Glucocorticoid and mineralocorticoid receptor polymorphisms and recurrence of major depressive disorder

Florian Hardeveld; Jan Spijker; Wouter J Peyrot; Ron de Graaf; Sanne M Hendriks; Willem A Nolen; Brenda W J H Penninx; Aartjan T F Beekman

doi:10.1016/j.psyneuen.2015.02.013

Glucocorticoid and mineralocorticoid receptor polymorphisms and recurrence of major depressive disorder

Psychoneuroendocrinology. 2015 May:55:154-63. doi: 10.1016/j.psyneuen.2015.02.013. Epub 2015 Feb 26.

Authors

Florian Hardeveld¹, Jan Spijker², Wouter J Peyrot³, Ron de Graaf⁴, Sanne M Hendriks⁵, Willem A Nolen⁶, Brenda W J H Penninx³, Aartjan T F Beekman³

Affiliations

¹ Pro Persona, Institute for Mental Health Care, PO Box 70, 6710 RR Ede, The Netherlands. Electronic address: f.hardeveld@propersona.nl.
² Pro Persona, Institute for Mental Health Care, PO Box 70, 6710 RR Ede, The Netherlands; Netherlands Institute of Mental Health and Addiction, PO Box 725, 3500 AS Utrecht, The Netherlands; Behavioral Science Institute, Radboud University Nijmegen, PO Box 9104, 6500 HE Nijmegen, The Netherlands.
³ Department of Psychiatry/EMGO Institute for Health and Care Research/Neuroscience Campus Amsterdam, VU University Medical Center Amsterdam, PO Box 7057, 1007 MB Amsterdam, The Netherlands.
⁴ Netherlands Institute of Mental Health and Addiction, PO Box 725, 3500 AS Utrecht, The Netherlands.
⁵ Pro Persona, Institute for Mental Health Care, PO Box 70, 6710 RR Ede, The Netherlands.
⁶ Department of Psychiatry, University Medical Center Groningen, University of Groningen, PO Box 72, 9700 AB Groningen, The Netherlands.

PMID: 25765757
DOI: 10.1016/j.psyneuen.2015.02.013

Abstract

Objective: Previous research found that variants of the glucocorticoid receptor (GR) (9β, ER22/23EK, BclI, TthIIIl, NR3C1-1 and N363S) and mineralocorticoid receptor (MR) gene polymorphism (-2 C/G and I180V) are associated with both glucocorticoid (GC) sensitivity and major depressive disorder (MDD). There are no data which investigated prospectively whether these variants are associated with recurrence of MDD.

Methods: Data were derived from the Netherlands Study of Depression and Anxiety (NESDA) which used the Composite International Diagnostic Interview (CIDI) to determine MDD. Polymorphisms in the GR and MR gene were determined and haplotypes were characterized. We analyzed in retrospect whether recurrent MDD (n=951) in comparison with first onset MDD (n=919) was associated with polymorphisms in the GR and MR gene. Furthermore, we analyzed prospectively for 4 years the time to recurrence among 683 subjects with a remitted MDD diagnosis. Time to recurrence of MDD was assessed using the CIDI and a life chart interview. Additionally, we analyzed interactions of the investigated polymorphisms with childhood trauma and recent negative life events.

Results: GR and MR gene polymorphisms and derived haplotypes were not associated with recurrence of depression in both retrospective and prospective analyses. In addition, no consistent interactions between GR and MR polymorphisms and childhood trauma or life events were found.

Conclusion: This study did not find consistent associations between GR and MR gene polymorphisms, interactions between GR and MR haplotypes and stressful conditions and recurrence of MDD.

Keywords: Glucocorticoid receptor polymorphisms; Major depressive disorder; Mineralocorticoid receptor polymorphisms; Recurrence.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Adult
Adult Survivors of Child Adverse Events / psychology
Aged
Cohort Studies
Depressive Disorder, Major / genetics*
Depressive Disorder, Major / psychology
Female
Genetic Predisposition to Disease
Humans
Male
Middle Aged
Polymorphism, Single Nucleotide
Prospective Studies
Receptors, Glucocorticoid / genetics*
Receptors, Mineralocorticoid / genetics*
Recurrence
Stress, Psychological / genetics
Stress, Psychological / psychology
Young Adult

Substances

Receptors, Glucocorticoid
Receptors, Mineralocorticoid