BDNF Val66Met polymorphism and hippocampal volume in neuropsychiatric disorders: A systematic review and meta-analysis

Neuroscience and Biobehavioral Reviews

Volumn 55, Issue , 2015, Pages 107-118

  Harrisberger, F ^a,b   Smieskova, R ^a,b   Schmidt, A ^a,b   Lenz, C ^a,b   Walter, A ^a,b   Wittfeld, K ^c   Grabe, H J ^c,d   Lang, U E ^a,b   Fusar Poli, P ^e,f   Borgwardt, S ^a,b,e  

^a UNIVERSITY OF BASEL   (Switzerland)

^b UNIVERSITY OF BASEL   (Switzerland)

^c GERMAN CENTER FOR NEURODEGENERATIVE DISEASES DZNE   (Germany)

^d UNIVERSITY MEDICINE GREIFSWALD   (Germany)

^e KING'S COLLEGE LONDON   (United Kingdom)

^f South London and Maudlsey   (United Kingdom)

Author keywords

Anxiety disorders; BDNF; BDNF Val66Met; Bipolar disorder; Brain derived neurotrophic factor; Depression; Hippocampus; Meta analysis; MRI; Neuropsychiatric patients; Rs6265; Schizophrenia; Structural

Indexed keywords

BRAIN DERIVED NEUROTROPHIC FACTOR; METHIONINE; VALINE;

ANXIETY DISORDER; BIPOLAR DISORDER; BRAIN SIZE; GENETIC ASSOCIATION; GENOTYPE; HETEROZYGOTE; HIPPOCAMPUS; HOMOZYGOTE; HUMAN; MAJOR DEPRESSION; NEUROPSYCHIATRY; PRIORITY JOURNAL; PSYCHOSIS; REVIEW; SCHIZOPHRENIA; SINGLE NUCLEOTIDE POLYMORPHISM; SYSTEMATIC REVIEW; GENETICS; MENTAL DISEASE; META ANALYSIS; PATHOLOGY;

BRAIN-DERIVED NEUROTROPHIC FACTOR; HIPPOCAMPUS; HUMANS; MENTAL DISORDERS; METHIONINE; POLYMORPHISM, SINGLE NUCLEOTIDE; VALINE;

EID: 84929300269     PISSN: 01497634     EISSN: 18737528     Source Type: Journal    
DOI: 10.1016/j.neubiorev.2015.04.017     Document Type: Review

References (115)

