2011

Klok, M.D., Vreeburg, S.A., Penninx, B.W., Zitman, F.G., de Kloet, E.R., De Rijk, R.H. , Common functional mineralocorticoid receptor polymorphisms modulate the cortisol awakening response: Interaction with SSRIs, Psychoneuroendocrinology, vol. 36, no. 4, pp. 484-494.

Klok, M.D., Alt, S.R., Irurzun Lafitte, A.J., Turner, J.D., Lakke, E.A., Huitinga, I, Muller, C.P., Zitman, F.G., de Kloet, E.R., De Rijk, R.H. , Decreased expression of mineralocorticoid receptor mRNA and its splice variants in postmortem brain regions of patients with major depressive disorder, J Psychiatr Res, vol. 45, no. 7, pp. 871-878.

2010

Alt, S.R., Turner, J.D., Klok, M.D., Meijer, O.C., Lakke, E.A., de Rijk, R.H., Muller, C.P. , Differential expression of glucocorticoid receptor transcripts in major depressive disorder is not epigenetically programmed, Psychoneuroendocrinology, vol. 35, no. 4, pp. 544-556.

2008

de Rijk, R.H., van Leeuwen, N., Klok, M.D., Zitman, F.G. , Corticosteroid receptor-gene variants: modulators of the stress-response and implications for mental health, Eur J Pharmacol, vol. 585, no. 2-3, pp. 492-501.

2007

Klok, M.D., Jakobsdottir, S., Drent, M.L. , The role of leptin and ghrelin in the regulation of food intake and body weight in humans: a review, Obes Rev, vol. 8, no. 1, pp. 21-34.

2006

Tjin, E.P., Groen, R.W., Vogelzang, I, Derksen, P.W., Klok, M.D., Meijer, H.P., van Eeden, S., Pals, S.T., Spaargaren, M. , Functional analysis of HGF/MET signaling and aberrant HGF-activator expression in diffuse large B-cell lymphoma, Blood, vol. 107, no. 2, pp. 760-8.

2004

Derksen, P.W., Tjin, E., Meijer, H.P., Klok, M.D., MacGillavry, H.D., van Oers, M.H., Lokhorst, H.M., Bloem, A.C., Clevers, H., Nusse, R., van der Neut, R., Spaargaren, M., Pals, S.T. , Illegitimate WNT signaling promotes proliferation of multiple myeloma cells, PNAS, vol. 101, no. 16, pp. 6122-7.

2003

Spaargaren, M., Beuling, E.A., Rurup, M.L., Meijer, H.P., Klok, M.D., Middendorp, S., Hendriks, R.W., Pals, S.T. , The B cell antigen receptor controls integrin activity through Btk and PLCgamma2, J Exp Med, vol. 198, no. 10, pp. 1539-50.

Mineralocorticoid receptor (MR) regulation in stress responsiveness and psychopathology: influence of single nucleotide polymorphisms (SNPs)

The aim of my project is to investigate the role of MR expression in stress responsiveness and psychopathology. We want to know if SNPs in the MR promoter region have influence on MR expression and if they are related to stress-related phenotypes and disorders like depression. SNPs and haplotypes in the MR promoter region are tested for functionality -their effect on MR-gene promoter activity- in vitro with the help of reporter assays. In addition, these MR gene variants are tested for association with stress-related phenotypes among adults and elderly subjects. Furthermore, the expression of different MR splice variants is quantified and compared between different key regions of human post-mortem brain of depressed patients and non-depressed controls. Finally, we will verify whether the differences in MR expression that are found are due to variation in methylation of the DNA. We hypothesise that genetic variants in the MR promoter region influence its activity and therefore MR expression, and are related to differences in the vulnerability for psychopathology.