Quest for biomarkers of treatment-resistant depression: shifting the paradigm toward risk

Donald F Smith, Donald F Smith

Abstract

The search for potential biomarkers of psychiatric disorders is a central topic in biological psychiatry. This review concerns published studies on potential biomarkers of treatment-resistant depression (TRD). The search for biomarkers of TRD in the bloodstream has focused on cytokines and steroids as well as brain-derived neurotropic factor. Additional approaches to identifying biomarkers of TRD have dealt with cerebrospinal fluid analysis, magnetic resonance imaging, and positron emission tomography. Some studies have also investigated potential genetic and epigenetic factors in TRD. Most studies have, however, used a post hoc experimental design that failed to determine the association between biomarkers and the initial risk of TRD. Particular attention in future studies should be on shifting the experimental paradigm toward procedures that can determine the risk for developing treatment resistance in untreated depressed individuals.

Keywords: biomarkers; brain imaging; cytokines; depressive disorders; experimental design; immune system; treatment resistance.

Figures

Figure 1
Figure 1
Annual number of publications on biomarkers of human depressive disorders (diamonds) and on biomarkers of human treatment-resistant depression (circles).

References

    1. Aklillu E., Karlsson S., Zachrisson O. O., Ozdemir V., Agren H. (2009). Association of MAOA gene functional promoter polymorphism with CSF dopamine turnover and atypical depression. Pharmacogenet. Genomics 19, 267–275 10.1097/FPC.0b013e328328d4d3
    1. Anttila S., Huuhka K., Huuhka M., Rontu R., Hurme M., Leinonen E., et al. (2007). Interaction between 5-HT1A and BDNF genotypes increases the risk of treatment-resistant depression. J. Neural Transm. 114, 1065–1068 10.1007/s00702-007-0705-9
    1. Autry A. E., Monteggia L. M. (2012). Brain-derived neurotrophic factor and neuropsychiatric disorders. Pharmacol. Rev. 64, 238–258 10.1124/pr.111.005108
    1. Bale T. L., Baram T. Z., Brown A. S., Goldstein J. M., Insel T. R., McCarthy M. M., et al. (2010). Early life programming and neurodevelopmental disorders. Biol. Psychiatry 68, 314–319 10.1016/j.biopsych.2010.05.028
    1. Bauer M. E., Papadopoulos A., Poon L., Perks P., Lightman S. L., Checkley S., et al. (2002). Dexamethasone-induced effects on lymphocyte distribution and expression of adhesion molecules in treatment-resistant depression. Psychiatry Res. 113, 1–15 10.1016/S0165-1781(02)00243-3
    1. Bauer M. E., Papadopoulos A., Poon L., Perks P., Lightman S. L., Checkley S., et al. (2003). Altered glucocorticoid immunoregulation in treatment resistant depression. Psychoneuroendocrinology 28, 49–65 10.1016/S0306-4530(02)00009-4
    1. Berlim M. T., Fleck M. P., Turecki G. (2008). Current trends in the assessment and somatic treatment of resistant/refractory major depression: an overview. Ann. Med. 40, 149–159 10.1080/07853890701769728
    1. Berlim M. T., Turecki G. (2007). Definition, assessment, and staging of treatment-resistant refractory major depression: a review of current concepts and methods. Can. J. Psychiatry 52, 46–54
    1. Bowell T., Kemp G. (2005). Critical Thinking. A Concise Guide, 2nd Edn. New York, NY: Routledge
    1. Brady L. S., Insel T. R. (2012). Translating discoveries into medicine: psychiatric drug development in 2011. Neuropsychopharmacology 37, 281–283 10.1038/npp.2011.106
    1. Cardoso de Almeida J. R., Phillips M. L. (2013). Distinguishing between unipolar depression and bipolar depression: current and future clinical and neuroimaging perspectives. Biol. Psychiatry 73, 111–118 10.1016/j.biopsych.2012.06.010
    1. Chen C. H., Ridler K., Suckling J., Williams S., Fu C. H., Merlo-Pich E., et al. (2007). Brain imaging correlates of depressive symptom severity and predictors of symptom improvement after antidepressant treatment. Biol. Psychiatry 62, 407–414 10.1016/j.biopsych.2006.09.018
    1. Dowlati Y., Herrmann N., Swardfager W., Liu H., Sham L., Reim E. K., et al. (2010). A meta-analysis of cytokines in major depression. Biol. Psychiatry 67, 446–457 10.1016/j.biopsych.2009.09.033
    1. Fava M. (2003). Diagnosis and definition of treatment-resistant depression. Biol. Psychiatry 53, 649–659 10.1016/S0006-3223(03)00231-2
    1. Fava M., Rush A. J., Trivedi M. H., Nierenberg A. A., Thase M. E., Sackeim H. A., et al. (2003). Background and rationale for the sequenced treatment alternatives to relieve depression (STAR∗D) study. Psychiatr. Clin. North Am. 26, 457–494 10.1016/S0193-953X(02)00107-7
