OBJECTIVE: Serotonin transporter(5-hydroxytryptamine transporter, 5-HTT) plays a critical role in the termination of serotonergic neurotransmission into the presynaptic neuron and represents an initial site of uptake inhibiting antidepressants, including tricyclic antidepressants and selective serotonin reuptake inhibitors. We investigated the possible association between the 5-HTT gene and major depression, and examined whether there are genotypic characteristics in 5-HTT gene that result in treatment nonresponsiveness to uptake inhibiting antidepressants. METHODS: 5-HTT gene polymorphisms are analyzed with the primers flanking the second intron and regulatory region from genomic DNA. We genotyped 142 patients with major depression and dysthymia, and 252 age and sex matched normal subjects. All individuals were Korean. RESULTS: We found no significant differences in the allele frequency(2 nd intron, p=0.941 : promoter, p=0.122) between patients and controls. However, in association studies between antidepressant responsiveness in depressive patients and allele frequencies of 5-HTT gene polymorphism in intron2 and promoter regions, there was shown significant differences in both(p<0.0001, p=0.0028, respectively by Fisher exact test). CONCLUSIONS: These results suggest that there is no major effect of 5-HTT gene polymorphisms on the susceptibility to major depressions, while antidepressant nonresponding is related with genotypic alteration in 5-HTT gene.
Alleles ; Antidepressive Agents ; Antidepressive Agents, Tricyclic ; Depression* ; DNA ; Gene Frequency ; Humans ; Introns ; Neurons ; Promoter Regions, Genetic ; Regulatory Sequences, Nucleic Acid ; Serotonin Plasma Membrane Transport Proteins* ; Serotonin Uptake Inhibitors ; Serotonin* ; Synaptic Transmission

OBJECTIVE: S100B is a neurotrophic factor that is involved in neuroplasticity. Neuroplasticity is disrupted in depression; however, treatment with antidepressants can restore neuroplasticity. S100B has previously been used as a biological marker for neuropathology and neuroplasticity; therefore, in this study, we compared serum S100B levels in depressive patients to those of normal controls. In addition, we compared the serum S100B levels of antidepressant responders to those of nonresponders. METHODS: Thirty five normal controls and 59 depressive patients were enrolled in this study. Depressive patients entered a 6 week clinical trial that included treatment with antidepressants. The serum S100B levels and clinical assessments, which included Hamilton depression rating scores, were measured at baseline and after 6 weeks of treatment with antidepressants. The difference in the serum S100B levels between depressive patients and normal controls and between antidepressant responders and nonresponders was then compared. RESULTS: There were no significant differences in the serum S100B levels of normal controls and depressive patients. In addition, 30 of the depressive patients responded to antidepressant treatment while 29 did not. Finally, the responders had significantly higher baseline serum S100B levels than the nonresponders. CONCLUSION: The results of this study suggest that the baseline serum S100B level is associated with the subsequent response to antidepressants. In addition, the high baseline serum S100B level that was observed in depressive patients may enhance neuroplasticity, which results in a favorable therapeutic response to antidepressants.
Antidepressive Agents ; Biomarkers ; Depression ; Depressive Disorder, Major* ; Humans ; Neuronal Plasticity

OBJECTIVE: The aim of this study was to compare the serum brain-derived neurotrophic factor (BDNF) in acute depression with that in chronic depression. METHODS: Eighty subjects who met criteria for major depressive disorder (MDD) were recruited. Patients experiencing at least their fourth episode or an episode of at least 24 months in duration were defined as chronically depressed (n=21). Other patients were classified as acutely depressed (n=59). Antidepressant medications were administered for 6 weeks. Serum BDNF and Hamilton rating scale for depression (HAM-D) scores were measure before and after the administration of medication. RESULTS: We found significant differences in serum BDNF between the two groups. Serum BDNF was significantly higher among those with chronic depression than among those with acute depression both at baseline and after medication. CONCLUSION: This study suggested that serum BDNF might constitute a potential biological marker for chronic depression.
Biomarkers ; Brain-Derived Neurotrophic Factor ; Depression ; Depressive Disorder, Major ; Humans