1. Aas M., Haukvik U.K., Djurovic S., Bergmann Ø., Athanasiu L., Tesli M.S., Hellvin T., Steen N.E., Agartz I., Lorentzen S., Sundet K., Andreassen O.A., Melle I. BDNF val66met modulates the association between childhood trauma, cognitive and brain abnormalities in psychoses. Prog. Neuro-Psychopharmacol. Biol. Psychiatry 2013, 46:181-188. 10.1016/j.pnpbp.2013.07.008.
2. Agartz I., Sedvall G.C., Terenius L., Kulle B., Frigessi A., Hall H., Jönsson E.G. BDNF gene variants and brain morphology in schizophrenia. Am. J. Med. Genet. B: Neuropsychiatr. Genet. 2006, 141B:513-523. 10.1002/ajmg.b.30338.
3. Baig B.J., Whalley H.C., Hall J., McIntosh A.M., Job D.E., Cunningham-Owens D.G., Johnstone E.C., Lawrie S.M. Functional magnetic resonance imaging of BDNF val66met polymorphism in unmedicated subjects at high genetic risk of schizophrenia performing a verbal memory task. Psychiatry Res.: Neuroimaging 2010, 183:195-201. 10.1016/j.pscychresns.2010.06.009.
4. Baj G., Carlino D., Gardossi L., Tongiorgi E. Toward a unified biological hypothesis for the BDNF Val66Met-associated memory deficits in humans: a model of impaired dendritic mRNA trafficking. Front Neurosci. 2013, 7:188. 10.3389/fnins.2013.00188.
5. Barde Y.-A. Trophic factors and neuronal survival. Neuron 1989, 2:1525-1534. 10.1016/0896-6273(89)90040-8.
6. Bora E., Yücel M., Pantelis C. Cognitive impairment in schizophrenia and affective psychoses: implications for DSM-V criteria and beyond. Schizophr. Bull. 2010, 36:36-42. 10.1093/schbul/sbp094.
7. Bourne C., Aydemir Ö., Balanzá-Martínez V., Bora E., Brissos S., Cavanagh J.T.O., Clark L., Cubukcuoglu Z., Dias V.V., Dittmann S., Ferrier I.N., Fleck D.E., Frangou S., Gallagher P., Jones L., Kieseppä T., Martínez-Aran A., Melle I., Moore P.B., Mur M., Pfennig A., Raust A., Senturk V., Simonsen C., Smith D.J., Bio D.S., Soeiro-de-Souza M.G., Stoddart S.D.R., Sundet K., Szöke A., Thompson J.M., Torrent C., Zalla T., Craddock N., Andreassen O.A., Leboyer M., Vieta E., Bauer M., Worhunsky P.D., Tzagarakis C., Rogers R.D., Geddes J.R., Goodwin G.M. Neuropsychological testing of cognitive impairment in euthymic bipolar disorder: an individual patient data meta-analysis. Acta Psychiatr. Scand. 2013, 128:149-162. 10.1111/acps.12133.
8. Buchmann A.F., Hellweg R., Rietschel M., Treutlein J., Witt S.H., Zimmermann U.S., Schmidt M.H., Esser G., Banaschewski T., Laucht M., Deuschle M. BDNF Val 66 Met and 5-HTTLPR genotype moderate the impact of early psychosocial adversity on plasma brain-derived neurotrophic factor and depressive symptoms: a prospective study. Eur. Neuropsychopharmacol. 2013, 23:902-909. 10.1016/j.euroneuro.2012.09.003.
9. Buehlmann E., Berger G.E., Aston J., Gschwandtner U., Pflueger M.O., Borgwardt S.J., Radue E.-W., Riecher-Rössler A. Hippocampus abnormalities in at risk mental states for psychosis?. A cross-sectional high resolution region of interest magnetic resonance imaging study. J. Psychiatr. Res. 2010, 44:447-453. 10.1016/j.jpsychires.2009.10.008.
10. Carballedo A., Morris D., Zill P., Fahey C., Reinhold E., Meisenzahl E., Bondy B., Gill M., Möller H.-J., Frodl T. Brain-derived neurotrophic factor Val66Met polymorphism and early life adversity affect hippocampal volume. Am. J. Med. Genet. 2013, 162:183-190. 10.1002/ajmg.b.32130.
11. Chen L., Lawlor D.A., Lewis S.J., Yuan W., Abdollahi M.R., Timpson N.J., Day I.N.M., Ebrahim S., Smith G.D., Shugart Y.Y. Genetic association study of BDNF in depression: Finding from two cohort studies and a meta-analysis. Am. J. Med. Genet. 2008, 147B:814-821. 10.1002/ajmg.b.30686.
12. Chen S.-P., Fuh J.-L., Wang S.-J., Tsai S.-J., Hong C.-J., Yang A.C. Brain-derived neurotrophic factor gene Val66Met polymorphism modulates reversible cerebral vasoconstriction syndromes. PLoS ONE 2011, 6:e18024. 10.1371/journal.pone.0018024.
13. Chen Z.-Y., Jing D., Bath K.G., Ieraci A., Khan T., Siao C.-J., Herrera D.G., Toth M., Yang C., McEwen B.S., Hempstead B.L., Lee F.S. Genetic variant BDNF (Val66Met) polymorphism alters anxiety-related behavior. Science 2006, 314:140-143. 10.1126/science.1129663.
14. Chen Z.-Y., Patel P.D., Sant G., Meng C.-X., Teng K.K., Hempstead B.L., Lee F.S. Variant brain-derived neurotrophic factor (BDNF) (Met66) alters the intracellular trafficking and activity-dependent secretion of wild-type BDNF in neurosecretory cells and cortical neurons. J. Neurosci. 2004, 24:4401-4411. 10.1523/JNEUROSCI.0348-04.2004.
15. Chepenik L.G., Fredericks C., Papademetris X., Spencer L., Lacadie C., Wang F., Pittman B., Duncan J.S., Staib L.H., Duman R.S., Gelernter J., Blumberg H.P. Effects of the brain-derived neurotrophic growth factor val66met variation on hippocampus morphology in bipolar disorder. Neuropsychopharmacology 2009, 34:944-951. 10.1038/npp.2008.107.
