Brief reportAssociation study of BDNF and CNTF polymorphism to depression in non-demented subjects of the “VITA” study
Introduction
Several evidence point to the involvement of neurotrophic factors in mood and depression (Angelucci et al., 2005, Duman, 2004). The most investigated neurotrophin in this context is the brain-derived neurotrophic factor (BDNF) that showed decreased levels in the prefrontal cortex and hippocampus of suicide victims who were depressed (Dwivedi et al., 2003, Dwivedi et al., 2001). Other studies have shown decreased plasma levels of BDNF in patients with major depression (Karege et al., 2002) and increased BDNF level in hippocampus in post-mortem tissue from patients treated with antidepressant drugs (Chen et al., 2001). Several studies attempted to correlate BDNF polymorphisms and major depression as well as bipolar disorder, with quite confusing results (Hashimoto et al., 2004, Jiang et al., 2005, Tsai et al., 2003). Recently, a new single nucleotide polymorphism (SNP) within a non-coding region of the BDNF gene, leading to a C→T substitution at position 270, was described in Alzheimer's disease (Bagnoli et al., 2004, Kunugi et al., 2001, Riemenschneider et al., 2002). This specific polymorphism has not been studied in depression or late onset depression, especially.
Ciliary neurotrophic factor (CNTF), a member of the cytokine family of neurotrophic factors, also promotes survival of embryonic motor neurons in vitro and in vivo (Arakawa et al., 1990, Forger et al., 1993, Forger et al., 1998). A null-mutation in the CNTF gene results in progressive motor neuron atrophy and postnatal neuron loss (Masu et al., 1993, Takahashi et al., 1994). This null-mutation was widely investigated in neurological and psychiatric disorders without consistent conclusions (Gelernter et al., 1998, Gelernter et al., 1997, Orrell et al., 1995, Thome et al., 1996a, Thome et al., 1996b, Thome et al., 1997a). The CNTF null-mutation has not been studied in late onset depression.
We questioned whether the CNTF null-mutation and the BDNF C270T polymorphism are associated with depression in the elderly and late-onset depression, especially. We used data from the basic recruitment of the Vienna Transdanube Aging (VITA) study, a prospective, community-based, cohort study of the elderly in which all subjects were 75 years of age (Fischer et al., 2002, Grünblatt et al., 2005).
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Patient recruitment and evaluation
Subjects of the present study are all participants from the basic recruitment of a community based cohort-study called the VITA study. Detailed information about the recruitment and character of the subjects have been described previously (Blasko et al., 2005, Grünblatt et al., 2005).
Depression was diagnosed and classified strictly according to the DSM-IV (Fischer et al., in press, Grünblatt et al., in press). We excluded subjects with dementia using CDR and MMSE. All subjects with CDR higher
CNTF null-mutation
The CNTF null-mutation in the VITA project showed no statistical deviation from the Hardy-Weinberg equilibrium. The genotype frequencies for CNTF null-mutation showed no significant differences between depressive and non-depressive subjects (trend test, p = 0.62; Table 2). To achieve a power larger than 80% for the comparison of proportions of CNTF by the trend test (α = 0.05, two-sided) with 259 subjects having GG, 126 GA and 14 AA the true difference has to be as large as 25% (e.g., GG: 25% vs.
Discussion
Recent evidence suggests that alterations in neurotrophic functions either due to age, genetic background or other factors might contribute to neurodegeneration and mood disorders (Hashimoto et al., 2004). Therefore, we questioned whether BDNF C270T polymorphism and CNTF null-mutations correlate to depression in the VITA project. We found rather no correlation between either CNTF null-mutation or BDNF C270T polymorphism and depression. As the BDNF polymorphism G196A was already extensively
Acknowledgement
This research was supported by the Ludwig Boltzmann Institute of Aging Research, Vienna, Austria.
References (40)
- et al.
Plasma amyloid beta protein 42 in non-demented persons aged 75 years: effects of concomitant medication and medial temporal lobe atrophy
Neurobiol. Aging
(2005) - et al.
Increased hippocampal BDNF immunoreactivity in subjects treated with antidepressant medication
Biol. Psychiatry
(2001) - et al.
Investigation of the effect of brain-derived neurotrophic factor (BDNF) polymorphisms on the risk of late-onset Alzheimer's disease (AD) and quantitative measures of AD progression
Neurosci. Lett.
(2005) - et al.
Population studies of polymorphisms at loci of neuropsychiatric interest (tryptophan hydroxylase (TPH), dopamine transporter protein (SLC6A3), D3 dopamine receptor (DRD3), apolipoprotein E (APOE), mu opioid receptor (OPRM1), and ciliary neurotrophic factor (CNTF))
Genomics
(1998) - et al.