OBJECTIVE: The molecules related with the intracellular signal transduction system are one of the main targets for the mode of mechanisms of antidepressant treatment in depressive patients. In vivo and in vitro studies have provided the evidence that the transcription factor, CREB (c-AMP response element binding protein) is the key mediator of the therapeutic response to antidepressants. We investigated the relationship between the treatment response to fluoxetine for 6 weeks and the change of CREB immunoreactivity in peripheral T lymphocyte. METHODS: CREB-expression and phosphorylation were quantified via western blot, and binding activity between transcription factor and CRE-oligonucleotide via electrophoretic mobility shift assay (EMSA) in nuclear extracts from 14 normal controls and 31 depressed patients at 0 and 6th week during fluoxetine treatment (20 mg/day). Responder was defined as the > or =50% of reduction or < or =7 of HAM-D score. We compared the changes of CREB during 6 weeks of fluoxetine treatment between drug responders and non-responders using SPSS11.0. RESULTS: After six weeks of treatment with fluoxetine, the drug responders showed a significant increase in CREB (p=0.024 by t-test) and p-CREB (p=0.045 by Mann-Whitney U test) compared with the non-responders. The change of CREB immunoreactivity was positively correlated with the change of p-CREB (r=0.770, p=0.000 by Spearman's rho), and the change of p-CREB was also positively correlated with CRE-DNA binding (r=0.753, p=0.000 by Spearman's rho). CONCLUSION: These results suggest that CREB response in peripheral lymphocyte may reflect and mediate the response to antidepressant treatment in depressed patients.
Antidepressive Agents ; Blotting, Western ; Depression ; Electrophoretic Mobility Shift Assay ; Fluoxetine ; Humans ; Lymphocytes* ; Phosphorylation ; Response Elements ; Signal Transduction ; Transcription Factors

OBJECTIVE: Serotonin transporter (5-HTT) is a key synaptic regulator of serotonergic neurotransmission and a major site of action of most antidepressants. The functional polymorphism of 5-HTT gene is reported to be associated with antidepressant responsiveness. Norepinephrine transporter (NET) and dopamine transporter (DAT) are also the targets for antidepressant drugs, and these biogenic amine transporters share a similar structure and mode of action as 5-HTT. We investigated the association between genetic polymorphisms of biogenic amine transporters and antidepressant response. METHODS: We genotyped 203 patients with major depressive disorder and 147 normal controls, using polymerase chain reaction (PCR) of genomic DNA with primers flanking the second intron and promoter regions of 5-HTT gene, and the 3' untranslated region of DAT. NET-1 (Thr99Ile) and NET-8 (1287 G/A) polymorphism were characterized by amplification and restriction fragment length polymorphisms (RFLP) analysis. RESULTS: VNTR polymorphism in the 3' untranslated region of DAT (p=0.020) was associated with a diagnosis of depression, but was influenced by age effect. We found that NET-8 polymorphism (p=0.015) in NET gene had significant associations with antidepressant response, as did the allelic variations of the promoter (p<0.0001) and intron2 (p=0.023) region in 5-HTT gene. The choice of drug had no effect on drug responsiveness. CONCLUSIONS: These results suggest that allelic variations of 5-HTT and NET genes affect the antidepressant responsiveness.
3' Untranslated Regions ; Antidepressive Agents ; Biogenic Amines* ; Depression ; Depressive Disorder, Major ; Diagnosis ; DNA ; Dopamine Plasma Membrane Transport Proteins ; Humans ; Introns ; Norepinephrine Plasma Membrane Transport Proteins ; Polymerase Chain Reaction ; Polymorphism, Genetic* ; Polymorphism, Restriction Fragment Length ; Promoter Regions, Genetic ; Serotonin Plasma Membrane Transport Proteins ; Synaptic Transmission

