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WFSBP Consensus Paper

Consensus paper of the WFSBP Task Force on Genetics: Genetics, epigenetics and gene expression markers of major depressive disorder and antidepressant response

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Pages 5-28 | Received 23 Jun 2016, Accepted 29 Jun 2016, Published online: 07 Sep 2016

References

  • Almeida OP, Norman PE, Allcock R, van Bockxmeer F, Hankey GJ, Jamrozik K, Flicker L. 2009. Polymorphisms of the CRP gene inhibit inflammatory response and increase susceptibility to depression: the Health in Men Study. Int J Epidemiol. 38:1049–1059.
  • Ancelin ML, Farre A, Carriere I, Ritchie K, Chaudieu I, Ryan J. 2015. C-reactive protein gene variants: independent association with late-life depression and circulating protein levels. Transl Psychiatry. 5:e499.
  • Baudry A, Mouillet-Richard S, Schneider B, Launay JM, Kellermann O. 2010. miR-16 targets the serotonin transporter: a new facet for adaptive responses to antidepressants. Science. 329:1537–1541.
  • Baune BT, Dannlowski U, Domschke K, Janssen DG, Jordan MA, Ohrmann P, Bauer J, Biros E, Arolt V, Kugel H, et al. 2010. The interleukin 1 beta (IL1B) gene is associated with failure to achieve remission and impaired emotion processing in major depression. Biol Psychiatry. 67:543–549.
  • Beck O, Borg S, Edman G, Fyro B, Oxenstierna G, Sedvall G. 1984. 5-hydroxytryptophol in human cerebrospinal fluid: conjugation, concentration gradient, relationship to 5-hydroxyindoleacetic acid, and influence of hereditary factors. J Neurochem. 43:58–61.
  • Belzeaux R, Bergon A, Jeanjean V, Loriod B, Formisano-Treziny C, Verrier L, Loundou A, Baumstarck-Barrau K, Boyer L, Gall V, et al. 2012. Responder and nonresponder patients exhibit different peripheral transcriptional signatures during major depressive episode. Transl Psychiatry. 2:e185.
  • Belzeaux R, Formisano-Treziny C, Loundou A, Boyer L, Gabert J, Samuelian JC, Feron F, Naudin J, Ibrahim EC. 2010. Clinical variations modulate patterns of gene expression and define blood biomarkers in major depression. J Psychiatr Res. 44:1205–1213.
  • Belzeaux R, Loundou A, Azorin JM, Naudin J, Ibrahim el C. 2014. Longitudinal monitoring of the serotonin transporter gene expression to assess major depressive episode evolution. Neuropsychobiology. 70:220–227.
  • Bessa JM, Ferreira D, Melo I, Marques F, Cerqueira JJ, Palha JA, Almeida OF, Sousa N. 2009. The mood-improving actions of antidepressants do not depend on neurogenesis but are associated with neuronal remodeling. Mol Psychiatry. 14:764-773–739.
  • Bilello JA, Thurmond LM, Smith KM, Pi B, Rubin R, Wright SM, Taub F, Henry ME, Shelton RC, Papakostas GI. 2015. MDDScore: confirmation of a blood test to aid in the diagnosis of major depressive disorder. J Clin Psychiatry. 76:e199–e206.
  • Binder EB. 2009. The role of FKBP5, a co-chaperone of the glucocorticoid receptor in the pathogenesis and therapy of affective and anxiety disorders. Psychoneuroendocrinology. 34:S186–S195.
  • Binder EB, Salyakina D, Lichtner P, Wochnik GM, Ising M, Putz B, Papiol S, Seaman S, Lucae S, Kohli MA, et al. 2004. Polymorphisms in FKBP5 are associated with increased recurrence of depressive episodes and rapid response to antidepressant treatment. Nat Genet. 36:1319–1325.
  • Bishop JR, Ellingrod VL, Akroush M, Moline J. 2009. The association of serotonin transporter genotypes and selective serotonin reuptake inhibitor (SSRI)-associated sexual side effects: possible relationship to oral contraceptives. Hum Psychopharmacol. 24:207–215.
  • Booij L, Szyf M, Carballedo A, Frey EM, Morris D, Dymov S, Vaisheva F, Ly V, Fahey C, Meaney J, et al. 2015. DNA methylation of the serotonin transporter gene in peripheral cells and stress-related changes in hippocampal volume: a study in depressed patients and healthy controls. PLoS One. 10:e0119061.
  • Borkowska P, Kucia K, Rzezniczek S, Paul-Samojedny M, Kowalczyk M, Owczarek A, Suchanek R, Medrala T, Kowalski J. 2011. Interleukin-1beta promoter (−31T/C and −511C/T) polymorphisms in major recurrent depression. J Mol Neurosci. 44:12–16.
  • Bosker FJ, Hartman CA, Nolte IM, Prins BP, Terpstra P, Posthuma D, van Veen T, Willemsen G, DeRijk RH, de Geus EJ, et al. 2011. Poor replication of candidate genes for major depressive disorder using genome-wide association data. Mol Psychiatry. 16:516–532.
  • Bradvik L, Mattisson C, Bogren M, Nettelbladt P. 2008. Long-term suicide risk of depression in the Lundby cohort 1947-1997-severity and gender. Acta Psychiatr Scand. 117:185–191.
  • Breitenstein B, Scheuer S, Bruckl TM, Meyer J, Ising M, Uhr M, Holsboer F. 2016. Association of ABCB1 gene variants, plasma antidepressant concentration, and treatment response: Results from a randomized clinical study. J Psychiatr Res. 73:86–95.
  • Breitenstein B, Scheuer S, Pfister H, Uhr M, Lucae S, Holsboer F, Ising M, Bruckl TM. 2014. The clinical application of ABCB1 genotyping in antidepressant treatment: a pilot study. CNS Spectr. 19:165–175.
  • Brennan FX, Gardner KR, Lombard J, Perlis RH, Fava M, Harris HW, Scott R. 2015. A naturalistic study of the effectiveness of pharmacogenetic testing to guide treatment in psychiatric patients with mood and anxiety disorders. Prim Care Companion CNS Disord. 17(2). doi:10.4088/PCC.14m01717.
  • Brunoni AR, Lopes M, Fregni F. 2008. A systematic review and meta-analysis of clinical studies on major depression and BDNF levels: implications for the role of neuroplasticity in depression. Int J Neuropsychopharmacol. 11:1169–1180.
  • Buist-Bouwman MA, De Graaf R, Vollebergh WA, Alonso J, Bruffaerts R, Ormel J, SEMeD/MHEDEA Investigators. 2006. Functional disability of mental disorders and comparison with physical disorders: a study among the general population of six European countries. Acta Psychiatr Scand. 113:492–500.
  • Bull SJ, Huezo-Diaz P, Binder EB, Cubells JF, Ranjith G, Maddock C, Miyazaki C, Alexander N, Hotopf M, Cleare AJ, et al. 2009. Functional polymorphisms in the interleukin-6 and serotonin transporter genes, and depression and fatigue induced by interferon-alpha and ribavirin treatment. Mol Psychiatry. 14:1095–1104.
  • Burcescu I, Wigg K, King N, Vetro A, Kiss E, Katay L, Kennedy JL, Kovacs M, Barr CL. 2005. Association study of CREB1 and childhood-onset mood disorders. Am J Med Genet B Neuropsychiatr Genet. 137B:45–50.
  • Burnet PW, Eastwood SL, Lacey K, Harrison PJ. 1995. The distribution of 5-HT1A and 5-HT2A receptor mRNA in human brain. Brain Res. 676:157–168.
  • Calati R, Crisafulli C, Balestri M, Serretti A, Spina E, Calabro M, Sidoti A, Albani D, Massat I, Hofer P, et al. 2013. Evaluation of the role of MAPK1 and CREB1 polymorphisms on treatment resistance, response and remission in mood disorder patients. Prog Neuropsychopharmacol Biol Psychiatry. 44:271–278.
  • Carlberg L, Scheibelreiter J, Hassler MR, Schloegelhofer M, Schmoeger M, Ludwig B, Kasper S, Aschauer H, Egger G, Schosser A. 2014. Brain-derived neurotrophic factor (BDNF)-epigenetic regulation in unipolar and bipolar affective disorder. J Affect Disord. 168:399–406.
  • Cattaneo A, Gennarelli M, Uher R, Breen G, Farmer A, Aitchison KJ, Craig IW, Anacker C, Zunsztain PA, McGuffin P, et al. 2013. Candidate genes expression profile associated with antidepressants response in the GENDEP study: differentiating between baseline ‘predictors’ and longitudinal ‘targets’. Neuropsychopharmacology. 38:377–385.
  • Cerri AP, Arosio B, Viazzoli C, Confalonieri R, Teruzzi F, Annoni G. 2009. −308(G/A) TNF-alpha gene polymorphism and risk of depression late in the life. Arch Gerontol Geriatr. 49:29–34.
