T-lymphocyte CREB as a potential biomarker of response to antidepressant drugs.

Lim, Shinn-Won,Kim, Seonwoo,Carroll, Bernard J,Kim, Doh Kwan Cambridge University Press 2013 International Journal of Neuropsychopharmacology Vol.16 No.5

<P>Response to drug treatment of major depression is variable and biomarkers of response are needed. Cyclic AMP response element binding protein (CREB) is considered a key mediator of antidepressant drug effect. We studied CREB in T-lymphocytes as a potential predictor of response to a selective serotonin reuptake inhibitor (SSRI) in 69 Korean depressed patients. We determined total CREB (tCREB), phosphorylated CREB (pCREB) and CRE-DNA binding using immunoblot and electrophoretic mobility shift assays, at baseline and after 6?wk treatment. Thirty-four healthy controls were also studied. The rate of response was 36 of 69 cases (52%). Baseline levels of tCREB and pCREB were lower in the total depressed group compared to controls (p?=?0.044 and p<0.001, respectively). Baseline tCREB values in responders were significantly reduced in comparison to non-responders and to controls. After 6?wk treatment, median values of change of all CREB measures were greater in responders (36) than in non-responders (33; p<0.001 for tCREB, p?=?0.003 for pCREB, and p=0.072 for CRE-DNA binding). Similar but less robust changes in CREB variables distinguished remitters from non-remitters. The optimum value of baseline tCREB predicted response with a positive predicted value of 0.778 [21/27; 95% confidence intervals (CI) 0.621-0.935], negative predictive value of 0.643 (27/42; 95% CI 0.498-0.788) and accuracy of 0.695 (48/69; 95% CI 0.586-0.804). Patients with low baseline tCREB had a significantly greater rate of response (78%) than patients with high baseline tCREB (36%), p?<?0.001. Moreover, the greatest changes in tCREB with treatment were observed in subjects who did respond. This preliminary study suggests that T-lymphocytic CREB biomarkers are reduced in depressed patients and may assist in the prediction of response to SSRI drugs in depression.</P>

Clinical epidemiology of long-term suicide risk in a nationwide population-based cohort study in South Korea

Lee, Hyewon,Myung, Woojae,Lee, Chunsoo,Choi, Junbae,Kim, Ho,Carroll, Bernard J.,Kim, Doh Kwan Pergamon Press 2018 Journal of psychiatric research Vol.100 No.-

<P>We investigated the effects of a large range of clinical factors on the long-term risk of suicide in the general population of South Korea. We analyzed the National Health Insurance Service-National Sample Cohort (NHISNSC) database in South Korea. A total of 300,232 individuals were followed for up to 12 years. We obtained information on demographic variables (age and sex), lifestyle variables (cigarette smoking, alcohol drinking and exercise), psychiatric and physical disorders, laboratory examination results and physical examination findings. We conducted a competing risk survival analysis to estimate the risk of completed suicide. 725 individuals (241/100,000) died by suicide in the follow-up period. After Bonferroni correction, we found a significant suicide risk associated with 6 variables: Parkinson's disease, depressive disorder, obsessive-compulsive disorder (inverted association), elevated serum aspartate aminotransferase levels, male gender and age. Before Bonferroni correction, variables such as cigarette smoking, heavy alcohol drinking, psychotic disorder, other psychiatric disorder, benzodiazepine use and higher fasting glucose showed some significant association. In addition, body mass index and height were inversely related to completed suicide before Bonferroni correction. However, only the 6 variables listed above were robust predictors of suicide in the fully adjusted analyses with multiple test correction. Common medical conditions had no clear influence on suicide. Diverse clinical factors influenced the long-term risk of completed suicide in this general population sample. Comprehensive assessment of these risk factors will facilitate more focused suicide surveillance measures.</P>

Association between the BDNF Val66Met Polymorphism and Chronicity of Depression

이유진,임신원,김수연,정재원,김진우,명우재,송지혜,김선우,Bernard J Carroll,김도관 대한신경정신의학회 2013 PSYCHIATRY INVESTIGATION Vol.10 No.1

Objective Both clinical and biological factors influence the course of depressive disorders. This study tested for associations between the brain-derived neurotrophic factor (BDNF) gene at the Val66Met locus and the course of major depressive disorder (MDD). Methods Three hundred ten Korean subjects (209 patients, 101 controls) were genotyped for rs6265 at nucleotide 196 (G/A), which produces an amino acid substitution at codon 66 (Val66Met) of the gene for BDNF. Course of illness was evaluated both by chronicity of current episode (episode duration >24 months) and by the lifetime history of recurrences. Results Patients with the Met/Met BDNF genotype had a significantly higher rate of chronic depression than all others. There was a significant dose effect of the Met allele on chronicity. Compared with the Val/Val genotype, the relative risk of chronicity was 1.67 for the Val/Met genotype, and 2.58 for the Met/Met genotype. Lifetime history of recurrent episodes was not related to BDNF genotypes but was significantly associated with younger age of onset and with a history of depression in first degree relatives. Conclusion BDNF genotyping may be informative for anticipating chronicity in major depression.

