Long-term cardiac outcomes of depression screening, diagnosis and treatment in patients with acute coronary syndrome: the DEPACS study.

BACKGROUND: To investigate the impacts of depression screening, diagnosis and treatment on major adverse cardiac events (MACEs) in acute coronary syndrome (ACS). METHODS: Prospective cohort study including a nested 24-week randomised clinical trial for treating depression was performed with 5-12 years after the index ACS. A total of 1152 patients recently hospitalised with ACS were recruited from 2006 to 2012, and were divided by depression screening and diagnosis at baseline and 24-week treatment allocation into five groups: 651 screening negative (N), 55 screening positive but no depressive disorder (S), 149 depressive disorder randomised to escitalopram (E), 151 depressive disorder randomised to placebo (P) and 146 depressive disorder receiving medical treatment only (M). RESULTS: Cumulative MACE incidences over a median 8.4-year follow-up period were 29.6% in N, 43.6% in S, 40.9% in E, 53.6% in P and 59.6% in M. Compared to N, screening positive was associated with higher incidence of MACE [adjusted hazards ratio 2.15 (95% confidence interval 1.63-2.83)]. No differences were found between screening positive with and without a formal depressive disorder diagnosis. Of those screening positive, E was associated with a lower incidence of MACE than P and M. M had the worst outcomes even compared to P, despite significantly milder depressive symptoms at baseline. CONCLUSIONS: Routine depression screening in patients with recent ACS and subsequent appropriate treatment of depression could improve long-term cardiac outcomes.

Modifying effects of depression on the association between BDNF methylation and prognosis of acute coronary syndrome.

AIMS: Brain-derived neurotrophic factor (BDNF) plays important roles in angiogenesis, inflammation, and neuronal plasticity. BDNF methylation has been extensively investigated in depression, but not in cardiac diseases. We asked whether BDNF methylation status is associated with a major adverse cardiac event (MACE), inflammation, and the association with depression comorbidity and its treatment in patients with acute coronary syndrome (ACS). METHODS AND RESULTS: A cross-sectional baseline study and nested 24 week double-blind escitalopram placebo-controlled trial (ClinicalTrial.gov identifier NCT00419471) were performed from 2006 to 2012, with 5-12 year follow-up for MACE. Patients with recent ACS (969 total) were divided into four groups according to depression comorbidity at baseline and treatment allocation: 591, absent depression; 127, depression on escitalopram; 128, depression on placebo; 123, depression on care as usual (CAU). BDNF methylation was measured in leucocyte DNA, and multiple demographic and clinical characteristics including interleukin 6 were evaluated as covariates at baseline. The primary outcome, time to first MACE (a composite of all-cause mortality, myocardial infarction and percutaneous coronary intervention), was investigated using Cox regression models after adjustment for covariates. Interleukin 6 level was significantly higher in patients with higher BDNF methylation values. Higher BDNF methylation was associated with increased MACE independent of confounding factors [HR (95% CI) = 1.45 (1.17-1.78)]. This association was significant in patients without depression [HR (95% CI) = 1.39 (1.01-1.90)] and depressive patients on placebo [HR (95% CI) = 1.72 (1.02-3.02)] or CAU [HR (95% CI) = 1.53 (1.01-2.61)], but not in those treated with escitalopram [HR (95% CI) = 1.00 (0.51-1.95)]. CONCLUSION: BDNF methylation was significantly associated with prognosis of ACS. Escitalopram may mitigate the deleterious effect of higher BDNF methylation in depressive patients with ACS. Further research is needed to elucidate the mechanistics and to assess the generalisability of these findings.

Feasibility of using laser-induced breakdown spectroscopy for analyzing deposit formation change of molybdenum disulfide on gas diffusion electrode due to coating method.

This study aimed to evaluate the relationship between the performance of electro-catalysis and the uniformity of molybdenum disulfide (MoS2) on carbon electrodes deposited according to three different coating methods, namely, drop-casting, brushing, and spraying. The electrochemical kinetics can be determined by how uniformly the catalyst is coated throughout the entire surface of the electrodes. Laser-induced breakdown spectroscopy was employed to investigate the uniformity and loading quantity of MoS2 on the electrode surface. The most uniform coating was achieved with the spraying method followed by brushing and drop-casting.

Social support deficit and depression treatment outcomes in patients with acute coronary syndrome: Findings from the EsDEPACS study.