  • Chang SC, Glymour MM, Walter S, Liang L, Koenen KC, Tchetgen EJ, Cornelis MC, Kawachi I, Rimm E, Kubzansky LD. 2014. Genome-wide polygenic scoring for a 14-year long-term average depression phenotype. Brain Behav. 4:298–311.
  • Chen ES, Ernst C, Turecki G. 2011. The epigenetic effects of antidepressant treatment on human prefrontal cortex BDNF expression. Int J Neuropsychopharmacol. 14:427–429.
  • Clerici M, Arosio B, Mundo E, Cattaneo E, Pozzoli S, Dell’osso B, Vergani C, Trabattoni D, Altamura AC. 2009. Cytokine polymorphisms in the pathophysiology of mood disorders. CNS Spectr. 14:419–425.
  • Copeland WE, Shanahan L, Worthman C, Angold A, Costello EJ. 2012. Cumulative depression episodes predict later C-reactive protein levels: a prospective analysis. Biol Psychiatry. 71:15–21.
  • Couch Y, Anthony DC, Dolgov O, Revischin A, Festoff B, Santos AI, Steinbusch HW, Strekalova T. 2013. Microglial activation, increased TNF and SERT expression in the prefrontal cortex define stress-altered behaviour in mice susceptible to anhedonia. Brain Behav Immun. 29:136–146.
  • Cowansage KK, LeDoux JE, Monfils MH. 2010. Brain-derived neurotrophic factor: a dynamic gatekeeper of neural plasticity. Curr Mol Pharmacol. 3:12–29.
  • Crisafulli C, Shim DS, Andrisano C, Pae CU, Chiesa A, Han C, Patkar AA, Lee SJ, Serretti A, De Ronchi D. 2012. Case-control association study of 14 variants of CREB1, CREBBP and CREM on diagnosis and treatment outcome in major depressive disorder and bipolar disorder. Psychiatry Res. 198:39–46.
  • D’Addario C, Dell’Osso B, Galimberti D, Palazzo MC, Benatti B, Di Francesco A, Scarpini E, Altamura AC, Maccarrone M. 2013. Epigenetic modulation of BDNF gene in patients with major depressive disorder. Biol Psychiatry. 73:e6–e7.
  • Davis MJ, Haley T, Duvoisin RM, Raber J. 2012. Measures of anxiety, sensorimotor function, and memory in male and female mGluR4–/– mice. Behav Brain Res. 229:21–28.
  • Dawood T, Lambert EA, Barton DA, Laude D, Elghozi JL, Esler MD, Haikerwal D, Kaye DM, Hotchkin EJ, Lambert GW. 2007. Specific serotonin reuptake inhibition in major depressive disorder adversely affects novel markers of cardiac risk. Hypertens Res. 30:285–293.
  • Dell’Osso B, D’Addario C, Carlotta Palazzo M, Benatti B, Camuri G, Galimberti D, Fenoglio C, Scarpini E, Di Francesco A, Maccarrone M, et al. 2014. Epigenetic modulation of BDNF gene: differences in DNA methylation between unipolar and bipolar patients. J Affect Disord. 166:330–333
  • Demirkan A, Penninx BW, Hek K, Wray NR, Amin N, Aulchenko YS, van Dyck R, de Geus EJ, Hofman A, Uitterlinden AG, et al. 2011. Genetic risk profiles for depression and anxiety in adult and elderly cohorts. Mol Psychiatry. 16:773–783.
  • Domschke K, Tidow N, Schwarte K, Deckert J, Lesch KP, Arolt V, Zwanzger P, Baune BT. 2014. Serotonin transporter gene hypomethylation predicts impaired antidepressant treatment response. Int J Neuropsychopharmacol. 17:1167–1176.
  • Dong C, Wong ML, Licinio J. 2009. Sequence variations of ABCB1, SLC6A2, SLC6A3, SLC6A4, CREB1, CRHR1 and NTRK2: association with major depression and antidepressant response in Mexican-Americans. Mol Psychiatry. 14:1105–1118.
  • Dowlati Y, Herrmann N, Swardfager W, Liu H, Sham L, Reim EK, Lanctot KL. 2010. A meta-analysis of cytokines in major depression. Biol Psychiatry. 67:446–457.
  • Ducray A, Krebs SH, Schaller B, Seiler RW, Meyer M, Widmer HR. 2006. GDNF family ligands display distinct action profiles on cultured GABAergic and serotonergic neurons of rat ventral mesencephalon. Brain Res. 1069:104–112.
  • Duivis HE, Vogelzangs N, Kupper N, de Jonge P, Penninx BW. 2013. Differential association of somatic and cognitive symptoms of depression and anxiety with inflammation: findings from the Netherlands Study of Depression and Anxiety (NESDA). Psychoneuroendocrinology. 38:1573–1585.
  • Duman RS, Voleti B. 2012. Signaling pathways underlying the pathophysiology and treatment of depression: novel mechanisms for rapid-acting agents. Trends Neurosci. 35:47–56.
  • Dwivedi Y. 2016. Pathogenetic and therapeutic applications of microRNAs in major depressive disorder. Prog Neuropsychopharmacol Biol Psychiatry. 64:341–348.
  • Ellsworth KA, Moon I, Eckloff BW, Fridley BL, Jenkins GD, Batzler A, Biernacka JM, Abo R, Brisbin A, Ji Y, et al. 2013. FKBP5 genetic variation: association with selective serotonin reuptake inhibitor treatment outcomes in major depressive disorder. Pharmacogenet Genomics. 23:156–166.
  • Elovainio M, Aalto AM, Kivimaki M, Pirkola S, Sundvall J, Lonnqvist J, Reunanen A. 2009. Depression and C-reactive protein: population-based Health 2000 Study. Psychosom Med. 71:423–430.
  • Fabbri C, Di Girolamo G, Serretti A. 2013a. Pharmacogenetics of antidepressant drugs: an update after almost 20 years of research. Am J Med Genet B Neuropsychiatr Genet. 162B:487–520.
  • Fabbri C, Marsano A, Albani D, Chierchia A, Calati R, Drago A, Crisafulli C, Calabro M, Kasper S, Lanzenberger R, et al. 2014. PPP3CC gene: a putative modulator of antidepressant response through the B-cell receptor signaling pathway. Pharmacogenomics J. 14:463–472.
  • Fabbri C, Marsano A, Serretti A. 2013b. Genetics of serotonin receptors and depression: state of the art. Curr Drug Targets. 14:531–548.
  • Fabbri C, Serretti A. 2015. Pharmacogenetics of major depressive disorder: top genes and pathways toward clinical applications. Curr Psychiatry Rep. 17:594.
  • Fagerness J, Fonseca E, Hess GP, Scott R, Gardner KR, Koffler M, Fava M, Perlis R, Brennan FX, Lombard J. 2014. Pharmacogenetic-guided psychiatric intervention associated with increased adherence and cost savings. Am J Manag Care. 20:e146–e156.
  • Fajardo O, Galeno J, Urbina M, Carreira I, Lima L. 2003. Serotonin, serotonin 5-HT(1A) receptors and dopamine in blood peripheral lymphocytes of major depression patients. Int Immunopharmacol. 3:1345–1352.
  • Ferres-Coy A, Pilar-Cuellar F, Vidal R, Paz V, Masana M, Cortes R, Carmona MC, Campa L, Pazos A, Montefeltro A, et al. 2013. RNAi-mediated serotonin transporter suppression rapidly increases serotonergic neurotransmission and hippocampal neurogenesis. Transl Psychiatry. 3:e211.
  • Ford DE, Erlinger TP. 2004. Depression and C-reactive protein in US adults: data from the Third National Health and Nutrition Examination Survey. Arch Intern Med. 164:1010–1014.
  • Frodl T, Carballedo A, Hughes MM, Saleh K, Fagan A, Skokauskas N, McLoughlin DM, Meaney J, O’Keane V, Connor TJ. 2012. Reduced expression of glucocorticoid-inducible genes GILZ and SGK-1: high IL-6 levels are associated with reduced hippocampal volumes in major depressive disorder. Transl Psychiatry. 2:e88.
  • Fuchikami M, Morinobu S, Segawa M, Okamoto Y, Yamawaki S, Ozaki N, Inoue T, Kusumi I, Koyama T, Tsuchiyama K, et al. 2011. DNA methylation profiles of the brain-derived neurotrophic factor (BDNF) gene as a potent diagnostic biomarker in major depression. PLoS One. 6:e23881.
  • Gaysina D, Pierce M, Richards M, Hotopf M, Kuh D, Hardy R. 2011. Association between adolescent emotional problems and metabolic syndrome: the modifying effect of C-reactive protein gene (CRP) polymorphisms. Brain Behav Immun. 25:750–758.
  • Gladkevich A, Kauffman HF, Korf J. 2004. Lymphocytes as a neural probe: potential for studying psychiatric disorders. Prog Neuropsychopharmacol Biol Psychiatry. 28:559–576.
  • Golden JP, Baloh RH, Kotzbauer PT, Lampe PA, Osborne PA, Milbrandt J, Johnson EM. Jr. 1998. Expression of neurturin, GDNF, and their receptors in the adult mouse CNS. J Comp Neurol. 398:139–150.
