Doh Kwan Kim

MEDIPOST Biomedical Research Institute, Sŏul, Seoul, South Korea

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Publications (36)93.61 Total impact

  • [show abstract] [hide abstract]
    ABSTRACT: We investigated the effects of galantamine on cognitive subdomains in Alzheimer's disease (AD). Sixty-six patients with mild-to-moderate AD received open-label galantamine for 52 weeks. Cognitive function was measured using the Korean version of the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog-K). Response to galantamine was defined as "improvement or no deterioration" on the total scores of the ADAS-cog-K at 26 weeks. In the overall intent-to-treat sample, we found less cognitive decline during 26 and 52 weeks than the expected untreated course as predicted by Stern's equation. The operationally defined response rate at 26 weeks was 66.7%. The responders differed significantly from the nonresponders only in the memory and language domains but not in the domains of praxis or frontal/executive function or in secondary outcome measures of neuropsychiatric symptoms and activities of daily living. The subdomain analysis revealed an effect of galantamine on preservation of memory that was not apparent in the overall analysis. Failure to achieve responder status by 26 weeks was associated with no further possibility of response.
    The Journal of nervous and mental disease 03/2014; 202(3):253-9. · 1.77 Impact Factor
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    ABSTRACT: Background: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.Methods: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.Results: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 (P < .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 (P < .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 (P < .001, regression coefficient = 3.19, and median regression). The GDS-15 scores were higher in the EPS group (P = .04, regression coefficient = 0.89, and median regression).Conclusion: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.
    Journal of Geriatric Psychiatry and Neurology 06/2013; · 3.53 Impact Factor
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    ABSTRACT: 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). 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. 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. BDNF genotyping may be informative for anticipating chronicity in major depression.
    Psychiatry investigation 03/2013; 10(1):56-61. · 1.06 Impact Factor
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    ABSTRACT: Suicide is not only an individual phenomenon, but it is also influenced by social and environmental factors. With the high suicide rate and the abundance of social media data in South Korea, we have studied the potential of this new medium for predicting completed suicide at the population level. We tested two social media variables (suicide-related and dysphoria-related weblog entries) along with classical social, economic and meteorological variables as predictors of suicide over 3 years (2008 through 2010). Both social media variables were powerfully associated with suicide frequency. The suicide variable displayed high variability and was reactive to celebrity suicide events, while the dysphoria variable showed longer secular trends, with lower variability. We interpret these as reflections of social affect and social mood, respectively. In the final multivariate model, the two social media variables, especially the dysphoria variable, displaced two classical economic predictors - consumer price index and unemployment rate. The prediction model developed with the 2-year training data set (2008 through 2009) was validated in the data for 2010 and was robust in a sensitivity analysis controlling for celebrity suicide effects. These results indicate that social media data may be of value in national suicide forecasting and prevention.
    PLoS ONE 01/2013; 8(4):e61809. · 3.73 Impact Factor
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    ABSTRACT: We compared the cell responsiveness of activated lymphocytes to rapamycin, which blocks the G1/S transition, between patients with Alzheimer's disease (AD) and normal controls to assess the early phase control defect in cell cycle. Blood samples of 26 patients with AD and 28 normal controls were collected to separate peripheral lymphocytes. We measured the proportion of each cell cycle phase in activated lymphocytes using flow cytometry and evaluated the responsiveness of these lymphocytes to rapamycin. The patients with AD were older than the normal controls (AD 74.03±7.90 yr vs. control 68.28±6.21 yr, p=0.004). The proportion of G1 phase cells in the AD group was significantly lower than that in the control group (70.29±6.32% vs. 76.03±9.05%, p=0.01), and the proportion of S phase cells in the AD group was higher than that in control group (12.45±6.09% vs. 6.03±5.11%, p=0.001). Activated lymphocytes in patients with AD were not arrested in the G1 phase and they progressed to the late phase of the cell cycle despite rapamycin treatment, in contrast to those of normal subjects. The patients with AD probably have a control defect of early phase cell cycle in peripheral lymphocytes that may be associated with the underlying pathology of neuronal death.
    Psychiatry investigation 12/2012; 9(4):413-7. · 1.06 Impact Factor
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    ABSTRACT: 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.
    The International Journal of Neuropsychopharmacology 11/2012; · 5.64 Impact Factor