16. Choi M.-J., Kang R.-H., Lim S.-W., Oh K.-S., Lee M.-S. Brain-derived neurotrophic factor gene polymorphism (Val66Met) and citalopram response in major depressive disorder. Brain Res. 2006, 1118:176-182. 10.1016/j.brainres.2006.08.012.
17. Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 (updated March 2011) 2011, The Cochrane Collaboration, Available from www.cochrane-handbook.org (accessed 06.07.14). J.P.T. Higgins, S. Green (Eds.).
18. Cole J., Weinberger D.R., Mattay V.S., Cheng X., Toga A.W., Thompson P.M., Powell-Smith G., Cohen-Woods S., Simmons A., McGuffin P., Fu C.H.Y. No effect of 5HTTLPR or BDNF Val66Met polymorphism on hippocampal morphology in major depression. Genes Brain Behav. 2011, 10:756-764. 10.1111/j.1601-183X.2011.00714.x.
19. Comasco E., Hahn A., Ganger S., Gingnell M., Bannbers E., Oreland L., Wikström J., Epperson C.N., Lanzenberger R., Sundström-Poromaa I. Emotional fronto-cingulate cortex activation and brain derived neurotrophic factor polymorphism in premenstrual dysphoric disorder. Hum. Brain Mapp. 2014, 35:4450-4458. 10.1002/hbm.22486.
20. Cooper H., Hedges L.V., Valentine J.C. The Handbook of Research Synthesis and Meta-Analysis 2009, Russell Sage Foundation, New York, NY, USA. second ed.
21. Cunha A.B.M., Frey B.N., Andreazza A.C., Goi J.D., Rosa A.R., Gonçalves C.A., Santin A., Kapczinski F. Serum brain-derived neurotrophic factor is decreased in bipolar disorder during depressive and manic episodes. Neurosci. Lett. 2006, 398:215-219. 10.1016/j.neulet.2005.12.085.
22. Cunha C., Brambilla R., Thomas K.L. A simple role for BDNF in learning and memory?. Front. Mol. Neurosci. 2010, 3:1. 10.3389/neuro.02.001.2010.
23. DerSimonian R., Laird N. Meta-analysis in clinical trials. Control Clin Trials 1986, 7:177-188.
24. Dinacci D., Tessitore A., Russo A., De Bonis M.L., Lavorgna L., Picconi O., Sacco R., Bonavita S., Gallo A., Servillo G., Marcuccio L., Comerci M., Galletti P., Alfano B., Tedeschi G. BDNF Val66Met polymorphism and brain volumes in multiple sclerosis. Neurol. Sci. 2011, 32:117-123. 10.1007/s10072-010-0433-z.
25. Dmitrzak-Weglarz M., Rybakowski J.K., Suwalska A., Skibinska M., Leszczynska-Rodziewicz A., Szczepankiewicz A., Hauser J. Association studies of the BDNF and the NTRK2 gene polymorphisms with prophylactic lithium response in bipolar patients. Pharmacogenomics 2008, 9:1595-1603. 10.2217/14622416.9.11.1595.
26. Dutt A., McDonald C., Dempster E., Prata D., Shaikh M., Williams I., Schulze K., Marshall N., Walshe M., Allin M., Collier D., Murray R., Bramon E. The effect of COMT, BDNF 5-HTT, NRG1 and DTNBP1 genes on hippocampal and lateral ventricular volume in psychosis. Psychol. Med. 2009, 39:1783-1797. 10.1017/S0033291709990316.
27. Duval S., Tweedie R. Trim and fill: a simple funnel-plot-based method of testing and adjusting for publication bias in meta-analysis. Biometrics 2000, 56:455-463.
28. Egan M.F., Kojima M., Callicott J.H., Goldberg T.E., Kolachana B.S., Bertolino A., Zaitsev E., Gold B., Goldman D., Dean M., Lu B., Weinberger D.R. The BDNF val66met polymorphism affects activity-dependent secretion of BDNF and human memory and hippocampal function. Cell 2003, 112:257-269.
29. Egger M., Davey Smith G., Schneider M., Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ 1997, 315:629-634.
30. El-Hage W., Vourc'h P., Gaillard P., Léger J., Belzung C., Ibarguen-Vargas Y., Andres C.R., Camus V. The BDNF Val66Met polymorphism is associated with escitalopram response in depressed patients. Psychopharmacology 2014, 1-7. 10.1007/s00213-014-3694-z.
31. Faul F., Erdfelder E., Lang A.-G., Buchner A. G*Power 3: a flexible statistical power analysis program for the social, behavioral, and biomedical sciences. Behav. Res. Methods 2007, 39:175-191.
32. Fernandes B.S., Berk M., Turck C.W., Steiner J., Gonçalves C.-A. Decreased peripheral brain-derived neurotrophic factor levels are a biomarker of disease activity in major psychiatric disorders: a comparative meta-analysis. Mol. Psychiatry 2014, 19:750-751. 10.1038/mp.2013.172.
33. Fernandes B.S., Gama C.S., Ceresér K.M., Yatham L.N., Fries G.R., Colpo G., de Lucena D., Kunz M., Gomes F.A., Kapczinski F. Brain-derived neurotrophic factor as a state-marker of mood episodes in bipolar disorders: a systematic review and meta-regression analysis. J. Psychiatr. Res. 2011, 45:995-1004. 10.1016/j.jpsychires.2011.03.002.
34. Frodl T., Schüle C., Schmitt G., Born C., Baghai T., Zill P., Bottlender R., Rupprecht R., Bondy B., Reiser M., Möller H.-J., Meisenzahl E.M. Association of the brain-derived neurotrophic factor Val66Met polymorphism with reduced hippocampal volumes in major depression. Arch. Gen. Psychiatry 2007, 64:410-416. 10.1001/archpsyc.64.4.410.