  • Gonzalez A, Fazzino F, Castillo M, Mata S, Lima L. 2007. Serotonin, 5-HT1A serotonin receptors and proliferation of lymphocytes in major depression patients. Neuroimmunomodulation. 14:8–15.
  • Gratacos M, Gonzalez JR, Mercader JM, de Cid R, Urretavizcaya M, Estivill X. 2007. 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. 61:911–922.
  • Gray NA, Milak MS, DeLorenzo C, Ogden RT, Huang YY, Mann JJ, Parsey RV. 2013. Antidepressant treatment reduces serotonin-1A autoreceptor binding in major depressive disorder. Biol Psychiatry. 74:26–31.
  • Gryglewski G, Lanzenberger R, Kranz GS, Cumming P. 2014. Meta-analysis of molecular imaging of serotonin transporters in major depression. J Cereb Blood Flow Metab. 34:1096–1103.
  • Guidotti G, Calabrese F, Anacker C, Racagni G, Pariante CM, Riva MA. 2013. Glucocorticoid receptor and FKBP5 expression is altered following exposure to chronic stress: modulation by antidepressant treatment. Neuropsychopharmacology. 38:616–627.
  • Guintivano J, Brown T, Newcomer A, Jones M, Cox O, Maher BS, Eaton WW, Payne JL, Wilcox HC, Kaminsky ZA. 2014. Identification and replication of a combined epigenetic and genetic biomarker predicting suicide and suicidal behaviors. Am J Psychiatry. 171:1287–1296.
  • Gutierrez B, Bellon JA, Rivera M, Molina E, King M, Marston L, Torres-Gonzalez F, Moreno-Kustner B, Moreno-Peral P, Motrico E, et al. 2015. The risk for major depression conferred by childhood maltreatment is multiplied by BDNF and SERT genetic vulnerability: a replication study. J Psychiatry Neurosci. 40:187–196.
  • Gyekis JP, Yu W, Dong S, Wang H, Qian J, Kota P, Yang J. 2013. No association of genetic variants in BDNF with major depression: a meta- and gene-based analysis. Am J Med Genet B Neuropsychiatr Genet. 162B:61–70.
  • Haastrup E, Bukh JD, Bock C, Vinberg M, Thorner LW, Hansen T, Werge T, Kessing LV, Ullum H. 2012. Promoter variants in IL18 are associated with onset of depression in patients previously exposed to stressful-life events. J Affect Disord. 136:134–138.
  • Hage FG, Szalai AJ. 2009. The role of C-reactive protein polymorphisms in inflammation and cardiovascular risk. Curr Atheroscler Rep. 11:124–130.
  • Halder I, Marsland AL, Cheong J, Muldoon MF, Ferrell RE, Manuck SB. 2010. Polymorphisms in the CRP gene moderate an association between depressive symptoms and circulating levels of C-reactive protein. Brain Behav Immun. 24:160–167.
  • Hall-Flavin DK, Winner JG, Allen JD, Carhart JM, Proctor B, Snyder KA, Drews MS, Eisterhold LL, Geske J, Mrazek DA. 2013. Utility of integrated pharmacogenomic testing to support the treatment of major depressive disorder in a psychiatric outpatient setting. Pharmacogenet Genomics. 23:535–548.
  • Hannestad J, DellaGioia N, Bloch M. 2011. The effect of antidepressant medication treatment on serum levels of inflammatory cytokines: a meta-analysis. Neuropsychopharmacology. 36:2452–2459.
  • Heils A, Teufel A, Petri S, Stober G, Riederer P, Bengel D, Lesch KP. 1996. Allelic variation of human serotonin transporter gene expression. J Neurochem. 66:2621–2624.
  • Hettema JM, An SS, van den Oord EJ, Neale MC, Kendler KS, Chen X. 2009. Association study of CREB1 with Major Depressive Disorder and related phenotypes. Am J Med Genet B Neuropsychiatr Genet. 150B:1128–1132.
  • Hickman RJ, Khambaty T, Stewart JC. 2014. C-reactive protein is elevated in atypical but not nonatypical depression: data from the National Health and Nutrition Examination survey (NHANES) 1999–2004. J Behav Med. 37:621–629.
  • Hiles SA, Baker AL, de Malmanche T, Attia J. 2012. Interleukin-6, C-reactive protein and interleukin-10 after antidepressant treatment in people with depression: a meta-analysis. Psychol Med. 42:2015–2026.
  • Hisaoka K, Maeda N, Tsuchioka M, Takebayashi M. 2008. Antidepressants induce acute CREB phosphorylation and CRE-mediated gene expression in glial cells: a possible contribution to GDNF production. Brain Res. 1196:53–58.
  • Hochstrasser T, Ullrich C, Sperner-Unterweger B, Humpel C. 2011. Inflammatory stimuli reduce survival of serotonergic neurons and induce neuronal expression of indoleamine 2,3-dioxygenase in rat dorsal raphe nucleus organotypic brain slices. Neuroscience. 184:128–138.
  • Hohne N, Poidinger M, Merz F, Pfister H, Bruckl T, Zimmermann P, Uhr M, Holsboer F, Ising M. 2015. FKBP5 genotype-dependent DNA methylation and mRNA regulation after psychosocial stress in remitted depression and healthy controls. Int J Neuropsychopharmacol. 18:pyu087. doi:10.1093/ijnp/pyu087.
  • Holmes RD, Tiwari AK, Kennedy JL. 2016. Mechanisms of the placebo effect in pain and psychiatric disorders. Pharmacogenomics J. Epub ahead of print. doi:10.1038/tpj.2016.15
  • Hong CJ, Yu YW, Chen TJ, Tsai SJ. 2005. Interleukin-6 genetic polymorphism and Chinese major depression. Neuropsychobiology. 52:202–205.
  • Horstmann S, Lucae S, Menke A, Hennings JM, Ising M, Roeske D, Muller-Myhsok B, Holsboer F, Binder EB. 2010. Polymorphisms in GRIK4, HTR2A, and FKBP5 show interactive effects in predicting remission to antidepressant treatment. Neuropsychopharmacology. 35:727–740.
  • Hosang GM, Shiles C, Tansey KE, McGuffin P, Uher R. 2014. Interaction between stress and the BDNF Val66Met polymorphism in depression: a systematic review and meta-analysis. BMC Med. 12:7.
  • Howren MB, Lamkin DM, Suls J. 2009. Associations of depression with C-reactive protein, IL-1, and IL-6: a meta-analysis. Psychosom Med. 71:171–186.
  • Hu XZ, Lipsky RH, Zhu G, Akhtar LA, Taubman J, Greenberg BD, Xu K, Arnold PD, Richter MA, Kennedy JL, et al. 2006. Serotonin transporter promoter gain-of-function genotypes are linked to obsessive-compulsive disorder. Am J Hum Genet. 78:815–826.
  • Hu XZ, Rush AJ, Charney D, Wilson AF, Sorant AJ, Papanicolaou GJ, Fava M, Trivedi MH, Wisniewski SR, Laje G, et al. 2007. Association between a functional serotonin transporter promoter polymorphism and citalopram treatment in adult outpatients with major depression. Arch Gen Psychiatry. 64:783–792.
  • Hufner K, Kandler C, Koudouovoh-Tripp P, Egeter J, Hochstrasser T, Stemer B, Malik P, Giesinger J, Humpel C, Sperner-Unterweger B. 2014. Bioprofiling of platelets in medicated patients with depression. J Affect Disord. 172:81–88.
  • Hunter AM, Leuchter AF, Power RA, Muthen B, McGrath PJ, Lewis CM, Cook IA, Garriock HA, McGuffin P, Uher R, et al. 2013. A genome-wide association study of a sustained pattern of antidepressant response. J Psychiatr Res. 47:1157–1165.
  • Iacob E, Light KC, Tadler SC, Weeks HR, White AT, Hughen RW, Vanhaitsma TA, Bushnell L, Light AR. 2013. Dysregulation of leukocyte gene expression in women with medication-refractory depression versus healthy non-depressed controls. BMC Psychiatry. 13:273.
  • Iga J, Ueno S, Yamauchi K, Motoki I, Tayoshi S, Ohta K, Song H, Morita K, Rokutan K, Ohmori T. 2005. Serotonin transporter mRNA expression in peripheral leukocytes of patients with major depression before and after treatment with paroxetine. Neurosci Lett. 389:12–16.
  • Iga J, Ueno S, Yamauchi K, Numata S, Kinouchi S, Tayoshi-Shibuya S, Song H, Ohmori T. 2007. Altered HDAC5 and CREB mRNA expressions in the peripheral leukocytes of major depression. Prog Neuropsychopharmacol Biol Psychiatry. 31:628–632.
  • Ignacio ZM, Reus GZ, Abelaira HM, Quevedo J. 2014. Epigenetic and epistatic interactions between serotonin transporter and brain-derived neurotrophic factor genetic polymorphism: insights in depression. Neuroscience. 275:455–468.
