Jin-Sang Yoon

Interactions Between Life Stressors and Susceptibility Genes (5-HTTLPR and BDNF) on Depression in Korean Elders

BACKGROUND It has been reported that the functional polymorphism in the serotonin transporter gene linked promoter region (5-HTTLPR) modifies the association between stressful life events (SLEs) and depression in child, adolescent, and adult populations. We sought to replicate this finding in elders and, additionally, to test modifying effects of the brain-derived neurotrophic factor (BDNF) val66met polymorphism. METHODS In 732 Korean community residents ages 65+, diagnosis of depression (Geriatric Mental State Schedule), information on SLEs, and genotypes for 5-HTTLPR and BDNF val66met were ascertained. Of those without depression at baseline, 521 (88%) were followed up 2.5 years later. Interactions between SLEs and the two genotypes were investigated for both prevalent depression at baseline and incident depression at follow-up. RESULTS Significant interactions of SLEs with both 5-HTTLPR and BDNF genotypes were observed on risk of depression after adjustment for age, gender, education, and disability. A significant three-way interaction between 5-HTTLPR, BDNF, and SLEs was also found. The same findings were observed for predictors of incident depression in the prospective analysis. CONCLUSIONS These findings suggest that environmental risk of depression is modified by at least two genes and that gene-environment interactions are found even into old age.

Predictive value of folate, vitamin B12 and homocysteine levels in late-life depression

BACKGROUND The role of folate, vitamin B(12) and homocysteine levels in depression is not clear. AIMS To investigate cross-sectional and prospective associations between folate, B(12) and homocysteine levels and late-life depression. METHOD A total of 732 Korean people aged 65 years or over were evaluated at baseline. Of the 631 persons who were not depressed, 521 (83%) were followed over a period of 2-3 years and incident depression was ascertained with the Geriatric Mental State schedule. Serum folate, serum vitamin B(12) and plasma homocysteine levels were assayed at both baseline and follow-up. RESULTS Lower levels of folate and vitamin B(12) and higher homocysteine levels at baseline were associated with a higher risk of incident depression at follow-up. Incident depression was associated with a decline in vitamin B(12) and an increase in homocysteine levels over the follow-up period. CONCLUSIONS Lower folate, lower vitamin B(12) and raised homocysteine levels may be risk factors for late-life depression.

Association of SLC6A4 methylation with early adversity, characteristics and outcomes in depression

Childhood adversities have been associated with onset and worse clinical presentations of depression. Epigenetic changes may reflect childhood adversities, while their effects on clinical characteristics of depression are unknown. This study aimed to investigate whether epigenetic changes were associated with childhood adversities, pretreatment characteristics, and treatment outcomes in depressive patients. In 108 patients with major depressive disorders, the methylation status in the promoter of gene encoding serotonin transporter (SLC6A4) was measured. Childhood adversities, socio-demographic and clinical characteristics including assessment scales for depression (Hamilton Depression Rating Scale, HAMD), anxiety (Hamilton Anxiety Rating Scale, HAMA), functioning (Social and Occupational Functioning Assessment Scale, SOFAS), disability (World Health Organization Disability Assessment Schedule-12, WHODAS-12), and quality of life (World Health Organization Quality of Life-Abbreviated form, WHOQOL-BREF) were evaluated at baseline. After a 12-week treatment with antidepressants, the assessment scales were reevaluated. To avoid type I error by multiple comparisons, Bonferroni corrections were applied. Higher SLC6A4 promoter methylation status was significantly associated with childhood adversities, worse clinical presentation (family history of depression, higher perceived stress, and more severe psychopathology assessed by SOFAS, WHODAS-12, and WHOQOL-BREF), but was not associated with treatment outcomes after considering multiple comparisons. SLC6A4 methylation status could be a proxy marker for childhood adversities and a clinical biomarker for certain presentations of depression.

BDNF promoter methylation and suicidal behavior in depressive patients

INTRODUCTION Suicide is a major health problem, and depression is a major psychiatric cause of suicide. Suicide is influenced by the multifactorial interaction of many risk factors. Therefore, epigenetic research may lead to understandings that are applicable to suicide. This study investigated whether epigenetic changes are associated with suicidal behavior and evaluated the treatment outcome of suicidal ideation in depressive patients. METHODS In 108 patients with major depression, the promoter methylation of the gene encoding brain-derived neurotrophic factor (BDNF) was measured. Sociodemographic and clinical characteristics including a history of previous depressive episodes, age at onset, duration of illnesses, family history of depression, and number of stressful life events as well as subjective perception of stress and assessment scales for depression (HAMD), anxiety (HAMA), function (SOFAS), disability (WHODAS-12), and quality of life (WHOQOL-BREF) were evaluated at baseline. Suicidal behavior was ascertained using a semistructured clinical interview with questions about severity and intent. Beck Scale for Suicide Ideation (BSS) was administered during 12 weeks of treatment with antidepressants. RESULTS A higher BDNF promoter methylation status was significantly associated with a previous suicidal attempt history, suicidal ideation during treatment, and suicidal ideation at last evaluation as well as with higher BSS scores and poor treatment outcomes for suicidal ideation. LIMITATIONS Methylation status was investigated with limited area of the BDNF gene and sample size was relatively small. CONCLUSIONS BDNF methylation status could be a proxy marker for previous suicidal attempts and a clinical biomarker for poor treatment outcomes of suicidal ideation in depression.