35. Frodl T., Skokauskas N., Frey E.-M., Morris D., Gill M., Carballedo A. BDNFVal66Met genotype interacts with childhood adversity and influences the formation of hippocampal subfields. Hum. Brain Mapp. 2014, 35:5776-5783. 10.1002/hbm.22584.
36. Frustaci A., Pozzi G., Gianfagna F., Manzoli L., Boccia S. Meta-analysis of the brain-derived neurotrophic factor gene (BDNF) Val66Met polymorphism in anxiety disorders and anxiety-related personality traits. Neuropsychobiology 2008, 58:163-170. 10.1159/000182892.
37. Fusar-Poli P., Deste G., Smieskova R., Barlati S., Yung A.R., Howes O., Stieglitz R.-D., Vita A., McGuire P., Borgwardt S. Cognitive functioning in prodromal psychosis: a meta-analysis. Arch. Gen. Psychiatry 2012, 69:562-571. 10.1001/archgenpsychiatry.2011.1592.
38. Fusar-Poli P., Perez J., Broome M., Borgwardt S., Placentino A., Caverzasi E., Cortesi M., Veggiotti P., Politi P., Barale F., McGuire P. Neurofunctional correlates of vulnerability to psychosis: a systematic review and meta-analysis. Neurosci. Biobehav. Rev. 2007, 31:465-484. 10.1016/j.neubiorev.2006.11.006.
39. Gatt J.M., Nemeroff C.B., Dobson-Stone C., Paul R.H., Bryant R.A., Schofield P.R., Gordon E., Kemp A.H., Williams L.M. Interactions between BDNF Val66Met polymorphism and early life stress predict brain and arousal pathways to syndromal depression and anxiety. Mol. Psychiatry 2009, 14:681-695. 10.1038/mp.2008.143.
40. Gerritsen L., Tendolkar I., Franke B., Vasquez A.A., Kooijman S., Buitelaar J., Fernández G., Rijpkema M. BDNF Val66Met genotype modulates the effect of childhood adversity on subgenual anterior cingulate cortex volume in healthy subjects. Mol. Psychiatry 2012, 17:597-603. 10.1038/mp.2011.51.
41. Geuze E., Vermetten E., Bremner J.D. MR-based in vivo hippocampal volumetrics: 2. Findings in neuropsychiatric disorders. Mol. Psychiatry 2005, 10:160-184. 10.1038/sj.mp.4001579.
42. Gonul A.S., Kitis O., Eker M.C., Eker O.D., Ozan E., Coburn K. Association of the brain-derived neurotrophic factor Val66Met polymorphism with hippocampus volumes in drug-free depressed patients. World J. Biol. Psychiatry 2011, 12:110-118. 10.3109/15622975.2010.507786.
43. González-Castro T.B., Nicolini H., Lanzagorta N., López-Narváez L., Genis A., Pool García S., Tovilla-Zárate C.A. The role of brain-derived neurotrophic factor (BDNF) Val66Met genetic polymorphism in bipolar disorder: a case-control study, comorbidities, and meta-analysis of 16,786 subjects. Bipolar Disord. 2014, n/a-n/a. 10.1111/bdi.12227.
44. Grande I., Magalhães P.V.S., Chendo I., Stertz L., Fries G.R., Cereser K.M., Cunha Â.B.M., Gói P., Kunz M., Udina M., Martín-Santos R., Frey B.N., Vieta E., Kapczinski F. Val66Met polymorphism and serum brain-derived neurotrophic factor in bipolar disorder: an open-label trial. Acta Psychiatr. Scand. 2014, 129:393-400. 10.1111/acps.12192.
45. Gratacòs M., González J.R., Mercader J.M., de Cid R., Urretavizcaya M., Estivill X. Brain-derived neurotrophic factor Val66Met and psychiatric disorders: meta-analysis of case-control studies confirm association to substance-related disorders, eating disorders, and schizophrenia. Biol. Psychiatry 2007, 61:911-922. 10.1016/j.biopsych.2006.08.025.
46. Green M.J., Matheson S.L., Shepherd A., Weickert C.S., Carr V.J. Brain-derived neurotrophic factor levels in schizophrenia: a systematic review with meta-analysis. Mol. Psychiatry 2011, 16:960-972. 10.1038/mp.2010.88.
47. Gruber O., Hasan A., Scherk H., Wobrock T., Schneider-Axmann T., Ekawardhani S., Schmitt A., Backens M., Reith W., Meyer J., Falkai P. Association of the brain-derived neurotrophic factor val66met polymorphism with magnetic resonance spectroscopic markers in the human hippocampus: in vivo evidence for effects on the glutamate system. Eur. Arch. Psychiatry Clin. Neurosci. 2012, 262:23-31. 10.1007/s00406-011-0214-6.
48. Harrisberger F., Spalek K., Smieskova R., Schmidt A., Coynel D., Milnik A., Fastenrath M., Freytag V., Gschwind L., Walter A., Vogel T., Bendfeldt K., de Quervain D.J.-F., Papassotiropoulos A., Borgwardt S. The association of the BDNF Val66Met polymorphism and the hippocampal volumes in healthy humans: a joint meta-analysis of published and new data. Neurosci. Biobehav. Rev. 2014, 42:267-278. 10.1016/j.neubiorev.2014.03.011.
49. Higgins J.P.T., Thompson S.G. Quantifying heterogeneity in a meta-analysis. Stat. Med. 2002, 21:1539-1558. 10.1002/sim.1186.
50. Ho B.-C., Milev P., O'Leary D.S., Librant A., Andreasen N.C., Wassink T.H. Cognitive and magnetic resonance imaging brain morphometric correlates of brain-derived neurotrophic factor Val66Met gene polymorphism in patients with schizophrenia and healthy volunteers. Arch. Gen. Psychiatry 2006, 63:731-740. 10.1001/archpsyc.63.7.731.