  • Illi A, Setala-Soikkeli E, Viikki M, Poutanen O, Huhtala H, Mononen N, Lehtimaki T, Leinonen E, Kampman O. 2009. 5-HTR1A, 5-HTR2A, 5-HTR6, TPH1 and TPH2 polymorphisms and major depression. Neuroreport. 20:1125–1128.
  • Insel T, Cuthbert B, Garvey M, Heinssen R, Pine DS, Quinn K, Sanislow C, Wang P. 2010. Research domain criteria (RDoC): toward a new classification framework for research on mental disorders. Am J Psychiatry. 167:748–751.
  • GENDEP Investigators, MARS Investigators, STAR*D Investigators 2013. Common genetic variation and antidepressant efficacy in major depressive disorder: a meta-analysis of three genome-wide pharmacogenetic studies. Am J Psychiatry. 170:207–217.
  • Issler O, Haramati S, Paul ED, Maeno H, Navon I, Zwang R, Gil S, Mayberg HS, Dunlop BW, Menke A, et al. 2014. MicroRNA 135 is essential for chronic stress resiliency, antidepressant efficacy, and intact serotonergic activity. Neuron. 83:344–360.
  • Jaenisch R, Bird A. 2003. Epigenetic regulation of gene expression: how the genome integrates intrinsic and environmental signals. Nat Genet. 33(Suppl):245–254.
  • Jans LA, Riedel WJ, Markus CR, Blokland A. 2007. Serotonergic vulnerability and depression: assumptions, experimental evidence and implications. Mol Psychiatry. 12:522–543.
  • Jansen R, Penninx BW, Madar V, Xia K, Milaneschi Y, Hottenga JJ, Hammerschlag AR, Beekman A, van der Wee N, Smit JH, et al. 2016. Gene expression in major depressive disorder. Mol Psychiatry. 21:339–347.
  • Januar V, Ancelin ML, Ritchie K, Saffery R, Ryan J. 2015. BDNF promoter methylation and genetic variation in late-life depression. Transl Psychiatry. 5:e619.
  • Jaumotte JD, Zigmond MJ. 2014. Comparison of GDF5 and GDNF as neuroprotective factors for postnatal dopamine neurons in ventral mesencephalic cultures. J Neurosci Res. 92:1425–1433.
  • Jia P, Kao CF, Kuo PH, Zhao Z. 2011. A comprehensive network and pathway analysis of candidate genes in major depressive disorder. BMC Syst Biol. 5:S12.
  • Juhasz G, Dunham JS, McKie S, Thomas E, Downey D, Chase D, Lloyd-Williams K, Toth ZG, Platt H, Mekli K, et al. 2011. The CREB1-BDNF-NTRK2 pathway in depression: multiple gene-cognition-environment interactions. Biol Psychiatry. 69:762–771.
  • Jun TY, Pae CU, Hoon H, Chae JH, Bahk WM, Kim KS, Serretti A. 2003. Possible association between -G308A tumour necrosis factor-alpha gene polymorphism and major depressive disorder in the Korean population. Psychiatr Genet. 13:179–181.
  • Kang HJ, Kim JM, Lee JY, Kim SY, Bae KY, Kim SW, Shin IS, Kim HR, Shin MG, Yoon JS. 2013a. BDNF promoter methylation and suicidal behavior in depressive patients. J Affect Disord. 151:679–685.
  • Kang HJ, Kim JM, Stewart R, Kim SY, Bae KY, Kim SW, Shin IS, Shin MG, Yoon JS. 2013b. Association of SLC6A4 methylation with early adversity, characteristics and outcomes in depression. Prog Neuropsychopharmacol Biol Psychiatry. 44:23–28.
  • Karg K, Burmeister M, Shedden K, Sen S. 2011. The serotonin transporter promoter variant (5-HTTLPR), stress, and depression meta-analysis revisited: evidence of genetic moderation. Arch Gen Psychiatry. 68:444–454.
  • Kato M, Serretti A. 2010. Review and meta-analysis of antidepressant pharmacogenetic findings in major depressive disorder. Mol Psychiatry. 15:473–500.
  • Kaufman J, Sullivan GM, Yang J, Ogden RT, Miller JM, Oquendo MA, Mann JJ, Parsey RV, DeLorenzo C. 2015. Quantification of the Serotonin 1A Receptor Using PET: Identification of a Potential Biomarker of Major Depression in Males. Neuropsychopharmacology. 40:1692–1699.
  • Keller S, Sarchiapone M, Zarrilli F, Videtic A, Ferraro A, Carli V, Sacchetti S, Lembo F, Angiolillo A, Jovanovic N, et al. 2010. Increased BDNF promoter methylation in the Wernicke area of suicide subjects. Arch Gen Psychiatry. 67:258–267.
  • Khait VD, Huang YY, Malone KM, Oquendo M, Brodsky B, Sher L, Mann JJ. 2002. Is there circannual variation of human platelet 5-HT(2A) binding in depression? J Affect Disord. 71:249–258.
  • Khait VD, Huang YY, Zalsman G, Oquendo MA, Brent DA, Harkavy-Friedman JM, Mann JJ. 2005. Association of serotonin 5-HT2A receptor binding and the T102C polymorphism in depressed and healthy Caucasian subjects. Neuropsychopharmacology. 30:166–172.
  • Kim JM, Stewart R, Kang HJ, Kim SY, Kim SW, Shin IS, Park MS, Kim HR, Shin MG, Cho KH, et al. 2013. A longitudinal study of BDNF promoter methylation and genotype with poststroke depression. J Affect Disord. 149:93–99.
  • Kim JM, Stewart R, Kim SW, Shin IS, Kim JT, Park MS, Park SW, Kim YH, Cho KH, Yoon JS. 2012. Associations of cytokine gene polymorphisms with post-stroke depression. World J Biol Psychiatry. 13:579–587.
  • Kishi T, Yoshimura R, Fukuo Y, Okochi T, Matsunaga S, Umene-Nakano W, Nakamura J, Serretti A, Correll CU, Kane JM, et al. 2013. The serotonin 1A receptor gene confer susceptibility to mood disorders: results from an extended meta-analysis of patients with major depression and bipolar disorder. Eur Arch Psychiatry Clin Neurosci. 263:105–118.
  • Kishi T, Yoshimura R, Kitajima T, Okochi T, Okumura T, Tsunoka T, Yamanouchi Y, Kinoshita Y, Kawashima K, Naitoh H, et al. 2009. HTR2A is Associated with SSRI Response in Major Depressive Disorder in a Japanese Cohort. Neuromolecular Med. 12:237–242.
  • Klengel T, Mehta D, Anacker C, Rex-Haffner M, Pruessner JC, Pariante CM, Pace TW, Mercer KB, Mayberg HS, Bradley B, et al. 2013. Allele-specific FKBP5 DNA demethylation mediates gene-childhood trauma interactions. Nat Neurosci. 16:33–41.
  • Koch JM, Hinze-Selch D, Stingele K, Huchzermeier C, Goder R, Seeck-Hirschner M, Aldenhoff JB. 2009. Changes in CREB phosphorylation and BDNF plasma levels during psychotherapy of depression. Psychother Psychosom. 78:187–192.
  • Koch JM, Kell S, Hinze-Selch D, Aldenhoff JB. 2002. Changes in CREB-phosphorylation during recovery from major depression. J Psychiatr Res. 36:369–375.
  • Kugaya A, Sanacora G, Staley JK, Malison RT, Bozkurt A, Khan S, Anand A, Van Dyck CH, Baldwin RM, Seibyl JP, et al. 2004. Brain serotonin transporter availability predicts treatment response to selective serotonin reuptake inhibitors. Biol Psychiatry. 56:497–502.
  • Lai IC, Hong CJ, Tsai SJ. 2003. Expression of cAMP response element-binding protein in major depression before and after antidepressant treatment. Neuropsychobiology. 48:182–185.
  • Lanquillon S, Krieg JC, Bening-Abu-Shach U, Vedder H. 2000. Cytokine production and treatment response in major depressive disorder. Neuropsychopharmacology. 22:370–379.
  • Launay JM, Mouillet-Richard S, Baudry A, Pietri M, Kellermann O. 2011. Raphe-mediated signals control the hippocampal response to SRI antidepressants via miR-16. Transl Psychiatry. 1:e56.
  • Lavebratt C, Aberg E, Sjoholm LK, Forsell Y. 2010. Variations in FKBP5 and BDNF genes are suggestively associated with depression in a Swedish population-based cohort. J Affect Disord. 125:249–255.
  • Lazary J, Juhasz G, Anderson IM, Jacob CP, Nguyen TT, Lesch KP, Reif A, Deakin JF, Bagdy G. 2011. Epistatic interaction of CREB1 and KCNJ6 on rumination and negative emotionality. Eur Neuropsychopharmacol. 21:63–70.
  • Lekman M, Laje G, Charney D, Rush AJ, Wilson AF, Sorant AJ, Lipsky R, Wisniewski SR, Manji H, McMahon FJ, et al. 2008. The FKBP5-gene in depression and treatment response–an association study in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) Cohort. Biol Psychiatry. 63:1103–1110.
