Ghrelin Modifies the Impact of Life Stress on Suicidality in Patients With Acute Coronary Syndrome

Objective@#This study investigated associations of life stressors and serum ghrelin levels with suicidal ideation (SI), and evaluated the potential mediating effect of ghrelin on associations between life stressors and SI in patients with acute coronary syndrome (ACS). @*Methods@#In total, 969 ACS patients recruited from a tertiary university hospital in Korea within 2 weeks of disease onset were evaluated in terms of life stressors (using the List of Threatening Events Questionnaire), serum ghrelin levels, and SI (using the “suicidal thoughts” item of the Montgomery–Asberg Depression Rating Scale). Covariates included sociodemographics, depression, vascular risk factors, and disease severity. After 1 year, 711 patients were re-evaluated in terms of SI; logistic regression was performed with adjustment for covariates. @*Results@#Life stressors were significantly associated with SI at baseline and follow-up. Serum ghrelin showed no such associations, but high levels thereof mediated associations of life stressors with SI; significant interaction terms were also observed after adjustment for covariates. @*Conclusion@#By evaluating life stressors and serum ghrelin levels, clinical prediction of SI in the acute and chronic phases of ACS could be improved.

Effect Modification of Cortisol on the Associations Between Obsessive-Compulsive Symptoms on Suicidality in Patients With Acute Coronary Syndrome

Objective@#Obsessive-compulsive symptoms (OCS) and suicidal ideation (SI) are common in patients with acute coronary syndrome (ACS). This study investigated the associations of OCS and serum cortisol levels with SI, and further evaluated the possible modifying effects of cortisol on the associations between OCS and SI in acute and chronic phases of ACS. @*Methods@#In total, 969 ACS patients were recruited from a tertiary university hospital in Korea within 2 weeks of disease onset and evaluated in terms of OCS (using the OCS dimension of the Symptom Checklist-90–Revised), serum cortisol levels, and SI (using the “suicidal thoughts” item of the Montgomery–Åsberg Depression Rating Scale). Covariates included sociodemographics, depression, vascular risk factors, and disease severity. After 1 year, 711 patients were re-evaluated in terms of SI. Logistic regression analysis was performed with adjustment for covariates. @*Results@#Higher OCS was significantly associated with SI both at baseline and follow-up. Serum cortisol showed no such association, but modified the association between OCS and SI. That was the associations were significant only in the higher but not in the lower serum cortisol levels, with significant interaction terms after adjusted for relevant covariates. @*Conclusion@#Evaluating OCS and serum cortisol levels at the acute phase could improve the accuracy of clinical predictions of SI both in the acute and chronic phases of ACS.

Suicide and Non-Suicidal Self-Injury From Internet Addiction Among Korean Adolescents

Objectives@#This study examined the associations between Internet addiction and suicide and non-suicidal self-injury (NSSI) among South Korean adolescents. @*Methods@#We conducted a cross-sectional study of 1694 Korean adolescents. The suicidal Ideation Questionnaire and Deliberate SelfHarm Inventories were used to identify high-risk suicide and NSSI groups, respectively. Internet addiction was assessed using the Internet Addiction Scale. Other questionnaires included sociodemographic data, perceived academic stress, and daily life-related factors. We also performed a logistic regression analysis using the high suicide risk and NSSI groups as dependent variables. @*Results@#The high suicide risk and NSSI prevalence rates among participants were 11.8% and 28.3%, respectively. A multivariable logistic regression analysis revealed that Internet addiction is associated with higher suicide risk and NSSI. Additionally, being female and academic stress were significant suicide risk factors, while male participants had a higher NSSI prevalence. @*Conclusion@#Our results suggest that monitoring adolescents’ Internet use and providing education to prevent Internet addiction would lower high suicide and NSSI risk. Moreover, suicide and NSSI risk screening in adolescents with Internet addiction and providing suitable interventions will be essential for the preventing suicide and NSSI.

Possible Link between Serotonin and Interleukin 18 on Suicidality in Patients with Acute Coronary Syndrome

Objective@#We investigated effects of serum serotonin and interleukin 18 levels on suicidal ideation (SI) at acute and chronic phases of acute coronary syndrome (ACS). @*Methods@#Recent-onset 969 ACS patients were evaluated for serum serotonin and interleukin 18 levels; and SI by the“suicidal thoughts” item of the Montgomery–Åsberg Depression Rating Scale. After 1-year, 711 patients were re-evaluated for SI. Logistic regression models were used adjustment for potential covariates. @*Results@#Associations between serum interleukin 18 and SI at both phases were significant only in the lower serotonin group. @*Conclusion@#By evaluating serum serotonin and interleukin 18 levels, the clinical prediction of SI of ACS may be improved.