51. Ho Beng-Choon, Andreasen Nancy, Dawson Jeffrey, Wassink Thomas Association between brain-derived neurotrophic factor Val66Met gene polymorphism and progressive brain volume changes in schizophrenia. Am. J. Psychiatry 2007, 164:1890-1899. 10.1176/appi.ajp.2007.05111903.
52. Honea R.A., Cruchaga C., Perea R.D., Saykin A.J., Burns J.M., Weinberger D.R., Goate A.M. Characterizing the role of brain derived neurotrophic factor genetic variation in Alzheimer's disease neurodegeneration. PLoS ONE 2013, 8:e76001. Alzheimer's Disease Neuroimaging Initiative (ADNI). 10.1371/journal.pone.0076001.
53. Hong C.-J., Yu Y.W.-Y., Lin C.-H., Tsai S.-J. An association study of a brain-derived neurotrophic factor Val66Met polymorphism and clozapine response of schizophrenic patients. Neurosci. Lett. 2003, 349:206-208. 10.1016/S0304-3940(03)00828-0.
54. Ioannidis J.P.A., Patsopoulos N.A., Evangelou E. Heterogeneity in meta-analyses of genome-wide association investigations. PLoS ONE 2007, 2:e841. 10.1371/journal.pone.0000841.
55. Jessen F., Schuhmacher A., von Widdern O., Guttenthaler V., Hofels S., Suliman H., Scheef L., Block W., Urbach H., Maier W., Zobel A. No association of the Val66Met polymorphism of the brain-derived neurotrophic factor with hippocampal volume in major depression. Psychiatr. Genet. 2009, 19:99-101. 10.1097/YPG.0b013e32832080ce.
56. Joffe R.T., Gatt J.M., Kemp A.H., Grieve S., Dobson-Stone C., Kuan S.A., Schofield P.R., Gordon E., Williams L.M. Brain derived neurotrophic factor Val66Met polymorphism, the five factor model of personality and hippocampal volume: implications for depressive illness. Hum. Brain Mapp. 2009, 30:1246-1256. 10.1002/hbm.20592.
57. Kambeitz J.P., Bhattacharyya S., Kambeitz-Ilankovic L.M., Valli I., Collier D.A., McGuire P. Effect of BDNF val(66)met polymorphism on declarative memory and its neural substrate: a meta-analysis. Neurosci. Biobehav. Rev. 2012, 36:2165-2177. 10.1016/j.neubiorev.2012.07.002.
58. Kanazawa T., Glatt S.J., Kia-Keating B., Yoneda H., Tsuang M.T. Meta-analysis reveals no association of the Val66Met polymorphism of brain-derived neurotrophic factor with either schizophrenia or bipolar disorder. Psychiatr. Genet. 2007, 17(June):165-170. 10.1097/YPG.0b013e32801da2e2.
59. Kandel E.R. The molecular biology of memory storage: a dialogue between genes and synapses. Science 2001, 294:1030-1038. 10.1126/science.1067020.
60. Kanellopoulos D., Gunning F.M., Morimoto S.S., Hoptman M.J., Murphy C.F., Kelly R.E., Glatt C., Lim K.O., Alexopoulos G.S. Hippocampal volumes and the BDNF val66met polymorphism in geriatric major depression. Am. J. Geriatr. Psychiatry 2011, 19:13-22.
61. Karege F., Perret G., Bondolfi G., Schwald M., Bertschy G., Aubry J.-M. Decreased serum brain-derived neurotrophic factor levels in major depressed patients. Psychiatry Res. 2002, 109:143-148. 10.1016/S0165-1781(02)00005-7.
62. Kempton M.J., Salvador Z., Munafò M.R., et al. Structural neuroimaging studies in major depressive disorder: meta-analysis and comparison with bipolar disorder. Arch. Gen. Psychiatry 2011, 68:675-690. 10.1001/archgenpsychiatry.2011.60.
63. Koolschijn P.C.M.P., van Haren N.E.M., Bakker S.C., Hoogendoorn M.L.C., Hulshoff Pol H.E., Kahn R.S. Effects of brain-derived neurotrophic factor Val66Met polymorphism on hippocampal volume change in schizophrenia. Hippocampus 2010, 20:1010-1017. 10.1002/hipo.20699.
64. Lang U.E., Borgwardt S. Molecular mechanisms of depression: perspectives on new treatment strategies. Cell. Physiol. Biochem. 2013, 31:761-777. 10.1159/000350094.
65. Lau J.Y.F., Goldman D., Buzas B., Hodgkinson C., Leibenluft E., Nelson E., Sankin L., Pine D.S., Ernst M. BDNF gene polymorphism (Val66Met) predicts amygdala and anterior hippocampus responses to emotional faces in anxious and depressed adolescents. NeuroImage: Imaging Genet. 2010, 53:952-961. 10.1016/j.neuroimage.2009.11.026.
66. Lee R., Kermani P., Teng K.K., Hempstead B.L. Regulation of cell survival by secreted proneurotrophins. Science 2001, 294:1945-1948. 10.1126/science.1065057.
67. Liguori M., Fera F., Patitucci A., Manna I., Condino F., Valentino P., Telarico P., Cerasa A., Gioia M.C., di Palma G., Quattrone A. A longitudinal observation of brain-derived neurotrophic factor mRNA levels in patients with relapsing-remitting multiple sclerosis. Brain Res. 2009, 1256:123-128. 10.1016/j.brainres.2008.11.047.
68. Lim Y.Y., Villemagne V.L., Laws S.M., Ames D., Pietrzak R.H., Ellis K.A., Harrington K., Bourgeat P., Bush A.I., Martins R.N., Masters C.L., Rowe C.C., Maruff P. Effect of BDNF Val66Met on memory decline and hippocampal atrophy in prodromal Alzheimer's disease: a preliminary study. PLoS ONE 2014, 9:e86498. AIBL Research Group. 10.1371/journal.pone.0086498.
69. Lin P.-Y. State-dependent decrease in levels of brain-derived neurotrophic factor in bipolar disorder: a meta-analytic study. Neurosci. Lett. 2009, 466:139-143. 10.1016/j.neulet.2009.09.044.