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    ABSTRACT: RATIONALE: 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. OBJECTIVES: Here, we study both 5-HTT gene polymorphisms and 5-HTT function as determinants of antidepressant response to SSRIs in Korean patients. METHODS: 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). RESULTS: 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. CONCLUSIONS: Both ethnicity and function must be considered in evaluating candidate gene biomarkers of response to SSRIs in depression.
    Psychopharmacology 08/2012; · 4.06 Impact Factor
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    ABSTRACT: The heritability of some individual depressive symptoms has been well established. However, the causal genes related to individual depressive symptoms and genetic effects on the courses of individual depressive symptoms are still unclear. We examined these issues in 241 Korean patients who met the DSM-IV-TR criteria for major depression. Patients entered a 12-week clinical trial with antidepressants. A total of 1399 single-nucleotide polymorphisms (SNPs) of 79 candidate genes were assessed. The rs557762 and the TT haplotype in the 11th haplotype block of the GRIA3 gene were associated with feelings of guilt in females. The GGCCGGGC haplotype in the first haplotype block of TPH1 was significantly associated with middle insomnia. The ACAG haplotype in the 13th haplotype block of the GRIK2 gene was associated with somatic anxiety. Moreover, the effect of the rs557762 on guilt significantly varied across times. Our results indicate that there are associations between particular gene polymorphisms and some individual depressive symptoms. These results could contribute to understanding the biological mechanisms of depression.
    Psychiatry Research 03/2012; · 2.46 Impact Factor
  • Alzheimers & Dementia - ALZHEIMERS DEMENT. 01/2011; 7(4).
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    ABSTRACT: Clinical course of depression is variable. The serotonin transporter gene is one of the most studied genes for depression. We examined the association of serotonin transporter gene polymorphisms with chronicity and recurrent tendency of depression in Korean subjects. This cross-sectional study involved 252 patients with major depression. Patients were genotyped for s/l polymorphisms in 5-HTT promoter region (5-HTTLPR), s/l variation in second intron of the 5-HTT gene (5-HTT VNTR intron2). Chronicity was associated with 5-HTTLPR. Patients with l/l had higher rate of chronicity than the other patients (l/l vs s/l or s/s; odds ratio, 4.45; 95% confidence interval, 1.59-12.46; P=0.005; logistic regression analysis). Recurrent tendency was not associated with 5-HTTLPR. Chronicity and recurrent tendency were not associated with 5-HTT VNTR intron2. These results suggest that chronic depression is associated with 5-HTTLPR.
    Journal of Korean medical science 12/2010; 25(12):1824-7. · 0.84 Impact Factor
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    ABSTRACT: We evaluated cell viability and proliferation activity of peripheral lymphocytes as potential models of neuronal death in Alzheimer's disease (AD). We analyzed the cell viability and proliferation activity of phytohemagglutinin (PHA)-activated lymphocytes from 68 AD patients and 33 normal controls. The cellular measures were made at baseline (0 hr), 24 hrs, 48 hrs, 72 hrs, and 96 hrs after PHA stimulation. Cell viability in the AD patients was significantly decreased at 72 hrs and 96 hrs, compared with the normal controls. The declining ramp of the proliferation activity from 48 hrs to 72 hrs after PHA stimulation was significantly related to cell viability at 72 hrs and at 96 hrs in the AD patients. Lymphocytes from patients with AD have altered viability and proliferation characteristics in culture following PHA stimulation. These findings suggest that lymphocytes may be used as a peripheral tissue model of cell cycle dysregulation in AD.
    Psychiatry investigation 03/2010; 7(1):68-71. · 1.06 Impact Factor
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    ABSTRACT: We designed this study to examine subsyndromes in Korean patients with Alzheimer's disease (AD) using exploratory factor analysis (EFA) and confirmatory factor analysis (CFA). Initial participants were 778 AD patients recruited from the Clinical Research Center for Dementia of South Korea and assessed via the Korean Neuropsychiatric Inventory. Those with > or =1 neuropsychiatric symptom were randomly divided into groups. Principal axis factoring with oblimin rotation was used to analyze group 1 inventory results, and maximum likelihood estimation extraction with Bollen-Stine bootstrapping was used for group 2. The results of the EFA showed the presence of 4 subsyndromes: hyperactivity, affect, psychosis and apathy/vegetative symptom. The CFA results indicated this model was the best-fitting model for explaining these subsyndromes. Our model showed the best fit and identified 4 subsyndromes. This study might contribute to a clearer understanding of the neuropsychiatric symptoms in AD.
    Dementia and Geriatric Cognitive Disorders 01/2010; 29(1):82-7. · 2.79 Impact Factor
  • Alzheimers & Dementia - ALZHEIMERS DEMENT. 01/2010; 6(4).
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    ABSTRACT: Carbonic anhydrase (CA) plays a critical role in pH regulation, long-term synaptic transformation, and is associated with mental retardation, Alzheimer's disease (AD), and Down syndrome. There is accumulating evidence that CAII is increased in AD brain. The present study focused on the determination of CAII protein level in blood plasma samples using immunoblot and ELISA methods. We compared plasma from 91 AD patients (average age 74.8 y), 83 persons with amnestic mild cognitive impairment (MCI) (average age 73.7 y), and 113 cognitively normal controls (average age 70.8 y). The plasma level of CAII was significantly increased in AD patients, as compared to control groups. CAII levels were higher in males than females. There was an age-dependent increase of CAII. These results provide further evidence that changes in CAII level may play a role in the pathogenesis of AD.