Development of a Checklist for Predicting Suicidality Based on Risk and Protective Factors: The Gwangju Checklist for Evaluation of Suicidality

Objective@#The aim of the study was to develop a checklist for mental health clinicians to predict and manage suicidality. @*Methods@#A literature review of the risk and protective factors for suicide was conducted to develop a checklist for evaluating suicidality. @*Results@#The fixed risk factors included sex (male), age (older individuals), history of childhood adversity, and a family history of suicide. Changeable risk factors included marital status (single), economic status (poverty), physical illness, history of psychiatric hospitalization, and history of suicide attempts. Recent discharge from a mental hospital and a recent history of suicide attempts were also included. Manageable risk factors included depression (history and current), alcohol problems (frequent drinking and alcohol abuse), hopelessness, agitation, impulsivity, impaired reality testing, and command hallucinations. Protective factors included responsibility to family, social support, moral objections to suicide, religiosity, motivation to get treatment, ability to cope with stress, and a healthy lifestyle. A final score was assigned based on the sum of the risk and protective factor scores. @*Conclusion@#We believe that the development of this checklist will help mental health clinicians to better assess those at risk for suicidal behavior. Further studies are necessary to validate the checklist.

Factors Associated With Depression and Anxiety in Korean Adolescents During the COVID-19 Pandemic

Objective@#This study was performed to identify factors associated with depression and anxiety among Korean adolescents during the coronavirus disease (COVID-19) pandemic. @*Methods@#We conducted a cross-sectional study of 1,898 Korean adolescents (55.2% male, 44.8% female) ranging in age from 12 to 17 years (mean±standard deviaion age, 15.4±2.6 years). Depression and anxiety were defined as a Patient Health Questionnaire-9 score ≥10 and Generalized Anxiety Disorder-7 score ≥10, respectively. Other questionnaires included sociodemographic data, psychosocial stresses, and experiences in association with COVID-19. Psychiatric scales included Gratitude Questionnaire-6, Perceived Stress Scale-10, and UCLA Loneliness Scale-3. @*Results@#The prevalence rates of depressive and anxiety symptoms among participants were 13.8% and 21.0%, respectively. Multivariable logistic regression analysis revealed that female sex, fear of COVID-19 infection, low gratitude were risk factors for depression. Fear of COVID-19 infection, increased TV watching time, and academic-related stress were risk factors for anxiety. @*Conclusion@#Depression and anxiety were prevalent during the pandemic in Korean adolescents, and were associated with fear of COVID-19 infection. Providing appropriate information on COVID-19, helping adolescents manage academic-related stress and maintain daily life patterns, and implementing interventions to foster gratitude are important for preventing depression and anxiety in Korean adolescents.

Associations of Serum Serotonin Levels with 12-week and 12-month Remission in Patients with Depressive Disorders

Objective@#To investigate associations between baseline serum serotonin levels and short- and long-term treatment outcomes in outpatients with depressive disorders in a naturalistic one-year prospective study design. @*Methods@#Patients were recruited at a University hospital in South Korea from March 2012 to April 2017. At baseline, blood samples were obtained from 1,094 patients who received initial antidepressant monotherapy (Step 1). After the Step 1 treatment, further treatment steps (at least Steps 2−4) could be administered every 3 weeks during the acute treatment phase (3, 6, 9, and 12 weeks; n = 1,086), and every 3 months during the continuation treatment phase (6, 9, and 12 months; n = 884). In cases showing an insufficient response or intolerable side effects, patients were asked to choose whether to remain at the current step or enter the next treatment step, with alternative strategies including switching, augmentation, combination, and a mixture of these approaches. Remission was defined as a Hamilton Depression Rating Scale score of ≤ 7. @*Results@#The remission group had significantly higher baseline serum serotonin levels among patients who received Step 1 monotherapy in both acute and continuation treatment phases. These associations remained significant after adjustment for relevant covariates. No associations were found with any other treatment steps. @*Conclusion@#Baseline serum serotonin levels may be used as a biomarker for predicting short- and long-term treatment outcomes in antidepressant monotherapy-treated patients with depressive disorders in a real-world clinical setting.

