J.S. Yoon

Limb length and dementia in an older Korean population

Objectives: There has been little research into risk factors for dementia outside Western settings, in particular the importance of early life nutrition as estimated by adult body size. This study investigated the associations of arm and leg length with cognitive impairment and dementia in a community sample of older Korean people. Methods: 746 community residents aged 65 or over were clinically assessed for dementia and cognitive impairment. The following were also measured: arm length (demispan), leg length (iliac crest height), and sitting height (standing height minus iliac crest height). Reproductive history was also ascertained in women. Results: Shorter demispan and leg length were associated with increased age and lower education. They were also associated with dementia and Alzheimer’s disease after adjustment for these factors. These associations were only significant in women but were not explained substantially by timing of the menarche or menopause. The association between lower education and dementia was also stronger in women, but was not explained substantially by limb length. Conclusions: Shorter limb length was associated with lower childhood socioeconomic status, as estimated by the presence/duration of formal education. It was also independently associated with dementia and Alzheimer’s disease. Sex differences in this association might be explained by gender disadvantage in early life for this cohort or by different associations with health states (for example, cardiovascular disease) later in life.

Changes in folate, vitamin B12, and homocysteine associated with incident dementia

Objectives: Prospective findings have not been consistent for folate, vitamin B12 and homocysteine concentrations as predictors of dementia. This study aimed to investigate both baseline concentrations of folate, vitamin B12 and homocysteine and changes in these concentrations as predictors/correlates of incident dementia. Methods: Of 625 elderly patients without dementia at baseline, 518 (83%) were followed over a 2.4 year period and were clinically assessed for incident dementia and Alzheimer’s disease (AD). Serum concentrations of folate, vitamin B12 and homocysteine were measured at the baseline and follow-up assessments. Covariates included age, sex, education, disability, depression, alcohol consumption, physical activity, vascular risk factors, serum creatinine concentration, vitamin intake and weight change. Results: Only baseline lower folate concentrations predicted incident dementia. The onset of dementia was significantly associated with an exaggerated decline in folate, a weaker increase in vitamin B12 concentrations and an exaggerated increase in homocysteine concentrations over the follow-up period. These associations were reduced following adjustment for weight change over the same period. Conclusions: Incident dementia is more strongly associated with changes in folate, vitamin B12 and homocysteine than with previous concentrations. These changes may be linked to other somatic manifestations of early dementia, such as weight loss.

Determinants of suicidal ideation in patients with breast cancer.

Breast cancer survivors are at higher risk of psychological problems including suicidal ideation. However, studies on suicidal ideation in breast cancer survivors have been rare and have not been investigated prospectively. This study aimed to investigate the prevalence and independent risk factors for suicidal ideation within 1 week and at 1 year after breast surgery for breast cancer.

A one year longitudinal study of cytokine genes and depression in breast cancer

BACKGROUND Since inflammatory cytokines have been implicated in the pathophysiology of both cancer and depression, genes that contribute to determining cytokine functional activity are reasonable candidate risk factors for depression related to cancer. This study aimed to investigate whether alleles related to higher pro-inflammatory and/or lower anti-inflammatory cytokine production would associate with depression in a cohort with breast cancer. METHODS A total of 309 women with breast cancer were evaluated one week after surgery, and 244 (79%) were followed one year later. Depression (major+minor depressive disorders) was diagnosed according to DSM-IV criteria using the Mini International Neuropsychiatric Interview on both occasions. Six pro-(TNF-α-850C/T and -308G/A, IL-1β-511C/T and +3953C/T, IL-6-174G/C, IL-8-251T/A) and two anti-inflammatory (IL-4 +33T/C, IL-10-1082G/A) cytokine polymorphisms were assayed, and total numbers of potential risk alleles were calculated for pro- and anti-inflammatory cytokine genes. Adjustments were made for demographic and clinical characteristics. RESULTS At baseline, 74 (24%) patients were classified with prevalent depression; and at follow-up, 19 (8%) and 25 (10%) patients were classified with persistent and incident depression, respectively. A higher number of pro-inflammatory cytokine risk alleles, and IL-1β-511T/T genotype individually, were independently associated with both prevalent depression at baseline and persistent depression at one year follow-up. LIMITATIONS Sample size was relatively small. CONCLUSIONS Our findings support the role of pro-inflammatory cytokines in the etiology of depression related to breast cancer, and provide novel evidence of a potential genetic basis for this.

