Transforming growth factor-β1 and major depressive disorder with and without attempted suicide: Preliminary study
A substantial body of evidence indicates that dysregulation of the immune system is associated with suicidal behavior in major depressive disorder (MDD). Transforming growth factor (TGF)-beta1 is believed to be an important factor in regulating inflammatory responses and to have anti-inflammatory effects. We aimed to identify the role of TGF-beta1 on suicidal depression. The TGF-beta1 polymorphisms at codons 10 and 25 were analyzed in 122 suicidal MDD patients, 61 non-suicidal MDD patients, and 120 control subjects and, among them, in vitro TGF-beta1 productions were measured in 48 suicidal MDD patients, 47 non-suicidal MDD patients, and 91 control subjects. There was no genetic polymorphism at codon 25 and three genotypes at codon 10. No significant difference in the distributions of the TGF-beta1 genotypes was found among the three groups. The in vitro TGF-beta1 productions were significantly higher in suicidal MDD patients (844.3+/-329.7 pg/ml) and in non-suicidal MDD patients (853.0+/-439.7 pg/ml) than in controls (683.0+/-397.0 pg/ml) (P=0.01). In vitro TGF-beta1 productions were not significantly different among patients with any of the TGF-beta1 alleles or genotypes. Our findings suggest that in vitro TGF-beta1 productions play an important role on MDD, but we found no associations between TGF-beta1 and suicidal behavior.

title: Catechol-O-methyltransferase Val158Met polymorphism affects therapeutic response to mood stabilizer in symptomatic manic patients
abstract: Catechol-O-methyltransferase (COMT) is a candidate gene for the pathogenesis of some psychiatric disorders. The aim of this study is to examine the role of the COMT gene Val158Met polymorphism on the clinical aspects of bipolar disorder including symptomatology and therapeutic response. This study comprised 144 unrelated manic patients who met strict DSM-IV criteria for bipolar I disorder and 157 healthy unrelated controls. All subjects were of Korean ethnicity. To evaluate the clinical symptoms, we used the Young Mania Rating Scale at baseline and 6 weeks after treatment. No statistically significant difference in genotype distribution was found between manic patients and normal controls. There was also no significant difference in symptomatology among the genotypes in manic patients. In therapeutic response, however, patients with the Met/Met genotype were significantly more frequent in the non-responder than in the responder group. Our results suggest that the COMT gene polymorphism in the therapeutic response to mood stabilizers in manic patients. Further studies with a larger number of subjects and well-controlled design will be required to better understand the role of the COMT gene polymorphism on the therapeutic response to mood stabilizer in manic patients.

title: Trial of aripiprazole in the treatment of first-episode schizophrenia.
abstract: Aripiprazole is an atypical antipsychotic indicated for the treatment of adult patients with schizophrenia. It is effective and well tolerated in patients with schizophrenia or schizoaffective disorder. The aim of the present study was to investigate therapeutic efficacy and tolerability of aripiprazole in patients with first-episode schizophrenia.



Twenty-one patients meeting the DSM-IV criteria for schizophrenia were recruited. The Positive and Negative Symptom Scale (PANSS) and the Clinical Global Impressions Scale (CGI) were completed at the beginning of the study and again after 1, 2, 4, and 8 weeks of aripiprazole treatment. Side-effects were analyzed using the Udvalg for Kliniske Undersøgelser Side-Effect Rating Scale. Weight was checked at each testing session, and prolactin levels were measured at baseline and after 8 weeks of aripiprazole treatment.



Significant benefits were observed after the first week of treatment. After 1 week of aripiprazole treatment, subscale and total scores on the PANSS had decreased significantly. This significant decrease was maintained throughout the study period. The mean score of CGI severity was also significantly different after 2 weeks of aripiprazole administration when compared to baseline score, and the significance was maintained thereafter. Weight did not significantly change after aripiprazole administration. Although mean prolactin level was decreased at 8 weeks, the difference was not significant.