OBJECTIVES: This study aimed to investigate whether social support deficit has moderating effects on depressive and cardiac outcomes in an antidepressant trial for depressed patients with acute coronary syndrome as a secondary analysis using Escitalopram for DEPression in acute coronary syndrome study (ClinicalTrial.gov registry number: NCT00419471). METHODS: In total, 217 acute coronary syndrome patients with Diagnostic and Statistical Manual of Mental Disorders, 4th edition depressive disorders were randomized into two groups that received escitalopram (N = 108) or placebo (N = 109) for 24 weeks. Social support deficit was evaluated by validated scales at study entry. Depressive outcomes were measured using the Hamilton Depression Rating Scale, the Montgomery Asberg Depression Rating Scale, and the Beck Depression Inventory. Cardiac outcomes included echocardiography (left ventricular ejection fraction and wall motion scores), electrocardiography (heart rate, PR interval, QRS duration, and QTc duration), and laboratory test results (troponin I and creatine kinase-MB). RESULTS: A higher social support deficit at baseline was significantly associated with less improvement in Hamilton Depression Rating Scale, Montgomery Asberg Depression Rating Scale, Beck Depression Inventory scores, and serum troponin I levels after adjustment for corresponding baseline scores, covariates associated with social support deficit at baseline, and treatment status. The strength of these associations was more prominent in the placebo group compared to the escitalopram group. CONCLUSIONS: Evaluation of social support deficit in depressed acute coronary syndrome is important, and particularly during the acute phase, depressed acute coronary syndrome patients with social support deficit should be treated more carefully to improve treatment outcomes, given that social support deficit was predictive of poorer depressive and cardiac outcomes during the 24-week treatment period. Acute coronary syndrome patients with social support deficit should be treated more carefully to improve treatment outcomes.

Prevalence and predictors of major depressive disorder in bereaved caregivers at 6 and 13 months.

OBJECTIVE: Depressive symptoms are common in bereaved caregivers; however, there have been few prospective studies using a structured interview. This study investigated the prevalence and preloss predictors of major depressive disorder (MDD) in bereaved caregivers of patients in a palliative care unit. METHOD: This prospective cohort study collected caregiver sociodemographic and psychological data before the death of a palliative care unit patient, including MDD, care-burden, coping style, and hopeful attitude. Postloss MDD was assessed 6 and 13 months after death, and a multivariate logistic regression analysis was conducted to identify its predictors.ResultOf 305 caregivers contacted, 92 participated in this study. The prevalence of preloss MDD was 21.8%; the prevalences of postloss MDD were 34.8% and 24.7% at 6 and 13 months, respectively. Preloss MDD predicted postloss MDD at 6 months (odds ratio [OR] = 5.38, 95% confidence interval [CI95%] = 1.29, 22.43); preloss nonhopeful attitude and unemployment status of caregivers predicted postloss MDD at 13 months (OR = 8.77, CI95% = 1.87, 41.13 and OR = 7.10, CI95% = 1.28, 39.36, respectively).Significance of resultsApproximately 35% of caregivers suffered from MDD at 6 months postloss, but the prevalence of MDD decreased to about 25% at 13 months. Preloss MDD significantly predicted postloss MDD at 6 months, whereas hopeful attitude and unemployment at baseline were significantly associated with postloss MDD at 13 months.

Gender-specific risk factors for low bone mineral density in patients taking antipsychotics for psychosis.

OBJECTIVE: This study examined clinical and gender-specific risk factors for low bone mineral density (BMD) in adult patients with psychotic disorders. METHODS: The study included 285 community-dwelling patients with psychotic disorders. Dual-energy X-ray absorptiometry was used to measure BMD. Clinical characteristics associated with low BMD were identified with logistic regression analysis in total population and each gender. RESULTS: Fifty-eight (20.4%) subjects had low BMD. Low BMD was more common in men and in patients with low body mass indices (BMIs), as well as in those with shorter treatment durations, those on Medicaid, and patients using serotonergic antidepressants. Logistic regression analysis revealed that low BMD was negatively associated with BMI and treatment duration and positively with gender (male) and serotonergic antidepressants use in the overall population. In men, low BMD was associated with treatment duration and BMI; in women, low BMD was associated with BMI, prolactin level, vitamin D, and serotonergic antidepressant use. CONCLUSION: Managing the risk factors associated with low BMD among patients with psychotic disorder should be done gender-specifically. Psychotropic agents should be prescribed mindful of their effects on bone, as use of these medications is a modifiable risk factor for osteoporosis in women with psychotic disorders.

