Is Methylation Of MORC1 A Depression Biomarker?

Major depressive disorder is a mental disorder with a high prevalence worldwide. With over 300 million affected people, it is one of the leading causes of disability. Its prevalence and the degree of burden are frequently underestimated, and the disorder is often not recognized, resulting in about 50% of people suffering from depression not getting treatment.

Early onset of the disorder and its high prevalence across all ages (from children to the elderly) make depression a lifelong burden with a high risk of suicide. Moreover, depression has high comorbidity with other mental disorders as well as with different kinds of physical illnesses or even severe accidents (e.g. resulting in paraplegia, cognitive impairment, or traumata).

New treatment options for depression are evolving (e.g. ketamine treatment, vagus nerve stimulation, and electro-convulsive therapy) but the disorder is often difficult to diagnose, especially in the early stages of the disease. To facilitate diagnosis and treatment outcome, it is necessary to find a valid biomarker which allows early detection of the disorder.

Recently, one specific gene, the MORC family CW-type zinc finger 1 (MORC1), has been associated with depression in human and animal studies. Nieratschker and colleagues found a significant association of a single nucleotide polymorphism (a change in one nucleotide of the DNA) in the MORC1 gene and major depressive disorder. When investigating the behavior of mice without a functional MORC1 gene (knockout), Schmidt and colleagues found depressive-like behavior in this specific mouse line. However, not only genes but multiple factors contribute to the onset of major depressive disorder. Environmental influences seem to play an important role as well. The environment is also able to influence our genes, with the so-called epigenetic changes. These changes, e.g. methylation of our DNA, can alter gene expression increasing the risk to develop major depressive disorder.

In a recent study, we investigated DNA methylation of MORC1 in buccal cells (saliva) in adults (30 men, 30 women). All participants were healthy and between 19 and 33 years old. During the study, they were asked to report depressive symptoms (by questionnaire) based on the Beck Depression Inventory (BDI), a widely-used scale for depression. As expected, all participants scored below the scale of a clinically relevant major depressive disorder. Nevertheless, there was a range in sub-clinical BDI scores.

Interestingly, we found a significant negative correlation between increased BDI scores and increased methylation of MORC1. We were the first to discover an association of increased MORC1 methylation and depressive symptoms in a non-clinical population. As the investigation of methylation status in buccal cells is an easy-to-apply, non-invasive method, MORC1 methylation might be a good biomarker to detect subclinical depressive symptoms. Further studies are needed to confirm the validity of MORC1 methylation as a biomarker for depression.

These findings are described in the article entitled Methylation of MORC1: A Possible Biomarker for Depression?, recently published in the Journal of Psychiatric Research. This work was conducted by Annakarina Mundorf, Judith Schmitz, Onur Güntürkün, Nadja Freund, and Sebastian Ocklenburg from Ruhr University Bochum.