ErbB3 mRNA leukocyte levels as a biomarker for major depressive disorder

BMC Psychiatry

Massimo Gennarelli⁴  Stefano Bignotti¹  Andreas Conca⁵  Vincenzo Florio⁵  Maurizio Popoli³  Alessandra Mallei³  Alessandro Barbon²  Cristina Mora²  Annamaria Cattaneo²  Nadia Cattane²  Alessandra Minelli²  Elena Milanesi² 

[1] Psychiatric Unit, I.R.C.C.S. “San Giovanni di Dio” - Fatebenefratelli, via Pilastoni 4, Brescia, 25123, Italy;Department of Biomedical Sciences and Biotechnologies - Biology and Genetic Division, University of Brescia, Viale Europa 11, Brescia, 25123, Italy;Department of Pharmacological Sciences, Center of Neuropharmacology, University of Milano, Via Balzaretti 9, Milano, Italy;Genetic Unit, I.R.C.C.S. “San Giovanni di Dio” - Fatebenefratelli, Via Pilastroni, 4, Brescia, 25123, Italy;Department of Psychiatry, Central Hospital of Bolzano, Bolzano, Italy

关键词: Leukocytes;    Biomarkers;    Fgfr1;    ErbB3;    Major Depressive Disorder MDD;   

Others  :  1124286
DOI  :  10.1186/1471-244X-12-145

 received in 2012-02-21, accepted in 2012-08-31,  发布年份 2012

【 摘 要 】

Background

In recent years, the identification of peripheral biomarkers that are associated with psychiatric diseases, such as Major Depressive Disorder (MDD), has become relevant because these biomarkers may improve the efficiency of the differential diagnosis process and indicate targets for new antidepressant drugs. Two recent candidate genes, ErbB3 and Fgfr1, are growth factors whose mRNA levels have been found to be altered in the leukocytes of patients that are affected by bipolar disorder in a depressive state. On this basis, the aim of the study was to determine if ErbB3 and Fgfr1 mRNA levels could be a biomarkers of MDD.

Methods

We measured by Real Time PCR ErbB3 and Fgfr1 mRNA expression levels in leukocytes of MDD patients compared with controls. Successively, to assess whether ErbB3 mRNA levels were influenced by previous antidepressant treatment we stratified our patients sample in two cohorts, comparing drug-naive versus drug-free patients. Moreover, we evaluated the levels of the transcript in MDD patients after 12 weeks of antidepressant treatment, and in prefrontal cortex of rats stressed and treated with an antidepressant drug of the same class.

Results

These results showed that ErbB3 but not Fgfr1 mRNA levels were reduced in leukocytes of MDD patients compared to healthy subjects. Furthermore, ErbB3 levels were not affected by antidepressant treatment in either human or animal models

Conclusions

Our data suggest that ErbB3 might be considered as a biomarker for MDD and that its deficit may underlie the pathopsysiology of the disease and is not a consequence of treatment. Moreover the study supports the usefulness of leukocytes as a peripheral system for identifying biomarkers in psychiatric diseases.