Contribution of stress and coping strategies to problematic Internet use in patients with schizophrenia spectrum disorders.

INTRODUCTION: Internet use is already high and increasing rapidly among people with psychotic disorders, but there have been few studies on problematic Internet use (PIU) among patients with schizophrenia spectrum disorders. This study aimed to measure the prevalence of PIU and identify the factors associated with PIU among patients with schizophrenia spectrum disorders. METHODS: A cross-sectional survey was performed that included 368 outpatients with schizophrenia spectrum disorders: 317 with schizophrenia, 22 with schizoaffective disorder, 9 with schizophreniform disorder, and 20 with other schizophrenia spectrum and psychotic disorders. The severity of psychotic symptoms and levels of personal and social functioning were assessed by the Clinician-rated Dimensions of Psychosis Symptom Severity (CRDPSS) scale and the Personal and Social Performance (PSP) scale, respectively. PIU was evaluated using Young's Internet Addiction Test (IAT). Additionally, the Hospital Anxiety and Depression Scale (HADS), Perceived Stress Scale (PSS), Rosenberg Selfesteem Scale (RSES), and Brief Coping Orientation to Problems Experienced (COPE) Inventory were administered. RESULTS: PIU was identified in 81 (22.0%) of the 368 patients with schizophrenia spectrum disorders. Subjects with PIU were significantly younger and more likely to be male. Scores on the HADS, PSS, and dysfunctional coping dimension of the Brief COPE Inventory were significantly higher, and RSES scores were significantly lower, in the PIU group. Logistic regression analysis indicated that PIU in patients was significantly associated with scores on the PSS and dysfunctional coping dimension of the Brief COPE Inventory. CONCLUSIONS: Patients with schizophrenia spectrum disorders and PIU were significantly more likely to have high levels of perceived stress and dysfunctional coping strategies. Patients with schizophrenia spectrum disorders who also engage in PIU may benefit from interventions that help them to develop appropriate skills for coping with stress.

Effect of Escitalopram vs Placebo Treatment for Depression on Long-term Cardiac Outcomes in Patients With Acute Coronary Syndrome: A Randomized Clinical Trial.

Importance: Depression has been associated with poorer medical outcomes in acute coronary syndrome (ACS), but there are few data on the effects of antidepressant treatment on long-term prognosis. Objective: To investigate the effect on long-term major adverse cardiac events (MACE) of escitalopram treatment of depression in patients with recent ACS. Design, Setting, and Participants: Randomized, double-blind, placebo-controlled trial conducted among 300 patients with recent ACS and depression enrolled from May 2007 to March 2013, with follow-up completed in June 2017, at Chonnam National University Hospital, Gwangju, South Korea. Interventions: Patients were randomly assigned to receive either escitalopram in flexible dosages of 5, 10, 15, or 20 mg/d (n = 149) or matched placebo (n = 151) for 24 weeks. Main Outcomes and Measures: The primary outcome was MACE, a composite of all-cause mortality, myocardial infarction (MI), and percutaneous coronary intervention (PCI). Four secondary outcomes were the individual MACE components of all-cause mortality, cardiac death, MI, and PCI. Cox proportional hazards models were used to compare the escitalopram and placebo groups by time to first MACE. Results: Among 300 randomized patients (mean age, 60 years; 119 women [39.3%]), 100% completed a median of 8.1 (interquartile range, 7.5-9.0) years of follow-up. MACE occurred in 61 patients (40.9%) receiving escitalopram and in 81 (53.6%) receiving placebo (hazard ratio [HR], 0.69; 95% CI, 0.49-0.96; P = .03). Comparing individual MACE outcomes between the escitalopram and placebo groups, respectively, incidences for all-cause mortality were 20.8% vs 24.5% (HR, 0.82; 95% CI, 0.51-1.33; P = .43), for cardiac death, 10.7% vs 13.2% (HR, 0.79; 95% CI, 0.41-1.52; P = .48); for MI, 8.7% vs 15.2% (HR, 0.54; 95% CI, 0.27-0.96; P = .04), and for PCI, 12.8% vs 19.9% (HR, 0.58; 95% CI, 0.33-1.04; P = .07). Conclusions and Relevance: Among patients with depression following recent acute coronary syndrome, 24-week treatment with escitalopram compared with placebo resulted in a lower risk of major adverse cardiac events after a median of 8.1 years. Further research is needed to assess the generalizability of these findings. Trial Registration: ClinicalTrials.gov Identifier: NCT00419471.

