The mRNA Expression Status of Dopamine Receptor D2, Dopamine Receptor D3 and DARPP-32 in T Lymphocytes of Patients with Early Psychosis
Abstract
:1. Introduction
2. Results and Discussion
2.1. Results
Characteristic | Control (n = 30) | Psychotic Disorder NOS (n = 18) | Schizophrenia/Schizophreniform Disorder (n = 14) | Medicated Group (n = 19) | Drug-naive/Drug-free Group (n = 13) |
---|---|---|---|---|---|
Mean age (SD) | 30.03 (8.35) | 29.61 (13.24) | 36.50 (12.95) | 31.63 (12.01) | 34.25 (16.20) |
Sex, m/f | 14/16 | 9/9 | 6/8 | 9/10 | 6/7 |
2.1.1. Comparison of DRD2, DRD3, and DARPP-32 mRNA Levels among Controls, and Patients with Psychotic Disorder NOS and Schizophrenia/Schizophreniform Disorder
Gene | Control (n) | Psychotic Disorder NOS (n) | Schizophrenia/Schizophreniform Disorder (n) | p-Value |
---|---|---|---|---|
DRD2 | 0.95 (0.67–1.45) (24) | 1.32 (1.05–1.87) (16) | 1.31 (0.95–1.98) (9) | 0.19 |
DRD3 | 1.22 (0.85–1.88) (28) | 1.41 (0.99–2.75) (17) | 2.30 (1.50–3.57) (13) † | 0.03 * |
DARPP-32 | 9.21 (6.38–30.93) (21) | 22.48 (12.77–33.46) (14) | 15.64 (8.92–37.08) (8) | 0.31 |
2.1.2. Comparison of DRD2, DRD3 and DARPP-32 mRNA Levels among Controls, and Drug-Naive/Drug-Free and Medicated Patients
Gene | Control (n) | Drug-Naive/Drug-Free Group (n) | Medicated Group (n) | p Value |
---|---|---|---|---|
DRD2 | 0.95 (0.67–1.45) (24) | 1.18 (0.94–2.03) (10) | 1.35 (1.12–1.79) (15) | 0.19 |
DRD3 | 1.22 (0.85–1.88) (28) | 1.78 (0.97–4.39) (12) | 1.88 (1.22–2.89) (18) | 0.08 |
DARPP-32 | 9.21 (6.38–30.93) (21) | 18.52 (12.86–33.46) (10) | 19.61(8.82–36.34) (12) | 0.30 |
2.1.3. Correlation Analysis between DRD2, DRD3, and DARPP-32 mRNA Levels and Five Factors of the PANSS in Patients with Psychotic Disorder NOS and Schizophrenia/Schizophreniform Disorder
PANSS Factors | Psychotic Disorder NOS | Schizophrenia/Schizophreniform Disorder | ||||
---|---|---|---|---|---|---|
DRD2 | DRD3 | DARPP-32 | DRD2 | DRD3 | DARPP-32 | |
Positive | −0.296 | −0.040 | 0.147 | 0.487 | −0.061 | 0.146 |
Cognitive | −0.287 | 0.043 | −0.157 | 0.393 | 0.092 | 0.254 |
Negative | −0.338 | 0.341 | 0.077 | 0.189 | −0.058 | 0.244 |
Excited | −0.396 | −0.065 | 0.176 | 0.616 * | 0.074 | −0.405 |
Anxiety/Depression | −0.093 | −0.076 | 0.252 | 0.326 | 0.292 | −0.319 |
2.2. Discussion
3. Experimental Section
3.1. Subjects
3.2. Preparation of T Lymphocytes
3.3. RNA Extraction, cDNA Synthesis and Quantitative Real-Time Polymerase Chain Reaction (RT-PCR)
Gene | Accession Code | Sequence | Size (bp) |
---|---|---|---|
DRD2 | NM_000795 | For: 5′-AGACCATGAGCCGTAGGAAG-3′ | 96 |
Rev: 5′-GCAGCCAGCAGATGATGA-3′ | |||
DRD3 | NM_000796 | For: 5′-CAACCCTGATTTTGTCATCTACTCT-3′ | 102 |
Rev: 5′-CTTTGTTTCAGCACCACATAGATTC-3′ | |||
DARPP-32 | NM_032192 | For: 5′-CTACACACCACCTTCGCTGA-3′ | 131 |
Rev: 5′-TCTGAGGCCTGGTTCTCATT-3′ | |||
β-Actin | NM_001101 | For: 5′-GAGCGGGAAATCGTGCGTGACATT-3′ | 76 |
Rev: 5′-GAAGGTAGTTTCGTGGATGCC-3′ |
3.4. Statistical Analysis
4. Conclusions
Acknowledgments
Author Contributions
Conflicts of Interest
References
- Kirkbride, J.B.; Errazuriz, A.; Croudace, T.J.; Morgan, C.; Jackson, D.; Boydell, J.; Murray, R.M.; Jones, P.B. Incidence of schizophrenia and other psychoses in England, 1950–2009: A systematic review and meta-analyses. PLoS ONE 2012, 7, e31660. [Google Scholar] [PubMed]
- Wiersma, D.; Nienhuis, F.J.; Slooff, C.J.; Giel, R. Natural course of schizophrenic disorders: A 15-year followup of a Dutch incidence cohort. Schizophr. Bull. 1998, 24, 75–85. [Google Scholar] [CrossRef] [PubMed]
