Leukocyte and Brain DDR1 Hypermethylation is Altered in Psychosis and is Correlated with Stress and Inflammatory Markers

Abstract

Aim: To investigate DDR1 methylation in blood and brain DNA in psychosis and its relationship with stress markers. Materials & methods: Saliva cortisol, blood neutrophil and lymphocyte counts, leukocyte DNA and psychological variables were collected from 60 patients with nonaffective psychosis and 40 healthy controls (HC). Brain dorsolateral prefrontal cortex DNA from 35 patients with schizophrenia and 34 HC was studied. DDR1 methylation at 43 CpG sites was measured using the MassARRAY EpiTYPER platform. Results: We describe leukocyte DDR1 hypermethylation in patients with psychosis compared with HC; this hypermethylation is associated with psychological stress, neutrophil-to-lymphocyte ratios, and, in the dorsolateral prefrontal cortex, DDR1 methylation correlated with DDR1 isoform expression. Conclusion: We confirmed a relationship between stress and blood and brain DDR1 methylation in psychosis.

Graphical abstract

Keywords::

• cortisol
• DDR1
• early psychosis
• methylation
• NLR
• psychological stress
• schizophrenia

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.tandfonline.com/doi/suppl/10.2217/epi-2019-0191

B Garcia-Ruiz, G Muntané and L Martorell participated in the design, analysis and interpretation of data; drafting and critically revising the manuscript content and approved the final version of the manuscript. L Moreno, V Sánchez-Gistau, A Gutiérrez-Zotes, J Labad and E Vilella participated in the design, acquisition, analysis and interpretation of data; drafting and critically revising the manuscript content and approved the final version of the manuscript.

Acknowledgments

The authors would like to thank the IISPV Biobank staff for their excellent technical support in preparing and storing all biological samples used in this work.

Financial & competing interests disclosure

This work was funded in part by Instituto de Salud Carlos III (grant number PI15-00852) co-founded by FEDER and by Brain and Behavior Research Foundation (NARSAD Independent grant number 2017) to E Vilella. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

All procedures were in accordance with the Declaration of Helsinki. Ethical approval was obtained from the local ethics committee (CEIm IISPV, www.iispv.cat). All subjects consented to participate in the study and signed an informed consent form after a complete explanation of all procedures.

Additional information

Funding

This work was funded in part by Instituto de Salud Carlos III (grant number PI15-00852) co-founded by FEDER and by Brain and Behavior Research Foundation (NARSAD Independent grant number 2017) to E Vilella. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.