Religiosity, depression, and quality of life in Korean patients with breast cancer: a 1-year prospective longitudinal study

To investigate the association among religiosity and depression, anxiety, and quality of life in women with breast cancer.

Serotonergic and BDNF Genes Associated With Depression 1 Week and 1 Year After Mastectomy for Breast Cancer

Objective Polymorphisms of serotonin transporter (5-HTT) and brain-derived neurotrophic factor (BDNF) genes have been investigated as candidate genes for depression occurring in medical disorders. The serotonin 2a receptor (5-HTR2a) genes have been investigated as risk factors for depression but rarely in combination with medical conditions. This study aimed to investigate whether polymorphisms of interest in 5-HTT, 5-HTR2a, and BDNF genes are associated with depression after mastectomy for breast cancer. Methods A total of 309 patients with breast cancer were evaluated 1 week after mastectomy, and 244 patients (79%) were followed up 1 year later. Depression (major and minor depressive disorders) was diagnosed according to DSM-IV criteria using the Mini-International Neuropsychiatric Interview and was classified into prevalent, persistent, and incident depression. Individual associations with 5-HTT gene–linked promoter region, serotonin transporter intron 2 variable number tandem repeat, 5-HTR2a 1438A/G, 5-HTR2a 102T/C, and BDNF Val66Met polymorphisms were estimated using logistic regression models, and gene-gene interactions were investigated using the generalized multifactor dimensionality reduction method. Results At baseline, 74 patients (24%) were classified with prevalent depression, and at follow-up, 19 patients (8%) and 25 patients (10%) were classified with persistent and incident depression, respectively. The BDNF Met/Met genotype was independently associated with prevalent (odds ratio = 2.63, 95% confidence interval = 1.12–6.14) and persistent (odds ratio = 8.07, 95% confidence interval = 1.26–51.6) depression. No associations with 5-HTT and 5-HTR2a genes (all p values > .21) were found, and no significant gene-gene interactions were identified (all p values > .36). Conclusions Our findings support a role of BDNF, not serotonin, in the etiology of depression occurring in women with breast cancer who received a mastectomy. Abbreviations 5-HTT = serotonin transporter; 5-HTTLPR = 5-HTT gene–linked promoter region; STin2 VNTR = serotonin transporter intron 2 variable number tandem repeat; 5-HTR2a = serotonin 2a receptor; BDNF = brain-derived neurotrophic factor; SOFAS = Social and Occupational Functioning Assessment Scale; PCR = polymerase chain reaction; GMDR = generalized multifactor dimensionality reduction

BDNF PROMOTER METHYLATION ASSOCIATED WITH SUICIDAL IDEATION IN PATIENTS WITH BREAST CANCER

Objective Brain-derived neurotrophic factor (BDNF) has been considered a risk factor for suicidality. BDNF secretion is influenced by epigenetic (DNA methylation) and genetic (val66met polymorphism) profiles. We aimed to investigate the independent effects of BDNF promoter methylation status on suicidal ideation as well as the effects of its interaction with the val66met polymorphism in patients with breast cancer. Methods A total of279 patients with breast cancer were evaluated 1 week after breast surgery, and 244 (87%) were followed up 1 year later. Suicidal ideation was identified using the item addressing suicidal thoughts on the Beck Depression Inventory. The independent effects of BDNF methylation status on suicidal ideation at two points was investigated using multivariable logistic regression models. The two-way interactive effects of BDNF methylation status and the val66met polymorphism on suicidal ideation were also estimated using the same models. Results Increased BDNF methylation was significantly associated with suicidal ideation and depression 1 year after breast surgery, and this association was independent of potential covariates, including previous depression, current depressive symptoms, and BDNF genotype. No significant methylation-genotype interactions were found. Conclusions The BDNF hypothesis and the epigenetic origin of suicidality in patients with breast cancer were supported. BDNF gene methylation status may be a biological marker for suicidality in patients with breast cancer.