- Thara, R. Twenty-year course of schizophrenia: The Madras Longitudinal Study. Can. J. Psychiatry 2004, 49, 564–569. [Google Scholar] [PubMed]
- Laursen, T.M.; Munk-Olsen, T.; Vestergaard, M. Life expectancy and cardiovascular mortality in persons with schizophrenia. Curr. Opin. Psychiatry 2012, 25, 83–88. [Google Scholar] [CrossRef] [PubMed]
- Waddington, J.L. Neuroimaging and other neurobiological indices in schizophrenia: Relationship to measurement of functional outcome. Br. J. Psychiatry Suppl. 2007, 50, s52–s57. [Google Scholar] [CrossRef] [PubMed]
- Szeszko, P.R.; Narr, K.L.; Phillips, O.R.; McCormack, J.; Sevy, S.; Gunduz-Bruce, H.; Kane, J.M.; Bilder, R.M.; Robinson, D.G. Magnetic resonance imaging predictors of treatment response in first-episode schizophrenia. Schizophr. Bull. 2012, 38, 569–578. [Google Scholar] [CrossRef] [PubMed]
- Cropley, V.; Wood, S.J.; Pantelis, C. Brain structural, neurochemical and neuroinflammatory markers of psychosis onset and relapse: Is there evidence for a psychosis relapse signature? Int. Clin. Psychopharmacol. 2013. [Google Scholar] [CrossRef] [PubMed]
- Gladkevich, A.; Kauffman, H.F.; Korf, J. Lymphocytes as a neural probe: Potential for studying psychiatric disorders. Prog. Neuro-Psychopharmacol. Biol. Psychiatry 2004, 28, 559–576. [Google Scholar] [CrossRef] [PubMed]
- Bergquist, J.; Silberring, J. Identification of catecholamines in the immune system by electrospray ionization mass spectrometry. Rapid Commun. Mass Spectrom. 1998, 12, 683–688. [Google Scholar] [CrossRef]
- Josefsson, E.; Bergquist, J.; Ekman, R.; Tarkowski, A. Catecholamines are synthesized by mouse lymphocytes and regulate function of these cells by induction of apoptosis. Immunology 1996, 88, 140–146. [Google Scholar] [CrossRef] [PubMed]
- Tsao, C.W.; Lin, Y.S.; Cheng, J.T. Inhibition of immune cell proliferation with haloperidol and relationship of tyrosine hydroxylase expression to immune cell growth. Life Sci. 1998, 62, 335–344. [Google Scholar] [CrossRef]
- Kirillova, G.P.; Hrutkay, R.J.; Shurin, M.R.; Shurin, G.V.; Tourkova, I.L.; Vanyukov, M.M. Dopamine receptors in human lymphocytes: Radioligand binding and quantitative RT-PCR assays. J. Neurosci. Methods 2008, 174, 272–280. [Google Scholar] [CrossRef] [PubMed]
- McKenna, F.; McLaughlin, P.J.; Lewis, B.J.; Sibbring, G.C.; Cummerson, J.A.; Bowen-Jones, D.; Moots, R.J. Dopamine receptor expression on human T- and B-lymphocytes, monocytes, neutrophils, eosinophils and NK cells: A flow cytometric study. J. Neuroimmunol. 2002, 132, 34–40. [Google Scholar] [CrossRef]
- Buttarelli, F.R.; Fanciulli, A.; Pellicano, C.; Pontieri, F.E. The dopaminergic system in peripheral blood lymphocytes: From physiology to pharmacology and potential applications to neuropsychiatric disorders. Curr. Neuropharmacol. 2011, 9, 278–288. [Google Scholar] [PubMed]
- Rollins, B.; Martin, M.V.; Morgan, L.; Vawter, M.P. Analysis of whole genome biomarker expression in blood and brain. Am. J. Med. Genet. Part B Neuropsychiatr. Genet. 2010, 153, 919–936. [Google Scholar] [CrossRef] [PubMed]
- Boneberg, E.M.; von Seydlitz, E.; Propster, K.; Watzl, H.; Rockstroh, B.; Illges, H. D3 dopamine receptor mRNA is elevated in T cells of schizophrenic patients whereas D4 dopamine receptor mRNA is reduced in CD4+-T cells. J. Neuroimmunol. 2006, 173, 180–187. [Google Scholar] [CrossRef] [PubMed]