Advanced Daily Prediction Model for National Suicide Numbers with Social Media Data

KyungSang Lee,Hyewon Lee,Woojae Myung,GilYoung Song,Kihwang Lee,Ho Kim,Bernard J. Carroll,DohKwan Kim 대한신경정신의학회 2018 PSYCHIATRY INVESTIGATION Vol.15 No.4

Objective-Suicide is a significant public health concern worldwide. Social media data have a potential role in identifying high suicide risk individuals and also in predicting suicide rate at the population level. In this study, we report an advanced daily suicide prediction model using social media data combined with economic/meteorological variables along with observed suicide data lagged by 1 week. Methods-The social media data were drawn from weblog posts. We examined a total of 10,035 social media keywords for suicide prediction. We made predictions of national suicide numbers 7 days in advance daily for 2 years, based on a daily moving 5-year prediction modeling period. Results-Our model predicted the likely range of daily national suicide numbers with 82.9% accuracy. Among the social media variables, words denoting economic issues and mood status showed high predictive strength. Observed number of suicides one week previously, recent celebrity suicide, and day of week followed by stock index, consumer price index, and sunlight duration 7 days before the target date were notable predictors along with the social media variables. Conclusion-These results strengthen the case for social media data to supplement classical social/economic/climatic data in forecasting national suicide events.

Serotonin transporter genotype and function in relation to antidepressant response in Koreans.

Myung, Woojae,Lim, Shinn-Won,Kim, Seonwoo,Kim, Hyeran,Chung, Jae Won,Seo, Min Young,Kim, Jong-Won,Carroll, Bernard J,Kim, Doh Kwan Springer-Verlag 2013 Psychophamacology Vol.225 No.2

<P>Serotonin transporter (5-HTT) gene polymorphisms are linked with antidepressant response to selective serotonin reuptake inhibitor drugs (SSRIs), though the favorable allelic variant differs by ethnic group (Caucasian versus Korean or Japanese). In Caucasian patients, response also is linked to measures of platelet 5-HTT function. Here, we study both 5-HTT gene polymorphisms and 5-HTT function as determinants of antidepressant response to SSRIs in Korean patients. We enrolled 99 patients with major depression and 48 control subjects. For statistical power, both samples were enriched with the l/l 5-HTTLPR polymorphism, which is uncommon in Koreans. Patients were treated with fluoxetine or sertraline. Response was assessed at 6 weeks. Subjects were genotyped for s/l polymorphism in the 5-HTT promoter region (5-HTTLPR). Platelet 5-HTT activity was determined as maximal uptake rate (Vmax) and affinity constant (Km). Response was differentially associated with the s allele of 5-HTTLPR, which also was significantly associated with Vmax. These associations are opposite to those reported in Caucasian populations. Responders had significantly higher Vmax and Km than nonresponders. In Koreans as well as Caucasians, high Vmax is related to antidepressant response to SSRIs, though the 5-HTTLPR polymorphism associations with both response and function differ by ethnicity. Both ethnicity and function must be considered in evaluating candidate gene biomarkers of response to SSRIs in depression.</P>

Association Between Functional Impairment, Depression, and Extrapyramidal Signs in Neuroleptic-Free Patients With Alzheimer Disease

Choi, Junbae,Myung, Woojae,Chung, Jae Won,Kang, Hyo Shin,Na, Duk L.,Kim, Seong Yoon,Lee, Jae-Hong,Han, Seol-Heui,Choi, Seong Hye,Kim, SangYun,Kim, Seonwoo,Carroll, Bernard J.,Kim, Doh Kwan SAGE Publications 2013 Journal of geriatric psychiatry and neurology Vol.26 No.3

<P><B>Background:</B></P><P>Extrapyramidal signs (EPSs) are commonly observed in patients with Alzheimer disease (AD). We report here the base rate of EPS in a large cohort of patients with AD who were not receiving neuroleptic drugs, and the associations of EPS with functional outcomes and depressive symptoms.</P><P><B>Methods:</B></P><P>In a consortium involving 56 clinics, we recruited 2614 patients with AD. We estimated basic activities of daily living (ADL) and instrumental ADL by the Barthel index and the Seoul-Instrumental Activities of Daily Living (S-IADL) scales, respectively. Depressive symptoms were assessed using the 15-item Geriatric Depression Scale (GDS-15). The EPS group was defined by the presence of at least 1 EPS based on a focused neurologic examination.</P><P><B>Results:</B></P><P>The prevalence of EPS-positive patients was 12%. These had lower Korean version of the Mini-Mental State Examination (K-MMSE) scores than the EPS-negative cases (<I>P</I> < .001). After controlling for demographic, medical, radiological, genetic, and cognitive (K-MMSE) factors, the proportion of patients with impaired ADL was significantly higher in the EPS group than in the non-EPS group (<I>P</I> < .001, odds ratio = 1.90, 95% confidence interval, 1.45–2.48, and logistic regression). The S-IADL scores were significantly higher in the EPS group than this in the non-EPS group (<I>P</I> < .001, regression coefficient = 3.19, and median regression). The GDS-15 scores were higher in the EPS group (<I>P</I> = .04, regression coefficient = 0.89, and median regression).</P><P><B>Conclusion:</B></P><P>The presence of EPS in patients with AD who were not receiving neuroleptic drugs was associated with more impaired basic and instrumental ADL functioning and with greater depression symptoms.</P>