Oxidatively-induced DNA base damage and base excision repair abnormalities in siblings of individuals with bipolar disorder DNA damage and repair in bipolar disorder.


Journal

Translational psychiatry
ISSN: 2158-3188
Titre abrégé: Transl Psychiatry
Pays: United States
ID NLM: 101562664

Informations de publication

Date de publication:
24 May 2024
Historique:
received: 17 08 2023
accepted: 05 04 2024
revised: 01 04 2024
medline: 25 5 2024
pubmed: 25 5 2024
entrez: 24 5 2024
Statut: epublish

Résumé

Previous evidence suggests elevated levels of oxidatively-induced DNA damage, particularly 8-hydroxy-2'-deoxyguanosine (8-OH-dG), and abnormalities in the repair of 8-OH-dG by the base excision repair (BER) in bipolar disorder (BD). However, the genetic disposition of these abnormalities remains unknown. In this study, we aimed to investigate the levels of oxidatively-induced DNA damage and BER mechanisms in individuals with BD and their siblings, as compared to healthy controls (HCs). 46 individuals with BD, 41 siblings of individuals with BD, and 51 HCs were included in the study. Liquid chromatography-tandem mass spectrometry was employed to evaluate the levels of 8-OH-dG in urine, which were then normalized based on urine creatinine levels. The real-time-polymerase chain reaction was used to measure the expression levels of 8-oxoguanine DNA glycosylase 1 (OGG1), apurinic/apyrimidinic endonuclease 1 (APE1), poly ADP-ribose polymerase 1 (PARP1), and DNA polymerase beta (POLβ). The levels of 8-OH-dG were found to be elevated in both individuals with BD and their siblings when compared to the HCs. The OGG1 and APE1 expressions were downregulated, while POLβ expressions were upregulated in both the patient and sibling groups compared to the HCs. Age, smoking status, and the number of depressive episodes had an impact on APE1 expression levels in the patient group while body mass index, smoking status, and past psychiatric history had an impact on 8-OH-dG levels in siblings. Both individuals with BD and unaffected siblings presented similar abnormalities regarding oxidatively-induced DNA damage and BER, suggesting a link between abnormalities in DNA damage/BER mechanisms and familial susceptibility to BD. Our findings suggest that targeting the oxidatively-induced DNA damage and BER pathway could offer promising therapeutic strategies for reducing the risk of age-related diseases and comorbidities in individuals with a genetic predisposition to BD.

Identifiants

pubmed: 38789433
doi: 10.1038/s41398-024-02901-3
pii: 10.1038/s41398-024-02901-3
doi:

Substances chimiques

DNA Glycosylases EC 3.2.2.-
oxoguanine glycosylase 1, human EC 3.2.2.-
8-Hydroxy-2'-Deoxyguanosine 88847-89-6
DNA Polymerase beta EC 2.7.7.7
DNA-(Apurinic or Apyrimidinic Site) Lyase EC 4.2.99.18
Deoxyguanosine G9481N71RO
APEX1 protein, human EC 4.2.99.18

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

207

Informations de copyright

© 2024. The Author(s).