70. Lipsey M.W., Wilson D.B. Practical Meta-Analysis 2000, SAGE.
71. Lohoff F.w., Sander T., Ferraro T., Dahl n.J., Gallinat p.J., Berrettini W.h. Confirmation of association between the Val66Met polymorphism in the brain-derived neurotrophic factor (BDNF) gene and bipolar I disorder. Am. J. Med. Genet. 2005, 139B:51-53. 10.1002/ajmg.b.30215.
72. Marqués-Iturria I., Garolera M., Pueyo R., Segura B., Hernan I., García-García I., Sánchez-Garre C., Vernet-Vernet M., Sender-Palacios M.J., Narberhaus A., Ariza M., Junqué C., Jurado M.Á. The interaction effect between BDNF val66met polymorphism and obesity on executive functions and frontal structure. Am. J. Med. Genet. B: Neuropsychiatr. Genet. 2014, 165B:245-253. 10.1002/ajmg.b.32229.
73. McDonald R.J., Hong N.S. How does a specific learning and memory system in the mammalian brain gain control of behavior?. Hippocampus 2013, 23:1084-1102. 10.1002/hipo.22177.
74. Moher D., Liberati A., Tetzlaff J., Altman D.G. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Int. J. Surg. 2010, 8:336-341. 10.1016/j.ijsu.2010.02.007.
75. Molendijk M.L., Bus B.A.A., Spinhoven P., Kaimatzoglou A., Oude Voshaar R.C., Penninx B.W.J.H., van IJzendoorn M.H., Elzinga B.M. A systematic review and meta-analysis on the association between BDNF val(66)met and hippocampal volume-a genuine effect or a winners curse?. Am. J. Med. Genet. B: Neuropsychiatr. Genet. 2012, 159B:731-740. 10.1002/ajmg.b.32078.
76. Molendijk M.L., Spinhoven P., Polak M., Bus B.a.A., Penninx B.W.J.H., Elzinga B.M. Serum BDNF concentrations as peripheral manifestations of depression: evidence from a systematic review and meta-analyses on 179 associations (N=9484). Mol. Psychiatry 2014, 19:791-800. 10.1038/mp.2013.105.
77. Molendijk M.L., van Tol M.-J., Penninx B.W.J.H., van der Wee N.J.A., Aleman A., Veltman D.J., Spinhoven P., Elzinga B.M. BDNF val66met affects hippocampal volume and emotion-related hippocampal memory activity. Transl. Psychiatry 2012, 2:e74. 10.1038/tp.2011.72.
78. Mon A., Durazzo T.C., Gazdzinski S., Hutchison K.E., Pennington D., Meyerhoff D.J. Brain-derived neurotrophic factor genotype is associated with brain gray and white matter tissue volumes recovery in abstinent alcohol-dependent individuals. Genes Brain Behav. 2013, 12:98-107. 10.1111/j.1601-183X.2012.00854.x.
79. Niitsu T., Ishima T., Yoshida T., Hashimoto T., Matsuzawa D., Shirayama Y., Nakazato M., Shimizu E., Hashimoto K., Iyo M. A positive correlation between serum levels of mature brain-derived neurotrophic factor and negative symptoms in schizophrenia. Psychiatry Res. 2014, 215:268-273. 10.1016/j.psychres.2013.12.009.
80. Ninan I. Synaptic regulation of affective behaviors; role of BDNF. Neuropharmacology 2014, 76(Part C):684-695. (BDNF Regulation of Synaptic Structure, Function, and Plasticity). 10.1016/j.neuropharm.2013.04.011.
81. Ninan I., Bath K.G., Dagar K., Perez-Castro R., Plummer M.R., Lee F.S., Chao M.V. The BDNF Val66Met polymorphism impairs NMDA receptor-dependent synaptic plasticity in the hippocampus. J. Neurosci. 2010, 30:8866-8870. 10.1523/JNEUROSCI.1405-10.2010.
82. Numata S., Ueno S., Iga J., Yamauchi K., Hongwei S., Ohta K., Kinouchi S., Shibuya-Tayoshi S., Tayoshi S., Aono M., Kameoka N., Sumitani S., Tomotake M., Kaneda Y., Taniguchi T., Ishimoto Y., Ohmori T. Brain-derived neurotrophic factor (BDNF) Val66Met polymorphism in schizophrenia is associated with age at onset and symptoms. Neurosci. Lett. 2006, 401:1-5. 10.1016/j.neulet.2006.02.054.
83. Pan W., Banks W.A., Fasold M.B., Bluth J., Kastin A.J. Transport of brain-derived neurotrophic factor across the blood-brain barrier. Neuropharmacology 1998, 37:1553-1561.
84. Park H., Poo M. Neurotrophin regulation of neural circuit development and function. Nat. Rev. Neurosci. 2013, 14:7-23. 10.1038/nrn3379.
85. Perkovic M.N., Erjavec G.N., Zivkovic M., Sagud M., Uzun S., Mihaljevic-Peles A., Kozumplik O., Muck-Seler D., Pivac N. Association between the brain-derived neurotrophic factor Val66Met polymorphism and therapeutic response to olanzapine in schizophrenia patients. Psychopharmacology 2014, 231:3757-3764. 10.1007/s00213-014-3515-4.
86. Petryshen T.L., Sabeti P.C., Aldinger K.A., Fry B., Fan J.B., Schaffner S.F., Waggoner S.G., Tahl A.R., Sklar P. Population genetic study of the brain-derived neurotrophic factor (BDNF) gene. Mol. Psychiatry 2010, 15:810-815. 10.1038/mp.2009.24.
87. Pillai A., Kale A., Joshi S., Naphade N., Raju M.S.V.K., Nasrallah H., Mahadik S.P. Decreased BDNF levels in CSF of drug-naive first-episode psychotic subjects: correlation with plasma BDNF and psychopathology. Int. J. Neuropsychopharmacol. 2010, 13:535-539. 10.1017/S1461145709991015.
88. Preston A.R., Eichenbaum H. Interplay of hippocampus and prefrontal cortex in memory. Curr. Biol. 2013, 23:R764-R773. 10.1016/j.cub.2013.05.041.