PURPOSE: To determine the extent to which magnetic resonance(MR) imaging findings can help differentiate between tuberculous arthritis (TA) and rheumatoid arthritis(RA). MATERIALS AND METHODS: This study involved sixteen patients with pathologically proven arthritis of the knee. In eight patients(mean age, 29.6 years; M:F=4:4) this was of the tuberculous variety, while eight (mean age, 47.5 years; M:F=2:6) suffered from the rheumatoid variety, which was monoarticular. For 14 patients, contrast enhancement studies were available. We retrospectively analyzed MR findings according to the demonstrated pattern of synovial thickening (regular and even, or irregular and nodular), bone erosion or abscess,bone marrow(BM) edema, the sites at which bursae were present, para-articular mass formation, and lymphadenopathy. RESULTS: In five of eight TA cases (62.5 %), irregular and nodular enhanced synovial thickening was present, while in six of eight RA cases (75%), thickening was regular and even. Bone erosions or subarticular abscesses were found in six TA cases (75%) and small erosions in three cases (37.5%) of RA. BM edema surrounding the erosion was found in four cases of TA (50%) and two of RA (25 %). In TA, edema was more extensive. In both TA and RA, all suprapatella bursae were distended while popliteal bursae were present in two cases of TA(25 %) and four of RA (50%). Para-articular masses with rim like enhancement were found in six cases of TA (75%) and in one case of RA (12.5 %). In particular, para-articular lymphadenopathy was seen in six cases of TA(75%), but not in RA. CONCLUSION: MR findings of irregular and nodular synovial thickening, extensive bone erosion, extensive BM edema, particular, para-articular abscess formation and ymphadenopathy, may help differentiate tuberculous arthritis of the knee from the rhumatoid variety.
Abscess ; Arthritis* ; Arthritis, Rheumatoid* ; Diagnosis, Differential* ; Edema ; Humans ; Knee* ; Lymphatic Diseases ; Magnetic Resonance Imaging* ; Retrospective Studies

OBJECTIVES: Serotonin transporter (5-HTT) is a key synaptic regulator of serotonergic neurotransmission and a major site of action of serotonin selective reuptake inhibitors (SSRIs) such as fluoxetine or paroxetine. Two PCR-fomatted polymorphisms at this locus have been described, the first of which is a repeat sequence polymorphism located in the promoter region (5-HTT gene-linked polymorphic region, 5-HTTLPR), and the second is a variable number tandem repeat located in intron2 (STin2). 5-HTTLPR insertion/deletion polymorphism with long (l) and short (s) forms affects the transcriptional efficiency of 5-HTT transporter expression. We examined the pharmacodynamic characteristic of 5-HTT gene polymorphism in the patients with major depression, which was expressed in the peripheral platelet. METHODS: 5-HTT gene polymophisms and pharmacodynamic characteristics of 5-HTT in the platelet was measured in 41 patients with major depression defined by DSM IV criteria and 35 healthy normal volunteers. 5-HTT gene polymophisms were analyzed with the primers flanking the regulatory region and the second intron from genomic DNA. Pharmacodynamic characteristics of 5-HTT in the platelet was measured with [3H]-serotonin uptake study. The uptake of [3H]-serotonin was quantified with Vmax and Km value. RESULTS: We found that the Vmax value of 5-HTT in peripheral platelet was higher in the patients with s/s genotype (2.17 pmol/10(4) platelets/min, 1.53-3.90 pmol/10(4) platelets/min) than with s/l (1.73 pmol/10(4) platelets/min, 0.83-3.40 pmol/10(4) platelets/min) or l/l (1.0(4) pmol/10(4) platelets/min, 0.88-1.31 pmol/10(4) platelets/min) genotype of 5-HTTLPR. Normal subjects with s/s genotype also had significantly higher Vmax value than those with s/l or l/l genotype. However, STin2 genotype showed no significant association with Vmax or Km in both groups. CONCLUSIONS: These results suggest that allelic variation of 5-HTT gene affects the phenotypic expression of 5-HTT in human platelet, and may be linked with phenotypic heterogeneity in the antidepressant responsiveness in depressed patients. This is another different finding based on ethnic variation with respect to pharmacodynamic characteristics of 5-HTT gene polymorphism.
Blood Platelets* ; Depression ; DNA ; Fluoxetine ; Genotype ; Healthy Volunteers ; Humans ; Introns ; Paroxetine ; Population Characteristics ; Promoter Regions, Genetic ; Regulatory Sequences, Nucleic Acid ; Serotonin Plasma Membrane Transport Proteins* ; Serotonin* ; Synaptic Transmission ; Tandem Repeat Sequences

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.

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.
Aged ; Chronic Disease ; Cross-Sectional Studies ; Depression/*genetics ; Female ; Genotype ; Humans ; Introns ; Male ; Middle Aged ; Odds Ratio ; *Polymorphism, Genetic ; Promoter Regions, Genetic ; Recurrence ; Serotonin Plasma Membrane Transport Proteins/*genetics