Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036341 (schizophrenia)
 60,220 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Schizophrenia is a severe psychiatric disease with a strong genetic component. Brain-derived neurotrophic factor (BDNF) has been implicated in the pathogenesis of schizophrenia and bipolar (BP) disorders. The present study has examined two polymorphisms in linkage disequilibrium in the BDNF gene, which have been variously reported as associated with schizophrenia and BP. In our study, 321 probands with a primary diagnosis of schizophrenia or schizoaffective disorder, and 263 with a diagnosis of bipolar affective disorder, were examined together with 350 controls drawn from the same geographical region of Scotland. The val66met single-nucleotide polymorphism (SNP) showed significant (P = 0.005) association for valine (allele G) with schizophrenia but not bipolar disorder. Haplotype analysis of val/met SNP and a dinucleotide repeat polymorphism in the putative promoter region revealed highly significant (P < 1 x 10(-8)) under-representation of the methionine or met-1 haplotype in the schizophrenic but not the BP population. We conclude that, although the val66met polymorphism has been reported to alter gene function, the risk may depend upon the haplotypic background on which the val/met variant is carried.
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PMID:BDNF gene is a risk factor for schizophrenia in a Scottish population. 1563 Apr 10

Understanding the etiology and pathogenesis schizophrenia and depression is a major challenge facing psychiatry. One hypothesis is that these disorders are secondary to a malfunction of neurotrophic factors. Inappropriate neurotrophic support during brain development could lead to structural disorganisation in which neuronal networks are established in a nonoptimal manner. Inadequate neurotrophic support in adult individuals could ultimately be an underlying mechanism leading to decreased capacity of brain to adaptive changes and increased vulnerability to neurotoxic damage. Brain-derived neurotrophic factor (BDNF) is a mediator involved in neuronal survival and plasticity of dopaminergic, cholinergic, and serotonergic neurons in the central nervous system (CNS). In this review, we summarize findings regarding altered BDNF in schizophrenia and depression and animal models, as well as the effects of antipsychotic and antidepressive treatments on the expression of BDNF.
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PMID:BDNF in schizophrenia, depression and corresponding animal models. 1565 62

Magnetic resonance (MR) imaging studies have identified hippocampal structural alterations in the pathogenesis of schizophrenia. Brain-derived neurotrophic factor (BDNF) is one of the neurotrophins that is widely expressed in the hippocampal formation and has been implicated in the neurobiology of schizophrenia. Polymorphisms in the BDNF gene may therefore confer risk for schizophrenia through hippocampal pathogenesis and/or making the hippocampus more susceptible to environmental insults. In this study, we investigated whether val66met, a functional and abundant missense polymorphism in the coding region of the BDNF gene, was associated with the volume of the hippocampal formation in 19 patients with first-episode schizophrenia and 25 healthy volunteers. A total of 124 contiguous T1-weighted coronal MR images (slice thickness=1.5 mm) were acquired through the whole head using a 3D Fast SPGR IR Prep sequence on a 1.5 T GE imaging system. Volumes of the right and left hippocampal formation were measured manually by an operator blind to group status and genotype. All participants were genotyped for the BDNF val66met locus. Mixed model analyses revealed a main effect of BDNF val66met genotype such that in the combined sample of patients and healthy volunteers, val/val homozygotes (N=27) had larger volumes of the hippocampal formation compared to val/met heterozygotes (N=17). In separate analyses by group, however, val66met genotype accounted for a greater proportion of the variance in the volume of the hippocampal formation in patients compared to healthy volunteers. These findings implicate genetic involvement of BDNF in variation of human hippocampal volume and suggest that this effect may be greater among patients compared to healthy volunteers.
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PMID:Brain-derived neurotrophic factor val66met polymorphism and volume of the hippocampal formation. 1576 49