  • Lemonde S, Turecki G, Bakish D, Du L, Hrdina PD, Bown CD, Sequeira A, Kushwaha N, Morris SJ, Basak A, et al. 2003. Impaired repression at a 5-hydroxytryptamine 1A receptor gene polymorphism associated with major depression and suicide. J Neurosci. 23:8788–8799.
  • Leo R, Di Lorenzo G, Tesauro M, Razzini C, Forleo GB, Chiricolo G, Cola C, Zanasi M, Troisi A, Siracusano A, et al. 2006. Association between enhanced soluble CD40 ligand and proinflammatory and prothrombotic states in major depressive disorder: pilot observations on the effects of selective serotonin reuptake inhibitor therapy. J Clin Psychiatry. 67:1760–1766.
  • Lesch KP. 2001. Serotonergic gene expression and depression: implications for developing novel antidepressants. J Affect Disord. 62:57–76.
  • Li XJ, Lee LW, Hayward C, Brusniak MY, Fong PY, McLean M, Mulligan J, Spicer D, Fang KC, Hunsucker SW, et al. 2015. An integrated quantification method to increase the precision, robustness, and resolution of protein measurement in human plasma samples. Clin Proteomics. 12:3.
  • Lim SW, Kim S, Carroll BJ, Kim DK. 2013. T-lymphocyte CREB as a potential biomarker of response to antidepressant drugs. Int J Neuropsychopharmacol. 16:967–974.
  • Lin E, Chen PS, Chang HH, Gean PW, Tsai HC, Yang YK, Lu RB. 2009. Interaction of serotonin-related genes affects short-term antidepressant response in major depressive disorder. Prog Neuropsychopharmacol Biol Psychiatry. 33:1167–1172.
  • Lin JY, Jiang MY, Kan ZM, Chu Y. 2014. Influence of 5-HTR2A genetic polymorphisms on the efficacy of antidepressants in the treatment of major depressive disorder: a meta-analysis. J Affect Disord. 168:430–438.
  • Lin PY, Tseng PT. 2015. Decreased glial cell line-derived neurotrophic factor levels in patients with depression: A meta-analytic study. J Psychiatr Res. 63:20–27.
  • Liu Y, Ho RC, Mak A. 2012. Interleukin (IL)-6, tumour necrosis factor alpha (TNF-alpha) and soluble interleukin-2 receptors (sIL-2R) are elevated in patients with major depressive disorder: a meta-analysis and meta-regression. J Affect Disord. 139:230–239.
  • Liukkonen T, Silvennoinen-Kassinen S, Jokelainen J, Rasanen P, Leinonen M, Meyer-Rochow VB, Timonen M. 2006. The association between C-reactive protein levels and depression: Results from the northern Finland 1966 birth cohort study. Biol Psychiatry. 60:825–830.
  • Lopez JP, Lim R, Cruceanu C, Crapper L, Fasano C, Labonte B, Maussion G, Yang JP, Yerko V, Vigneault E, et al. 2014. miR-1202 is a primate-specific and brain-enriched microRNA involved in major depression and antidepressant treatment. Nat Med. 20:764–768.
  • Lopez JP, Mamdani F, Labonte B, Beaulieu MM, Yang JP, Berlim MT, Ernst C, Turecki G. 2013. Epigenetic regulation of BDNF expression according to antidepressant response. Mol Psychiatry. 18:398–399.
  • Lorenzo-Luaces L. 2015. Heterogeneity in the prognosis of major depression: from the common cold to a highly debilitating and recurrent illness. Epidemiol Psychiatr Sci. 24:466–472.
  • Luciano M, Houlihan LM, Harris SE, Gow AJ, Hayward C, Starr JM, Deary IJ. 2010. Association of existing and new candidate genes for anxiety, depression and personality traits in older people. Behav Genet. 40:518–532.
  • Maes M, Anderson G, Kubera M, Berk M. 2014. Targeting classical IL-6 signalling or IL-6 trans-signalling in depression? Expert Opin Ther Targets. 18:495–512.
  • Malberg JE, Duman RS. 2003. Cell proliferation in adult hippocampus is decreased by inescapable stress: reversal by fluoxetine treatment. Neuropsychopharmacology. 28:1562–1571.
  • Malone KM, Ellis SP, Currier D, John Mann J. 2007. Platelet 5-HT2A receptor subresponsivity and lethality of attempted suicide in depressed in-patients. Int J Neuropsychopharmacol. 10:335–343.
  • Malynn S, Campos-Torres A, Moynagh P, Haase J. 2013. The pro-inflammatory cytokine TNF-α regulates the activity and expression of the serotonin transporter (SERT) in astrocytes. Neurochem Res. 38:694–704.
  • Mann JJ, Huang YY, Underwood MD, Kassir SA, Oppenheim S, Kelly TM, Dwork AJ, Arango V. 2000. A serotonin transporter gene promoter polymorphism (5-HTTLPR) and prefrontal cortical binding in major depression and suicide. Arch Gen Psychiatry. 57:729–738.
  • Maron E, Tammiste A, Kallassalu K, Eller T, Vasar V, Nutt DJ, Metspalu A. 2009. Serotonin transporter promoter region polymorphisms do not influence treatment response to escitalopram in patients with major depression. Eur Neuropsychopharmacol. 19:451–456.
  • Martins-de-Souza D, Maccarrone G, Ising M, Kloiber S, Lucae S, Holsboer F, Turck CW. 2014. Blood mononuclear cell proteome suggests integrin and Ras signaling as critical pathways for antidepressant treatment response. Biol Psychiatry. 76:e15–e17.
  • Masi G, Brovedani P. 2011. The hippocampus, neurotrophic factors and depression: possible implications for the pharmacotherapy of depression. CNS Drugs. 25:913–931.
  • Matsumoto Y, Fabbri C, Pellegrini S, Porcelli S, Politi P, Bellino S, Iofrida C, Mariotti V, Melissari E, Menchetti M, et al. 2014. Serotonin transporter gene: a new polymorphism may affect response to antidepressant treatments in major depressive disorder. Mol Diagn Ther. 18:567–577.
  • McKinnon MC, Yucel K, Nazarov A, MacQueen GM. 2009. A meta-analysis examining clinical predictors of hippocampal volume in patients with major depressive disorder. J Psychiatry Neurosci. 34:41–54.
  • Mendelson SD. 2000. The current status of the platelet 5-HT(2A) receptor in depression. J Affect Disord. 57:13–24.
  • Meyer JH, Kapur S, Eisfeld B, Brown GM, Houle S, DaSilva J, Wilson AA, Rafi-Tari S, Mayberg HS, Kennedy SH. 2001. The effect of paroxetine on 5-HT(2A) receptors in depression: an [(18)F]setoperone PET imaging study. Am J Psychiatry. 158:78–85.
  • Miller AH, Maletic V, Raison CL. 2009. Inflammation and its discontents: the role of cytokines in the pathophysiology of major depression. Biol Psychiatry. 65:732–741.
  • Misener VL, Gomez L, Wigg KG, Luca P, King N, Kiss E, Daroczi G, Kapornai K, Tamas Z, Mayer L, et al. International Consortium for Childhood-Onset Mood D. 2008. Cytokine Genes TNF, IL1A, IL1B, IL6, IL1RN and IL10, and childhood-onset mood disorders. Neuropsychobiology. 58:71–80.
  • Molendijk ML, Spinhoven P, Polak M, Bus BA, Penninx BW, Elzinga BM. 2014. Serum BDNF concentrations as peripheral manifestations of depression: evidence from a systematic review and meta-analyses on 179 associations (N = 9484). Mol Psychiatry. 19:791–800.
  • Mota R, Gazal M, Acosta BA, de Leon PB, Jansen K, Pinheiro RT, Souza LD, Silva RA, Oses JP, Quevedo L, et al. 2013. Interleukin-1beta is associated with depressive episode in major depression but not in bipolar disorder. J Psychiatr Res. 47:2011–2014.
  • Munafo MR, Durrant C, Lewis G, Flint J. 2009. Gene X environment interactions at the serotonin transporter locus. Biol Psychiatry. 65:211–219.
  • Murphy GM Jr, Hollander SB, Rodrigues HE, Kremer C, Schatzberg AF. 2004. Effects of the serotonin transporter gene promoter polymorphism on mirtazapine and paroxetine efficacy and adverse events in geriatric major depression. Arch Gen Psychiatry. 61:1163–1169.
  • Murray CJ, Atkinson C, Bhalla K, Birbeck G, Burstein R, Chou D, Dellavalle R, Danaei G, Ezzati M, Fahimi A, et al. US Burden of Disease Collaborators. 2013. The state of US health, 1990-2010: burden of diseases, injuries, and risk factors. JAMA. 310:591–608.
  • Musliner KL, Seifuddin F, Judy JA, Pirooznia M, Goes FS, Zandi PP. 2015. Polygenic risk, stressful life events and depressive symptoms in older adults: a polygenic score analysis. Psychol Med. 45:1709–1720.