    Journal of Alzheimer's disease: JAD 01/2010; 21(3):939-45. · 4.17 Impact Factor
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    ABSTRACT: Ubiquitin-conjugating enzyme E2I (Ubc9) ligates small ubiquitin-related modifier (SUMO) to target proteins, resulting in changes of their localization, activity, or stability. Sumoylation of amyloid precursor protein (APP) was reported to be associated with decreased levels of beta amyloid (Abeta) aggregates, suggesting that sumoylation may play a role in the pathogenesis of Alzheimer's disease (AD). We investigated the association between genetic variations of Ubc9 gene (UBE2I) and late-onset Alzheimer's disease (AD). Five single nucleotide polymorphisms (SNPs) in UBE2I were genotyped in the DNA samples of 312 AD patients, 347 subjects with mild cognitive impairment (MCI), and 489 cognitively healthy controls. The genotype distribution of a polymorphism in intron 7 (rs761059) differed between AD cases and controls, with an adjusted odds ratio (OR) of 1.45 (p=0.046, 95% CI: 1.01-2.08). One haplotype (ht2 CAGAG) was found in 14.0% of the AD patients and in 11.1% of the controls (p=0.04, OR=1.43. 95% CI; 1.01-2.01). Stratification by the ApoE-epsilon4 allele gave no significant difference between the groups. When the samples were stratified by gender, the genotypes of two SNPs (rs8052688, rs8063) were significantly associated with the risk of MCI among women. Our investigation suggests that UBE2I polymorphisms might be associated with a risk of AD and MCI.
    Neuroscience Letters 09/2009; 465(3):272-5. · 2.03 Impact Factor
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    ABSTRACT: THIS STUDY WAS CONDUCTED TO EXAMINE THE FOLLOWING: whether patients with mild cognitive impairment (MCI) show impairments in instrumental activities of daily living (IADL) as compared to controls; to identify the functional sub-domains of instrumental activities of daily living (IADL) that are affected in MCI and, finally, to identify the Seoul-Instrumental Activities of Daily Living (S-IADL) scale cut-off score that best differentiated between MCI and controls. This study was carried out at the geropsychiatry clinic, university hospital. The study participants included 66 patients with MCI and 61 normal elderly. The S-IADL and Seoul-Activities of Daily Living (S-ADL) scales were administered to the main caregivers of all participants in order to assess everyday functioning. The total S-IADL score was significantly higher in the patients with MCI [mean (SD) score=4.47 (2.06)] than in the controls [mean (SD) score=1.44 (1.65)] (p<0.001). The patients with MCI performed significantly worse on IADLs, such as the ability to use the telephone, prepare meals, take medication, manage belongings, keep appointments, talk about recent events, and perform leisure activities/hobbies (p<0.05). The S-IADL scale discriminated well between patients with MCI and controls (Area Under Curve=87%). The patients with MCI showed impairments in the ability to perform complex ADL in comparison to healthy controls. IADLs related to memory and frontal/executive functioning were particularly affected in MCI.
    Psychiatry investigation 09/2009; 6(3):180-4. · 1.06 Impact Factor
  • Alzheimers & Dementia - ALZHEIMERS DEMENT. 01/2009; 5(4).
  • Alzheimers & Dementia - ALZHEIMERS DEMENT. 01/2009; 5(4).
  • Alzheimers & Dementia - ALZHEIMERS DEMENT. 01/2008; 4(4).
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    ABSTRACT: Beta-site amyloid precursor protein cleaving enzyme (BACE) is a candidate risk factor for Alzheimer's disease (AD) from its key role in beta-amyloid generation. Previous genetic association studies of BACE1 gene have yielded conflicting results. This study is an attempt to clarify whether the common SNP in exon 5 of BACE1 (rs638405, Val262) is associated with a risk for late-onset AD. We genotyped a synonymous C/G polymorphism of BACE1 located in exon 5 and apolipoprotein E (ApoE) in 248 AD patients and 224 healthy persons. A meta-analysis with pooled data from four Chinese studies and our results was performed. The allele and genotype frequencies of BACE1 polymorphism were not significantly different between cases and controls (p > 0.05) in the Korean population. A meta-analysis of previously published Asian populations including Koreans showed evidence of a weak association (p = 0.0555 for genotypes, p = 0.0352 for alleles). However, a significant association between the CC genotype and AD was observed in the ApoE-epsilon4-positive groups (p = 0.0044, OR = 1.995; 95% CI = 1.319-3.018). These data suggest that BACE1 polymorphism in exon 5 influences risk for late-onset AD in those carrying the ApoE epsilon4 allele.
    Dementia and Geriatric Cognitive Disorders 01/2008; 25(2):165-9. · 2.79 Impact Factor

Publication Stats

203 Citations
27 Downloads
2k Views
93.61 Total Impact Points

Institutions

  • 2010–2013
    • MEDIPOST Biomedical Research Institute
      Sŏul, Seoul, South Korea
  • 1999–2013
    • Sungkyunkwan University
      • Department of Psychiatry
      Sŏul, Seoul, South Korea
  • 2007
    • Samsung Medical Center
      Sŏul, Seoul, South Korea
  • 2006
    • National Institute of Health, Korea
      Seishō-gun, North Gyeongsang, South Korea