Factors associated with posttraumatic stress disorder symptoms among community volunteers during the Sewol ferry disaster in Korea.

BACKGROUND: The aim of this study was to investigate the characteristics associated with volunteerism and identify the factors that contributed to posttraumatic stress disorder symptoms among community volunteers following the Sewol ferry disaster in Korea. METHODS: In total, 2,298 adults (aged 30-70 years) from the Jin-do area, where the Sewol ferry disaster occurred, participated in this study. A cross-sectional survey was conducted 1 month after the disaster. Posttraumatic stress disorder (PTSD), depression, and anxiety symptoms were assessed using the Impact of Events Scale Revised (IES-R), Center for Epidemiologic Studies Depression Scale (CES-D), and Beck Anxiety Inventory (BAI). RESULTS: Clinically relevant PTSD symptoms were observed in 151 (19.7%) community volunteers. Age, education, socioeconomic status, religion, and lifetime experiences of natural disasters were associated with volunteering following the disaster. Logistic regression analysis revealed that volunteering was a significant risk factor for the development of PTSD symptoms in this sample. Personal experience with property damage associated with a traumatic event, depression, and anxiety were also significantly associated with the PTSD symptoms of community volunteers. CONCLUSIONS: Our results suggest the need for assessment and mental health programs for community volunteers performing rescue work to prevent posttraumatic stress symptoms following a community disaster.

Anxiety symptoms in Korean elderly individuals: a two-year longitudinal community study.

BACKGROUND: Although late-life anxiety occurs frequently and is associated with higher morbidity, few longitudinal studies have been concerned with the evaluation thereof. We investigated the prevalence, incidence, and persistence of anxiety and related factors over a two-year period in community-dwelling Korean elderly individuals. METHODS: A total of 1,204 Korean elderly individuals were evaluated at baseline, and 909 were followed up two years later. The community version of the Geriatric Mental State Schedule was used to estimate anxiety at both baseline and follow-up interviews. We defined "prevalence" as the rate of anxiety symptoms (for both anxiety cases and sub-threshold anxiety) at baseline; "incidence" as the rate of anxiety symptoms at follow-up in those without baseline anxiety symptoms; and "persistence" as the rate of anxiety symptoms at follow-up in those with baseline anxiety symptoms. Associations between various covariates and anxiety status were examined using multivariate logistic regression models. RESULTS: The prevalence, incidence, and persistence of anxiety symptoms were 38.1%, 29.3%, and 41.1%, respectively. Prevalent anxiety symptoms were associated independently with female, rented housing, more stressful life event and medical illness, physical inactivity, depression, insomnia, and lower cognitive function. Incident anxiety symptoms were predicted by older age, female gender, depression, and insomnia; persistent anxiety symptoms were predicted by older age, more medical illness, and baseline depression. CONCLUSIONS: Since depression was associated with prevalent, incident, and persistent anxiety symptoms, effective detection and management thereof is important in older adults to reduce anxiety. Furthermore, preventive collaborative care should be considered, particularly for older, female, insomniac patients.

Influence of caregiver personality on the burden of family caregivers of terminally ill cancer patients.

OBJECTIVE: To determine the influence of caregiver personality and other factors on the burden of family caregivers of terminally ill cancer patients. METHOD: We investigated a wide range of factors related to the patient-family caregiver dyad in a palliative care setting using a cross-sectional design. Caregiver burden was assessed using the seven-item short version of the Zarit Burden Interview (ZBI-7). Caregiver personality was assessed using the 10-item short version of the Big Five Inventory (BFI-10), which measures the following five personality dimensions: extroversion, agreeableness, conscientiousness, neuroticism, and openness. Patient- and caregiver-related sociodemographic and psychological factors were included in the analysis because of their potential association with caregiver burden. Clinical patient data were obtained from medical charts or by using other measures. Multivariate linear regression analysis was performed to identify the independent factors associated with caregiver burden. RESULTS: We analyzed 227 patient-family caregiver dyads. The multivariate analysis revealed that caregiver extroversion was protective against caregiver burden, whereas depressive symptoms in caregivers were related to increased burden. Neuroticism was positively correlated with caregiver burden, but this relationship was nonsignificant following adjustment for depressive symptoms. Patient-related factors were not significantly associated with caregiver burden. SIGNIFICANCE OF RESULTS: Evaluating caregiver personality traits could facilitate identification of individuals at greater risk of high burden. Furthermore, depression screening and treatment programs for caregivers in palliative care settings are required to decrease caregiver burden.