Références

Fries GR, Zamzow MJ, Andrews T, Pink O, Scaini G, Quevedo J. Accelerated aging in bipolar disorder: a comprehensive review of molecular findings and their clinical implications. Neurosci Biobehav Rev. 2020;112:107–16.
pubmed: 32018037 doi: 10.1016/j.neubiorev.2020.01.035
Jorgensen A, Baago IB, Rygner Z, Jorgensen MB, Andersen PK, Kessing LV, et al. Association of oxidative stress-induced nucleic acid damage with psychiatric disorders in adults: a systematic review and meta-analysis. JAMA Psychiatry. 2022;79:920–31.
pubmed: 35921094 pmcid: 9350850 doi: 10.1001/jamapsychiatry.2022.2066
Goh XX, Tang PY, Tee SF. 8-Hydroxy-2’-Deoxyguanosine and reactive oxygen species as biomarkers of oxidative stress in mental illnesses: a meta-analysis. Psychiatry Investig. 2021;18:603–18.
pubmed: 34340273 pmcid: 8328836 doi: 10.30773/pi.2020.0417
Arat Çelik HE, Tuna G, Ceylan D, Küçükgöncü S. A comparative meta-analysis of peripheral 8-hydroxy-2’-deoxyguanosine (8-OHdG) or 8-oxo-7,8-dihydro-2’-deoxyguanosine (8-oxo-dG) levels across mood episodes in bipolar disorder. Psychoneuroendocrinology. 2023;151:106078.
doi: 10.1016/j.psyneuen.2023.106078
Atamna H, Cheung I, Ames BN. A method for detecting abasic sites in living cells: age-dependent changes in base excision repair. Proc Natl Acad Sci USA. 2000;97:686–91.
pubmed: 10639140 pmcid: 15391 doi: 10.1073/pnas.97.2.686
Coppedè F, Migliore L. DNA repair in premature aging disorders and neurodegeneration. Curr Aging Sci. 2010;3:3–19.
pubmed: 20298165 doi: 10.2174/1874609811003010003
Berk M, Kapczinski F, Andreazza AC, Dean OM, Giorlando F, Maes M, et al. Pathways underlying neuroprogression in bipolar disorder: focus on inflammation, oxidative stress and neurotrophic factors. Neurosci Biobehav Rev. 2011;35:804–17.
pubmed: 20934453 doi: 10.1016/j.neubiorev.2010.10.001
McGorry P, Keshavan M, Goldstone S, Amminger P, Allott K, Berk M, et al. Biomarkers and clinical staging in psychiatry. World Psychiatry. 2014;13:211–23.
pubmed: 25273285 pmcid: 4219053 doi: 10.1002/wps.20144
Rizzo LB, Costa LG, Mansur RB, Swardfager W, Belangero SI, Grassi-Oliveira R, et al. The theory of bipolar disorder as an illness of accelerated aging: implications for clinical care and research. Neurosci Biobehav Rev. 2014;42:157–69.
pubmed: 24548785 doi: 10.1016/j.neubiorev.2014.02.004
Özerdem A, Ceylan D. Chapter 20 - DNA damage and repair mechanisms in bipolar disorder. In: Machado-Vieira R, Soares JC, editors. Biomarkers in Bipolar Disorders. Academic Press; 2022. p. 361–83.
Dizdaroglu M, Jaruga P, Birincioglu M, Rodriguez H. Free radical-induced damage to DNA: mechanisms and measurement. Free Radic Biol Med. 2002;32:1102–15.
pubmed: 12031895 doi: 10.1016/S0891-5849(02)00826-2
Dizdaroglu M. Oxidatively induced DNA damage: mechanisms, repair and disease. Cancer Lett. 2012;327:26–47.
pubmed: 22293091 doi: 10.1016/j.canlet.2012.01.016
Steenken S, Telo J, Novais H, Candeias L. One-electron-reduction potentials of pyrimidine bases, nucleosides, and nucleotides in aqueous solution. Consequences for DNA redox chemistry. J Am Chem Soc. 1992;114:4701–9.
doi: 10.1021/ja00038a037
Steenken S, Jovanovic SV. How easily oxidizable is DNA? One-electron reduction potentials of adenosine and guanosine radicals in aqueous solution. J Am Chem Soc. 1997;119:617–8.
