Objectives: This study aimed at investigating the pharmacological and physiological effects of cannabidiol (CBD) oil on weight loss in diet-induced obese (DIO) mice. Methods: A DIO mice model was constructed with 33 C57BL/6 male mice, aged six weeks, who had been fed a high-fat diet for 13 weeks. Subsequently, 20 mg/kg (n=11) or 60 mg/kg (n=11) of CBD oil or sesame seed oil (n=11) per day was given along with a high-fat diet for four weeks. The body weight of each subject was measured weekly, and venous blood was drawn for biochemistry and enzyme-linked immunoassay before and after the four-week trial period. An oral glucose tolerance test was performed to assess glucose metabolism. At the end of the CBD oil treatment, dual-energy X-ray absorptiometry was used to calculate body fat composition, and the mesenteric adipose tissue was measured as representative of the fat mass of each subject. For statistical analysis, we used the Kruskal-Wallis test, Turkey’s test using ranks and generalized estimating equations. Results: After administration of CBD oil (60 mg/kg) for four weeks, the DIO mice showed significant weight loss, compared to the sham control mice (p=0.027). Mice fed with 60 mg/kg of CBD oil also had a significant reduction in fat percentage (p=0.009) and mesenteric fat weight loss (p=0.024), compared to the sham control mice, even with higher food intake (p=0.029). Moreover, mice fed with 60 mg/kg of CBD oil showed a significant improvement in glucose tolerance (p=0.003) and lower plasma leptin levels (p=0.006). Conclusion This study shows that orally administered CBD oil induces weight loss in DIO mice. It has been postulated that CBD oil attenuates an over-activated endocannabinoid system, thereby increasing energy expenditure, and improving glucose metabolism and leptin resistance.

Methods: A total of 12 C57BL/6 male mice (Orient Bio), aged 6 weeks, were fed a high-fat diet for 13 weeks to construct a diet-induced obesity model. During the following 5 weeks, diet-induced obese mice were daily administered cannabis extract or sesame seed oil orally along with the high-fat diet. The body weight of each subject was measured weekly. Venous blood was drawn for biochemistry, enzyme-linked immunoassay, and oral glucose tolerance test before and after treatment. Body fat was measured by dual-energy X-ray absorptiometry, and the mesenteric adipose tissue was also measured after sacrifice. We used exact Wilcoxon’s two-sample analyses and generalized estimating equations to test the differences between the cannabis-treated group and control. Results: There was significant weight loss (p=0.009) observed in the cannabis-treated mice compared to the control group after 5 weeks of treatment. High-fat diet-induced glucose intolerance in the cannabis-treated group was significantly ameliorated (p=0.032), whereas there were no profound differences between the two groups in terms of other physiological markers, including corticosterone level. Conclusion This study shows that orally administered cannabis extract had a pharmacological effect of weight loss in diet-induced obese mice. This weight loss might be attributed to an increase in energy expenditure and regulation of glucose homeostasis.

OBJECTIVE: Extrapyramidal signs (EPS) are common in patients with mild cognitive impairment (MCI). However, few studies have assessed the effect of EPS on the clinical course of MCI. We aimed to evaluate whether patients with EPS show more frequent progression from MCI to Alzheimer's disease (AD) and to other types of dementia. METHODS: Participants (n=882) with MCI were recruited, and were followed for up to 5 years. The EPS positive group was defined by the presence of at least one EPS based on a focused neurologic examination at baseline. RESULTS: A total of 234 converted to dementia during the follow-up period. The risk of progression to AD was lower in the patients with EPS after adjusting for potential confounders [hazard ratio (HR)=0.70, 95% confidence interval (CI)=0.53–0.93, p=0.01]. In contrast, the patients with EPS had a six-fold elevated risk of progression to dementia other than AD (HR=6.33, 95%CI=2.30–17.39, p < 0.001). CONCLUSION: EPS in patients with MCI is a strong risk factor for progression of MCI to non-Alzheimer dementia. The careful neurologic examination for EPS in patients with MCI can yield important clinical information for prognosis.
Alzheimer Disease ; Dementia* ; Follow-Up Studies ; Humans ; Korea* ; Mild Cognitive Impairment* ; Neurologic Examination ; Prognosis ; Risk Factors