Relationship between a hopeful attitude and cellular immunity in patients with breast cancer

OBJECTIVES To evaluate the relationship between hopefulness and immune function in patients with breast cancer. METHODS A total of 196 patients with breast cancer were enrolled. The subjects were divided into two groups using the abbreviated version of the seven-item Beck Hopelessness Scale (BHS-7). Subsets of circulating lymphocytes were assessed using flow cytometry: CD3(+), CD4(+), CD8(+), CD19(+) and CD56(+). The Beck Depression Inventory (BDI), Montgomery-Asberg Depression Rating Scale (MADRS) and EORTC QLQ-C30 were administered. RESULTS A total of 104 patients (53.6%) showed a hopeful attitude, with a score of 0 on the BHS-7. Scores on the MADRS and BDI were significantly higher in the nonhopeful group, whereas global and total functioning scores on the EORTC QLQ-C-30 were significantly higher in the hopeful group. The hopeful group showed significantly higher CD8(+) T-cell percentage and counts and significantly lower CD4(+) T-cell percentage and CD19(+) B-cell percentage and counts compared with the nonhopeful group. All statistically significant differences between the two groups were maintained after adjusting for age and scores on the BDI and EORTC QLQ-C-30 as covariates, except for CD 19(+) cell counts. CONCLUSION The results suggest that hopefulness may be associated with immunity in patients with breast cancer, independent of depression and quality of life.

Associations between Plasma Cytokines and Depressive Mood in Patients with Breast Cancer

Objective: The few studies on the associations between cytokines and depressive mood in patients with cancer have produced conflicting results. This study investigated the associations between plasma cytokines and depressive mood in patients with breast cancer using a large panel of pro-inflammatory, anti-inflammatory, and immune-modulating cytokines. Methods: We recruited 273 hospitalized patients with breast cancer awaiting surgery. Preoperative plasma samples were obtained for cytokine analysis, including pro-inflammatory (interleukin [IL]-2, IL-12, interferon [IFN]-γ, and tumor necrosis factor [TNF-α]), anti-inflammatory (IL-4, IL-5, IL-10, and IL-13), and immune-modulating (granulocyte/macrophage colony-stimulating factor [GM-CSF]) cytokines. Depressive mood was measured using the Montgomery—Asberg Depression Rating Scale (MADRS) at 2–5 days postoperatively, when the patients could cooperate. Covariates included various demographic and clinical characteristics. The association between the MADRS score and each cytokine level was estimated using linear regression models. Results: Cytokine levels were significantly inter-correlated. Depressive mood was associated with lower levels of pro-inflammatory (IL-2, IL-12, and TNF-α), anti-inflammatory (IL-5, IL-10, and IL-13), and immune-modulating (GM-CSF) cytokines independent of potential covariates such as living area or functional level. Conclusions: The findings suggest that depressive mood is associated with a generally decreased inflammatory reaction or immune function in patients with breast cancer.

Effects of depression co-morbidity and treatment on quality of life in patients with acute coronary syndrome: the Korean depression in ACS (K-DEPACS) and the escitalopram for depression in ACS (EsDEPACS) study

BACKGROUND Depression is common after acute coronary syndrome (ACS) with adverse effects on prognosis. There is little evidence on whether depression treatment improves quality of life (QoL) in ACS patients. The aim of this study was to investigate the effects of co-morbid depression and its treatment on QoL in ACS. METHOD In total, 1152 patients were recruited at baseline, 2-14 weeks after a confirmed ACS episode, and 828 were followed 1 year thereafter. Of 446 baseline participants with co-morbid depressive disorders, 300 were randomized to a 24-week double blind trial of escitalopram or placebo, while the remaining 146 received medical treatment only (MTO). QoL was measured by the World Health Organization Quality of Life -Abbreviated form (WHOQOL-BREF). RESULTS At baseline, QoL was significantly lower in patients with co-morbid depressive disorder than those without. QoL improvement was significantly greater in those receiving escitalopram than those receiving placebo over the 24-week treatment period. In the 1-year follow-up, the better outcomes associated with escitalopram remained evident against both placebo and MTO. CONCLUSIONS Depression was significantly associated with worse QoL even in patients with recently developed ACS. Depression treatment was associated with QoL improvement in ACS patients in the 24-week treatment period, the effects of which extended to 1 year.