doi: 10.1021/ja962255b
Ceylan D, Scola G, Tunca Z, Isaacs-Trepanier C, Can G, Andreazza AC, et al. DNA redox modulations and global DNA methylation in bipolar disorder: effects of sex, smoking and illness state. Psychiatry Res. 2018;261:589–96.
pubmed: 29407727 doi: 10.1016/j.psychres.2017.12.051
Huzayyin AA, Andreazza AC, Turecki G, Cruceanu C, Rouleau GA, Alda M, et al. Decreased global methylation in patients with bipolar disorder who respond to lithium. Int J Neuropsychopharmacol. 2014;17:561–9.
pubmed: 24345589 doi: 10.1017/S1461145713001569
Jacoby AS, Vinberg M, Poulsen HE, Kessing LV, Munkholm K. Increased DNA and RNA damage by oxidation in patients with bipolar I disorder. Transl Psychiatry. 2016;6:e867.
pubmed: 27505230 pmcid: 5022087 doi: 10.1038/tp.2016.141
Munkholm K, Poulsen HE, Kessing LV, Vinberg M. Elevated levels of urinary markers of oxidatively generated DNA and RNA damage in bipolar disorder. Bipolar Disord. 2015;17:257–68.
pubmed: 25118140 doi: 10.1111/bdi.12245
Ermis B, Sagaltici E, Unal A, Alici D, Ozyurt AB. Oxidative metabolism and oxidative DNA damage in bipolar disorder: there are no difference in acute and Euthymic state. Psychiatry Behav Sci. 2021;11:249.
doi: 10.5455/PBS.20210610075010
Lin C, Jin Y, Cheng S, Wang W. Association between APE1 ASP148GLU and colorectal cancer risk: a meta-analysis. Clin Investig Med. 2020;43:E24–34.
doi: 10.25011/cim.v43i4.34987
Wang Z, Gan L, Nie W, Geng Y. The OGG1 Ser326Cys polymorphism and the risk of esophageal cancer: a meta-analysis. Genet Test Mol Biomark. 2013;17:780–5.
doi: 10.1089/gtmb.2013.0224
Kumagae Y, Hirahashi M, Takizawa K, Yamamoto H, Gushima M, Esaki M, et al. Overexpression of MTH1 and OGG1 proteins in ulcerative colitis-associated carcinogenesis. Oncol Lett. 2018;16:1765–76.
pubmed: 30008864 pmcid: 6036322
Sampath H, Vartanian V, Rollins MR, Sakumi K, Nakabeppu Y, Lloyd RS. 8-Oxoguanine DNA glycosylase (OGG1) deficiency increases susceptibility to obesity and metabolic dysfunction. PLoS One 2012;7:e51697.
pubmed: 23284747 pmcid: 3524114 doi: 10.1371/journal.pone.0051697
Kucuker MU, Ozerdem A, Ceylan D, Cabello-Arreola A, Ho AMC, Joseph B, et al. The role of base excision repair in major depressive disorder and bipolar disorder. J Affect Disord. 2022;306:288–300.
pubmed: 35306122 doi: 10.1016/j.jad.2022.03.033
Ceylan D, Tuna G, Kirkali G, Tunca Z, Can G, Arat HE, et al. Oxidatively-induced DNA damage and base excision repair in euthymic patients with bipolar disorder. DNA Repair. 2018;65:64–72.
pubmed: 29626765 pmcid: 7243967 doi: 10.1016/j.dnarep.2018.03.006
Munkholm K, Peijs L, Vinberg M, Kessing LV. A composite peripheral blood gene expression measure as a potential diagnostic biomarker in bipolar disorder. Transl Psychiatry. 2015;5:e614.
pubmed: 26241352 pmcid: 4564565 doi: 10.1038/tp.2015.110
Ceylan D, Yılmaz S, Tuna G, Kant M, Er A, Ildız A, et al. Alterations in levels of 8-Oxo-2’-deoxyguanosine and 8-Oxoguanine DNA glycosylase 1 during a current episode and after remission in unipolar and bipolar depression. Psychoneuroendocrinology. 2020;114:104600.
pubmed: 32062372 doi: 10.1016/j.psyneuen.2020.104600
Cai L, Fu Y, Zhang Y. APE1 Asp148Glu polymorphism and lung cancer susceptibility. Tumour Biol. 2014;35:5237–44.