Brain-derived neurotrophic factor (BDNF) regulates a variety of neuromodulatory processes during development, as well as in adulthood. It has been proposed as a risk factor for schizophrenia. We have investigated a possible association between schizophrenia and the C-270T polymorphism in the brain-derived neurotrophic factor (BDNF) gene in 397 schizophrenic patients and 380 control subjects. The diagnosis of schizophrenia was made for each patient by at least two psychiatrists, using DSM-IV and ICD-10 criteria in structured clinical interviews for DSM-IV Axis I disorders (SCID). No association was found between schizophrenia and the analyzed polymorphism, for either genotype or allele distribution (for genotype: p=0.513, for alleles: p=0.812). Differences were not statistically significant when analyzed separately by sex. For males, the differences for genotype distribution and allele frequency were p=0.078 and p=0.162 respectively and for females: p=0.441 and p=0.315. Thus, our data indicate that variations in the BDNF gene are unlikely to be an important factor in susceptibility to schizophrenia.
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PMID:No association of the brain-derived neurotrophic factor (BDNF) gene C-270T polymorphism with schizophrenia. 1594 51

Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family and plays an important role in neuronal survival and plasticity in the CNS. The proform of BDNF (pro-BDNF) is secreted and cleaved extracellularly by the serine protease plasmin to mature BDNF, which potentiates synaptic plasticity and long-term potentiation. Recent findings in animal models suggest an involvement of BDNF and its genetic functional single nucleotide polymorphism in the pathogenesis of different psychiatric diseases including depression, mania, schizophrenia, eating disorders, dementia, and Huntington's disease. In the brain and serum, BDNF is modulated by different factors. It is downregulated by stress and upregulated by learning processes, several antidepressive treatments, physical activity, and dietary restriction. Measurement of BDNF serum concentrations may be of diagnostic value. Additionally, the influence of different strategies for BDNF allocation seems to be relevant for the treatment and prevention of the above psychiatric disorders.
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PMID:[Brain-derived neurotrophic factor: from nerve growth factor to modulator of brain plasticity in cognitive processes and psychiatric diseases]. 1607 56

Schizophrenia (SZ) is a prevalent and severe mental disorder. One of the most favored hypotheses for the etiology of SZ is the neurodevelopmental hypothesis. Brain-derived neurotrophic factor (BDNF), a member of the neurotrophin growth factor family, promotes the development, regeneration, and survival of neurons and has been linked to the neuropathology of SZ. The present study tested, in a sample of 94 nuclear families, the hypothesis that the BDNF gene Val66Met polymorphism is associated to SZ and its psychopathologic phenotype using a multidimensional symptom approach. Furthermore, considering a reported reduction of BDNF in the frontal cortex of patients with SZ, we studied the relationship between this polymorphism and prefrontal function. The transmission disequilibrium test (TDT) showed a preferential transmission of allele Val from heterozygous parents to the affected offspring (P = 0.002), suggesting a possible role of this gene in the vulnerability to SZ spectrum disorders. The findings remained essentially unchanged when the analysis was restricted to the subgroup of patients with SZ (P = 0.009) and when a multidimensional approach to the diagnosis was used. Quantitative transmission disequilibrium test (QTDT) analyses did not demonstrate a significant association between the prefrontal tests assessed (Wisconsin Card Sorting Test and Trail Making Test) and the transmission of the BDNF alleles. Our finding suggests that the investigated BDNF polymorphism plays an important role in the phenotype of psychosis, but not in the performance of tests of prefrontal cognitive functions analyzed in these patients.
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PMID:The Val66Met polymorphism of the brain-derived neurotrophic factor gene is associated with risk for psychosis: evidence from a family-based association study. 1638 85

Brain-derived neurotrophic factor (BDNF) belongs to a family of the neurotrophin which plays important roles in the development of the brain. BDNF has been suggested as a factor that increases the risk of schizophrenia. In this study, we genotyped three single nucleotide polymorphisms (SNPs) in the BDNF gene using a set sample of Han Chinese subjects consisting of 560 schizophrenes and 576 controls. No significant differences were found for either the genotype or allele distribution of analyzed polymorphisms, nor was any gender-specific association found. Thus, our data suggest that the BDNF gene may not be an important factor in susceptibility to schizophrenia.
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PMID:Association between the brain-derived neurotrophic factor (BDNF) gene and schizophrenia in the Chinese population. 1640 71