【 授权许可】

   
2012 Milanesi et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

【 参考文献 】

• [1]Belmaker RH, Agam G: Major depressive disorder. N Engl J Med 2008, 358(1):55-68.
• [2]Levinson DF: The genetics of depression: a review. Biol Psychiatry 2006, 60(2):84-92.
• [3]Lesko LJ, Atkinson AJ Jr: Use of biomarkers and surrogate endpoints in drug development and regulatory decision making: criteria, validation, strategies. Annu Rev Pharmacol Toxicol 2001, 41:347-366.
• [4]Schmidt HD, Shelton RC, Duman RS: Functional biomarkers of depression: diagnosis, treatment, and pathophysiology. Neuropsychopharmacology 2011, 36(12):2375-2394.
• [5]Bocchio-Chiavetto L, Bagnardi V, Zanardini R, Molteni R, Nielsen MG, Placentino A, Giovannini C, Rillosi L, Ventriglia M, Riva MA, et al.: Serum and plasma BDNF levels in major depression: a replication study and meta-analyses. World J Biol Psychiatry 2010, 11(6):763-773.
• [6]Bocchio-Chiavetto L, Zanardini R, Bortolomasi M, Abate M, Segala M, Giacopuzzi M, Riva MA, Marchina E, Pasqualetti P, Perez J, et al.: Electroconvulsive Therapy (ECT) increases serum Brain Derived Neurotrophic Factor (BDNF) in drug resistant depressed patients. Eur Neuropsychopharmacol 2006, 16(8):620-624.
• [7]Minelli A, Zanardini R, Abate M, Bortolomasi M, Gennarelli M, Bocchio-Chiavetto L: Vascular Endothelial Growth Factor (VEGF) serum concentration during electroconvulsive therapy (ECT) in treatment resistant depressed patients. Prog Neuropsychopharmacol Biol Psychiatry 2011, 35(5):1322-1325.
• [8]Le-Niculescu H, Kurian SM, Yehyawi N, Dike C, Patel SD, Edenberg HJ, Tsuang MT, Salomon DR, Nurnberger JI Jr, Niculescu AB: Identifying blood biomarkers for mood disorders using convergent functional genomics. Mol Psychiatry 2009, 14(2):156-174.
• [9]Gaughran F, Payne J, Sedgwick PM, Cotter D, Berry M: Hippocampal FGF-2 and FGFR1 mRNA expression in major depression, schizophrenia and bipolar disorder. Brain Res Bull 2006, 70(3):221-227.
• [10]Aston C, Jiang L, Sokolov BP: Transcriptional profiling reveals evidence for signaling and oligodendroglial abnormalities in the temporal cortex from patients with major depressive disorder. Mol Psychiatry 2005, 10(3):309-322.
• [11]Tochigi M, Iwamoto K, Bundo M, Sasaki T, Kato N, Kato T: Gene expression profiling of major depression and suicide in the prefrontal cortex of postmortem brains. Neurosci Res 2008, 60(2):184-191.
• [12]Sibilia M, Kroismayr R, Lichtenberger BM, Natarajan A, Hecking M, Holcmann M: The epidermal growth factor receptor: from development to tumorigenesis. Differentiation 2007, 75(9):770-787.
• [13]Lemke G: Neuregulin-1 and myelination. Sci STKE 2006, 2006(325):pe11.
• [14]Riethmacher D, Sonnenberg-Riethmacher E, Brinkmann V, Yamaai T, Lewin GR, Birchmeier C: Severe neuropathies in mice with targeted mutations in the ErbB3 receptor. Nature 1997, 389(6652):725-730.
• [15]Borroto-Escuela DO, Romero-Fernandez W, Mudo G, Perez-Alea M, Ciruela F, Tarakanov AO, Narvaez M, Di Liberto V, Agnati LF, Belluardo N, et al.: Fibroblast growth factor receptor 1–5-Hydroxytryptamine 1A Heteroreceptor complexes and their enhancement of hippocampal plasticity. Biol Psychiatry 2012, 71(1):84-91.
• [16]Sheehan DV, Lecrubier Y, Sheehan KH, Amorim P, Janavs J, Weiller E, Hergueta T, Baker R, Dunbar GC: The Mini-International Neuropsychiatric Interview (M.I.N.I.): the development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. J Clin Psychiatry 1998, 59(Suppl 20):22-33. quiz 34–57
• [17]Musazzi L, Milanese M, Farisello P, Zappettini S, Tardito D, Barbiero VS, Bonifacino T, Mallei A, Baldelli P, Racagni G, et al.: Acute stress increases depolarization-evoked glutamate release in the rat prefrontal/frontal cortex: the dampening action of antidepressants. PLoS One 2010, 5(1):e8566.