Glial cell-derived neurotrophic factor and other neurotrophins have an important role in the development of mental disorders. Here, we aim to assess the effects of single nucleotide polymorphisms at potentially regulated regions of GDNF on the severity and functionality of bipolar disorders and GDNF serum levels in bipolar disorder patients and healthy volunteers. Severity and functionality of bipolar disorders were evaluated using the Clinical Global Impression and Global Assessment of Functioning scales in sixty-six bipolar disorder patients. The GDNF serum levels obtained from bipolar disorder patients and healthy volunteers who had reported SNPs information by our group. GAF scales were lower and GDNF serum levels were higher in bipolar disorder patients with T/A genotype at 5:37812784 and 5:37812782 compared to patients with T/T genotype. There were significant differences in severity and functionality scores, but not in GDNF serum levels, between patients with G/G and G/A genotype of rs62360370 G > A SNP.rs2075680 C > A and rs79669773 T > C SNPs had no effect on bipolar disorder severity and functionality scores and GDNF serum levels. The results suggest that some SNPs of GDNF have potential association with severity and functionality of bipolar disorder. In addition, except two SNPs, none of GDNF SNPs were associated with GDNF serum levels.
AasI.H., Guidelines for rating Global Assessment of Functioning (GAF), Ann Gen Psychiatry10 (2011), 2.
2.
AiraksinenM.S. and SaarmaM., The GDNF family: Signalling, biological functions and therapeutic value, Nat Rev Neurosci3(5) (2002), 383–394. doi:10.1038/nrn812.
3.
BarbosaI.G., HuguetR.B., SousaL.P., AbreuM.N., RochaN.P., BauerM.E., CarvalhoL.A. and TeixeiraA.L., Circulating levels of GDNF in bipolar disorder, Neurosci Lett502(2) (2011), 103–106. doi:10.1016/j.neulet.2011.07.031.
4.
BarnettJ.H. and SmollerJ.W., The genetics of bipolar disorder, Neuroscience164(1) (2009), 331–343. doi:10.1016/j.neuroscience.2009.03.080.
5.
BarrettL.W., FletcherS. and WiltonS.D., Regulation of eukaryotic gene expression by the untranslated gene regions and other non-coding elements, Cell Mol Life Sci69(21) (2012), 3613–3634. doi:10.1007/s00018-012-0990-9.
6.
BorroniB., ArchettiS., CostanziC., GrassiM., FerrariM., RadeghieriA., CaimiL., CaltagironeC., Di LucaM. and PadovaniA., Role of BDNF Val66Met functional polymorphism in Alzheimer's disease-related depression, Neurobiol Aging30(9) (2009), 1406–1412. doi:10.1016/j.neurobiolaging.2007.11.023.
7.
BusnerJ. and TargumS.D., The clinical global impressions scale: Applying a research tool in clinical practice, Psychiatry (Edgmont)4(7) (2007), 28–37.
8.
ChaoH.M., KaoH.T. and PortonB., BDNF Val66Met variant and age of onset in schizophrenia, Am J Med Genet B Neuropsychiatr Genet147b(4) (2008), 505–506. doi:10.1002/ajmg.b.30619.
9.
EganM.F., KojimaM., CallicottJ.H., GoldbergT.E., KolachanaB.S., BertolinoA., ZaitsevE., GoldB., GoldmanD., DeanM., LuB. and WeinbergerD.R., The BDNF val66met polymorphism affects activity-dependent secretion of BDNF and human memory and hippocampal function, Cell112(2) (2003), 257–269. doi:10.1016/S0092-8674(03)00035-7.
10.
EnochM.A., WhiteK.V., WaheedJ. and GoldmanD., Neurophysiological and genetic distinctions between pure and comorbid anxiety disorders, Depress Anxiety25(5) (2008), 383–392. doi:10.1002/da.20378.
11.