Genetic Differences between Physical Injury Patients With and Without Post-traumatic Syndrome: Focus on Secondary Findings and Potential Variants Revealed by Whole Exome Sequencing

Objective@#Sudden traumatic physical injuries often cause psychological distress, which may be associated with chronic disability. Although considerable effort has been expended to identify genetic predictors of post-traumatic stress disorder (PTSD) after traumatic events, genetic predictors of psychological distress in response to severe physical injuries have been yet to be elucidated using whole exome sequencing (WES). Here, the genetic architecture of post-traumatic syndrome (PTS), which encompasses a broad range of psychiatric disorders after traumatic events including depression, anxiety disorder, acute stress disorder, and PTSD, was explored using WES in severely physically injured patients, focusing on secondary findings and potential PTS-related variants. @*Methods@#In total, 141 severely physically injured patients were consecutively recruited, and PTS was evaluated within 1 month of the injury. Secondary findings were analyzed according to PTS status. To identify PTS-related variants, genome-wide association analyses and the optimal sequencing kernel association test were performed. @*Results@#Of the 141 patients, 88 (62%) experienced PTS. There were 108 disease-causing variants in severely physically injured patients. As secondary findings, the stress- and inflammation-related signaling pathways were enriched in the PTS patients, while the glucose metabolism pathway was enriched in those without PTS. However, no significant PTS-related variants were identified. @*Conclusion@#Our findings suggest that genetic alterations in stress and inflammatory pathways might increase the likelihood of PTS immediately after severe physical injury. Future studies with larger samples and longitudinal designs are needed.

Predictors of Remission in Acute and Continuation Treatment of Depressive Disorders

Objective@#To identify factors predicting remission of depression during acute (12 weeks) and continuation treatment (12 months) using a 1-year, naturalistic prospective study design. @*Methods@#Patients with depressive disorders were recruited from Chonnam National University Hospital in South Korea from March 2012 to April 2017. At baseline, 1,262 patients received outpatient therapy, and sociodemographic and clinical data were obtained. Clinical visits took place every 3 weeks during the acute treatment phase (at 3, 6, 9, and 12 weeks; n = 1,246), and every 3 months during the continuation treatment phase (at 6, 9, and 12 months;n = 1,015). Remission was defined as a Hamilton Depression Rating Scale score ≤ 7. @*Results@#The remission rate was 43.3% at 12 weeks and 70.4% at 12 months. In multivariate analyses, remission during the acute treatment phase was more likely in patients with a shorter-duration present episode, higher functioning, and good social support. Remission during the continuation treatment phase was more likely in patients with fewer previous depressive episodes and/or a lower baseline stress score. @*Conclusion@#Factors predicting depressive disorder remission may differ between the acute and continuation treatment phases.

Delayed Onset of Manic Symptoms in a Patient with Influenza A (H1N1) after administration of Oseltamivir (Tamiflu): A Case Report

Psychiatric side effects of oseltamivir can result in accident-proneness and suicide. Reportedly, such adverse psychiatric events are more common in children than in adults, but other risk factors are not known. We present a 13-year-old girl with influenza infection who developed manic symptoms after taking oseltamivir and receiving the human papillomavirus vaccination. While other research has found that psychiatric side effects associated with oseltamivir generally occur within 48 hours after beginning administration, in this case the manic symptoms developed on the fourth day after cessation of 5-day course of oseltamivir administration. Based on our review of this case, we recommend that clinicians should carry out vigilant monitoring of each patient’s mental state when the patient is young, has a family history of psychiatric disorder, has drug sensitivity and has received medical treatments such as vaccination before or after taking oseltamivir. In addition, as side effects of oseltamivir may occur more than 48 hours after administration, it will be necessary to observe patients for several days after the prescription of oseltamivir.