  • Myung W, Lim SW, Kim S, Kim H, Chung JW, Seo MY, Kim JW, Carroll BJ, Kim DK. 2013. Serotonin transporter genotype and function in relation to antidepressant response in Koreans. Psychopharmacology (Berl). 225:283–290.
  • Niitsu T, Fabbri C, Bentini F, Serretti A. 2013. Pharmacogenetics in major depression: a comprehensive meta-analysis. Prog Neuropsychopharmacol Biol Psychiatry. 45:183–194.
  • O’Brien SM, Scott LV, Dinan TG. 2006. Antidepressant therapy and C-reactive protein levels. Br J Psychiatry. 188:449–452.
  • Odgerel Z, Talati A, Hamilton SP, Levinson DF, Weissman MM. 2013. Genotyping serotonin transporter polymorphisms 5-HTTLPR and rs25531 in European- and African-American subjects from the National Institute of Mental Health’s Collaborative Center for Genomic Studies. Transl Psychiatry. 3:e307.
  • Okada S, Morinobu S, Fuchikami M, Segawa M, Yokomaku K, Kataoka T, Okamoto Y, Yamawaki S, Inoue T, Kusumi I, et al. 2014. The potential of SLC6A4 gene methylation analysis for the diagnosis and treatment of major depression. J Psychiatr Res. 53:47–53.
  • Olsson CA, Foley DL, Parkinson-Bates M, Byrnes G, McKenzie M, Patton GC, Morley R, Anney RJ, Craig JM, Saffery R. 2010. Prospects for epigenetic research within cohort studies of psychological disorder: a pilot investigation of a peripheral cell marker of epigenetic risk for depression. Biol Psychol. 83:159–165.
  • Otsuki K, Uchida S, Watanuki T, Wakabayashi Y, Fujimoto M, Matsubara T, Funato H, Watanabe Y. 2008. Altered expression of neurotrophic factors in patients with major depression. J Psychiatr Res. 42:1145–1153.
  • Oxenstierna G, Edman G, Iselius L, Oreland L, Ross SB, Sedvall G. 1986. Concentrations of monoamine metabolites in the cerebrospinal fluid of twins and unrelated individuals–a genetic study. J Psychiatr Res. 20:19–29.
  • Pallavi P, Sagar R, Mehta M, Sharma S, Subramanium A, Shamshi F, Sengupta U, Qadri R, Pandey RM, Mukhopadhyay AK. 2013. Serum neurotrophic factors in adolescent depression: gender difference and correlation with clinical severity. J Affect Disord. 150:415–423.
  • Papakostas GI, Shelton RC, Kinrys G, Henry ME, Bakow BR, Lipkin SH, Pi B, Thurmond L, Bilello JA. 2013. Assessment of a multi-assay, serum-based biological diagnostic test for major depressive disorder: a pilot and replication study. Mol Psychiatry. 18:332–339.
  • Parsey RV, Ogden RT, Miller JM, Tin A, Hesselgrave N, Goldstein E, Mikhno A, Milak M, Zanderigo F, Sullivan GM, et al. 2010. Higher serotonin 1A binding in a second major depression cohort: modeling and reference region considerations. Biol Psychiatry. 68:170–178.
  • Pasco JA, Nicholson GC, Williams LJ, Jacka FN, Henry MJ, Kotowicz MA, Schneider HG, Leonard BE, Berk M. 2010. Association of high-sensitivity C-reactive protein with de novo major depression. Br J Psychiatry. 197:372–377.
  • Pena S, Baccichet E, Urbina M, Carreira I, Lima L. 2005. Effect of mirtazapine treatment on serotonin transporter in blood peripheral lymphocytes of major depression patients. Int Immunopharmacol. 5:1069–1076.
  • Perlis RH, Mischoulon D, Smoller JW, Wan YJ, Lamon-Fava S, Lin KM, Rosenbaum JF, Fava M. 2003. Serotonin transporter polymorphisms and adverse effects with fluoxetine treatment. Biol Psychiatry. 54:879–883.
  • Perlis RH, Purcell S, Fava M, Fagerness J, Rush AJ, Trivedi MH, Smoller JW. 2007. Association between treatment-emergent suicidal ideation with citalopram and polymorphisms near cyclic adenosine monophosphate response element binding protein in the STAR*D study. Arch Gen Psychiatry. 64:689–697.
  • Perlis RH, Fijal B, Adams DH, Sutton VK, Trivedi MH, Houston JP. 2009. Variation in catechol-O-methyltransferase is associated with duloxetine response in a clinical trial for major depressive disorder. Biol Psychiatry. 65:785–791.
  • Peters EJ, Slager SL, Jenkins GD, Reinalda MS, Garriock HA, Shyn SI, Kraft JB, McGrath PJ, Hamilton SP. 2009. Resequencing of serotonin-related genes and association of tagging SNPs to citalopram response. Pharmacogenet Genomics. 19:1–10.
  • Philibert RA, Sandhu H, Hollenbeck N, Gunter T, Adams W, Madan A. 2008. The relationship of 5HTT (SLC6A4) methylation and genotype on mRNA expression and liability to major depression and alcohol dependence in subjects from the Iowa Adoption Studies. Am J Med Genet B Neuropsychiatr Genet. 147B:543–549.
  • Pilc A, Chaki S, Nowak G, Witkin JM. 2008. Mood disorders: regulation by metabotropic glutamate receptors. Biochem Pharmacol. 75:997–1006.
  • Pineyro G, Blier P. 1999. Autoregulation of serotonin neurons: role in antidepressant drug action. Pharmacol Rev. 51:533–591.
  • Pizarro JM, Lumley LA, Medina W, Robison CL, Chang WE, Alagappan A, Bah MJ, Dawood MY, Shah JD, Mark B, et al. 2004. Acute social defeat reduces neurotrophin expression in brain cortical and subcortical areas in mice. Brain Res. 1025:10–20.
  • Pizzi C, Mancini S, Angeloni L, Fontana F, Manzoli L, Costa GM. 2009. Effects of selective serotonin reuptake inhibitor therapy on endothelial function and inflammatory markers in patients with coronary heart disease. Clin Pharmacol Ther. 86:527–532.
  • Polesskaya OO, Sokolov BP. 2002. Differential expression of the “C” and “T” alleles of the 5-HT2A receptor gene in the temporal cortex of normal individuals and schizophrenics. J Neurosci Res. 67:812–822.
  • Polyakova M, Stuke K, Schuemberg K, Mueller K, Schoenknecht P, Schroeter ML. 2015. BDNF as a biomarker for successful treatment of mood disorders: a systematic quantitative meta-analysis. J Affect Disord. 174:432–440.
  • Popp J, Leucht S, Heres S, Steimer W. 2006. Serotonin transporter polymorphisms and side effects in antidepressant therapy-a pilot study. Pharmacogenomics. 7:159–166.
  • Porcelli S, Fabbri C, Serretti A. 2012. Meta-analysis of serotonin transporter gene promoter polymorphism (5-HTTLPR) association with antidepressant efficacy. Eur Neuropsychopharmacol. 22:239–258.
  • Porcelli S, Fabbri C, Spina E, Serretti A, De Ronchi D. 2011. Genetic polymorphisms of cytochrome P450 enzymes and antidepressant metabolism. Expert Opin Drug Metab Toxicol. 7:1101–1115.
  • Powell TR, Schalkwyk LC, Heffernan AL, Breen G, Lawrence T, Price T, Farmer AE, Aitchison KJ, Craig IW, Danese A, et al. 2013. Tumor necrosis factor and its targets in the inflammatory cytokine pathway are identified as putative transcriptomic biomarkers for escitalopram response. Eur Neuropsychopharmacol. 23:1105–1114.
  • Rapaport MH, Nierenberg AA, Schettler PJ, Kinkead B, Cardoos A, Walker R, Mischoulon D. 2015. Inflammation as a predictive biomarker for response to omega-3 fatty acids in major depressive disorder: a proof-of-concept study. Mol Psychiatry. 21:71–79.
  • Rausch JL, Hobby HM, Shendarkar N, Johnson ME, Li J. 2001. Fluvoxamine treatment of mixed anxiety and depression: evidence for serotonergically mediated anxiolysis. J Clin Psychopharmacol. 21:139–142.
  • Rausch JL, Johnson ME, Fei YJ, Li JQ, Shendarkar N, Hobby HM, Ganapathy V, Leibach FH. 2002. Initial conditions of serotonin transporter kinetics and genotype: influence on SSRI treatment trial outcome. Biol Psychiatry. 51:723–732.
  • Rausch JL, Moeller FG, Johnson ME. 2003. Initial platelet serotonin (5-HT) transport kinetics predict nortriptyline treatment outcome. J Clin Psychopharmacol. 23:138–144.
  • Ren X, Dwivedi Y, Mondal AC, Pandey GN. 2011. Cyclic-AMP response element binding protein (CREB) in the neutrophils of depressed patients. Psychiatry Res. 185:108–112.
  • Rief W, Nestoriuc Y, Weiss S, Welzel E, Barsky AJ, Hofmann SG. 2009. Meta-analysis of the placebo response in antidepressant trials. J Affect Disord. 118:1–8.