Aripiprazole is an effective and well-tolerated antipsychotic agent in patients with first-episode schizophrenia. Further investigations with larger samples are needed.

title: No Association between Serotonin Receptor 2C-759C/T Polymorphism and Weight Change or Treatment Response to Mirtazapine in Korean Depressive Patients
abstract: Activation of one or more serotonin (5-HT) receptors may play a role in mediating the antidepressant effects of serotonergic antidepressants. The serotonin 2C (5HT 2C) receptor is known to be associated with antidepressant action and weight gain. We sought to determine whether the 5-HTR 2C receptor -759C/T polymorphism was associated with weight gain and treatment response to mirtazapine in major depressive disorder (MDD) patients.  The 5-HT 2C receptor -759C/T polymorphism was analyzed in 323 MDD patients. All patients were evaluated using the 21-item Hamilton Depression Rating Scale at the beginning of the study and at 1, 2, 4, and 8 weeks of mirtazapine treatment.  There was no significant difference in the 5-HT 2C receptor -759C/T genotype distribution between responder and non-responder groups. The 5-HT 2C receptor -759C/T polymorphism was not associated with weight change over time after mirtazapine administration.  The 5-HT 2C receptor -759C/T polymorphism does not appear to be a predictor of treatment response to mirtazapine. This polymorphism was not associated with weight change after 8 weeks of mirtazapine treatment. Further investigation on other polymorphisms of the 5-HT 2C gene is required to determine whether the 5-HT 2C gene influences treatment response and weight change after mirtazapine administration in patients with major depressive disorder.

title: Gender Effect of Catechol-O-Methyltransferase Val158Met Polymorphism on Suicidal Behavior
abstract: Genetic factors and catecholaminergic dysfunction have been suggested as the etiology of suicide. The catechol-O-methyltransferase (COMT) 158Val/Met polymorphism affects COMT activity; that is, the alleles encoding Val and Met are associated with relatively high and relatively low COMT activity, respectively. We aimed to identify the role of the COMT Val158Met polymorphism in suicidal attempt behavior. The COMT 158Val/Met polymorphisms were analyzed in 197 suicide attempters (male/female: 70/127), 170 control subjects (male/female: 85/85). All subjects were ethnic Korean. The Lethality Suicide Attempt Rating Scale (LSARS) and risk-rescue rating (RRR) system were explored. For the male subjects, there was a significant difference in genotype distributions and allele frequencies between control subjects and suicide attempters. That is, Val/Val genotype and Val carriers were more frequent in suicide attempters than in control subjects. For the female subjects, however, no significant difference was shown in genotype distributions and allele frequencies between control subjects and suicide attempters. There were no significant differences in LSARS and RRR according to the genotypes. The distribution of the COMT 158Val/Met polymorphism showed a biologically meaningful difference between control subjects and suicide attempters among the male subjects although selection bias should be considered.

title: Demonstration of decreased gray matter concentration in the midbrain encompassing the dorsal raphe nucleus and the limbic subcortical regions in major depressive disorder: an optimized voxel-based morphometry study.
abstract: Previous neuroimaging studies in patients with major depressive disorder (MDD) have reported changes in several brain areas, such as the medial and dorsolateral orbital cortex, amygdala, hippocampus, and basal ganglia. However, the results of these studies are inconsistent, and relatively few studies have been conducted using voxel-based morphometry (VBM) to detect gray matter concentration (GMC) abnormalities in patients with MDD.



We examined 47 MDD patients and 51 healthy controls to investigate structural abnormalities using a 1.5 T magnetic resonance imaging system, which was normalized to a customized T1 template and segmented with optimized VBM. Analysis of covariance with age and gender as covariates was adopted for the VBM statistics; the level of statistical significance was set at P<0.05 for the corrected false discovery rate.



Decreased GMC was found in MDD patients in the bilateral amygdalae, hippocampi, fusiform gyri, lingual gyri, insular gyri, middle-superior temporal gyri, thalami, cingulate gyri, the central lobule of the cerebellum, and the midbrain encompassing the dorsal raphe nuclei (DRN).



Half of our study subjects were taking antidepressants. This may have been a potential confounding factor if any of the medications affected cortical volume.



The results suggest that the GMC of several regions associated with emotion regulation was lower in MDD patients. In particular, we found decreased GMC in the DRN. These findings may provide a better understanding of the anatomical properties of the neural mechanisms underlying the etiology of MDD.

title: Risk of suicidal ideation in diabetes varies by diabetes regimen, diabetes duration, and HbA1c level.
abstract: To investigate patient subgroups based on the clinical characteristics of diabetes to evaluate risk factors for suicidal ideation using a large population-based sample in South Korea.