Predictors of Remission in Acute and Continuation Treatment of Depressive Disorders

Objective@#To identify factors predicting remission of depression during acute (12 weeks) and continuation treatment (12 months) using a 1-year, naturalistic prospective study design. @*Methods@#Patients with depressive disorders were recruited from Chonnam National University Hospital in South Korea from March 2012 to April 2017. At baseline, 1,262 patients received outpatient therapy, and sociodemographic and clinical data were obtained. Clinical visits took place every 3 weeks during the acute treatment phase (at 3, 6, 9, and 12 weeks; n = 1,246), and every 3 months during the continuation treatment phase (at 6, 9, and 12 months;n = 1,015). Remission was defined as a Hamilton Depression Rating Scale score ≤ 7. @*Results@#The remission rate was 43.3% at 12 weeks and 70.4% at 12 months. In multivariate analyses, remission during the acute treatment phase was more likely in patients with a shorter-duration present episode, higher functioning, and good social support. Remission during the continuation treatment phase was more likely in patients with fewer previous depressive episodes and/or a lower baseline stress score. @*Conclusion@#Factors predicting depressive disorder remission may differ between the acute and continuation treatment phases.

Psychosocial Correlates of Suicidal Attempts / 생물치료정신의학

Objectives@#：This study investigated psychosocial risk and protective factors associated with suicide attempt. @*Methods@#：This cross-sectional study included 1,466 participants. Socio-demographic and clinical variables were collected. The following scales were used : Hospital Anxiety and Depression Scale (HADS), Perceived Stress Scale (PSS), Alcohol Use Disorder Identification Test-Korean version (AUDIT-K), Family Adaptability & Cohesion Evaluation Scale III (FACES-III), Korean version of Connor-Davidson Resilience Scale (K-CD-RISC), Rosenberg Self-Esteem Scale (RSES), and Korean version of Gratitude Questionnaire 6 (K-GQ-6). Univariate and logistic regression analyses were used to identify factors associated with a history of suicide attempt. @*Results@#：Seventy-one of the 1,466 participants (4.8%) reported a history of suicide attempt. Attempted suicide was less common in married individuals, but more common in Medicaid recipients and smokers. Compared with participants who had not attempted suicide, participants who had attempted suicide had higher scores for the HADS, AUDIT-K, and PSS, whereas they had lower scores for the FACES-III, RSES, K-GQ-6, and four subscales of the K-CDRISC (Hardiness, Persistence, Optimism, and Support). Logistic regression analysis revealed that Medicaid use [odds ratio (OR)=5.837] and AUDIT-K score (OR=1.066) were positively associated with a history of suicide attempt. Marriage (OR=0.451), FACES-III score (OR=0.971), and K-CD-RISC Support subscale score (OR=0.711) were negatively associated with a history of suicide attempt. @*Conclusion@#：Low income and alcohol abuse were positively associated with attempted suicide, whereas marriage, high family cohesion, and social support were negatively associated with attempted suicide in the general population.A social and economic support system might aid suicide prevention.

Standardization of the Discrimination and Stigma Scale-Korean Version (DISC 12-K) in Patients with Depressive Disorders

Objective@#The Discrimination and Stigma Scale (DISC 12), which assesses behavioral and experienced stigma, has not been translated into Korean. We developed and standardized the Korean version of the DISC 12 (DISC 12-K) in patients with depressive disorders. @*Methods@#The study included 230 patients with depressive disorders who were assessed on the four subscales of the DISC 12-K: Unfair Treatment, Stopping Self, Overcoming Stigma, and Positive Treatment. Additionally, stigma was assessed using the Internalized Stigma of Mental Illness scale, depressive symptoms using the Hamilton Depression Rating Scale and Beck Depression Inventory, level of functioning using the Social and Occupational Functioning Assessment Scale, self-esteem using the Rosenberg Self-Esteem Scale, and quality of life was assessed using the EuroQol-5D. The reliability of DISC 12 was assessed by internal consistency using Cronbach’s alpha coefficient and estimating the intercorrelation of items and corrected item-total correlations; interrater reliability and test–retest reliability were assessed using intraclass correlation coefficients at the item and subscale levels; and the concurrent validity of the DISC 12-K relative to the other assessment scales was assessed using Spearman’s correlation coefficient. @*Results@#All of the DISC 12-K subscales had high reliability. The validity was good for the Unfair Treatment and Stopping Self subscales, but only fair for the Overcoming Stigma and Positive Treatment subscales. @*Conclusion@#The Unfair Treatment and Stopping Self subscales of the new DISC 12-K are reliable and valid measures of stigma in patients with depressive disorders. Future studies are needed to test the validity of this scale in other mental disorders.