  • Risch N, Herrell R, Lehner T, Liang KY, Eaves L, Hoh J, Griem A, Kovacs M, Ott J, Merikangas KR. 2009. Interaction between the serotonin transporter gene (5-HTTLPR), stressful life events, and risk of depression: a meta-analysis. JAMA. 301:2462–2471.
  • Rivera-Baltanas T, Olivares JM, Martinez-Villamarin JR, Fenton EY, Kalynchuk LE, Caruncho HJ. 2014. Serotonin 2A receptor clustering in peripheral lymphocytes is altered in major depression and may be a biomarker of therapeutic efficacy. J Affect Disord. 163:47–55.
  • Rocha TB, Hutz MH, Salatino-Oliveira A, Genro JP, Polanczyk GV, Sato JR, Wehrmeister FC, Barros FC, Menezes AM, Rohde LA, et al. 2015. Gene-Environment Interaction in Youth Depression: Replication of the 5-HTTLPR Moderation in a Diverse Setting. Am J Psychiatry. 172:978–985.
  • Rojas PS, Fritsch R, Rojas RA, Jara P, Fiedler JL. 2011. Serum brain-derived neurotrophic factor and glucocorticoid receptor levels in lymphocytes as markers of antidepressant response in major depressive patients: a pilot study. Psychiatry Res. 189:239–245.
  • Rosenfeld RD, Zeni L, Haniu M, Talvenheimo J, Radka SF, Bennett L, Miller JA, Welcher AA. 1995. Purification and identification of brain-derived neurotrophic factor from human serum. Protein Expr Purif. 6:465–471.
  • Sakaue M, Somboonthum P, Nishihara B, Koyama Y, Hashimoto H, Baba A, Matsuda T. 2000. Postsynaptic 5-hydroxytryptamine(1A) receptor activation increases in vivo dopamine release in rat prefrontal cortex. Br J Pharmacol. 129:1028–1034.
  • Serretti A, Chiesa A, Calati R, Massat I, Linotte S, Kasper S, Lecrubier Y, Antonijevic I, Forray C, Snyder L, et al. 2011. A preliminary investigation of the influence of CREB1 gene on treatment resistance in major depression. J Affect Disord. 128:56–63.
  • Singh AB. 2015. Improved Antidepressant Remission in Major Depression via a Pharmacokinetic Pathway Polygene Pharmacogenetic Report. Clin Psychopharmacol Neurosci. 13:150–156.
  • Singh YS, Altieri SC, Gilman TL, Michael HM, Tomlinson ID, Rosenthal SJ, Swain GM, Murphey-Corb MA, Ferrell RE, Andrews AM. 2012. Differential serotonin transport is linked to the rh5-HTTLPR in peripheral blood cells. Transl Psychiatry. 2:e77.
  • Smith RM, Papp AC, Webb A, Ruble CL, Munsie LM, Nisenbaum LK, Kleinman JE, Lipska BK, Sadee W. 2013. Multiple regulatory variants modulate expression of 5-hydroxytryptamine 2A receptors in human cortex. Biol Psychiatry. 73:546–554.
  • Smits K, Smits L, Peeters F, Schouten J, Janssen R, Smeets H, van Os J, Prins M. 2007. Serotonin transporter polymorphisms and the occurrence of adverse events during treatment with selective serotonin reuptake inhibitors. Int Clin Psychopharmacol. 22:137–143.
  • Sobocki P, Jonsson B, Angst J, Rehnberg C. 2006. Cost of depression in Europe. J Ment Health Policy Econ. 9:87–98.
  • Soule J, Messaoudi E, Bramham CR. 2006. Brain-derived neurotrophic factor and control of synaptic consolidation in the adult brain. Biochem Soc Trans. 34:600–604.
  • Stamm TJ, Rampp C, Wiethoff K, Stingl J, Mossner R, G OM, Ricken R, Seemuller F, Keck M, Fisher R, et al. 2016. The FKBP5 polymorphism rs1360780 influences the effect of an algorithm-based antidepressant treatment and is associated with remission in patients with major depression. J Psychopharmacol. 30:40–47.
  • Stein DJ, Hemmings S, Moolman-Smook H, Audenaert K. 2007. 5-HT2A: its role in frontally mediated executive function and related psychopathology. CNS Spectr. 12:512–516.
  • Strohmaier J, Wust S, Uher R, Henigsberg N, Mors O, Hauser J, Souery D, Zobel A, Dernovsek MZ, Streit F, et al. 2011. Sexual dysfunction during treatment with serotonergic and noradrenergic antidepressants: clinical description and the role of the 5-HTTLPR. World J Biol Psychiatry. 12:528–538.
  • Su S, Miller AH, Snieder H, Bremner JD, Ritchie J, Maisano C, Jones L, Murrah NV, Goldberg J, Vaccarino V. 2009. Common genetic contributions to depressive symptoms and inflammatory markers in middle-aged men: the Twins Heart Study. Psychosom Med. 71:152–158.
  • Szczepankiewicz A, Leszczynska-Rodziewicz A, Pawlak J, Narozna B, Rajewska-Rager A, Wilkosc M, Zaremba D, Maciukiewicz M, Twarowska-Hauser J. 2014. FKBP5 polymorphism is associated with major depression but not with bipolar disorder. J Affect Disord. 164:33–37.
  • Tadic A, Rujescu D, Muller MJ, Kohnen R, Stassen HH, Szegedi A, Dahmen N. 2008. Association analysis between variants of the interleukin-1beta and the interleukin-1 receptor antagonist gene and antidepressant treatment response in major depression. Neuropsychiatr Dis Treat. 4:269–276.
  • Taler M, Gil-Ad I, Lomnitski L, Korov I, Baharav E, Bar M, Zolokov A, Weizman A. 2007. Immunomodulatory effect of selective serotonin reuptake inhibitors (SSRIs) on human T lymphocyte function and gene expression. Eur Neuropsychopharmacol. 17:774–780.
  • Tansey KE, Guipponi M, Hu X, Domenici E, Lewis G, Malafosse A, Wendland JR, Lewis CM, McGuffin P, Uher R. 2013. Contribution of common genetic variants to antidepressant response. Biol Psychiatry. 73:679–682.
  • Tardito D, Musazzi L, Tiraboschi E, Mallei A, Racagni G, Popoli M. 2009. Early induction of CREB activation and CREB-regulating signalling by antidepressants. Int J Neuropsychopharmacol. 12:1367–1381.
  • Thakker DR, Natt F, Husken D, van der Putten H, Maier R, Hoyer D, Cryan JF. 2005. siRNA-mediated knockdown of the serotonin transporter in the adult mouse brain. Mol Psychiatry. 10:782–714.
  • Tiwari AK, Zai CC, Sajeev G, Arenovich T, Muller DJ, Kennedy JL. 2013. Analysis of 34 candidate genes in bupropion and placebo remission. Int J Neuropsychopharmacol. 16:771–781.
  • Tsao CW, Lin YS, Chen CC, Bai CH, Wu SR. 2006. Cytokines and serotonin transporter in patients with major depression. Prog Neuropsychopharmacol Biol Psychiatry. 30:899–905.
  • Tuglu C, Kara SH, Caliyurt O, Vardar E, Abay E. 2003. Increased serum tumor necrosis factor-alpha levels and treatment response in major depressive disorder. Psychopharmacology (Berl). 170:429–433.
  • Tylee DS, Kawaguchi DM, Glatt SJ. 2013. On the outside, looking in: a review and evaluation of the comparability of blood and brain “-omes”. Am J Med Genet B Neuropsychiatr Genet. 162B:595–603.
  • Uddin M, Koenen KC, Aiello AE, Wildman DE, de los Santos R, Galea S. 2011. Epigenetic and inflammatory marker profiles associated with depression in a community-based epidemiologic sample. Psychol Med. 41:997–1007.
  • Udina M, Moreno-Espana J, Navines R, Gimenez D, Langohr K, Gratacos M, Capuron L, de la Torre R, Sola R, Martin-Santos R. 2013. Serotonin and interleukin-6: the role of genetic polymorphisms in IFN-induced neuropsychiatric symptoms. Psychoneuroendocrinology. 38:1803–1813.
  • Uher R, Huezo-Diaz P, Perroud N, Smith R, Rietschel M, Mors O, Hauser J, Maier W, Kozel D, Henigsberg N, et al. 2009. Genetic predictors of response to antidepressants in the GENDEP project. Pharmacogenomics J. 9:225–233.
  • Uher R, Perroud N, Ng MY, Hauser J, Henigsberg N, Maier W, Mors O, Placentino A, Rietschel M, Souery D, et al. 2010. Genome-wide pharmacogenetics of antidepressant response in the GENDEP project. Am J Psychiatry. 167:555–564.
  • Utge S, Soronen P, Partonen T, Loukola A, Kronholm E, Pirkola S, Nyman E, Porkka-Heiskanen T, Paunio T. 2010. A population-based association study of candidate genes for depression and sleep disturbance. Am J Med Genet B Neuropsychiatr Genet. 153B:468–476.