Effectiveness of mirtazapine for nausea and insomnia in cancer patients with depression

Aims:  The purpose of the present paper was to evaluate the effectiveness of mirtazapine orally disintegrating tablets for nausea and sleep disturbance, which are common and distressing symptoms of cancer.

Risperidone versus olanzapine for the treatment of delirium

This study compared the effectiveness of risperidone and olanzapine in the treatment of delirium.

Differences in predictors of traditional and cyber-bullying: a 2-year longitudinal study in Korean school children

Traditional bullying has received considerable research but the emerging phenomenon of cyber-bullying much less so. Our study aims to investigate environmental and psychological factors associated with traditional and cyber-bullying. In a school-based 2-year prospective survey, information was collected on 1,344 children aged 10 including bullying behavior/experience, depression, anxiety, coping strategies, self-esteem, and psychopathology. Parents reported demographic data, general health, and attention-deficit hyperactivity disorder (ADHD) symptoms. These were investigated in relation to traditional and cyber-bullying perpetration and victimization at age 12. Male gender and depressive symptoms were associated with all types of bullying behavior and experience. Living with a single parent was associated with perpetration of traditional bullying while higher ADHD symptoms were associated with victimization from this. Lower academic achievement and lower self esteem were associated with cyber-bullying perpetration and victimization, and anxiety symptoms with cyber-bullying perpetration. After adjustment, previous bullying perpetration was associated with victimization from cyber-bullying but not other outcomes. Cyber-bullying has differences in predictors from traditional bullying and intervention programmes need to take these into consideration.

Diagnostic validity of assessment scales for depression in patients with schizophrenia.

The aim of this study was to examine the diagnostic validity of four commonly used assessment scales for depression in schizophrenia. The study population consisted of 84 inpatients meeting the DSM-IV criteria for schizophrenia. Depression in the study subjects was defined by the DSM-IV criteria for major depressive episode. The Positive and Negative Syndrome Scale (PANSS) and the Simpson-Angus Rating Scale (SARS) were used to differentiate depression from the negative and extrapyramidal symptom-related depressive phenomena in schizophrenia. The following four depression scales were assessed for their diagnostic validity as measures of depressive disorder in schizophrenia: the Calgary Depression Scale for Schizophrenia (CDSS), the Beck Depression Inventory (BDI), the Hamilton Rating Scale for Depression (HAM-D), and the depression subscale of the PANSS (PANSS-D). Of 84 patients with schizophrenia, 32 were diagnosed as having comorbid depressive disorder. The areas under the Receiver Operating Characteristic (ROC) curves of the CDSS, HAM-D, PANSS-D, and BDI were 0.94, 0.89, 0.90, and 0.81, respectively. The area under the ROC curve of the CDSS was significantly greater than that of the BDI and tended to be more favorable than those for the HAM-D and the PANSS-D. Our study suggests that the CDSS may provide the best assessment for depression in patients with schizophrenia.

Effects of quetiapine on the brain-derived neurotrophic factor expression in the hippocampus and neocortex of rats

The effects of antipsychotics on the brain-derived neurotrophic factor (BDNF) expression have been controversial. This study aimed to investigate the effects of chronic quetiapine administration on the BDNF mRNA expression in hippocampus and neocortex of rats with or without immobilization stress. The chronic administration (21 days) of quetiapine (10 mg/kg) significantly attenuated the decreased BDNF mRNA expression in the both hippocampal and cortical regions of rats caused by immobilization stress, and significantly increased the BDNF mRNA expression in the dentate gyrus of rats even without the immobilization stress. These results could add some theoretical bases to explain why quetiapine may improve cognitive symptoms of schizophrenia by stimulating BDNF mRNA expression.

BDNF genotype potentially modifying the association between incident stroke and depression.

OBJECTIVE To investigate the role of the brain-derived neurotrophic factor (BDNF) gene val66met polymorphism in the association between stroke and depression. METHOD Five hundred community residents aged >65 years without stroke or depression at baseline were re-evaluated after 2 years. Disability (World Health Organization Disability Assessment Schedule, WHODAS II), cognitive function (Mini-Mental State Examination, MMSE), and BDNF genotype were also measured at baseline. RESULTS The association between incident stroke and depression was strengthened progressively with increasing numbers of met alleles, and was only significant in subjects with the met/met genotype after adjustment for disability and cognitive function. CONCLUSION The BDNF val66met polymorphism may modify the association between stroke and depression.