S14. ANALYSIS OF METHYLATION AGE AND BLOOD CELL COMPOSITION IN SUBJECTS WITH CURRENT SUICIDE IDEATION

BACKGROUND: Suicidal Ideation (SI) remain an important and common risk factor affecting people with SCZ, who eventually attempt or complete suicide. Then the question is, what if factors (such as stressful life events and related molecular biomarkers) known to be involved in the aetiology of SCZ could help in predicting SI in this population? The accelerated aging hypothesis of SCZ posits that physiological changes associated with normal aging occur at an earlier age in individuals with SCZ than in the general population. Importantly, epigenetic changes may constitute an important component of aging process. Based on this, the chronological age can be predicted by the epigenetic clock in a highly consistent manner. The aims of this research were to determine the effect chronological and biological age on current SI and secondly, to determine the effect of the variation of cellular blood cell composition on current SI. METHODS: A total of 103 participants with a DSM-IV diagnosis of schizophrenia spectrum and other psychotic disorders were recruited from the Center of Addiction and Mental Health. The SI was assessed by the Columbia-Suicide Severity Rating Scale. Genome-wide DNA methylation analysis was generated from whole blood cells. The DNA methylation was assessed using the Illumina Infinium HumanMethylation450 Bead Chip while the DNA methylation-based age prediction and white blood cell composition were performed using the statistical pipeline developed by Horvath. RESULTS: Out of 103 participants, 18 had current SI (17%) while 85 had NSI. The DNAm age correlated with chronological age in the overall sample (r=0.814, p<0.0001), NSI (r=0.823, p<0.0001) and SI subjects (r=0.734, p=0.001). The strong linear relationship between DNAm age and chronological age showed a high accuracy of the epigenetic clock. However, DNAm age acceleration residuals did not differ between NSI and SI groups (t=1.532, p= 0.129). Comparison of the cellular cell blood composition between the NSI and SI groups indicated no significant differences between the NSI and SI groups (lymphocytes (t= -0.338, p=0.736), monocytes (t=-1.405, p=0.163) and granulocytes (t=0.924, p=0.358)). Furthermore, there were no significant differences between the SI and NSI groups in the analysis of the plasmablast (t=0.138, p=0.890), CD4 naïve (t=0.010, p=0.992) and CD8 naïve (t=0.681, p=0.497) DISCUSSION: Stressful life events may change DNA methylation, which in turn can affect suicide ideation and suicidal behavior. Although SCZ is associated with age-related physiological factors, we were unable to find accelerated aging in our study. Nevertheless, we cannot rule out the possibility of other aging mechanism independent of epigenetic aging in SCZ patients. Conclusion: Further studies aimed at investigating the accelerated aging hypothesis in peripheral tissue are warranted to identify individuals with SCZ at risk for suicide. This will permit a tailored treatment and will prevent suicide in SCZ individuals.