Abstract
Glial cell line-derived neurotrophic factor (GDNF) is a neurotrophic factor for dopaminergic neurons with promising therapeutic potential in Parkinson's disease. A few association analyses between GDNF gene polymorphisms and psychiatric disorders such as schizophrenia, attention deficit hyperactivity disorder and drug abuse have also been published but little is known about any effects of these polymorphisms on mood characteristics such as anxiety and depression. Here we present an association study between eight (rs1981844, rs3812047, rs3096140, rs2973041, rs2910702, rs1549250, rs2973050 and rs11111) GDNF single nucleotide polymorphisms (SNPs) and anxiety and depression scores measured by the Hospital Anxiety and Depression Scale (HADS) on 708 Caucasian young adults with no psychiatric history. Results of the allele-wise single marker association analyses provided significant effects of two single nucleotide polymorphisms on anxiety scores following the Bonferroni correction for multiple testing (p = 0.00070 and p = 0.00138 for rs3812047 and rs3096140, respectively), while no such result was obtained on depression scores. Haplotype analysis confirmed the role of these SNPs; mean anxiety scores raised according to the number of risk alleles present in the haplotypes (p = 0.00029). A significant sex-gene interaction was also observed since the effect of the rs3812047 A allele as a risk factor of anxiety was more pronounced in males. In conclusion, this is the first demonstration of a significant association between the GDNF gene and mood characteristics demonstrated by the association of two SNPs of the GDNF gene (rs3812047 and rs3096140) and individual variability of anxiety using self-report data from a non-clinical sample.
Highlights
Glial cell line-derived neurotrophic factor (GDNF), a member of the TGFb superfamily that signals via cell-surface tyrosine kinase receptors, is considered an essential neuroprotective ligand for midbrain dopaminergic neurons [1] with promising clinical trials in Parkinson’s disease [2]
Here we present an association analysis between eight single nucleotide polymorphisms (SNPs) of the GDNF gene and mood characteristics assessed by the Hospital Anxiety and Depression Scale (HADS) questionnaire using data from 708 healthy Caucasians
Genotype frequencies of GDNF SNPs were similar in the subgroups, the total sample was used for association analyses
Summary
Glial cell line-derived neurotrophic factor (GDNF), a member of the TGFb superfamily that signals via cell-surface tyrosine kinase receptors, is considered an essential neuroprotective ligand for midbrain dopaminergic neurons [1] with promising clinical trials in Parkinson’s disease [2]. Analysis of GDNF level changes in depressive disorders revealed contradictory results. Both elevated [11,12] and reduced [13,14] GDNF plasma concentrations have been reported in patients with late-onset depression, major depression or bipolar disorder. Antidepressants and electroconvulsive therapy seemed to enhance rat hippocampal [15] and human plasma GDNF levels [16,17] possibly via altered epigenetic regulation of the GDNF promoter [18]. A recent post mortem analysis of human brain samples disclosed elevated GDNF protein levels in the parietal cortex but not in limbic areas and basal ganglia of patients with depressive disorder [19]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