  • Valkanova V, Ebmeier KP, Allan CL. 2013. CRP, IL-6 and depression: a systematic review and meta-analysis of longitudinal studies. J Affect Disord. 150:736–744.
  • van de Veerdonk FL, Netea MG. 2013. New Insights in the Immunobiology of IL-1 Family Members. Front Immunol. 4:167.
  • van der Doelen RH, Deschamps W, D’Annibale C, Peeters D, Wevers RA, Zelena D, Homberg JR, Kozicz T. 2014. Early life adversity and serotonin transporter gene variation interact at the level of the adrenal gland to affect the adult hypothalamo-pituitary-adrenal axis. Transl Psychiatry. 4:e409.
  • Vermeer H, Hendriks-Stegeman BI, van der Burg B, van Buul-Offers SC, Jansen M. 2003. Glucocorticoid-induced increase in lymphocytic FKBP51 messenger ribonucleic acid expression: a potential marker for glucocorticoid sensitivity, potency, and bioavailability. J Clin Endocrinol Metab. 88:277–284.
  • Vogelzangs N, Duivis HE, Beekman AT, Kluft C, Neuteboom J, Hoogendijk W, Smit JH, de Jonge P, Penninx BW. 2012. Association of depressive disorders, depression characteristics and antidepressant medication with inflammation. Transl Psychiatry. 2:e79.
  • Wainwright SR, Galea LA. 2013. The neural plasticity theory of depression: assessing the roles of adult neurogenesis and PSA-NCAM within the hippocampus. Neural Plast. 2013:805497.
  • Walsh BT, Seidman SN, Sysko R, Gould M. 2002. Placebo response in studies of major depression: variable, substantial, and growing. JAMA. 287:1840–1847.
  • Wang XC, Xu DJ, Chen GH, Xia Q, Liu LN. 2014. Association of 2 neurotrophic factor polymorphisms with efficacy of paroxetine in patients with major depressive disorder in a Chinese population. Ther Drug Monit. 36:612–617.
  • Wilkie MJ, Smith D, Reid IC, Day RK, Matthews K, Wolf CR, Blackwood D, Smith G. 2007. A splice site polymorphism in the G-protein beta subunit influences antidepressant efficacy in depression. Pharmacogenet Genomics. 17:207–215.
  • Winner J, Allen JD, Altar CA, Spahic-Mihajlovic A. 2013a. Psychiatric pharmacogenomics predicts health resource utilization of outpatients with anxiety and depression. Transl Psychiatry. 3:e242.
  • Winner JG, Carhart JM, Altar CA, Allen JD, Dechairo BM. 2013b. A prospective, randomized, double-blind study assessing the clinical impact of integrated pharmacogenomic testing for major depressive disorder. Discov Med. 16:219–227.
  • Winner JG, Carhart JM, Altar CA, Goldfarb S, Allen JD, Lavezzari G, Parsons KK, Marshak AG, Garavaglia S, Dechairo BM. 2015. Combinatorial pharmacogenomic guidance for psychiatric medications reduces overall pharmacy costs in a one year prospective evaluation. Curr Med Res. 31:1633–1643.
  • Wium-Andersen MK, Orsted DD, Nielsen SF, Nordestgaard BG. 2013. Elevated C-reactive protein levels, psychological distress, and depression in 73, 131 individuals. JAMA Psychiatry. 70:176–184.
  • Won E, Ham BJ. 2016. Imaging genetics studies on monoaminergic genes in major depressive disorder. Prog Neuropsychopharmacol Biol Psychiatry. 64:311–319.
  • Xu HB, Zhang RF, Luo D, Zhou Y, Wang Y, Fang L, Li WJ, Mu J, Zhang L, Zhang Y, et al. 2012. Comparative proteomic analysis of plasma from major depressive patients: identification of proteins associated with lipid metabolism and immunoregulation. Int J Neuropsychopharmacol. 15:1413–1425.
  • Yatham LN, Liddle PF, Shiah IS, Lam RW, Adam MJ, Zis AP, Ruth TJ. 2001. Effects of rapid tryptophan depletion on brain 5-HT(2) receptors: a PET study. Br J Psychiatry. 178:448–453.
  • Yeh YW, Ho PS, Chen CY, Kuo SC, Liang CS, Ma KH, Shiue CY, Huang WS, Cheng CY, Wang TY, et al. 2014. Incongruent reduction of serotonin transporter associated with suicide attempts in patients with major depressive disorder: a positron emission tomography study with 4-[18F]-ADAM. Int J Neuropsychopharmacol. 18:pyu065.
  • Yeh YW, Ho PS, Kuo SC, Chen CY, Liang CS, Yen CH, Huang CC, Ma KH, Shiue CY, Huang WS, et al. 2015. Disproportionate reduction of serotonin transporter may predict the response and adherence to antidepressants in patients with major depressive disorder: a positron emission tomography study with 4-[18F]-ADAM. Int J Neuropsychopharmacol. 18:pyu120.
  • Yoshimura R, Hori H, Ikenouchi-Sugita A, Umene-Nakano W, Katsuki A, Atake K, Nakamura J. 2013. Plasma levels of interleukin-6 and selective serotonin reuptake inhibitor response in patients with major depressive disorder. Hum Psychopharmacol. 28:466–470.
  • Yu YW, Chen TJ, Hong CJ, Chen HM, Tsai SJ. 2003. Association Study of the interleukin-1 beta (C-511T) genetic polymorphism with major depressive disorder, associated symptomatology, and antidepressant response. Neuropsychopharmacology. 28:1182–1185.
  • Yubero-Lahoz S, Robledo P, Farre M, de laTorre R. 2013. Platelet SERT as a peripheral biomarker of serotonergic neurotransmission in the central nervous system. Curr Med Chem. 20:1382–1396.
  • Zakharyan R, Petrek M, Arakelyan A, Mrazek F, Atshemyan S, Boyajyan A. 2012. Interleukin-6 promoter polymorphism and plasma levels in patients with schizophrenia. Tissue Antigens. 80:136–142.
  • Zalli A, Jovanova O, Hoogendijk WJ, Tiemeier H, Carvalho LA. 2015. Low-grade inflammation predicts persistence of depressive symptoms. Psychopharmacology (Berl). 233:1669-1678.
  • Zannas AS, Binder EB. 2014. Gene-environment interactions at the FKBP5 locus: sensitive periods, mechanisms and pleiotropism. Genes Brain Behav. 13:25–37.
  • Zhang X, Zhang Z, Sha W, Xie C, Xi G, Zhou H, Zhang Y. 2009. Electroconvulsive therapy increases glial cell-line derived neurotrophic factor (GDNF) serum levels in patients with drug-resistant depression. Psychiatry Res. 170:273–275.
  • Zhang X, Zhang Z, Xie C, Xi G, Zhou H, Zhang Y, Sha W. 2008. Effect of treatment on serum glial cell line-derived neurotrophic factor in depressed patients. Prog Neuropsychopharmacol Biol Psychiatry. 32:886–890.
  • Zhang ZJ, Wang D, Man SC, Ng R, McAlonan GM, Wong HK, Wong W, Lee J, Tan QR. 2014. Platelet 5-HT(1A) receptor correlates with major depressive disorder in drug-free patients. Prog Neuropsychopharmacol Biol Psychiatry. 53:74–79.
  • Zhao X, Huang Y, Li J, Ma H, Jin Q, Wang Y, Wu L, Zhu G. 2012. Association between the 5-HT1A receptor gene polymorphism (rs6295) and antidepressants: a meta-analysis. Int Clin Psychopharmacol. 27:314–320.
  • Zhao X, Sun L, Sun YH, Ren C, Chen J, Wu ZQ, Jiang YH, Lv XL. 2014. Association of HTR2A T102C and A-1438G polymorphisms with susceptibility to major depressive disorder: a meta-analysis. Neurol Sci. 35:1857–1866.
  • Zobel A, Schuhmacher A, Jessen F, Hofels S, von Widdern O, Metten M, Pfeiffer U, Hanses C, Becker T, Rietschel M, et al. 2010. DNA sequence variants of the FKBP5 gene are associated with unipolar depression. Int J Neuropsychopharmacol. 13:649–660.
  • Zubenko GS, Hughes HB, 3rd, Stiffler JS, Brechbiel A, Zubenko WN, Maher BS, Marazita ML. 2003a. Sequence variations in CREB1 cosegregate with depressive disorders in women. Mol Psychiatry. 8:611–618.
  • Zubenko GS, Maher B, Hughes HB, 3rd, Zubenko WN, Stiffler JS, Kaplan BB, Marazita ML. 2003b. Genome-wide linkage survey for genetic loci that influence the development of depressive disorders in families with recurrent, early-onset, major depression. Am J Med Genet B Neuropsychiatr Genet. 123B:1–18.
  • Zunszain PA, Anacker C, Cattaneo A, Choudhury S, Musaelyan K, Myint AM, Thuret S, Price J, Pariante CM. 2012. Interleukin-1β: a new regulator of the kynurenine pathway affecting human hippocampal neurogenesis. Neuropsychopharmacology. 37:939–949.

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