Oxidative stress related markers in the “VITA” and the centenarian projects
Neurobiol. Aging
(2005) - et al.
Critical role of brain-derived neurotrophic factor in mood disorders
Brain Res. Brain Res. Rev.
(2004) - et al.
Decreased serum brain-derived neurotrophic factor levels in major depressed patients
Psychiatry Res.
(2002) - et al.
Low brain-derived neurotrophic factor (BDNF) levels in serum of depressed patients probably results from lowered platelet BDNF release unrelated to platelet reactivity
Biol. Psychiatry
(2005) - et al.
Risk of late-onset Alzheimer's disease associated with BDNF C270T polymorphism
Neurosci. Lett.
(2005) - et al.
Investigation of a null mutation of the CNTF gene in familial amyotrophic lateral sclerosis
J. Neurol. Sci.
(1995)
Association of a variation in the promoter region of the brain-derived neurotrophic factor gene with familial Parkinson's disease
Parkinsonism Relat. Disord.
Alterations of serum levels of brain-derived neurotrophic factor (BDNF) in depressed patients with or without antidepressants
Biol. Psychiatry
No association of the brain-derived neurotrophic factor (BDNF) gene polymorphisms with panic disorder
Prog. Neuro-psychopharmacol. Biol. Psychiatry
The C270T polymorphism of the brain-derived neurotrophic factor gene is associated with schizophrenia
Schizophr. Res.
Association between a null mutation in the human ciliary neurotrophic factor (CNTF) gene and increased incidence of psychiatric diseases?
Neurosci. Lett.
BDNF in schizophrenia, depression and corresponding animal models
Mol. Psychiatry
Survival effect of ciliary neurotrophic factor (CNTF) on chick embryonic motoneurons in culture: comparison with other neurotrophic factors and cytokines
J. Neurosci.
Brain-derived neurotrophic factor genetic variants are not susceptibility factors to Alzheimer's disease in Italy
Ann. Neurol.
Role of neurotrophic factors in the etiology and treatment of mood disorders
Neuromolecular. Med.
Reduced activation and expression of ERK1/2 MAP kinase in the post-mortem brain of depressed suicide subjects
J. Neurochem.
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The association between BDNF C270T genetic variants and smoking in patients with mental disorders and in healthy controls
2022, Progress in Neuro-Psychopharmacology and Biological PsychiatryCitation Excerpt :Although we have included 996 patients with schizophrenia, our result of the similar frequency of the BDNF C270T genotypes between smokers and non-smokers with schizophrenia agrees with no significant association between BDNF C270T and smoking in a small study using 149 Chinese patients with schizophrenia (Wang et al., 2007). In line with other report (Grünblatt et al., 2006), in our study BDNF C270T polymorphism was not associated with depression. It was not related to smoking status or the number of cigarettes smoked per day in depression.
Systematic review and meta-analysis of genetic studies of late-life depression
2017, Neuroscience and Biobehavioral ReviewsReprint of: Effects of BDNF polymorphisms on brain function and behavior in health and disease
2012, Brain Research BulletinCitation Excerpt :No genetic association with geriatric depression was found in any BDNF polymorphism tested; however, they found that several haplotypes constructed by these polymorphisms were associated with geriatric depression. In 2006, Grünblatt et al. [45] tested the BDNF C270T genetic variant in a community-based cohort of 75-year-old inhabitants in a region of Vienna. They found no association between this BDNF polymorphism and any depressive symptoms.
Effects of BDNF polymorphisms on brain function and behavior in health and disease
2011, Brain Research BulletinCitation Excerpt :No genetic association with geriatric depression was found in any BDNF polymorphism tested; however, they found that several haplotypes constructed by these polymorphisms were associated with geriatric depression. In 2006, Grünblatt et al. [45] tested the BDNF C270T genetic variant in a community-based cohort of 75-year-old inhabitants in a region of Vienna. They found no association between this BDNF polymorphism and any depressive symptoms.
Genetic risk factors and markers for Alzheimer's disease and/or depression in the VITA study
2009, Journal of Psychiatric ResearchCitation Excerpt :From the last group of subjects we only have minimal information (failing information: MMSE, diagnosis of depression, CERAD, IDSR-7) (see Supplementary Table S1). As already described in previous studies, subjects were diagnosed and classified strictly according to the DSM-IV for depression (Grünblatt et al., 2006a; Grünblatt et al., 2006b). Questions regarding history of depressive episodes and age at onset of depressive disorder were derived from the SKID interview (Wittchen et al., 1997) the German translation of the SCID-I (First et al., 1997; Williams et al., 1992) which has excellent reliability (Zanarini and Frankenburg, 2001).
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