    1. Fernandes B., Gama C. S., Massuda R., Torres M., Camargo D., Kunz M., et al. (2009). Serum brain-derived neurotrophic factor (BDNF) is not associated with response to electroconvulsive therapy (ECT): a pilot study in drug resistant depressed patients. Neurosci. Lett. 453, 195–198 10.1016/j.neulet.2009.02.032
    1. Frey B. N., Andreazza A. C., Houenou J., Jamain S., Goldstein B. I., Frye M. A., et al. (2013). Biomarkers in bipolar disorder: a positional paper from the International Society for Bipolar Disorders Biomarkers Task Force. Aust. N. Z. J. Psychiatry 47, 321–332 10.1177/0004867413478217
    1. Gilovich T. (1993). How We Know What Isn’t So. The Fallibility of Human Reason in Everyday Life. New York, NY: The Free Press
    1. Hoflich A., Baldinger P., Savli M., Lanzenberger R., Kasper S. (2012). Imaging treatment effects in depression. Rev. Neurosci. 23, 227–252
    1. Ingle D. J. (1972). Fallacies and errors in the wonderlands of biology, medicine, and Lewis Carroll. Perspect. Biol. Med. 15, 254–281
    1. Jaenisch R., Bird A. (2003). Epigenetic regulation of gene expression: how the genome integrates intrinsic and environmental signals. Nat. Genet. 33, 245–254 10.1038/ng1089
    1. Li B., Liu L., Friston K. J., Shen H., Wang L., Zeng L. L., et al. (2012). A treatment-resistant default mode subnetwork in major depression. Biol. Psychiatry (in press). 10.1016/j.biopsych.2012.11.007
    1. Liu F., Guo W., Yu D., Gao Q., Gao K., Xue Z., et al. (2012). Classification of different therapeutic responses of major depressive disorder with multivariate pattern analysis method based on structural MR scans. PLoS ONE 7:e40968 10.1371/journal.pone.0040968
    1. Macaluso M., Preskorn S. H. (2012). How biomarkers will change psychiatry: from clinical trials to practice. Part I: introduction. J. Psychiatr. Pract. 18, 118–121 10.1097/01.pra.0000413277.11091.25
    1. Markopoulou K., Papadopoulos A., Juruena M. F., Poon L., Pariante C. M., Cleare A. J. (2009). The ratio of cortisol/DHEA in treatment resistant depression. Psychoneuroendocrinology 34, 19–26 10.1016/j.psyneuen.2008.08.004
    1. Martin R. M. (1997). Scientific Thinking. Peterborough, ON: Broadview Press
    1. Mayberg H. S. (2007). Defining the neural circuitry of depression: toward a new nosology with therapeutic implications. Biol. Psychiatry 61, 729–730 10.1016/j.biopsych.2007.01.013
    1. Mayberg H. S., Brannan S. K., Tekell J. L., Silva J. A., Mahurin R. K., McGinnis S., et al. (2000). Regional metabolic effects of fluoxetine in major depression: serial changes and relationship to clinical response. Biol. Psychiatry 48, 830–843 10.1016/S0006-3223(00)01036-2
    1. Miller A. H., Maletic V., Raison C. L. (2009). Inflammation and its discontents: the role of cytokines in the pathophysiology of major depression. Biol. Psychiatry 65, 732–741 10.1016/j.biopsych.2008.11.029
    1. Naish J. H., Baldwin R. C., Patankar T., Jeffries S., Burns A. S., Taylor C. J., et al. (2006). Abnormalities of CSF flow patterns in the cerebral aqueduct in treatment-resistant late-life depression: a potential biomarker of microvascular angiopathy. Magn. Reson. Med. 56, 509–516 10.1002/mrm.20999
    1. O’Brien S. M., Scully P., Fitzgerald P., Scott L. V., Dinan T. G. (2007). Plasma cytokine profiles in depressed patients who fail to respond to selective serotonin reuptake inhibitor therapy. J. Psychiatr. Res. 41, 326–331 10.1016/j.jpsychires.2006.05.013
    1. Pariante C. M., Miller A. H. (2001). Glucocorticoid receptors in major depression: relevance to pathophysiology and treatment. Biol. Psychiatry 49, 391–404 10.1016/S0006-3223(00)01088-X
    1. Perlis R. H. (2013). A clinical risk stratification tool for predicting treatment resistance in major depressive disorder. Biol. Psychiatry (in press). 10.1016/j.biopsych.2012.12.007
    1. Purcell S. M. (2013). Antidepressant response and polygenes. Biol. Psychiatry 73, 600–601 10.1016/j.biopsych.2013.01.023
    1. Raison C. L., Rutherford R. E., Woolwine B. J., Shuo C., Schettler P., Drake D. F., et al. (2013). A randomized controlled trial of the tumor necrosis factor antagonist infliximab for treatment-resistant depression: the role of baseline inflammatory biomarkers. JAMA Psychiatry 70, 31–41 10.1001/2013.jamapsychiatry.4
    1. Rothschild A. J. (2003). Challenges in the treatment of depression with psychotic features. Biol. Psychiatry 53, 680–690 10.1016/S0006-3223(02)01747-X
