The C270T polymorphism of the brain-derived neurotrophic factor gene is associated with schizophrenia
Introduction
The neurodevelopmental hypothesis of schizophrenia has two key predictions Weinberger, 1987, Bassett et al., 2001. First, this hypothesis suggests that abnormal molecular events during brain development lead to altered differentiation, migration and survival of neurons, as well as to changes in synaptic morphology and physiology. The second prediction is related to the genetic background of schizophrenia; it is evident to conceptualize that certain genetic variations may result in an increased possibility for molecular events that eventually lead to abnormal functioning of neuronal microcircuits. One possible candidate is the group of neurotrophic factors, potentially responsible for alterations in neuron number, cytoarchitecture and white-matter neuron distribution (Arnold and Rioux, 2001). In this respect, a considerable attention has been paid to brain-derived neurotrophic factor (BDNF). Post mortem studies found altered levels of BDNF in numerous neocortical and limbic regions of schizophrenia patients Takahashi et al., 2000, Durany et al., 2001. The role of BDNF has been raised in connection with age at onset and substance abuse in schizophrenia (Krebs et al., 2000), antipsychotic medication effects Angelucci et al., 2000, Krebs et al., 2000, Lipska et al., 2001, consequences of neonatal hippocampal damage Lipska et al., 2001, Molteni et al., 2001, vulnerability for stress (Molteni et al., 2001) and changes in brain morphology (Wassink et al., 1999).
Despite this research, there is no evidence that a certain polymorphism of the BDNF gene would be associated with schizophrenia Hawi et al., 1998, Wassink et al., 1999, Krebs et al., 2000, Virgos et al., 2001. The negative studies concerning this issue were focused on the dinucleotide repeat polymorphism (166–174 bp) of the BDNF gene. Recently, a new polymorphism of single nucleotide substitution (C270T) has been reported in the 5′-noncoding region of the gene, which can be detected by polymerase chain reaction and digestion by the restriction enzyme of HinfI (Kunugi et al., 2001). In this study, we investigated whether this new polymorphism of the BDNF gene is associated with schizophrenia. We also compared the clinical and psychosocial characteristics of schizophrenia patients with different genotypes.
Section snippets
Subjects
A total of 169 Caucasian volunteers participated in the study. About 101 of them (62 men and 39 women) received the DSM-IV diagnosis of schizophrenia (American Psychiatric Association, 1994) (mean age: 39.8 years, S.D.=11.8), and 68 (39 men and 29 women) were healthy controls (mean age: 36.8 years, S.D.=11.1) who were recruited from the hospital staff and general population. Clinical symptoms were evaluated with the Positive and Negative Symptom Scale (PANSS) (Kay et al., 1987) and the Global
Results and discussion
Table 1 shows the genotype and allele frequencies for patients with schizophrenia and healthy control participants. The genotype distributions for the patient and control groups were not significantly deviated from the Hardy–Weinberg equilibrium. Concerning the genotype frequency, the C/T genotype was over-represented in the schizophrenia patients (25.7%) compared with the controls (5.9%) (χ2=11.17, df=1, p=0.0008). Similarly, the 270T allele was more frequent in the patients (13.9%) than in
Acknowledgments
This work was supported by the Hungarian Ministry of Education and Health (ETT 2001/016OM, FKFP 008262001). S. Kéri was supported by the Wenner-Gren Foundation, Stockholm, Sweden.
References (16)
- et al.
Brain-derived neurotrophic factor and neurotrophin 3 in schizophrenic psychoses
Schizophr. Res.
(2001) - et al.
No linkage or linkage disequilibrium between brain-derived neurotrophic factor (BDNF) dinucleotide repeat polymorphism and schizophrenia in Irish families
Psychiatry Res.
(1998) - et al.
Association study of schizophrenia with polymorphisms at six candidate genes
Schizophr. Res.
(2001) DSM-IV: Diagnostic and Statistical Manual of Mental Disorders
(1994)- et al.
Brain-derived neurotrophic factor and tyrosine kinase receptor TrkB in rat brain are significantly altered after haloperidol and risperidone administration
J. Neurosci. Res.
(2000) - et al.
Challenges, status, and opportunities for studying developmental neuropathology in adult schizophrenia
Schizophr. Bull.
(2001) - et al.
Study on construct validity of the M.I.N.I. PLUS interview
Psychiat. Hung.
(2000) - et al.
Genetic insights into the neurodevelopmental hypothesis of schizophrenia
Schizophr. Bull.
(2001)
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