FirstM.B., SpitzerR.L., GibbonM. and WilliamsJ.B.W., Structured Clinical Interview for DSM-IV-TR Axis I Disorders, Research Version, Biometrics Research, New York, 2002.
12.
GibsonG., Rare and common variants: Twenty arguments, Nat Rev Genet13(2) (2012), 135–145. doi:10.1038/nrg3118.
13.
GoodwinF.K. and JamisonK.R., Manic-Depressive Illness: Bipolar Disorders and Recurrent Depression, Oxford University Press, Oxford, USA, 2007.
14.
HemmingsS.M., KinnearC.J., Van der MerweL., LochnerC., CorfieldV.A., Moolman-SmookJ.C. and SteinD.J., Investigating the role of the brain-derived neurotrophic factor (BDNF) val66met variant in obsessive-compulsive disorder (OCD), World J Biol Psychiatry9(2) (2008), 126–134. doi:10.1080/15622970701245003.
15.
HoB.C., AndreasenN.C., DawsonJ.D. and WassinkT.H., Association between brain-derived neurotrophic factor Val66Met gene polymorphism and progressive brain volume changes in schizophrenia, Am J Psychiatry164(12) (2007), 1890–1899. doi:10.1176/appi.ajp.2007.05111903.
16.
JiaoY., ChenR., KeX., ChengL., ChuK., LuZ. and HerskovitsE.H., Single nucleotide polymorphisms predict symptom severity of autism spectrum disorder, J Autism Dev Disord42(6) (2012), 971–983. doi:10.1007/s10803-011-1327-5.
KotyukE., NemethN., HalmaiZ., FaludiG., Sasvari-SzekelyM. and SzekelyA., Association between mood characteristics and polymorphisms of glial cell line-derived neurotrophic factor (GNDF) in patients with depression, Neuropsychopharmacol Hung15(2) (2013), 63–72.
19.
McIntoshA.M., MoorheadT.W., McKirdyJ., SussmannJ.E., HallJ., JohnstoneE.C. and LawrieS.M., Temporal grey matter reductions in bipolar disorder are associated with the BDNF Val66Met polymorphism, Mol Psychiatry. England.12 (2007), 902–903. doi:10.1038/sj.mp.4002044.
20.
MullerD.J., de LucaV., SicardT., KingN., StraussJ. and KennedyJ.L., Brain-derived neurotrophic factor (BDNF) gene and rapid-cycling bipolar disorder: Family-based association study, Br J Psychiatry189 (2006), 317–323. doi:10.1192/bjp.bp.105.010587.
21.
NibuyaM., TakahashiM., RussellD.S. and DumanR.S., Repeated stress increases catalytic TrkB mRNA in rat hippocampus, Neurosci Lett267(2) (1999), 81–84. doi:10.1016/S0304-3940(99)00335-3.
22.
NunkesserR., BernholtT., SchwenderH., IckstadtK. and WegenerI., Detecting high-order interactions of single nucleotide polymorphisms using genetic programming, Bioinformatics23(24) (2007), 3280–3288. doi:10.1093/bioinformatics/btm522.
23.
OtsukiK., UchidaS., WatanukiT., WakabayashiY., FujimotoM., MatsubaraT., FunatoH. and WatanabeY., Altered expression of neurotrophic factors in patients with major depression, J Psychiatr Res42(14) (2008), 1145–1153. doi:10.1016/j.jpsychires.2008.01.010.
24.
PichonX., WilsonL.A., StoneleyM., BastideA., KingH.A., SomersJ. and WillisA.E., RNA binding protein/RNA element interactions and the control of translation, Curr Protein Pept Sci13(4) (2012), 294–304. doi:10.2174/138920312801619475.
25.
RosaA.R., FreyB.N., AndreazzaA.C., CereserK.M., CunhaA.B., QuevedoJ., SantinA., GottfriedC., GoncalvesC.A., VietaE. and KapczinskiF., Increased serum glial cell line-derived neurotrophic factor immunocontent during manic and depressive episodes in individuals with bipolar disorder, Neurosci Lett407(2) (2006), 146–150. doi:10.1016/j.neulet.2006.08.026.