Differential Associations Between Delirium and Mortality According to Delirium Subtype and Age: A Prospective Cohort Study.

OBJECTIVE: This study investigated the differential associations between delirium and mortality in terminally ill patients according to delirium subtype and age. METHODS: This was a prospective cohort study of terminally ill patients. Delirium was diagnosed using the confusion assessment method. Delirium subtypes were defined based on Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition criteria and the Delirium Rating Scale-98-R. A multivariate Cox proportional hazards regression analysis was used to examine predictors of mortality. RESULTS: Of the 322 cases, 98 patients (30.4%) were diagnosed as having delirium. The median (interquartile range) number of survival days after admission was 17.0 (10.0-36.0) days for patients with delirium and 28.0 (16.0-57.0) days for patients without delirium (p = .002). A multivariate analysis revealed that patients with hypoactive and mixed subtypes of delirium survived for shorter periods compared with patients without delirium (hazard ratio [HR] = 1.65 [95% confidence interval {CI} = 1.05-2.59, p = .029] and HR = 2.30 [95% CI = 1.44-3.69, p = .001], respectively). The hypoactive and mixed delirium subtypes exhibited significant interactions with age: younger age was associated with shorter periods of survival in patients with hypoactive and mixed subtype delirium (HR = 0.95 [95% CI = 0.93-0.98, p < .001] and HR = 0.97 [95% CI = 0.93-1.00, p = .038], respectively). CONCLUSIONS: The hypoactive and mixed subtypes of delirium were associated with shorter survival periods in terminally ill patients, and these associations interacted significantly with age. These findings support the clinical and academic value of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition specifiers that differentiate the diagnoses of delirium subtypes.

Associations of cytokine genes with Alzheimer's disease and depression in an elderly Korean population.

BACKGROUND: Inflammatory processes regulated by cytokines are important in the aetiology of Alzheimer's disease (AD) and depression. Differences in transcriptional activities associated with several genetic polymorphisms affect cytokine production. We investigated the involvement of alleles associated with higher production of proinflammatory and lower production of anti-inflammatory cytokines in AD and depression in a community-dwelling sample of elderly individuals. METHOD: A total of 732 community-dwelling elders were clinically evaluated for AD applying the NINCDS-ADRDA criteria and for depression applying the Geriatric Mental State Schedule. Genotyping was performed for six proinflammatory (interleukin (IL)-1ß -511C/T and +3953C/T, IL-6 -174G/C, IL-8 -251T/A, tumour necrosis factor (TNF)-α -850C/T) and two anti-inflammatory (IL-4 +33T/C, IL-10 -1082G/A) cytokines. The sums of risk alleles of proinflammatory and anti-inflammatory cytokine genes were estimated. Age, gender, education and apolipoprotein E genotype were considered covariates. RESULTS: TNF-α -308G/A and IL-8 -251T/A were significantly associated with AD and IL-1ß +3953C/T with late-life depression, while the significance of these associations was lost after Bonferroni correction. A greater number of risk alleles producing proinflammatory cytokines was significantly associated with AD, but not with depression, after adjustment for the covariates. No association was found between an increased number of risk alleles for anti-inflammatory cytokine production and either AD or depression. CONCLUSIONS: The present findings support the inflammatory hypothesis in the aetiology of AD as measured by several cytokine genes associated with increased proinflammatory cytokine production.

Factors associated with self-rated sexual function in Korean patients with schizophrenia receiving risperidone monotherapy.