Factors Associated with Suicidal Behavior of Psychiatric Inpatients / 신경정신의학

OBJECTIVES: This study examined the factors associated with suicidal behavior in psychiatric inpatients. METHODS: The medical records of 208 psychiatric inpatients were reviewed retrospectively. The factors related to suicide attempts and ideation at the time of admission, and during outpatient follow-up, were investigated. RESULTS: In total, 120 patients (57.7%) with a history of at least one suicide attempt, and 163 patients (78.4%) who reported active suicide ideation (e.g., a suicide plan or intention to commit suicide) at the time of admission were reviewed. Being unmarried or divorced, substance abuse, impulsivity, and a poor social support system were associated with a history of suicide attempts. The suicidal ideation group had significantly higher rates of coexisting depression, severe depressive symptoms, hopelessness, and impulsivity, as well as a lower incidence of moral objection to suicide and high religiosity. In total, 15 out of 193 patients (7.8%) who were followed-up at outpatient clinics attempted suicide after discharge. Patients who attempted suicide or reported suicidal ideation at the outpatient clinic after discharge were significantly more likely to have a history of previous suicide attempts, or have had active suicide ideation at the time of admission. Good social support and high responsibility to family were inversely associated with suicidal ideation as an outpatient. CONCLUSION: A history of suicide attempts and ideation at the time of hospital admission were the risk factors for future outpatient suicidal behavior. Further study is warranted to develop a checklist and assessment measures of the various risk and protective factors associated with suicidal behavior.

Association between Anxiety and Functional Outcomes in Patients with Stroke: A 1-Year Longitudinal Study

OBJECTIVE: Anxiety is one of the most common complications in patients with stroke, but studies on its relationship to functional outcomes are limited and controversial. We investigated the association between post-stroke anxiety (PSA) and a 1-year trajectory of functional outcome.METHODS: A total of 423 patients were recruited within 2 weeks after a stroke (acute phase) during hospitalization. Of them, 306 (72.3%) completed follow-up examinations 1 year thereafter (chronic phase). Anxiety was evaluated using the Hospital Anxiety and Depression Scale-Anxiety subscale, and functional outcomes were measured using the National Institutes of Health Stroke Scale for stroke severity, the Barthel Index for activities of daily living (ADL), and the Mini-Mental State Examination for cognitive function at 2 weeks and 1 year. A range of demographic and clinical covariates were considered. The cross-sectional and longitudinal associations between PSA and functional outcomes were investigated.RESULTS: PSA at the acute phase was not associated with functional outcomes at the cross-sectional point, but predicted worsening of outcome on stroke severity and ADL 1 year after stroke. PSA at the chronic phase was cross-sectionally associated with poor functional outcomes in all three measures. All associations were independent of potential covariates.CONCLUSION: Screening for anxiety is recommended even during the acute phase of stroke, considering its independent detrimental effect on functional prognosis. Screening for anxiety during the chronic phase is also encouraged, as this may reflect the functional status of stroke.

Similarities of Aspects of Biological Rhythms between Major Depression and Bipolar II Disorder Compared to Bipolar I Disorder: A Finding from the Early-Onset Mood Disorder Cohort

OBJECTIVE: The biological rhythm is closely related to mood symptoms. The purpose of this study was to assess the differences in biological rhythms among subjects with mood disorder [bipolar I disorder (BD I), bipolar II disorder (BD II), major depressive disorder (MDD)] and healthy control subjects.METHODS: A total of 462 early-onset mood disorder subjects were recruited from nine hospitals. The controls subjects were recruited from the general population of South Korea. Subject groups and control subject were evaluated for the Korean language version of Biological Rhythms Interview of Assessment in Neuropsychiatry (K-BRIAN) at the initial evaluation.RESULTS: The mean K-BRIAN scores were 35.59 [standard deviation (SD)=13.37] for BD I, 43.05 (SD=11.85) for BD II, 43.55 (SD=12.22) for MDD, and 29.1 (SD=8.15) for the control group. In the case of mood disorders, biological rhythm disturbances were greater than that in the control group (p<0.05). A significant difference existed between BD I and BD II (BD I <BD II, p<0.001) and between BD I and MDD (BD I<MDD, p< 0.001) but no difference was observed between BD II and MDD.CONCLUSION: BD II and MDD are similar to each other but different from BD I in biological rhythm patterns in early-onset mood disorder cases. Biological rhythm disturbances are similar for early-onset major depression and BD II.

