Navegando por Palavras-chave "First Psychotic Episode"
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- ItemSomente MetadadadosAlteração Da Expressão Gênica Relacionada A Sintomas Psicóticos E De Mania Em Pacientes Em Primeiro Episódio Psicótico Virgens De Tratamento(Universidade Federal de São Paulo (UNIFESP), 2017-05-31) Gouvea, Eduardo Sauerbronn [UNIFESP]; Belangero, Sintia Iole Nogueira [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)Psychoses are among serious mental disorders and affect approximately 3% of the general population. In the initial stages, the non-specific syndromic clinical aspects do not allow diagnostic clarity between the tables. The broad psychopathological nuance in the First Psychotic Episode (PEP) reinforces the need to investigate biomarkers that refine early diagnosis. We investigated the difference in gene expression among patients with schizophrenic symptoms (PEP-S, N = 53), with manifest symptoms (PEP-M, N = 16) and healthy controls (N = 76). We also analyzed the variation of gene expression with the severity of psychotic symptoms, manifested symptoms, depressive symptoms, and functional performance. All participants were treatment-naive with antipsychotics. After blood collection, 12 genes related to psychotic manifestations were evaluated by quantitative PCR. The expression levels of AKT1 and DICER1 were higher in patients with manifest symptoms (PEP-M) when compared to both patients with schizophrenic symptoms (PEP-S) and controls, suggesting that the expression of these genes is more specific to the occurrence of manifest symptoms . The expression of the MBP and NDEL1 genes was higher among the patients (both PEP-S and PEP-M) than in the healthy controls indicating a relationship with the psychotic manifestation itself independent of the diagnosis. We found no correlation between the levels of gene expression and the severity of symptoms or functional performance. Our findings suggest that the expression of genes related to neurodevelopment is altered in the psychoses, and can thus serve the differential diagnosis between schizophrenia and bipolar affective disorder and consequently to a better therapeutic definition.
- ItemSomente MetadadadosAtividade das Oligopeptidases Ndel1 e ECA na Esquizofrenia e no Transtorno Bipolar(Universidade Federal de São Paulo (UNIFESP), 2019-04-25) Mas, Caroline Dal [UNIFESP]; Hayashi, Mirian Akemi Furuie [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)Schizophrenia (SCZ) and bipolar disorder (BD) are severe and disabling mental disorders (MDs), which share pathophysiological and symptomatological characteristics. Until the present, the neurobiological and etiological aspects of these illnesses remain little known. Oligopeptidases are enzymes with ability to cleave neuropeptides acting on the modulation of neural pathways described to be altered in MDs, as for instance the neurotensin (NT) and bradykinin (BK) signaling pathways. In the last years, our group has demonstrated changes in the activity of neuropeptides cleaving oligopeptidases, as the nuclear distribution element like-1 (Ndel1) and angiotensin-converting enzyme I (ACE) in chronic SCZ patients. The aim of the present thesis was to evaluate the role of Ndel1 and ACE activity in the SCZ and TB pathophysiology, evaluate their potential as indicator of susceptibility to SCZ or illness progression, and if the Ndel1 and ACE activity was also altered in TB patients. Aiming this, we evaluated the Ndel1 activity in individuals at high risk for psychosis (UHR), in first episode of psychosis (PEP) before (PEP-0), and after 2 months (PEP-2M) and one year (PEP-1A) of treatment with risperidone, as the main drug. We also evaluated the activity of Ndel1 and ECA in euthymic TB patients. and olfactory neuroepithelial cells (OE-cells) of patients with SCZ and BD was also investigated as possible alternative biological sample source to understand the changes that occur in the central nervous system (CNS), as these cells share the same embryonic leaflet origin with neurons. We demonstrated here that PEP-0 patients showed lower Ndel1 activity compared to healthy controls (HC), as we have previously demonstrated for chronic SCZ patients. In addition, no significant difference in Ndel1 activity was observed between UHR and CS individuals, but the Ndel1 activity was significantly lower in PEP, before or after the treatment compared to HC, and this activity decreased with the treatment with risperidone. On the other hand, the mean value of this activity in PEP was lower than chronic SCZ. Euthymic BD individuals also presented lower Ndel1 activity compared to HC, although ACE activity was not different between TB and HC. Although still preliminary, it was possible to observe that Ndel1 activity in OE cells correlates with that found in the peripheral blood of SCZ and TB patients compared to HC, suggesting a possible correlation between Ndel1 activity in plasma and OE cells, as already suggested by others for expression profile and phenotypic correspondence with CNS. Therefore, we suggest that enzymes as Ndel1 and ACE are potential biomarkers or new targets for the treatment of MDs as SCZ and BD. The present work contributes to the knowledge in Ndel1 and ECA activity changes in different stages of these serious MDs, in addition to opening new roads for the discovery of possible new treatments considering the important roles of peptidergic signaling pathways in the pathophysiology of these disorders.