pubmed: 24523018 doi: 10.1007/s13277-014-1681-y
Czarny P, Kwiatkowski D, Toma M, Kubiak J, Sliwinska A, Talarowska M, et al. Impact of single nucleotide polymorphisms of base excision repair genes on DNA damage and efficiency of DNA repair in recurrent depression disorder. Mol Neurobiol. 2017;54:4150–9.
pubmed: 27324896 doi: 10.1007/s12035-016-9971-6
Hoeijmakers JH. Genome maintenance mechanisms for preventing cancer. Nature 2001;411:366–74.
pubmed: 11357144 doi: 10.1038/35077232
Howes TR, Tomkinson AE. DNA ligase I, the replicative DNA ligase. Subcell Biochem. 2012;62:327–41.
pubmed: 22918593 doi: 10.1007/978-94-007-4572-8_17
Lillenes MS, Støen M, Gómez-Muñoz M, Torp R, Günther CC, Nilsson LN, et al. Transient OGG1, APE1, PARP1 and Polβ expression in an Alzheimer’s disease mouse model. Mech Ageing Dev. 2013;134:467–77.
pubmed: 24121118 doi: 10.1016/j.mad.2013.09.002
Sliwinska A, Sitarek P, Toma M, Czarny P, Synowiec E, Krupa R, et al. Decreased expression level of BER genes in Alzheimer’s disease patients is not derivative of their DNA methylation status. Prog Neuropsychopharmacol Biol Psychiatry. 2017;79:311–6.
pubmed: 28710029 doi: 10.1016/j.pnpbp.2017.07.010
Ahmadimanesh M, Abbaszadegan MR, Morshedi Rad D, Moallem SA, Mohammadpour AH, Ghahremani MH, et al. Effects of selective serotonin reuptake inhibitors on DNA damage in patients with depression. J Psychopharmacol. 2019;33:1364–76.
pubmed: 31556787 doi: 10.1177/0269881119874461
Almeida KH, Sobol RW. A unified view of base excision repair: lesion-dependent protein complexes regulated by post-translational modification. DNA Repair. 2007;6:695–711.
pubmed: 17337257 pmcid: 1995033 doi: 10.1016/j.dnarep.2007.01.009
Fotiadou P, Henegariu O, Sweasy JB. DNA polymerase beta interacts with TRF2 and induces telomere dysfunction in a murine mammary cell line. Cancer Res. 2004;64:3830–7.
pubmed: 15172990 doi: 10.1158/0008-5472.CAN-04-0136
Kidane D, Jonason AS, Gorton TS, Mihaylov I, Pan J, Keeney S, et al. DNA polymerase beta is critical for mouse meiotic synapsis. EMBO J. 2010;29:410–23.
pubmed: 20019666 doi: 10.1038/emboj.2009.357
Ray S, Breuer G, DeVeaux M, Zelterman D, Bindra R, Sweasy JB. DNA polymerase beta participates in DNA End-joining. Nucleic Acids Res. 2018;46:242–55.
pubmed: 29161447 doi: 10.1093/nar/gkx1147
Horton JK, Srivastava DK, Zmudzka BZ, Wilson SH. Strategic down-regulation of DNA polymerase beta by antisense RNA sensitizes mammalian cells to specific DNA damaging agents. Nucleic Acids Res. 1995;23:3810–5.
pubmed: 7479021 pmcid: 307295 doi: 10.1093/nar/23.19.3810
Coello K, Bøgh HL, Stanislaus S, Kjærstad HL, Melbye SA, Ormstrup Sletved KS, et al. Higher systemic oxidatively generated DNA and RNA damage in patients with newly diagnosed bipolar disorder and their unaffected first-degree relatives. Free Radic Biol Med. 2021;168:226–33.
pubmed: 33798615 doi: 10.1016/j.freeradbiomed.2021.03.022
Ottesen NM, Meluken I, Frikke-Schmidt R, Plomgaard P, Scheike T, Fernandes BS, et al. Are remitted affective disorders and familial risk of affective disorders associated with metabolic syndrome, inflammation and oxidative stress? - a monozygotic twin study. Psychol Med. 2020;50:1736–45.
pubmed: 31482770 doi: 10.1017/S003329171900182X