OBJECTIVE: Cytokines have been reported to have key roles in major depressive disorder (MDD). However, much less is known about cytokines in MDD and antidepressant treatment due to the diversity of cytokines and the heterogeneity of depression. We investigated the levels of cytokines in patients with MDD compared with healthy subjects and their associations with antidepressant response. METHODS: We investigated the changes of several cytokines (eotaxin, sCD40L, IL-8, MCP-1alpha, TNF-alpha, INF-gamma and MIP-1alpha) by Luminex assay in 66 patients with MDD and 22 healthy controls. The antidepressant response was assessed by 17-item Hamilton Rating Scale for Depression. RESULTS: We found the levels of sCD40L (p=0.001), IL-8 (p=0.004) and MCP-1 (p=0.03) of healthy controls were significantly higher than those of depressive patients. However, the level of eotaxin and TNF-alpha were not associated with MDD. In addition, we found the level of MCP-1 was significantly changed after antidepressant treatment (p=0.01). CONCLUSION: These findings suggest the roles of cytokines in MDD are complex, and could vary according to the individual characteristics of each patient. Further studies regarding the relationship between cytokines and MDD will be required.
Antidepressive Agents ; Cytokines ; Depression ; Depressive Disorder, Major* ; Healthy Volunteers ; Humans ; Immune System ; Interleukin-8 ; Population Characteristics ; Tumor Necrosis Factor-alpha

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.
Age of Onset ; Alleles ; Amino Acid Substitution ; Biological Factors ; Brain-Derived Neurotrophic Factor ; Codon ; Depression ; Depressive Disorder ; Depressive Disorder, Major ; Genotype ; Humans

OBJECTIVES: We aimed to identify the association depression with education level in patients with Alzheimer's dementia (AD). METHODS: We examined 911 patients with AD in CREDOS (Clinical Research Center for Dementia of South Korea) study and designed cross-sectional study. Each patient underwent psychiatrical, neurological and medical examination, interview for caregivers, laboratory tests, neuropsychological tests, and brain MRI. Cognitive function was measured using Korean version of Mini-Mental State Examination, Global Deterioration Scale and Clinical Dementia Rating. Psycho-Behavioral symptom was measured using Caregiver-Administered Neuropsychiatric Inventory. Daily Living was measured using Barthel Index for daily living activities and Seoul-Instrumental Activities of Daily Living. Depressive symptoms using the Korean version of the Short form on Geriatric Depression Scale were measured. Education was classified into low, intermediate, and high levels. 621 patients were performed APOE genotyping among the 911 patients. RESULTS: Out of the 911 patients, 477 were low education, 287 were intermediate education, and 147 were high education. 341 patients had depression. In logistic regression model we confirmed low education was the risk factor of depression (OR 2.26, 95% CI 1.66-3.07). CONCLUSION: This study confirmed that low education was associated with depression in Alzheimer's dementia.
Activities of Daily Living ; Apolipoproteins E ; Brain ; Caregivers ; Cross-Sectional Studies ; Dementia ; Depression ; Humans ; Logistic Models ; Neuropsychological Tests ; Risk Factors

OBJECTIVES: CREB (c-AMP response element binding protein) is known as a key mediator of the therapeutic response to antidepressants. We investigated the change of CREB-phosphorylation (pCREB) at the early point of the fluoxetine treatment to find out it can be a predictor for antidepressant response. METHODS: We evaluated the pCREB of T - lymphocyte nuclear extracts from 18 depressed patients at 0 and 1th week during fluoxetine treatment (20 mg/day). Responders were defined as the > or = 50% reduction of HAM-D score in 4 weeks. We compared the changes of pCREB at 0 and 1th week between responders and non-responders. RESULTS: The responders showed a significant increase of pCREB at week 1 compared with week 0. The HAM-D difference between week 0 and 4 was positively correlated with the change of pCREB response. CONCLUSION: These results suggest that the early change of pCREB in peripheral lymphocyte can predict the later response of antidepressant. The correlation showed pCREB directly reflects a response status to the antidepressant fluoxetine and clinical improvement.
Antidepressive Agents ; Depression ; Fluoxetine ; Humans ; Lymphocytes ; Response Elements