89. Rabl U., Meyer B.M., Diers K., Bartova L., Berger A., Mandorfer D., Popovic A., Scharinger C., Huemer J., Kalcher K., Pail G., Haslacher H., Perkmann T., Windischberger C., Brocke B., Sitte H.H., Pollak D.D., Dreher J.-C., Kasper S., Praschak-Rieder N., Moser E., Esterbauer H., Pezawas L. Additive gene-environment effects on hippocampal structure in healthy humans. J. Neurosci. 2014, 34:9917-9926. 10.1523/JNEUROSCI.3113-13.2014.
90. Ramasamy D.P., Ramanathan M., Cox J.L., Antulov R., Weinstock-Guttman B., Bergsland N., Benedict R.H.B., Dwyer M.G., Minagar A., Zivadinov R. Effect of Met66 allele of the BDNF rs6265 SNP on regional gray matter volumes in patients with multiple sclerosis: a voxel-based morphometry study. Pathophysiology 2011, 18:53-60. 10.1016/j.pathophys.2010.04.006.
91. R Core Team R: A Language and Environment for Statistical Computing 2012, R Core Team.
92. Ricken R., Adli M., Lange C., Krusche E., Stamm T.J., Gaus S., Koehler S., Nase S., Bschor T., Richter C., Steinacher B., Heinz A., Rapp M.A., Borgwardt S., Hellweg R., Lang U.E. Brain-derived neurotrophic factor serum concentrations in acute depressive patients increase during lithium augmentation of antidepressants. J. Clin. Psychopharmacol. 2013, 33(December):806-809. 10.1097/JCP.0b013e3182a412b8.
93. Rosas-Vidal L.E., Do-Monte F.H., Sotres-Bayon F., Quirk G.J. Hippocampal-prefrontal BDNF and memory for fear extinction. Neuropsychopharmacology 2014, 39:2161-2169. 10.1038/npp.2014.64.
94. Rybakowski J.K., Suwalska A., Skibinska M., Szczepankiewicz A., Leszczynska-Rodziewicz A., Permoda A., Czerski P.M., Hauser J. Prophylactic lithium response and polymorphism of the brain-derived neurotrophic factor gene. Pharmacopsychiatry 2005, 38:166-170. 10.1055/s-2005-871239.
95. Schaefer J., Giangrande E., Weinberger D.R., Dickinson D. The global cognitive impairment in schizophrenia: consistent over decades and around the world. Schizophr. Res. 2013, 150:42-50. 10.1016/j.schres.2013.07.009.
96. Shepherd A.M., Laurens K.R., Matheson S.L., Carr V.J., Green M.J. Systematic meta-review and quality assessment of the structural brain alterations in schizophrenia. Neurosci. Biobehav. Rev. 2012, 36:1342-1356. 10.1016/j.neubiorev.2011.12.015.
97. Shimizu E., Hashimoto K., Iyo M. Ethnic difference of the BDNF 196G/A (val66met) polymorphism frequencies: the possibility to explain ethnic mental traits. Am. J. Med. Genet. 2004, 126B:122-123. 10.1002/ajmg.b.20118.
98. Shimizu E., Hashimoto K., Okamura N., Koike K., Komatsu N., Kumakiri C., Nakazato M., Watanabe H., Shinoda N., Okada S., Iyo M. Alterations of serum levels of brain-derived neurotrophic factor (BDNF) in depressed patients with or without antidepressants. Biol. Psychiatry 2003, 54:70-75. 10.1016/S0006-3223(03)00181-1.
99. Sklar P., Gabriel S.B., McInnis M.G., Bennett P., Lim Y.-M., Tsan G., Schaffner S., Kirov G., Jones I., Owen M., Craddock N., DePaulo J.R., Lander E.S. Family-based association study of 76 candidate genes in bipolar disorder: BDNF is a potential risk locus Brain-derived neutrophic factor. Mol. Psychiatry 2002, 7:579-593. 10.1038/sj.mp.4001058.
100. Smith G.N., Thornton A.E., Lang D.J., Macewan G.W., Ehmann T.S., Kopala L.C., Tee K., Shiau G., Voineskos A.N., Kennedy J.L., Honer W.G. Hippocampal volume and the brain-derived neurotrophic factor Val66Met polymorphism in first episode psychosis. Schizophr. Res. 2012, 134:253-259. 10.1016/j.schres.2011.11.022.
101. Snyder H.R. Major depressive disorder is associated with broad impairments on neuropsychological measures of executive function: a meta-analysis and review. Psychol. Bull. 2013, 139:81-132. 10.1037/a0028727.
102. Stein J.L., Medland S.E., Vasquez A.A., Hibar D.P., Senstad R.E., Winkler A.M., Toro R., Appel K., Bartecek R., Bergmann Ø., Bernard M., Brown A.A., Cannon D.M., Chakravarty M.M., Christoforou A., Domin M., Grimm O., Hollinshead M., Holmes A.J., Homuth G., Hottenga J.-J., Langan C., Lopez L.M., Hansell N.K., Hwang K.S., Kim S., Laje G., Lee P.H., Liu X., Loth E., Lourdusamy A., Mattingsdal M., Mohnke S., Maniega S.M., Nho K., Nugent A.C., O'Brien C., Papmeyer M., Pütz B., Ramasamy A., Rasmussen J., Rijpkema M., Risacher S.L., Roddey J.C., Rose E.J., Ryten M., Shen L., Sprooten E., Strengman E., Teumer A., Trabzuni D., Turner J., van Eijk K., van Erp T.G.M., van Tol M.