OBJECTIVE: This study aims to investigate the factors associated with sexual function in Korean patients with schizophrenia. METHODS: This study evaluated 169 patients with schizophrenia who were receiving risperidone monotherapy. The Visual Analog Scale was used to assess sexual function in terms of sexual desire, sexual arousal, and sexual satisfaction. The Positive and Negative Syndrome Scale, the Beck Depression Inventory, the Korean version of the Subjective Well-being under Neuroleptic Treatment-Brief Form (SWN-K) scale, and the Drug Attitude Inventory (DAI) were also administered. RESULTS: Sexual function was negatively associated with age, duration of illness, gender (female), marital status (single), the presence of tardive dyskinesia, and Beck Depression Inventory score, but positively associated with the SWN-K and DAI scores. A linear regression analysis revealed that being male and married had significant positive associations with sexual arousal, sexual satisfaction, and/or sexual desire, while the presence of tardive dyskinesia and a longer duration of illness were associated with poor sexual arousal and/or sexual desire. Additionally, sexual function was significantly associated with the SWN-K and DAI scores in multivariate analysis. CONCLUSIONS: The acknowledgement and management of sexual dysfunction in patients with schizophrenia by clinicians may be important for improvement of their quality of life and adherence to medication.

Refinement of the SWN-20 based on the Rasch rating model.

OBJECTIVES: The aim of the present study was to refine the 20-item Subjective Well-Being under Neuroleptic Treatment Scale (SWN-20) using the Rasch rating model to validate measurements of subjective well-being in patients with schizophrenia undergoing antipsychotic treatment. METHODS: In total, 854 (403 males, 451 females) inpatients (n=213) and outpatients (n=641) with schizophrenia participated in this study, which was designed as an open-label investigation of paliperidone extended release. The participants completed the Korean version of the SWN-20 themselves. Refinement of the Korean version of the SWN-20 was accomplished using the Rasch rating model. RESULTS: Infit and outfit statistics for all 20 items satisfied the criterion for construct validity. Second, all items except items 2 and 20 had suitable point-measure correlations, reflecting content validity. Third, item characteristic curves indicated that roughly 18 items were evenly distributed along the person ability continuum. Finally, option analysis of the category characteristics showed that categories 3 and 4 in the SWN-20 response format were unnecessary. CONCLUSIONS: We offer several recommendations for improving the SWN-20: (a) items 2 and 20 should be omitted to ensure construct validity; (b) easier items would be added related to the person ability estimates in the process of validating a short form of the SWN scale based on item response theory; and (c) the number of response categories should be reduced for schizophrenic patients.

A prospective study of statin use and poststroke depression.

Associations between serum cholesterol levels or lipid-lowering treatment and depression risk have been controversial. Associations between statin use and depression risk have been investigated in patients with coronary artery diseases but have not been examined after stroke. This study aimed to investigate whether statin use was associated with depression ascertained at 2 weeks and 1 year after stroke. A total of 423 patients were evaluated 2 weeks after stroke, and 288 (68%) were followed 1 year later. At the 2 examinations, depression (major or minor depressive disorder) was diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria, and depression severity was assessed by the Hospital Anxiety and Depression Scale-Depression subscale and the Hamilton Depression Rating Scale. Logistic regression and repeated-measures analyses of variance were carried out. Statins were used in 251 (59%) of 423 patients at baseline. Statin use was not associated with poststroke depression (PSD) status at baseline but was significantly associated with reduced risk of all PSD, and of major PSD specifically, at follow-up. Statin use was also associated with better trajectories of depression assessment scale scores over the 1-year follow-up. Statin use was associated with a reduced risk of depression at 1 year after stroke. Likely causality and underlying mechanisms need to be further clarified.

Effect of the allelic variant of alcohol dehydrogenase ADH1B*2 on ethanol metabolism.

