Clinical Psychopharmacology and Neuroscience Papers in Press available online.

Methylome-Wide Association Study in Patients with Recent onset Psychosis
Yan-Hong Piao 1,7, Yin Cui 2, Fatima Zahra Rami 1,7, Ling Li 1,7, Maryam Karamikheirabad 1,7, Shi Hyun Kang 3, Sung-Wan Kim 4, Jung Jin Kim 5, Bong Ju Lee 6, Young-Chul Chung 1,7,*
1Department of Psychiatry, Jeonbuk National University Medical School, Jeonju, Republic of Korea, 2Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, PR China, 3Department of Social Psychiatry and Rehabilitation, National Center for Mental Health, Seoul, Republic of Korea, 4Department of Psychiatry, Chonnam National University Medical School, Gwangju, Republic of Korea, 5Department of Psychiatry, The Catholic University of Korea, Seoul St. Mary’s Hospital, Seoul, Republic of Korea, 6Department of Psychiatry, Inje University Haeundae Paik Hospital, Inje University College of Medicine, Busan, Republic of Korea, 7Research Institute of Clinical Medicine of Jeonbuk National University-Biomedical Research Institute of Jeonbuk National University Hospital, Jeonju 561-756, Korea.
Objective: Dysregulation of gene expression through epigenetic mechanisms may have a vital role in the pathogenesis of schizophrenia (SZ). In this study, we investigated the association of altered methylation patterns with SZ symptoms and early trauma in patients and healthy controls.
Method: The present study was conducted to identify methylation changes in CpG sites in peripheral blood associated with recent-onset (RO) psychosis using methylome-wide analysis. Lifestyle factors, such as smoking, alcohol, exercise, and diet, were controlled for.
Results: We identified 2,912 differentially methylated CpG sites in patients with RO psychosis compared to controls. Most of the genes associated with the top 20 differentially methylated sites had not been reported in previous methylation studies and were involved in apoptosis, autophagy, axonal growth, neuroinflammation, protein folding, etc. The top 15 significantly enriched KEGG pathways included the oxytocin signaling pathway, long-term depression pathway, axon guidance, endometrial cancer, long-term potentiation, MAPK signaling pathway, and glutamatergic pathway, among others. In the patient group, significant associations of novel methylated genes with early trauma and psychopathology were observed.
Conclusions: Our results suggest an association of differential DNA methylation with the pathophysiology of psychosis and early trauma. Blood DNA methylation signatures show promise as biomarkers of future psychosis.
Key Words: DNA methylation, Early trauma, Psychosis, Schizophrenia, Biomarker, Psychopathology
Accepted Manuscript [Submitted on 2021-01-09, Accepted on 2021-04-17]