-J., Wittfeld K., Wolf C., Woudstra S., Aleman A., Alhusaini S., Almasy L., Binder E.B., Brohawn D.G., Cantor R.M., Carless M.A., Corvin A., Czisch M., Curran J.E., Davies G., de Almeida M.A.A., Delanty N., Depondt C., Duggirala R., Dyer T.D., Erk S., Fagerness J., Fox P.T., Freimer N.B., Gill M., Göring H.H.H., Hagler D.J., Hoehn D., Holsboer F., Hoogman M., Hosten N., Jahanshad N., Johnson M.P., Kasperaviciute D., Kochunov J.W.K., Lancaster P., Lawrie J.L., Liewald S.M., Mandl D.C., Matarin R., Mattheisen M., Meisenzahl M., Melle E., Moses I., Mühleisen E.K., Nauck T.W., Nöthen M., Olvera M.M., Pandolfo R.L., Pike M., Puls G.B., Reinvang R., Rentería I., Rietschel M.E., Roffman M., Royle J.L., Rujescu N.A., Savitz D., Schnack J., Schnell H.G., Seiferth K., Smith N., Steen C., Valdés Hernández V.M., Van den Heuvel M.C., van der Wee M., Van Haren N.J., Veltman N.E.M., Völzke J.A., Walker H., Westlye R., Whelan L.T., Agartz C.D., Boomsma I., Cavalleri D.I., Dale G.L., Djurovic A.M., Drevets S., Hagoort W.C., Hall P., Heinz A., Foroud C.R.J., Le Hellard T.M., Macciardi S., Montgomery F., Poline G.W., Porteous J.B., Sisodiya D.J., Starr S.M., Sussmann J.M., Toga J.A.W., Veltman D.J., Walter H., Bis J.C., Ikram M.A., Smith A.V., Gudnason V., Tzourio C., Vernooij M.W., Launer L.J., DeCarli C., Seshadri S., EPIGEN Consortium, IMAGEN Consortium, Saguenay Youth Study Group, Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium (CHARGE) Identification of common variants associated with human hippocampal and intracranial volumes. Nat. Genet. 2012, 44:552-561. Alzheimer's Disease Neuroimaging Initiative. 10.1038/ng.2250.
103. Szeszko P.R., Lipsky R., Mentschel C., Robinson D., Gunduz-Bruce H., Sevy S., Ashtari M., Napolitano B., Bilder R.M., Kane J.M., Goldman D., Malhotra A.K. Brain-derived neurotrophic factor val66met polymorphism and volume of the hippocampal formation. Mol. Psychiatry 2005, 10:631-636. 10.1038/sj.mp.4001656.
104. Takahashi T., Suzuki M., Tsunoda M., Kawamura Y., Takahashi N., Tsuneki H., Kawasaki Y., Zhou S.-Y., Kobayashi S., Sasaoka T., Seto H., Kurachi M., Ozaki N. Association between the brain-derived neurotrophic factor Val66Met polymorphism and brain morphology in a Japanese sample of schizophrenia and healthy comparisons. Neurosci. Lett. 2008, 435:34-39. 10.1016/j.neulet.2008.02.004.
105. Tsai S.-J., Cheng C.-Y., Yu Y.W.-Y., Chen T.-J., Hong C.-J. Association study of a brain-derived neurotrophic-factor genetic polymorphism and major depressive disorders, symptomatology, and antidepressant response. Am. J. Med. Genet. 2003, 123B:19-22. 10.1002/ajmg.b.20026.
106. Verhagen M., van der Meij A., van Deurzen P.A.M., Janzing J.G.E., Arias-Vásquez A., Buitelaar J.K., Franke B. Meta-analysis of the BDNF Val66Met polymorphism in major depressive disorder: effects of gender and ethnicity. Mol. Psychiatry 2008, 15:260-271. 10.1038/mp.2008.109.
107. Viechtbauer W., Cheung M.W.-L. Outlier and influence diagnostics for meta-analysis. Res. Synth. Method 2010, 1:112-125. 10.1002/jrsm.11.
108. Voineskos A.N., Lerch J.P., Felsky D., Shaikh S., Rajji T.K., Miranda D., Lobaugh N.J., Mulsant B.H., Pollock B.G., Kennedy J.L. The brain-derived neurotrophic factor Val66Met polymorphism and prediction of neural risk for Alzheimer disease. Arch. Gen. Psychiatry 2011, 68:198-206. 10.1001/archgenpsychiatry.2010.194.
109. Weinstock-Guttman B., Zivadinov R., Tamaño-Blanco M., Abdelrahman N., Badgett D., Durfee J., Hussein S., Feichter J., Patrick K., Benedict R., Ramanathan M. Immune cell BDNF secretion is associated with white matter volume in multiple sclerosis. J. Neuroimmunol. 2007, 188:167-174. 10.1016/j.jneuroim.2007.06.003.
110. Wells G., Shea B., O'Connell D., Peterson J., Welch V., Losos M., Tugwell P. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses 2014, (accessed 6.7.14) [WWW Document].
111. Wolfgang Viechtbauer Conducting meta-analyses in {R} with the {metafor} package. J. Stat. Softw. 2010, 36:1-48.
112. Xu M., Li S., Xing Q., Gao R., Feng G., Lin Z., St Clair D., He L. Genetic variants in the BDNF gene and therapeutic response to risperidone in schizophrenia patients: a pharmacogenetic study. Eur. J. Hum. Genet. 2010, 18:707-712. 10.1038/ejhg.2009.238.
113. Zai G.C.M., Zai C.C.H., Chowdhury N.I., Tiwari A.K., Souza R.P., Lieberman J.A., Meltzer H.Y., Potkin S.G., Müller D.J., Kennedy J.L. The role of brain-derived neurotrophic factor (BDNF) gene variants in antipsychotic response and antipsychotic-induced weight gain. Prog. Neuro-Psychopharmacol. Biol. Psychiatry 2012, 39:96-101. 10.1016/j.pnpbp.2012.05.014.
114. Zivadinov R., Weinstock-Guttman B., Benedict R., Tamaño-Blanco M., Hussein S., Abdelrahman N., Durfee J., Ramanathan M. Preservation of gray matter volume in multiple sclerosis patients with the Met allele of the rs6265 (Val66Met) SNP of brain-derived neurotrophic factor. Hum. Mol. Genet. 2007, 16:2659-2668. 10.1093/hmg/ddm189.
115. Zou Y.-F., Ye D.-Q., Feng X.-L., Su H., Pan F.-M., Liao F.-F. Meta-analysis of BDNF Val66Met polymorphism association with treatment response in patients with major depressive disorder. Eur. Neuropsychopharmacol. 2010, 20:535-544. 10.1016/j.euroneuro.2009.12.005.