- Kwak, Y.T.; Koo, M.S.; Choi, C.H.; Sunwoo, I. Change of dopamine receptor mRNA expression in lymphocyte of schizophrenic patients. BMC Med. Genet. 2001, 2, 3. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Ilani, T.; Ben-Shachar, D.; Strous, R.D.; Mazor, M.; Sheinkman, A.; Kotler, M.; Fuchs, S. A peripheral marker for schizophrenia: Increased levels of D3 dopamine receptor mRNA in blood lymphocytes. Proc. Natl. Acad. Sci. USA 2001, 98, 625–628. [Google Scholar] [CrossRef] [PubMed]
- Ahmadian, S.; Delavari, G.; Ghanbari, D.; Zaeifi, D. D3 as a possible marker based on D1–D4 dopamine receptors expression in paranoid schizophrenia patients. J. Mol. Biomark. Diagn. 2014, 5, 1000171. [Google Scholar]
- Parslow, T.G. Lymphocytes and lymphoid tissues. In Medical Immunology, 10th ed.; McGraw-Hill: New York, NY, USA, 2001; pp. 40–45. [Google Scholar]
- Association, A.P. Diagnostic and Statistical Manual of Mental Disorders (DSM-IV)), 4th ed.; American Psychiatric Association: Washington, DC, USA, 1994. [Google Scholar]
- Emsley, R.; Rabinowitz, J.; Torreman, M. The factor structure for the Positive and Negative Syndrome Scale (PANSS) in recent-onset psychosis. Schizophr. Res. 2003, 61, 47–57. [Google Scholar] [CrossRef]
- Brito-Melo, G.E.; Nicolato, R.; de Oliveira, A.C.; Menezes, G.B.; Lelis, F.J.; Avelar, R.S.; Sa, J.; Bauer, M.E.; Souza, B.R.; Teixeira, A.L.; et al. Increase in dopaminergic, but not serotoninergic, receptors in T-cells as a marker for schizophrenia severity. J. Psychiatr. Res. 2012, 46, 738–742. [Google Scholar] [CrossRef] [PubMed]
- Liu, L.; Yuan, G.; Cheng, Z.; Zhang, G.; Liu, X.; Zhang, H. Identification of the mRNA expression status of the dopamine D2 receptor and dopamine transporter in peripheral blood lymphocytes of schizophrenia patients. PLoS ONE 2013, 8, e75259. [Google Scholar] [CrossRef] [PubMed]
- Yao, Y.; Schroder, J.; Karlsson, H. Verification of proposed peripheral biomarkers in mononuclear cells of individuals with schizophrenia. J. Psychiatr. Res. 2008, 42, 639–643. [Google Scholar] [CrossRef] [PubMed]
- Zvara, A.; Szekeres, G.; Janka, Z.; Kelemen, J.Z.; Cimmer, C.; Santha, M.; Puskas, L.G. Over-expression of dopamine D2 receptor and inwardly rectifying potassium channel genes in drug-naive schizophrenic peripheral blood lymphocytes as potential diagnostic markers. Dis. Mark. 2005, 21, 61–69. [Google Scholar] [CrossRef]
- Singh, S.P.; Burns, T.; Amin, S.; Jones, P.B.; Harrison, G. Acute and transient psychotic disorders: Precursors, epidemiology, course and outcome. Br. J. Psychiatry: J. Ment. Sci. 2004, 185, 452–459. [Google Scholar] [CrossRef] [PubMed]
- Urhan-Kucuk, M.; Erdal, M.E.; Ozen, M.E.; Kul, S.; Herken, H. Is the dopamine D3 receptor mRNA on blood lymphocytes help to for identification and subtyping of schizophrenia? Mol. Biol. Rep. 2011, 38, 2569–2572. [Google Scholar] [CrossRef] [PubMed]
- Vogel, M.; Pfeifer, S.; Schaub, R.T.; Grabe, H.J.; Barnow, S.; Freyberger, H.J.; Cascorbi, I. Decreased levels of dopamine D3 receptor mRNA in schizophrenic and bipolar patients. Neuropsychobiology 2004, 50, 305–310. [Google Scholar] [CrossRef] [PubMed]
- Landwehrmeyer, B.; Mengod, G.; Palacios, J.M. Dopamine D3 receptor mRNA and binding sites in human brain. Brain Res. Mol. Brain Res. 1993, 18, 187–192. [Google Scholar] [CrossRef]
- Bordet, R.; Ridray, S.; Carboni, S.; Diaz, J.; Sokoloff, P.; Schwartz, J.C. Induction of dopamine D3 receptor expression as a mechanism of behavioral sensitization to levodopa. Proc. Natl. Acad. Sci. USA 1997, 94, 3363–3367. [Google Scholar] [CrossRef] [PubMed]
