RESUMO
BACKGROUND/AIMS: The brain-derived neurotrophic factor (BDNF) levels in serum and the central nervous system are altered in patients with schizophrenia, suggesting that changes in the expression of BDNF might contribute to the disease pathophysiology. Long duration of untreated psychosis (DUP) has been associated with poorer prognosis in patients with schizophrenia. Such a relationship of untreated psychosis to outcome may indicate a neurodegenerative process and may have important implications for understanding the pathophysiology of schizophrenia. METHODS: In this study, we investigated the association between serum BDNF levels and DUP in a sample of drug-naïve patients in their first episode of schizophrenia (FEP). We investigated serum BDNF levels in a sample of 37 drug-naïve FEP patients and 21 matched healthy subjects. RESULTS: The serum BDNF level in the sample of FEP was significantly reduced compared to the healthy subjects (18.87 +/- 8.23 vs. 29.2 +/- 7.73 ng/ml, t = 4.76, d.f. = 57, p = 0.01). A negative correlation was found between serum BDNF levels and DUP in the group of patients (r = -0.346, p = 0.036). CONCLUSIONS: Our findings indicate that low serum BDNF levels at the onset of schizophrenia were associated with a long DUP and this could reflect an acute neurodegenerative reaction during the untreated phase of psychosis.
Assuntos
Fator Neurotrófico Derivado do Encéfalo/sangue , Esquizofrenia/sangue , Esquizofrenia/fisiopatologia , Adulto , Estudos de Casos e Controles , Ensaio de Imunoadsorção Enzimática/métodos , Feminino , Humanos , Masculino , Escalas de Graduação Psiquiátrica , Estatísticas não Paramétricas , Adulto JovemRESUMO
The role of brain-derived neurotrophic factor (BDNF) is to promote and modulate the neuronal responses across neurotransmitter systems in the brain. Therefore, abnormal BDNF signaling may be associated with the pathophysiology of schizophrenia. Decreased BDNF levels in the brain and the serum of patients with psychotic disorders have been reported. In the present study, we assessed serum BDNF levels in a group of 14 drug-naive first-episode patients with schizophrenia (FEP), compared to 15 healthy controls. The serum BDNF levels in the sample of FEP patients was significantly reduced compared to normal controls (23.92+/-5.99 ng/ml vs. 30.0+/-8.43 ng/ml, F=5.01, df=1, p=.034). Negative correlations were shown between serum BDNF levels of the patients and the PANSS Positive and Negative subscale scores. Our findings indicate that BDNF levels at the onset of schizophrenia may reflect associated pathophysiological processes as well as the severity of positive and negative psychotic symptoms.
Assuntos
Fator Neurotrófico Derivado do Encéfalo/sangue , Esquizofrenia/sangue , Adulto , Análise de Variância , Feminino , Humanos , Modelos Lineares , Masculino , Estudos RetrospectivosRESUMO
Evidence suggests that hippocampal volumetric abnormalities are present in first-episode schizophrenia. The hippocampus contains the highest brain levels of neurotrophic factors, which are major determinants of neuronal plasticity. Brain-derived neurotrophic factor (BDNF) influences neuronal survival, differentiation, synaptogenesis, and maintenance and is also correlated with neuronal activation in the hippocampus. BDNF is also involved in the development and modulation of dopaminergic-related systems. Alterations of serum BDNF levels have been shown in a number of studies with first episode patients with schizophrenia, probably reflecting an association between BDNF and the pathogenesis of the disorder. In the present study we investigated the correlation between serum BDNF levels and hippocampal volumes in a sample of first episode drug-naïve patients with schizophrenia (FEP) and healthy control subjects. We found that hippocampal volume (HV) was decreased in FEP patients. Corrected right HV of FEP patients were significantly smaller compared to corrected right HVs of healthy subjects. The serum BDNF levels in the sample of FEP patients was significantly reduced compared to the healthy subjects. A significant positive association was found between serum BDNF and the corrected right HV in the group of patients such that the smaller the HV, the more reduced the serum BDNF levels. (Pearson r=0.452, p=0.045). Our findings indicate that low serum BDNF levels are associated with reduction in HV at the onset of schizophrenia and may further support the theory of a neuroprogressive-neurotoxic reaction associated with the onset of psychosis.
Assuntos
Fator Neurotrófico Derivado do Encéfalo/sangue , Hipocampo/patologia , Transtornos Psicóticos , Esquizofrenia/complicações , Adulto , Feminino , Lateralidade Funcional , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Transtornos Psicóticos/sangue , Transtornos Psicóticos/etiologia , Transtornos Psicóticos/patologia , Estatística como Assunto , Adulto JovemRESUMO
Polymorphisms in the brain-derived neurotrophic factor (BDNF) gene have been indicated to be associated with schizophrenia. Previous studies have suggested that val66met polymorphism may increase the risk for schizophrenia, although other studies have not confirmed this association. Decreased BDNF levels in the brain and the serum of patients with psychotic disorders have been reported in first episode psychotic (FEP) patients. In our study we investigated the potential genetic association of this polymorphism with schizophrenia in a sample of 38 FEP patients with schizophrenia compared with a sample of 21 normal controls. Furthermore, we assessed serum BDNF levels and investigated whether there was an association between this polymorphism and alterations of serum BDNF levels between the investigated groups. There was a significant difference in genotyped frequencies between cases and controls (p=0.030). The homozygous carriers Met/Met were over-represented in the schizophrenia group (13/31, 41.9%), compared to controls (2/19, 10.5%). The serum BDNF levels in the sample of FEP patients was significantly reduced compared to controls (18.87±8.23 ng/mL vs 29.2±7.73ng/mL, U=140, p=0.0). No association was found between alterations of serum BDNF levels and Val66Met polymorphism in the group of patients (p=0.198). Negative correlations were shown between serum BDNF levels of the patients and the PANSS Negative subscale scores (p=0.015). There was found no significant difference between genotypes and memory scores in the sample of patients. Our findings indicate that serum BDNF levels at the onset of schizophrenia and BDNF Val66Met variant may be susceptibility risk factors for schizophrenia.