Kant M, Akış M, Çalan M, Arkan T, Bayraktar F, Dizdaroglu M, et al. Elevated urinary levels of 8-oxo-2’-deoxyguanosine, (5’R)- and (5’S)-8,5’-cyclo-2’-deoxyadenosines, and 8-iso-prostaglandin F(2α) as potential biomarkers of oxidative stress in patients with prediabetes. DNA Repair. 2016;48:1–7.
pubmed: 27769710 doi: 10.1016/j.dnarep.2016.09.004
Tuna G, Bekar NED, İşlekel S, İşlekel GH. Urinary 8-hydroxy-2’-deoxyguanosine levels are elevated in patients with IDH1-wildtype glioblastoma and are associated with tumor recurrence in gliomas. DNA Repair. 2023;124:103463.
pubmed: 36841018 doi: 10.1016/j.dnarep.2023.103463
Bustin SA, Benes V, Garson JA, Hellemans J, Huggett J, Kubista M, et al. The MIQE guidelines: minimum information for publication of quantitative real-time PCR experiments. Clin Chem. 2009;55:611–22.
pubmed: 19246619 doi: 10.1373/clinchem.2008.112797
Black CN, Bot M, Scheffer PG, Cuijpers P, Penninx BW. Is depression associated with increased oxidative stress? A systematic review and meta-analysis. Psychoneuroendocrinology. 2015;51:164–75.
pubmed: 25462890 doi: 10.1016/j.psyneuen.2014.09.025
Jorgensen A, Köhler-Forsberg K, Henriksen T, Weimann A, Brandslund I, Ellervik C, et al. Systemic DNA and RNA damage from oxidation after serotonergic treatment of unipolar depression. Transl Psychiatry. 2022;12:204.
pubmed: 35577781 pmcid: 9110351 doi: 10.1038/s41398-022-01969-z
Włodarczyk M, Jabłonowska-Lietz B, Olejarz W, Nowicka G. Anthropometric and dietary factors as predictors of DNA damage in obese women. Nutrients. 2018;10:578.
Alano CC, Kauppinen TM, Valls AV, Swanson RA. Minocycline inhibits poly(ADP-ribose) polymerase-1 at nanomolar concentrations. Proc Natl Acad Sci USA. 2006;103:9685–90.
pubmed: 16769901 pmcid: 1480467 doi: 10.1073/pnas.0600554103
Rosenblat JD, McIntyre RS. Efficacy and tolerability of minocycline for depression: a systematic review and meta-analysis of clinical trials. J Affect Disord. 2018;227:219–25.
pubmed: 29102836 doi: 10.1016/j.jad.2017.10.042
Ordway GA, Szebeni A, Hernandez LJ, Crawford JD, Szebeni K, Chandley MJ, et al. Antidepressant-Like Actions of Inhibitors of Poly(ADP-Ribose) polymerase in rodent models. Int J Neuropsychopharmacol. 2017;20:994–1004.
pubmed: 29016792 pmcid: 5716178
Steardo L Jr., Manchia M, Carpiniello B, Pisanu C, Steardo L, Squassina A. Clinical, genetic, and brain imaging predictors of risk for bipolar disorder in high-risk individuals. Expert Rev Mol Diagn. 2020;20:327–33.
pubmed: 32054361 doi: 10.1080/14737159.2020.1727743
Bora E, Özerdem A. A meta-analysis of neurocognition in youth with familial high risk for bipolar disorder. Eur Psychiatry. 2017;44:17–23.
pubmed: 28531561 doi: 10.1016/j.eurpsy.2017.02.483
Johnsen LK, Ver Loren van Themaat AH, Larsen KM, Burton BK, Baaré WFC, Madsen KS, et al. Alterations in Task-related brain activation in children, adolescents and young adults at familial high-risk for schizophrenia or bipolar disorder - a systematic review. Front Psychiatry. 2020;11:632.
pubmed: 32754058 pmcid: 7365908 doi: 10.3389/fpsyt.2020.00632
Miskowiak KW, Kjærstad HL, Meluken I, Petersen JZ, Maciel BR, Köhler CA, et al. The search for neuroimaging and cognitive endophenotypes: a critical systematic review of studies involving unaffected first-degree relatives of individuals with bipolar disorder. Neurosci Biobehav Rev. 2017;73:1–22.