BACKGROUND: It has been known that ADH1B*2 allele has a protective effect against the development of alcohol dependence. However, the protection mechanism is still unknown. We investigated whether ADH1B gene polymorphism affects ethanol (EtOH) metabolism. METHODS: In a parent study, we conducted a randomized crossover trials on 24 healthy male subjects who were selected by genotyping: 12 with ALDH2*1/*1 (active form) and 12 with ALDH2*1/*2 (inactive form). In the present study, the 24 subjects were reclassified into 2 groups of 11 with ADH1B*1/*2 and 13 with ADH1B*2/*2 according to the ADH1B genotypes. Each subject was administered 1 of 3 doses of EtOH (0.25, 0.5, 0.75 g/kg) or a placebo in 4 trials. After the administration of alcohol, blood EtOH and acetaldehyde concentrations were measured 9 times over 4 hours. RESULTS: In the case of EtOH, the area under the concentration-time curve from 0 to 4 hours (AUC0-4 ) and the peak blood concentration of EtOH (Cmax ) in subjects with ADH1B*2/*2 were significantly higher than those in subjects with ADH1B*1/*2 at all 3 dosages before stratifying by ALDH2 genotype. However, after stratifying by ALDH2 genotype, a statistically significant difference between ADH1B*2/*2 and ADH1B*1/*2 was found only at the 0.5 g/kg dosage regardless of ALDH2 genotype. In the case of acetaldehyde, the AUC0-4 and Cmax of acetaldehyde of ADH1B*2/*2 after administration of 0.25 g/kg alcohol and the AUC0-4 of acetaldehyde of ADH1B*2/*2 at 0.5 g/kg were significantly higher than corresponding values of ADH1B*1/*2 only in the group of ALDH2*1/*2. CONCLUSIONS: Our findings indicate that the blood EtOH concentrations of ADH1B*2/*2 group are higher than those of ADH1B*1/*2 group regardless of ALDH2 genotype, and the blood acetaldehyde concentrations of ADH1B*2/*2 are also higher than those of ADH1B*1/*2 only in the ALDH2*1/*2 group. To our knowledge, this is the first report to demonstrate the association of ADH1B*2 allele with blood EtOH and acetaldehyde levels in humans, and these results suggest that higher blood EtOH and acetaldehyde concentrations in ADH1B*2/*2 may constitute the mechanism of protection against alcoholism by ADH1B*2/*2.

Association of BDNF promoter methylation and genotype with suicidal ideation in elderly Koreans.

OBJECTIVES: Brain-derived neurotrophic factor (BDNF) has been considered a risk factor for suicidal behavior in adult populations. BDNF secretion is influenced by epigenetic (DNA promoter methylation) and genetic (val66met polymorphism) profiles. We investigated the independent and interactive effects of BDNF methylation status and val66met polymorphisms on late-life suicidal ideation. METHODS: In total, 732 Korean community residents aged 65+ years were evaluated; of 639 without suicidal ideation, 579 (90.6%) were followed up 2 years later. The prevalence and incidence of suicidal ideation were ascertained using the Geriatric Mental State Schedule. Sociodemographic and clinical covariates included age, sex, education, depressive symptoms, cognitive function, and disability. The independent effects of BDNF methylation status on the prevalence and incidence of suicidal ideation were investigated using multivariate logistic regression models. The two-way interactions of BDNF methylation status and val66met polymorphism on suicidal ideation were assessed using the same models. RESULTS: Higher BDNF methylation status was significantly associated with both prevalence and incidence of suicidal ideation, independent of potential covariates. No significant methylation-genotype interaction was found. CONCLUSIONS: The BDNF hypothesis and the epigenetic origin of the suicidal behavior were supported, even in old age. BDNF promoter methylation status may be useful as a biological marker for suicidality in late life.

Serotonergic genes and suicidal ideation 2 weeks and 1 year after stroke in Korea.

OBJECTIVES: Serotonergic genes are associated with suicidal behavior; this association has not been tested in stroke survivors, however. In this study, we investigated whether serotonin transporter (5-HTT) and serotonin 2a receptor (5-HTR2a) genes were associated with suicidal ideation at 2 weeks and at 1 year after stroke. METHODS: A total of 286 patients were evaluated 2 weeks after stroke, and 222 (78%) participated in a follow-up evaluation one year later. Suicidal ideation was ascertained using the "suicidal thoughts" item of the Montgomery and Asberg Depression Rating Scale. Associations between suicidal ideation and 5-HTTLPR, STin2 VNTR, 5-HTR2a 1438A/G, and 5-HTR2a 102T/C genotypes were estimated using logistic regression models, and gene-gene interactions were investigated using the generalized multifactor dimensionality reduction method after adjustment for potential covariates, including depression. RESULTS: The 5-HTR2a 1438 A/A genotype was significantly associated with suicidal ideation 2 weeks after stroke, before and after statistical adjustment. The 5-HTTLPR short allele was associated with suicidal ideation 2 weeks after stroke, although the significance of this finding was not evident after adjustment. No significant associations were observed between any genotype and suicidal ideation one year after stroke. No significant gene-gene interactions were detected. CONCLUSIONS: Individuals with the 5-HTR2a 1438 A/A genotype were more susceptible to suicidal ideation 2 weeks after stroke. Careful evaluation and management are indicated for those with increased genetic vulnerability, particularly during the acute phase of stroke.