Genetic Variations Within Metalloproteinases Impact on the Prophylaxis of Depressive Phases in Bipolar Patients

Overview

Journal Neuropsychobiology

Specialty Neurology

Date 2014 Mar 1

PMID 24576976

Citations 2

Authors

Antonio Drago

Barbara Monti

Diana De Ronchi

Alessandro Serretti

Affiliations

Soon will be listed here.

Abstract

Background: The genetic background of the antidepressant response to pharmacological treatment in bipolar disorder (BD) remains elusive. This issue is of primary relevance in that the depressive phases of BD are difficult to treat and they are associated with suicide.

Aim: We investigated the role of a set of genetic variations (single-nucleotide polymorphisms) harbored by matrix metalloproteinases (MMPs) as predictors of response to treatment in depressed BD patients.

Methods: 654 BD patients from the publicly available Systematic Treatment Enhancement Program for Bipolar Disorder study were investigated. The outcome was the number of depressive events corrected by the number of times patients were assessed. Clinical and sociodemographic variables were tested as possible stratification factors and included in the analysis if necessary. Genetic predictors were 43 SNPs harbored by 17 MMPs. Imputation, quality check and pruning were conducted according to standards. RESULTS were corrected for multitesting.

Results: rs486055 (MMP-10) was associated with the outcome. TT homozygotes had 5.08 ± 3.51 events, CT had 3.47 ± 3.18 and CC had 2.57 ± 2.96 depressive events corrected for the times they had been assessed. The time during which BD patients were observed was not significantly different between the rs486055 genotypes. We found evidence that MMP-10 may be a mediator of the number of depressive phases during BD. Due to the limits of the study including the small-to-medium sample size, the naturalistic design and the possible occurrence of false-positive findings, independent analyses are warranted.

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References

Rybakowski J, Skibinska M, Kapelski P, Kaczmarek L, Hauser J . Functional polymorphism of the matrix metalloproteinase-9 (MMP-9) gene in schizophrenia. Schizophr Res. 2009; 109(1-3):90-3. DOI: 10.1016/j.schres.2009.02.005. View

Nagy V, Bozdagi O, Huntley G . The extracellular protease matrix metalloproteinase-9 is activated by inhibitory avoidance learning and required for long-term memory. Learn Mem. 2007; 14(10):655-64. PMC: 2044557. DOI: 10.1101/lm.678307. View

Stertz L, Magalhaes P, Kapczinski F . Is bipolar disorder an inflammatory condition? The relevance of microglial activation. Curr Opin Psychiatry. 2012; 26(1):19-26. DOI: 10.1097/YCO.0b013e32835aa4b4. View

Falo M, Fillmore H, Reeves T, Phillips L . Matrix metalloproteinase-3 expression profile differentiates adaptive and maladaptive synaptic plasticity induced by traumatic brain injury. J Neurosci Res. 2006; 84(4):768-81. DOI: 10.1002/jnr.20986. View

Kucukali C, Aydin M, Ozkok E, Bilge E, Orhan N, Zengin A . Do schizophrenia and bipolar disorders share a common disease susceptibility variant at the MMP3 gene?. Prog Neuropsychopharmacol Biol Psychiatry. 2009; 33(3):557-61. DOI: 10.1016/j.pnpbp.2009.02.012. View

Graeber M, Li W, Rodriguez M . Role of microglia in CNS inflammation. FEBS Lett. 2011; 585(23):3798-805. DOI: 10.1016/j.febslet.2011.08.033. View

Beumer W, Gibney S, Drexhage R, Pont-Lezica L, Doorduin J, Klein H . The immune theory of psychiatric diseases: a key role for activated microglia and circulating monocytes. J Leukoc Biol. 2012; 92(5):959-75. DOI: 10.1189/jlb.0212100. View

Popovic D, Reinares M, Goikolea J, Bonnin C, Gonzalez-Pinto A, Vieta E . Polarity index of pharmacological agents used for maintenance treatment of bipolar disorder. Eur Neuropsychopharmacol. 2011; 22(5):339-46. DOI: 10.1016/j.euroneuro.2011.09.008. View

Sachs G, Thase M, Otto M, Bauer M, Miklowitz D, Wisniewski S . Rationale, design, and methods of the systematic treatment enhancement program for bipolar disorder (STEP-BD). Biol Psychiatry. 2003; 53(11):1028-42. DOI: 10.1016/s0006-3223(03)00165-3. View

10.

Mizoguchi H, Nakade J, Tachibana M, Ibi D, Someya E, Koike H . Matrix metalloproteinase-9 contributes to kindled seizure development in pentylenetetrazole-treated mice by converting pro-BDNF to mature BDNF in the hippocampus. J Neurosci. 2011; 31(36):12963-71. PMC: 6623408. DOI: 10.1523/JNEUROSCI.3118-11.2011. View

11.

Paradise M, Naismith S, Norrie L, Graeber M, Hickie I . The role of glia in late-life depression. Int Psychogeriatr. 2012; 24(12):1878-90. DOI: 10.1017/S1041610212000828. View

12.

Rybakowski J, Remlinger-Molenda A, Czech-Kucharska A, Wojcicka M, Michalak M, Losy J . Increased serum matrix metalloproteinase-9 (MMP-9) levels in young patients during bipolar depression. J Affect Disord. 2012; 146(2):286-9. DOI: 10.1016/j.jad.2012.07.019. View

13.

Michaluk P, Wawrzyniak M, Alot P, Szczot M, Wyrembek P, Mercik K . Influence of matrix metalloproteinase MMP-9 on dendritic spine morphology. J Cell Sci. 2011; 124(Pt 19):3369-80. DOI: 10.1242/jcs.090852. View

14.

Van Hove I, Lemmens K, Van de Velde S, Verslegers M, Moons L . Matrix metalloproteinase-3 in the central nervous system: a look on the bright side. J Neurochem. 2012; 123(2):203-16. DOI: 10.1111/j.1471-4159.2012.07900.x. View

15.

Miller J, Holcomb J, Al-Ramahi I, de Haro M, Gafni J, Zhang N . Matrix metalloproteinases are modifiers of huntingtin proteolysis and toxicity in Huntington's disease. Neuron. 2010; 67(2):199-212. PMC: 3098887. DOI: 10.1016/j.neuron.2010.06.021. View

16.

Duran-Vilaregut J, Del Valle J, Manich G, Camins A, Pallas M, Vilaplana J . Role of matrix metalloproteinase-9 (MMP-9) in striatal blood-brain barrier disruption in a 3-nitropropionic acid model of Huntington's disease. Neuropathol Appl Neurobiol. 2010; 37(5):525-37. DOI: 10.1111/j.1365-2990.2010.01157.x. View

17.

Rybakowski J, Skibinska M, Leszczynska-Rodziewicz A, Kaczmarek L, Hauser J . Matrix metalloproteinase-9 gene modulates prefrontal cognition in bipolar men. Psychiatr Genet. 2009; 19(2):108-9. DOI: 10.1097/YPG.0b013e32832080be. View

18.

Bodey B, Bodey Jr B, Siegel S, Kaiser H . Matrix metalloproteinase expression in childhood astrocytomas. Anticancer Res. 2000; 20(5A):3287-92. View

19.

Renaud S, Leppert D . Matrix metalloproteinases in neuromuscular disease. Muscle Nerve. 2007; 36(1):1-13. DOI: 10.1002/mus.20772. View

20.

Blobel C . Remarkable roles of proteolysis on and beyond the cell surface. Curr Opin Cell Biol. 2000; 12(5):606-12. DOI: 10.1016/s0955-0674(00)00139-3. View