OBJECTIVES: CREB (c-AMP response element binding protein) is known as a key mediator of the therapeutic response to antidepressants. We investigated the change of CREB-phosphorylation (pCREB) at the early point of the fluoxetine treatment to find out it can be a predictor for antidepressant response. METHODS: We evaluated the pCREB of T - lymphocyte nuclear extracts from 18 depressed patients at 0 and 1th week during fluoxetine treatment (20 mg/day). Responders were defined as the > or = 50% reduction of HAM-D score in 4 weeks. We compared the changes of pCREB at 0 and 1th week between responders and non-responders. RESULTS: The responders showed a significant increase of pCREB at week 1 compared with week 0. The HAM-D difference between week 0 and 4 was positively correlated with the change of pCREB response. CONCLUSION: These results suggest that the early change of pCREB in peripheral lymphocyte can predict the later response of antidepressant. The correlation showed pCREB directly reflects a response status to the antidepressant fluoxetine and clinical improvement.
Antidepressive Agents ; Depression ; Fluoxetine ; Humans ; Lymphocytes ; Response Elements

OBJECTIVES: Genetic differences may contribute to the inter-individual differences in treatment response to antidepressants among patients suffering from major depression. This study investigated a possible association of treatment response to mirtazapine with various adrenergic alpha 2 receptor polymorphisms in major depressive patients. METHODS: A 6-week naturalistic treatment study with a blinded outcome examined 84 Korean patients with major depression. Treatment response to mirtazapine was defined as > or =50% decrease in HAM-D scores at six weeks. In this study, four genetic polymorphisms were selected ; ADRA2A MspI, ADRA2A DraI, alpha2BDel301-303, and alpha2CDel322-325. RESULTS: The Del/Del genotype of alpha2CDel322-325 exhibited a significant association with response to mirtazapine through multiple logistic regression. ADRA2A DraI, alpha2BDel301-303, and alpha2CDel322-325 did not showed a significant association with response to mirtazapine. CONCLUSION: Based on the finding that alpha2CDel322-325 polymorphism had an association with the mirtazapine response, we postulate that the polymorphism related to the mechanism of the antidepressant effect is important in predicting the response to antidepressants.
Antidepressive Agents ; Depression ; Genotype ; Humans ; Logistic Models ; Mianserin ; Pharmacogenetics ; Polymorphism, Genetic ; Polymorphism, Single Nucleotide ; Receptors, Adrenergic ; Stress, Psychological

OBJECTIVES: Genetic differences may contribute to the inter-individual differences in treatment response to antidepressants among patients suffering from major depression. This study investigated a possible association of treatment response to mirtazapine with various adrenergic alpha 2 receptor polymorphisms in major depressive patients. METHODS: A 6-week naturalistic treatment study with a blinded outcome examined 84 Korean patients with major depression. Treatment response to mirtazapine was defined as > or =50% decrease in HAM-D scores at six weeks. In this study, four genetic polymorphisms were selected ; ADRA2A MspI, ADRA2A DraI, alpha2BDel301-303, and alpha2CDel322-325. RESULTS: The Del/Del genotype of alpha2CDel322-325 exhibited a significant association with response to mirtazapine through multiple logistic regression. ADRA2A DraI, alpha2BDel301-303, and alpha2CDel322-325 did not showed a significant association with response to mirtazapine. CONCLUSION: Based on the finding that alpha2CDel322-325 polymorphism had an association with the mirtazapine response, we postulate that the polymorphism related to the mechanism of the antidepressant effect is important in predicting the response to antidepressants.
Antidepressive Agents ; Depression ; Genotype ; Humans ; Logistic Models ; Mianserin ; Pharmacogenetics ; Polymorphism, Genetic ; Polymorphism, Single Nucleotide ; Receptors, Adrenergic ; Stress, Psychological