    1. Ruhe H. G., Rooijen R. G., Spijker J., Peeters F. P., Schene A. H. (2012). Staging methods for treatment resistant depression. A systematic review. J. Affect. Disord. 137, 35–45 10.1016/j.jad.2011.02.020
    1. Rush A. J., Warden D., Wisniewski S. R., Fava M., Trivedi M. H., Gaynes B. N., et al. (2009). STAR∗D: revising conventional wisdom. CNS Drugs 23, 627–647
    1. Schildkraut J. J. (1965). The catecholamine hypothesis of affective disorders: a review of supporting evidence. Am. J. Psychiatry 122, 509–522
    1. Schlaepfer T. E., Agren H., Monteleone P., Gasto C., Pitchot W., Rouillon F., et al. (2012). The hidden third: improving outcome in treatment-resistant depression. J. Psychopharmacol. (Oxford) 26, 587–602 10.1177/0269881111431748
    1. Schneider B., Prvulovic D. (2013). Novel biomarkers in major depression. Curr. Opin. Psychiatry 26, 47–53 10.1097/YCO.0b013e32835a5947
    1. Schosser A., Serretti A., Souery D., Mendlewicz J., Zohar J., Montgomery S., et al. (2012). European Group for the Study of Resistant Depression (GSRD) – where have we gone so far: review of clinical and genetic findings. Eur. Neuropsychopharmacol. 22, 453–468 10.1016/j.euroneuro.2012.02.006
    1. Sen S., Duman R., Sanacora G. (2008). Serum brain-derived neurotrophic factor, depression, and antidepressant medications: meta-analyses and implications. Biol. Psychiatry 64, 527–532 10.1016/j.biopsych.2008.05.005
    1. Shah P. J., Ebmeier K. P., Glabus M. F., Goodwin G. M. (1998). Cortical grey matter reductions associated with treatment-resistant chronic unipolar depression. Controlled magnetic resonance imaging study. Br. J. Psychiatry 172, 527–532 10.1192/bjp.172.6.527
    1. Shah P. J., Glabus M. F., Goodwin G. M., Ebmeier K. P. (2002). Chronic, treatment-resistant depression and right fronto-striatal atrophy. Br. J. Psychiatry 180, 434–440 10.1192/bjp.180.5.434
    1. Simpson S., Baldwin R. C., Jackson A., Burns A. S. (1998). Is subcortical disease associated with a poor response to antidepressants? Neurological, neuropsychological and neuroradiological findings in late-life depression. Psychol. Med. 28, 1015–1026 10.1017/S003329179800693X
    1. Smith D. F., Stork B. S., Wegener G., Ashkanian M., Jakobsen S., Bender D., et al. (2009). [11C]Mirtazapine binding in depressed antidepressant nonresponders studied by PET neuroimaging. Psychopharmacology (Berl.) 206, 133–140 10.1007/s00213-009-1587-3
    1. Stewart J. A., Kampman O., Huuhka M., Anttila S., Huuhka K., Lehtimaki T., et al. (2009). ACE polymorphism and response to electroconvulsive therapy in major depression. Neurosci. Lett. 458, 122–125 10.1016/j.neulet.2009.04.057
    1. Tammen S. A., Friso S., Choi S. W. (2013). Epigenetics: the link between nature and nurture. Mol. Aspects Med. 34, 753–764 10.1016/j.mam.2012.07.018
    1. Tansey K. E., Guipponi M., Hu X., Domenici E., Lewis G., Malafosse A., et al. (2013). Contribution of common genetic variants to antidepressant response. Biol. Psychiatry 73, 679–682 10.1016/j.biopsych.2012.10.030
    1. Thase M. E., Rush A. J. (1995). “Treatment-resistant depression,” in Psychopharmacology: The Fourth Generation of Progress, eds Bloom F. E., Kupfer D. J. (New York: Raven Press; ), 1081–1097
    1. Uher R., Perlis R. H., Henigsberg N., Zobel A., Rietschel M., Mors O., et al. (2012). Depression symptom dimensions as predictors of antidepressant treatment outcome: replicable evidence for interest-activity symptoms. Psychol. Med. 42, 967–980 10.1017/S0033291711001905
    1. Wittchen H. U., Jacobi F., Rehm J., Gustavsson A., Svensson M., Jonsson B., et al. (2011). The size and burden of mental disorders and other disorders of the brain in Europe 2010. Eur. Neuropsychopharmacol. 21, 655–679 10.1016/j.euroneuro.2011.07.018
    1. Xiang Y. T., Wang G., Hu C., Guo T., Ungvari G. S., Kilbourne A. M., et al. (2012). Demographic and clinical features and prescribing patterns of psychotropic medications in patients with the melancholic subtype of major depressive disorder in China. PLoS ONE 7:e39840 10.1371/journal.pone.0039840
    1. Zhang T. J., Wu Q. Z., Huang X. Q., Sun X. L., Zou K., Lui S., et al. (2009). Magnetization transfer imaging reveals the brain deficit in patients with treatment-refractory depression. J. Affect. Disord. 117, 157–161 10.1016/j.jad.2009.01.003

Source: PubMed

Patrocinadores e Colaboradores

Condições médicas

Intervenções de drogas

3
Se inscrever