pubmed: 27979650 doi: 10.1016/j.neubiorev.2016.12.011
Mikolas P, Bröckel K, Vogelbacher C, Müller DK, Marxen M, Berndt C, et al. Individuals at increased risk for development of bipolar disorder display structural alterations similar to people with manifest disease. Transl Psychiatry. 2021;11:485.
pubmed: 34545071 pmcid: 8452775 doi: 10.1038/s41398-021-01598-y
Hu R, Stavish C, Leibenluft E, Linke JO. White matter microstructure in individuals with and at risk for bipolar disorder: evidence for an endophenotype from a Voxel-Based meta-analysis. Biol Psychiatry Cogn Neurosci Neuroimaging. 2020;5:1104–13.
pubmed: 32839153 pmcid: 11102922
Duffy A, Horrocks J, Doucette S, Keown-Stoneman C, Grof P, Andreazza A, et al. Immunological and neurotrophic markers of risk status and illness development in high-risk youth: understanding the neurobiological underpinnings of bipolar disorder. Int J Bipolar Disord. 2014;2:29.
pubmed: 26092400 doi: 10.1186/2194-7511-2-4
Guglielmo R, Miskowiak KW, Hasler G. Evaluating endophenotypes for bipolar disorder. Int J Bipolar Disord. 2021;9:17.
pubmed: 34046710 pmcid: 8160068 doi: 10.1186/s40345-021-00220-w
Craddock N, Forty L. Genetics of affective (mood) disorders. Eur J Hum Genet. 2006;14:660–8.
pubmed: 16721402 doi: 10.1038/sj.ejhg.5201549
Poulsen HE, Nadal LL, Broedbaek K, Nielsen PE, Weimann A. Detection and interpretation of 8-oxodG and 8-oxoGua in urine, plasma and cerebrospinal fluid. Biochim Biophys Acta. 2014;1840:801–8.
pubmed: 23791936 doi: 10.1016/j.bbagen.2013.06.009
Wu LL, Chiou CC, Chang PY, Wu JT. Urinary 8-OHdG: a marker of oxidative stress to DNA and a risk factor for cancer, atherosclerosis and diabetics. Clin Chim Acta. 2004;339:1–9.
pubmed: 14687888 doi: 10.1016/j.cccn.2003.09.010
Sajatovic M, Strejilevich SA, Gildengers AG, Dols A, Al Jurdi RK, Forester BP, et al. A report on older-age bipolar disorder from the International Society for Bipolar Disorders Task Force. Bipolar Disord. 2015;17:689–704.
pubmed: 26384588 pmcid: 4623878 doi: 10.1111/bdi.12331
Radak Z, Zhao Z, Goto S, Koltai E. Age-associated neurodegeneration and oxidative damage to lipids, proteins and DNA. Mol Asp Med. 2011;32:305–15.
doi: 10.1016/j.mam.2011.10.010
Liguori I, Russo G, Curcio F, Bulli G, Aran L, Della-Morte D, et al. Oxidative stress, aging, and diseases. Clin Inter Aging. 2018;13:757–72.
doi: 10.2147/CIA.S158513
Kurhan F, Alp HH. Dynamic Thiol/Disulfide homeostasis and oxidative DNA damage in adult attention deficit hyperactivity disorder. Clin Psychopharmacol Neurosci. 2021;19:731–8.
pubmed: 34690128 pmcid: 8553522 doi: 10.9758/cpn.2021.19.4.731
Christensen MR, Poulsen HE, Henriksen T, Weimann A, Ellervik C, Lynnerup N, et al. Elevated levels of 8-oxoGuo and 8-oxodG in individuals with severe mental illness - An autopsy-based study. Free Radic Biol Med. 2018;126:372–8.
pubmed: 30145229 doi: 10.1016/j.freeradbiomed.2018.08.029
Knorr U, Simonsen AH, Roos P, Weimann A, Henriksen T, Christensen EM, et al. Cerebrospinal fluid oxidative stress metabolites in patients with bipolar disorder and healthy controls: a longitudinal case-control study. Transl Psychiatry. 2019;9:325.
pubmed: 31780642 pmcid: 6882849 doi: 10.1038/s41398-019-0664-6