Data from the Fifth Korea National Health and Nutrition Examination Survey, a cross-sectional, nationally representative survey, were analyzed. The participants were 9159 subjects aged ≥40years. We defined patients with diabetes based on self-reported physician-diagnosed diabetes. We evaluated clinical risk factors for suicidal ideation according to diabetes regimen, diabetes duration, and glycated hemoglobin (HbA1c) level compared with no diabetes. Given the complex sample design and unequal weights, we analyzed weighted percentages and used survey logistic regression.



Diabetes per se was not associated with suicidal ideation. However, suicidal ideation was significantly more prevalent among patients who had injected insulin, had a duration of diabetes ≥5years and had HbA1c levels ≥6.5 compared with those without diabetes. Depressive symptoms were the most prominent predictor of suicidal ideation.



Insulin therapy, diabetes of long duration, and unsatisfactory glycemic control were identified as risk factors for suicidal ideation; thus, patients with these characteristics warrant special attention. Our findings suggest the need to integrate efforts to manage emotional distress into diabetes care.

title: Differential association of socio-economic status with gender- and age-defined suicidal ideation among adult and elderly individuals in South Korea
abstract: South Korea has the highest suicide rate among countries in the Organisation for Economic Co-operation and Development (OECD), with a rising trend that contrasts with the trend in most other OECD countries. This study assessed differential associations of socio-demographic factors with suicidal ideation in South Korea. We used five waves of data from the 2010 Korea National Health and Nutrition Examination Survey. Study subjects included 5803 men and women aged >25 years. We analysed weighted percentages with consideration of the complex survey sample design and unequal weights. Surveylogistic regressions were applied. Protective effects against suicidal ideation were found for higher household income, higher educational attainment, and being married. Functional limitations and depressive symptoms were risk factors for suicidal ideation. However, these significant factors may exert different effects on vulnerability for suicidal ideation among different genders and age groups. Thus, household income was mainly protective for women and subjects aged 25-44 years, and educational attainment was protective for individuals aged >65 years. Our findings suggest the need for extended social protection policies for the less privileged population and special strategies for different groups.

title: Differential distribution of human mitochondrial DNA in somatic tissues and hairs.
abstract: To investigate mitochondrial DNA (mtDNA) distribution within tissues during life, we observed length heteroplasmy in a polycytosine tract of the mitochondrial HV2 region by size-based separation of PCR products, using a mutagenic primer which was designed to avoid stutter production. Blood, brain, heart, liver, skeletal muscle and hair shaft samples were collected during autopsies of 25 individuals. Here, we demonstrate differences in the level of mtDNA length heteroplasmy both within and between individuals and tissues. We also show that mtDNA is distributed randomly in varying proportions in various somatic tissues during growth, resulting in an imbalance in the composition of mtDNA pools among tissues. This mtDNA distribution appears not to be strictly random, and can be explained by the random somatic segregation of nucleoids. On the other hand, significant qualitative/quantitative mtDNA peak pattern variations in hair shafts are thought to be a result of the different developmental origins of hairs. Each hair shaft may have a restricted or clonal set of mtDNA molecules derived from a discrete group of stem cells.

title: Test and teach. Number fifty-three. Diagnosis: Calcifying fibrous pseudotumour.

title: Rapid direct PCR for ABO blood typing.
abstract: Many different molecular typing methods have been reported to complement routine serological ABO blood typing in forensics. However, these ABO genotyping methods are often time-consuming and call for an initial DNA isolation step that requires the use of expensive kits or reagents. We report here a rapid direct ABO genotyping method that eliminates the need for DNA extraction from fresh blood, hair, and body fluid stains before PCR. Using a fast PCR instrument and an optimized polymerase, the genotyping method-which employs a multiplex allele-specific primer set for the simultaneous detection of three single-nucleotide polymorphism (SNP) sites (nucleotides 261, 526, and 803)-identifies A, B, O01/O02, O03, and cis-AB01 alleles in around 70 min from sample collection to electropherogram. Not only will this ABO genotyping method be efficiently used in forensic practice for rapid screening of samples before full-blown multilocus short tandem repeat profiling, but it will also demonstrate an example of rapid direct genotyping of SNPs that offers the advantages of time- and cost-efficiency, convenience, and reduced contamination during DNA analysis.