26.
SafariR., SalimiR., TuncaZ., OzerdemA., CeylanD. and SakizliM., Mutation/SNP analysis in EF-hand calcium binding domain of mitochondrial CA2+ uptake 1 gene in bipolar disorder patients, J Integr Neurosci15(2) (2016), 163–173. doi:10.1142/S0219635216500096.
27.
SafariR., TuncaZ., OzerdemA., CeylanD., YaziciogluC.E. and SakizliM., New alterations at potentially regulated regions of the Glial Derived Neurotrophic Factor gene in bipolar disorder, J Affect Disord167 (2014), 244–250. doi:10.1016/j.jad.2014.06.002.
28.
SchloesserR.J., HuangJ., KleinP.S. and ManjiH.K., Cellular plasticity cascades in the pathophysiology and treatment of bipolar disorder, Neuropsychopharmacology33(1) (2008), 110–133. doi:10.1038/sj.npp.1301575.
29.
SchwenderH., IckstadtK. and RahnenfuhrerJ., Classification with high-dimensional genetic data: Assigning patients and genetic features to known classes, Biom J50(6) (2008), 911–926. doi:10.1002/bimj.200810475.
30.
ShiY.Y. and HeL., SHEsis, a powerful software platform for analyses of linkage disequilibrium, haplotype construction, and genetic association at polymorphism loci, Cell Res15(2) (2005), 97–98. doi:10.1038/sj.cr.7290272.
31.
TakebayashiM., HisaokaK., NishidaA., TsuchiokaM., MiyoshiI., KozuruT., HikasaS., OkamotoY., ShinnoH., MorinobuS. and YamawakiS., Decreased levels of whole blood glial cell line-derived neurotrophic factor (GDNF) in remitted patients with mood disorders, Int J Neuropsychopharmacol9(5) (2006), 607–612. doi:10.1017/S1461145705006085.
32.
TuncaZ., BaynM., AlknT., OzerdemA., ResmiH. and AkanP., A Preliminary Observation of Increased Glial Cell Line-Derived Neurotrophic Factor in Manic Switch due to Electroconvulsive Treatment in Depressive Patients, J ect31(3) (2015), 167–172. doi:10.1097/YCT.0000000000000198.
33.
TuncaZ., OzerdemA., CeylanD., YalcinY., CanG., ResmiH., AkanP., ErgorG., AydemirO., CengisizC. and KerimD., Alterations in BDNF (brain derived neurotrophic factor) and GDNF (glial cell line-derived neurotrophic factor) serum levels in bipolar disorder: The role of lithium, J Affect Disord166 (2014), 193–200. doi:10.1016/j.jad.2014.05.012.
34.
WangX., HouZ., YuanY., HouG., LiuY., LiH. and ZhangZ., Association study between plasma GDNF and cognitive function in late-onset depression, J Affect Disord132(3) (2011), 418–421. doi:10.1016/j.jad.2011.03.043.
35.
WestA.E., PruunsildP. and TimmuskT., Neurotrophins: Transcription and translation, Handb Exp Pharmacol220 (2014), 67–100. doi:10.1007/978-3-642-45106-5_4.
36.
ZeevB.B., BebbingtonA., HoG., LeonardH., de KlerkN., GakE., VecslerM. and ChristodoulouJ., The common BDNF polymorphism may be a modifier of disease severity in Rett syndrome, Neurology72(14) (2009), 1242–1247. doi:10.1212/01.wnl.0000345664.72220.6a.
37.
ZhangX., ZhangZ., ShaW., XieC., XiG., ZhouH. and ZhangY., Effect of treatment on serum glial cell line-derived neurotrophic factor in bipolar patients, J Affect Disord126(1–2) (2010), 326–329. doi:10.1016/j.jad.2010.03.003.
