F14. GENOME-WIDE METHYLATION EFFECT ON CURRENT AND EMERGENT SUICIDAL IDEATION: AN EPIGENOME-WIDE ASSOCIATION ANALYSIS IN SCHIZOPHRENIA
Bibliographic record
Abstract
Suicide is one of the causes of reduced life expectancy in patients with schizophrenia (SCZ). Despite the importance of suicidal ideation (SI) in predicting future suicide attempts, little empirical research has been conducted on its patterns. Therefore, there is an urgent need to provide a better prediction of SI for SCZ patients and identifying biomarkers is a necessary step in this path. The prevailing theory is that suicidal behavior requires a genetic predisposition (diathesis) and stressful life events which have been conceptualized in the stress-diathesis model of suicide. To date, large-scale GWAS of suicidal ideation and behavior have failed to identify risks associated with DNA sequence variants. Epigenetic modifications, such as DNA methylation have been shown to play a significant role in gene expression and may serve in part, to quantify the “missing heritability” of SI and suicidal behavior. Epigenetic changes can partially explain the stress-diathesis model of suicide since these DNA markers are sensitive to the environmental risk factors of suicide (i.e. childhood trauma). This longitudinal project provided a comprehensive epigenetic investigation of genome-wide methylation in relation to current and emergent SI in schizophrenia patients. We assessed 136 SCZ patients aged between 18 and 45 for the presence of suicidal ideation and genome-wide methylation status. All participants were assessed at the study entry (baseline) and after three months in order to evaluate emergent SI and exposure to stressful events in the short term. SCZ diagnosis was ascertained using the Structured Clinical Interview (SCID) as part of the baseline assessment. Using the Columbia Suicide Severity Rating Scale (C-SSRS), current SI was defined by a severity score between 1 (thoughts about death) and 5 (SI with intent and plan) at study entry. Emergent SI was defined as an increased C-SSRS severity score at the three-month follow-up visit compared to the baseline visit. Genomic DNA was extracted from white blood cells using a high-salt protocol. The overall stress load and specific stressful events (i.e., family, finance, medical, legal and work problems) were measured at study entry and three-month follow-up, using a modified version of the Holmes and Rahe’s Social Readjustment Rating Scale (SRRS). Genome-wide DNA methylation levels at baseline and three-month follow-up were measured, using the Infinium MethylationEPIC BeadChip. We tested the effect of the methylation status of each CpG site across the genome in predicting subjects who were experiencing SI (current and emergent SI), using a logistic regression model (SPSS Ver. 24). We found that higher SRRS score was associated with an increased risk for emergent and current SI (p=0.003). Our findings also showed that a higher methylation level in the CpG cg06121808 on chromosome 2 was associated with current SI (p= 0.00000353). Furthermore, we found that increased methylation from baseline in the CpG cg15097580 on chromosome 18 was associated with emergent SI at three-month follow-up (p= 0.000002). This study is the first that has investigated genome-wide methylation status and current and emergent suicidal ideation in schizophrenia. Identifying epigenetic biomarkers and mechanisms that modulate suicidal ideation in SCZ may enhance our understanding of the pathways resulting in suicide in this population. These biological pathways may determine why some individuals with SCZ are more likely to experience SI than others that in turn may help us to develop treatment specifically targeting the underlying neurobiology to reduce suicide risk.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.002 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.002 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.007 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".