The measures of prefrontal cognition have been used as endophenotype in molecular-genetic studies. Brain-derived neurotrophic factor (BDNF) has been implicated in cognitive functions and in the pathogenesis of major psychoses. This study investigates the relationship between Val66Met polymorphisms of the BDNF gene and prefrontal cognitive function in 129 patients with schizophrenia and 111 patients with bipolar mood disorder. Cognitive tests included the Wisconsin Card Sorting Test (WCST), with such domains as number of perseverative errors, non-perseverative errors, completed corrected categories, conceptual level responses, and set to the first category, and the N-back test, where mean reaction time and percent of correct reactions were measured. Genotyping for Val66Met BDNF polymorphism was done by polymerase chain reaction method. In schizophrenia, no relationship between Val66Met polymorphism of the BDNF gene and the results of the WCST was observed. Patients with Val/Val genotype had a higher percentage of correct reactions in the N-back test than those with the remaining genotypes. Bipolar patients with Val/Val genotype obtained significantly better results on three of five domains of the WCST. No relationship between BDNF polymorphism and the results of the N-back test was found in this group. A limitation to the results could be variable psychopathological state and medication during cognitive testing and lack of Hardy-Weinberg equilibrium in schizophrenia group. Val66Met polymorphism of the BDNF gene may be associated with cognitive performance on the WCST in bipolar mood disorder but not in schizophrenia. An association of this polymorphism with performance on the N-back test in schizophrenia and not in bipolar illness may suggest that in schizophrenia, the BDNF system may be connected with early phases of information processing.
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PMID:Prefrontal cognition in schizophrenia and bipolar illness in relation to Val66Met polymorphism of the brain-derived neurotrophic factor gene. 1647 61

Brain-derived neurotrophic factor (BDNF) is a neurotrophic factor that promotes several functions of neurons and modulates neurotransmissions. It has been reported that there are alterations of BDNF levels in schizophrenic brains and that BDNF gene expressional changes would be responsible for the etiology of schizophrenia. Recent studies have shown that a variation of BDNF gene (Val66Met polymorphism) affects the function of neurons, and is associated with several neurological and psychiatrical disorders. We investigated the relationship between BDNF Val66Met polymorphism and the onset age as well as levels of clinical symptoms in 159 of chronic schizophrenia in-patients diagnosed by DSM-IV. The mean onset ages were 27.5+/-9.5 for BDNF Val/Val, 25.5+/-7.4 for BDNF Val/Met and 22.9+/-6.0 for BDNF Met/Met and this polymorphism was significantly associated with age at onset (P=0.023). The mean Brief Psychiatric Rating Scale scores (BPRS) were significantly different among those three groups (P=0.003). No significant differences were demonstrated comparing the BDNF genotype distributions of positive and negative family history (P=0.21). Our investigation indicates that the BDNF gene Val66Met polymorphism is related to the onset age of schizophrenia and the levels of clinical symptoms that remain after long-term antipsychotic treatment.
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PMID:Brain-derived neurotrophic factor (BDNF) Val66Met polymorphism in schizophrenia is associated with age at onset and symptoms. 1653 63

Brain-derived neurotrophic factor (BDNF) plays important roles in the survival, maintenance and growth of neurons. Several studies have indicated that BDNF is likely to be related to the pathogenesis of schizophrenia. Recent genetic analyses have revealed that BDNF gene polymorphisms are associated with schizophrenia, although contradictory negative findings have also been reported. To assess whether three BDNF gene polymorphisms (rs988748, C132T and rs6265) could be implicated in vulnerability to schizophrenia, we conducted a case-control association analysis (349 patients and 423 controls) in Japanese subjects. We found no association between these BDNF gene polymorphisms and schizophrenia using both single-marker and haplotype analyses. The results of the present study suggest that these three BDNF gene polymorphisms do not play major roles in conferring susceptibility to schizophrenia in a Japanese population. However, further studies assessing the associations between these BDNF gene polymorphisms and schizophrenia should be performed in several other ethnic populations.
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PMID:No association between the brain-derived neurotrophic factor gene and schizophrenia in a Japanese population. 1663 52


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