- Schwartz, J.C.; Diaz, J.; Pilon, C.; Sokoloff, P. Possible implications of the dopamine D3 receptor in schizophrenia and in antipsychotic drug actions. Brain Res. Brain Res. Rev. 2000, 31, 277–287. [Google Scholar] [CrossRef]
- Gurevich, E.V.; Bordelon, Y.; Shapiro, R.M.; Arnold, S.E.; Gur, R.E.; Joyce, J.N. Mesolimbic dopamine D3 receptors and use of antipsychotics in patients with schizophrenia. A postmortem study. Arch. Gen. Psychiatry 1997, 54, 225–232. [Google Scholar] [CrossRef] [PubMed]
- Van Os, J.; Linscott, R.J.; Myin-Germeys, I.; Delespaul, P.; Krabbendam, L. A systematic review and meta-analysis of the psychosis continuum: Evidence for a psychosis proneness-persistence-impairment model of psychotic disorder. Psychol. Med. 2009, 39, 179–195. [Google Scholar] [CrossRef] [PubMed]
- Torres, K.C.; Souza, B.R.; Miranda, D.M.; Nicolato, R.; Neves, F.S.; Barros, A.G.; Dutra, W.O.; Gollob, K.J.; Correa, H.; Romano-Silva, M.A. The leukocytes expressing DARPP-32 are reduced in patients with schizophrenia and bipolar disorder. Prog. Neuro-Psychopharmacol. Biol. Psychiatry 2009, 33, 214–219. [Google Scholar] [CrossRef] [PubMed]
- Svenningsson, P.; Nishi, A.; Fisone, G.; Girault, J.A.; Nairn, A.C.; Greengard, P. DARPP-32: An integrator of neurotransmission. Annu. Rev. Pharmacol. Toxicol. 2004, 44, 269–296. [Google Scholar] [CrossRef] [PubMed]
- Guo, Y.; Xiao, P.; Lei, S.; Deng, F.; Xiao, G.G.; Liu, Y.; Chen, X.; Li, L.; Wu, S.; Chen, Y.; et al. How is mRNA expression predictive for protein expression? A correlation study on human circulating monocytes. Acta Biochim. Biophys. Sin. 2008, 40, 426–436. [Google Scholar] [CrossRef] [PubMed]
- Lundberg, E.; Fagerberg, L.; Klevebring, D.; Matic, I.; Geiger, T.; Cox, J.; Algenas, C.; Lundeberg, J.; Mann, M.; Uhlen, M. Defining the transcriptome and proteome in three functionally different human cell lines. Mol. Syst. Biol. 2010, 6, 450. [Google Scholar] [CrossRef] [PubMed]
- First, M.B.; Gibbon, M.; Spitzer, R.L.; Williams, J. Structured Clinical Interview for DSM-IV Axis I Disorders, Research Version, Non-patient Edition; Biometrics Research: New York, NY, USA, 1997. [Google Scholar]
- Han, O.S.; Hong, J.P. Structured Clinical Interview for DSM-IV Axis I Disorder—Korean Version; Hana Medical Publishing Co.: Seoul, Korea, 2000. [Google Scholar]
© 2015 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons by Attribution (CC-BY) license (http://creativecommons.org/licenses/by/4.0/).
Share and Cite
Cui, Y.; Prabhu, V.; Nguyen, T.B.; Yadav, B.K.; Chung, Y.-C. The mRNA Expression Status of Dopamine Receptor D2, Dopamine Receptor D3 and DARPP-32 in T Lymphocytes of Patients with Early Psychosis. Int. J. Mol. Sci. 2015, 16, 26677-26686. https://doi.org/10.3390/ijms161125983
Cui Y, Prabhu V, Nguyen TB, Yadav BK, Chung Y-C. The mRNA Expression Status of Dopamine Receptor D2, Dopamine Receptor D3 and DARPP-32 in T Lymphocytes of Patients with Early Psychosis. International Journal of Molecular Sciences. 2015; 16(11):26677-26686. https://doi.org/10.3390/ijms161125983
Chicago/Turabian StyleCui, Yin, Vishwanath Prabhu, Thong Ba Nguyen, Binod Kumar Yadav, and Young-Chul Chung. 2015. "The mRNA Expression Status of Dopamine Receptor D2, Dopamine Receptor D3 and DARPP-32 in T Lymphocytes of Patients with Early Psychosis" International Journal of Molecular Sciences 16, no. 11: 26677-26686. https://doi.org/10.3390/ijms161125983