldo F.; DAVATZIKOS, ChristosBackground: The application of pattern classification approaches is thought to hold promise as an auxiliary tool to aid clinical diagnoses in psychiatric practice. However, few neuroimaging studies to date have investigated the usefulness of these methods in the evaluation of schizophrenia and related psychoses. Moreover, most of patients enrolled in such studies were already receiving antipsychotic medication, an important confounding factor for brain measures. Methods: Eleven treatment-naïve first-episode psychosis (FEP) individuals and 19 controls underwent T1-MPRAGE and 64-direction diffusion tensor imaging (DTI) acquisitions using a 1.5T MRI scanner. Volumetric maps of gray matter, white matter and ventricular compartments were generated through a robust routine of deformation-based morphometry. A new approach adequate for spatial normalization of tensor fields was used to generate fractional anisotropy (FA) and mean diffusivity maps. A multivariate classifier based on support vector machine was employed to identify the best set of morphological and DTI features that discriminate FEP individuals from controls. Diagnostic measures were obtained through ROC curve analyses. Results: The discrimination performance of the classifier varied according to the combination of different features, and the greater area under the curve value (0.68) was obtained when the FA map was employed in isolation. The resulting spatial map revealed a predominant pattern of increased FA in the right parietal region of FEP patients relative to controls, which may reflect differences in functional activity. Conclusions: This preliminary report suggests that FA indices afford the best discrimination between treatment-naïve FEP patients and controls relative to other morphometric and DTI features.conferenceObject Inflammatory Activity and Brain Volumes in Drug-Naive Patients with First-Episode Psychosis: A State-Dependent Study(2015) SERPA, Mauricio H.; DOSHI, Jimit; VIERA, Erica L. M.; CHAIM, Tiffany M.; BILT, Martinus T. van de; SALLET, Paulo; GATTAZ, Wagner F.; TEIXEIRA, Antonio L.; BUSATTO, Geraldo F.; DAVATZIKOS, Christos; ZANETTI, Marcus V.conferenceObject Increased Lactate Levels During Depressive Episodes and Reversal Effects by Lithium Monotherapy in Subjects with Bipolar Disorder(2013) MACHADO-VIEIRA, Rodrigo; ZANETTI, Marcus V.; OTADUY, Maria C. G.; SOUSA, Rafael T. de; COSTA, Alana C.; CHAIM, Tiffany M.; LEITE, Claudia C.; BUSATTO, Geraldo F.; GATTAZ, Wagner F.Background: Altered energy metabolism has been widely described in Bipolar Disorder (BD). However, brain lactate levels have been only evaluated in few studies with heterogeneous samples using magnetic resonance spectroscopy (MRS). These findings support the presence of dysfunctional brain energy production as a central component in the pathophysiology of BD. However, no study to date has evaluated brain lactate levels specifically in bipolar depression or even the effects of lithium treatment in brain lactate levels in subjects with BD. Methods: Twenty-four BD individuals (up to 5 years of illness duration) presenting with an acute depressive episode underwent MRS at baseline and after 6 weeks of lithium therapy at therapeutic doses. Lactate levels were measures in the cingulated cortex (CC). Clinical assessment was performed weekly using the 21-item Hamilton Depression Rating Scale (HDRS) and the Young Mania Rating Scale (YMRS). A group of age and gender-matched healthy controls (n=18) was also studied. Results: BD patients exhibited increased brain lactate in the CC relative to healthy controls at baseline. A significant decrease in brain lactate levels was observed after 6 weeks of lithium treatment, and correlated with clinical response (reduction ≥ 50% in HDRS scores). Conclusions: Lithium treatment produces a significant decrease in brain lactate levels of acutely depressed BD patients. This suggests that the clinical efficacy of lithium is also associated with reduction in the shift from aerobic to anaerobic metabolism observed in BD.- Classification of MRI under the Presence of Disease Heterogeneity using Multi-Task Learning: Application to Bipolar Disorder(2015) WANG, Xiangyang; ZHANG, Tianhao; CHAIM, Tiffany M.; ZANETTI, Marcus V.; DAVATZIKOS, ChristosHeterogeneity in psychiatric and neurological disorders has undermined our ability to understand the pathophysiology underlying their clinical manifestations. In an effort to better distinguish clinical subtypes, many disorders, such as Bipolar Disorder, have been further sub-categorized into subgroups, albeit with criteria that are not very clear, reproducible and objective. Imaging, along with pattern analysis and classification methods, offers promise for developing objective and quantitative ways for disease subtype categorization. Herein, we develop such a method using learning multiple tasks, assuming that each task corresponds to a disease subtype but that subtypes share some common imaging characteristics, along with having distinct features. In particular, we extend the original SVM method by incorporating the sparsity and the group sparsity techniques to allow simultaneous joint learning for all diagnostic tasks. Experiments on Multi-Task Bipolar Disorder classification demonstrate the advantages of our proposed methods compared to other state-of-art pattern analysis approaches.
- Multimodal Magnetic Resonance Imaging Study of Treatment-Naive Adults with Attention-Deficit/Hyperactivity Disorder(2014) CHAIM, Tiffany M.; ZHANG, Tianhao; ZANETTI, Marcus V.; SILVA, Maria Aparecida da; LOUZA, Mario R.; DOSHI, Jimit; SERPA, Mauricio H.; DURAN, Fabio L. S.; CAETANO, Sheila C.; DAVATZIKOS, Christos; BUSATTO, Geraldo F.Background: Attention-Deficit/Hiperactivity Disorder (ADHD) is a prevalent disorder, but its neuroanatomical circuitry is still relatively understudied, especially in the adult population. The few morphometric magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) studies available to date have found heterogeneous results. This may be at least partly attributable to some well-known technical limitations of the conventional voxel-based methods usually employed to analyze such neuroimaging data. Moreover, there is a great paucity of imaging studies of adult ADHD to date that have excluded patients with history of use of stimulant medication. Methods: A newly validated method named optimally-discriminative voxel-based analysis (ODVBA) was applied to multimodal (structural and DTI) MRI data acquired from 22 treatment-naive ADHD adults and 19 age-and gender-matched healthy controls (HC). Results: Regarding DTI data, we found higher fractional anisotropy in ADHD relative to HC encompassing the white matter (WM) of the bilateral superior frontal gyrus, right middle frontal left gyrus, left postcentral gyrus, bilateral cingulate gyrus, bilateral middle temporal gyrus and right superior temporal gyrus; reductions in trace (a measure of diffusivity) in ADHD relative to HC were also found in fronto-striatal-parieto-occipital circuits, including the right superior frontal gyrus and bilateral middle frontal gyrus, right precentral gyrus, left middle occipital gyrus and bilateral cingulate gyrus, as well as the left body and right splenium of the corpus callosum, right superior corona radiata, and right superior longitudinal and fronto-occipital fasciculi. Volumetric abnormalities in ADHD subjects were found only at a trend level of significance, including reduced gray matter (GM) in the right angular gyrus, and increased GM in the right supplementary motor area and superior frontal gyrus. Conclusions: Our results suggest that adult ADHD is associated with neuroanatomical abnormalities mainly affecting the WM microstructure in fronto-parieto-temporal circuits that have been implicated in cognitive, emotional and visuomotor processes.