Auteurs

Hidayet Ece Arat Çelik (HE)

Department of Psychiatry, School of Medicine, Maltepe University, Istanbul, Turkey. ecearat@yahoo.com.

Selda Yılmaz (S)

Department of Molecular Medicine, Institute of Health Sciences, Dokuz Eylul University, Izmir, Turkey.

İzel Cemre Akşahin (İC)

Graduate School of Health Sciences, Koc University, Istanbul, Turkey.
Research Center for Translational Medicine (KUTTAM), School of Medicine, Koc University, Istanbul, Turkey.

Burcu Kök Kendirlioğlu (B)

Department of Psychiatry, School of Medicine, Maltepe University, Istanbul, Turkey.

Esma Çörekli (E)

Department of Psychiatry, School of Medicine, Maltepe University, Istanbul, Turkey.

Nazlı Ecem Dal Bekar (NE)

Chair of Proteomics and Bioanalytics, School of Life Sciences, Technical University of Munich, Munich, Germany.

Ömer Faruk Çelik (ÖF)

Department of Medical Biochemistry, Sancaktepe Sehit Prof. Dr. Ilhan Varank Training and Research Hospital, Istanbul, Turkey.

Neşe Yorguner (N)

Department of Psychiatry, School of Medicine, Marmara University, Istanbul, Turkey.

Bilge Targıtay Öztürk (B)

Department of Psychiatry, School of Medicine, Dokuz Eylul University, Izmir, Turkey.

Hüray İşlekel (H)

Department of Molecular Medicine, Institute of Health Sciences, Dokuz Eylul University, Izmir, Turkey.
Department of Medical Biochemistry, School of Medicine, Dokuz Eylul University, Izmir, Turkey.

Ayşegül Özerdem (A)

Department of Psychiatry and Psychology, Mayo Clinic, Rochester, MN, USA.

Pınar Akan (P)

Department of Neuroscience, Institute of Health Sciences, Dokuz Eylul University, Izmir, Turkey.
BioIzmir - Izmir Health Technologies Development and Accelerator Research and Application Center, Dokuz Eylul University, Izmir, Turkey.

Deniz Ceylan (D)

Research Center for Translational Medicine (KUTTAM), School of Medicine, Koc University, Istanbul, Turkey. dozalp@ku.edu.tr.
Department of Psychiatry, School of Medicine, Koc University, Istanbul, Turkey. dozalp@ku.edu.tr.

Gamze Tuna (G)

Department of Molecular Medicine, Institute of Health Sciences, Dokuz Eylul University, Izmir, Turkey.
BioIzmir - Izmir Health Technologies Development and Accelerator Research and Application Center, Dokuz Eylul University, Izmir, Turkey.

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