Association between Obsessive-Compulsive Symptoms and Long-Term Cardiac Outcomes in Patients with Acute Coronary Syndrome: Effects of Depression Comorbidity and Treatment

OBJECTIVE: The role of obsessive-compulsive symptoms (OCS) in patients with acute coronary syndrome (ACS) is not well elucidated. This study investigated the association between OCS and the long-term prognosis of ACS in tandem with depression comorbidity and treatment.METHODS: A cross-sectional baseline study and a nested 24-week double-blind escitalopram-placebo controlled trial were carried out between May 2007 and March 2013, and then a 5–12-year follow-up for major adverse cardiac events (MACE) was conducted. A total of 1,152 patients with ACS were stratified by baseline depression comorbidity and treatment allocation into four groups: no depression (706 patients), depression and taking escitalopram (149 patients), depression and taking a placebo (151 patients), and depression and receiving medical care as usual (CAU; 146 patients). OCS were evaluated using the Symptom Checklist-90-Revised Obsessive-Compulsive symptom domain. During the follow-up, Kaplan-Meier event rates for MACE outcomes were calculated, and hazard ratios were estimated using Cox regression models after adjusting for a range of covariates.RESULTS: A higher OCS score at baseline was associated with a worse ACS prognosis after adjusting for relevant covariates and across MACE outcomes. This association varied according to the depression comorbidity. The association was significant in patients without depression and depressive patients receiving placebos and CAU, but not in depressive patients on escitalopram.CONCLUSION: Evaluating OCS and depression is recommended during the early phase of ACS. Treatment for OCS may improve the long-term cardiac outcomes of patients with ACS.

Suicidal Ideation Predicts Functioning and Quality of Life Over One Year after Acute Coronary Syndrome

OBJECTIVE: This study investigated the associations of suicidal ideation (SI) evaluated within 2 weeks after an acute coronary syndrome (ACS) episode with functioning, disability, and quality of life (QOL) at a 1-year follow-up assessment. METHODS: This study recruited 1152 consecutive patients within 2 weeks of a confirmed ACS episode; 828 of these patients who were followed up 1 year later comprised the study sample. SI was determined at baseline using the “suicidal thoughts” item of the MontgomeryÅsberg Depression Rating Scale. At both examinations, social and occupational functioning were measured by the Social and Occupational Functioning Assessment Scale (SOFAS), disability was estimated by World Health Organization Disability Assessment Schedule-12 (WHODAS-12), and QOL was assessed using the World Health Organization Quality of Life-Abbreviated form (WHOQOL-BREF). Baseline covariates included sociodemographic data, depression characteristics, cardiovascular risk factors, and current cardiac status. RESULTS: SI at baseline was independently associated with less improved or decreased scores on the SOFAS, WHODAS-12, and WHOQOL-BREF over 1 year after adjusting for relevant covariates. CONCLUSION: SI within 2 weeks of an ACS episode predicted poorer functioning and QOL at a 1-year follow-up assessment. Thus, the simple evaluation of SI in patients with recently developed ACS could be helpful in screening for functioning and QOL during the chronic phase of this disease.

Erratum: The MAKE Biomarker Discovery for Enhancing anTidepressant Treatment Effect and Response (MAKE BETTER) Study: Design and Methodology

In the original publication, the schedule of follow-up assessment was incorrect.

BDNF Methylation and Suicidal Ideation in Patients with Acute Coronary Syndrome

OBJECTIVE: Patients with acute coronary syndrome (ACS) are at an increased risk of suicide. It is well known that epigenetic mechanisms may explain the pathophysiology of suicidal behavior including suicidal ideation (SI), but no study has explored these mechanisms in ACS populations. METHODS: In total, 969 patients were initially recruited within 2 weeks of the acute coronary event and, 711 patients were successfully followed up 1 year after ACS. SI was evaluated using the relevant items on the Montgomery-Åsberg Depression Rating Scale and covariates potentially affecting SI were estimated. RESULTS: Brain-derived neurotrophic factor (BDNF) hypermethylation was associated with SI in both the acute and chronic phases of ACS, although the association was not statistically significant in the acute phase after applying Bonferroni’s correction. CONCLUSION: These results suggested that BDNF hypermethylation may have played a role in an epigenetic predisposition for SI in ACS patients, particularly during the chronic phase.