Catechol-O-methyltransferase Val158Met polymorphism affects therapeutic response to mood stabilizer in symptomatic manic patients
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: 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: 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: 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: 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: Anterior clinoid process and optic strut in Koreans.
abstract: The anterior clinoid process and the optic strut are often removed during operation on the anterior part of the cavernous sinus. Therefore it is important for neurosurgeons to verify their dimensions and variations. The purpose of this study was to investigate the dimension and the variation of the anterior clinoid process and to describe the locational variation of the optic strut. Seventy-three skulls of Korean adults were used. The average length, basal width and thickness of the anterior clinoid process were 9.18 +/- 1.55, 9.63 +/- 1.49 and 5.32 +/- 1.07 mm, respectively. The average thickness of the optic strut was 2.9 +/- 1.15 mm and it was commonly attached to anterior two-fifths of the anterior clinoid process. The complete caroticoclinoid canal was observed in 4.1%, however it was incomplete in 11.6%. The incidence of a caroticoclinoid canal in Koreans was relatively low compared with other races.

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: P2X receptor immunoreactivity in the male genital organs of the rat
abstract: The distribution of ATP ionotropic P2X receptors in the genital organs of the male rat has been investigated with immunohistochemical techniques using specific antibodies to P2X1–7 receptors. In the excretory ducts of the testis (ductus epididymidis, vas deferens and its associated seminal vesicles), the major signals were seen with antibodies to P2X1 and P2X2 in the membranes of the smooth muscle layer, suggesting that these receptors are involved in the process of sperm transport and ejaculation. In the penis body, strong P2X1 and weaker P2X2 immunoreactivity was seen in the smooth muscle of blood vessels and the corpus cavernosum, suggesting a participation in the detumescence process. P2X5 immunoreactivity, a marker for differentiating cells in stratified squamous epithelia, was observed in the epithelia of the terminal urethra, the "horny spur" (spine-studded epithelium of the glans) and the inner surface of the prepuce. Antibodies to P2X3 reacted with nerve fibres in the adventitia of vas deferens, and the P2X6 receptor was localised in the basal lamina of the epithelium. In the prostate, there was immunostaining of the smooth muscle between the tubules with antibody for P2X1, but not with P2X2; P2X3 immunostaining of nerves and strong P2X7 immunostaining of the glandular epithelium of the prostate were also present.

title: Aging and arterial stiffness.
abstract: Arterial walls stiffen with age. The most consistent and well-reported changes are luminal enlargement with wall thickening and a reduction of elastic properties at the level of large elastic arteries. Longstanding arterial pulsation in the central artery causes elastin fiber fatigue and fracture. Increased vascular calcification and endothelial dysfunction are also characteristic of arterial aging. These changes lead to increased pulse wave velocity, especially along central elastic arteries, and increases in systolic blood pressure and pulse pressure. Vascular aging is accelerated by coexisting cardiovascular risk factors, such as hypertension, metabolic syndrome and diabetes. Vascular aging is an independent risk factor for cardiovascular disease, from atherosclerosis to target organ damage, including coronary artery disease, stroke and heart failure. Various strategies, especially controlling hypertension, show benefit in preventing, delaying or attenuating vascular aging.

title: New CT response criteria in non-small cell lung cancer: proposal and application in EGFR tyrosine kinase inhibitor therapy.
abstract: We aimed to devise new CT response criteria (new response criteria, NRC) in patients with non-small cell lung cancer (NSCLC) and to evaluate the efficacy of the criteria for stratifying patient responses and predicting patient survival compared to that of the traditional size-based criteria RECIST version 1.1. Our institutional review board approved this study with a waiver of informed consent. We enrolled 80 NSCLC patients as an experimental arm and treated them with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs). Two blinded, independent radiologists assessed CT images for tumor response using the NRC, which were also validated in a separate arm (75 NSCLC patients). Tumor responses evaluated by RECIST 1.1 and the new criteria were compared from each other and correlated with patient survival. For statistical analyses, Kaplan-Meier method and kappa statistics were used. In the experimental arm (n=80), interobserver agreements for the assessment of patient response were excellent for both RECIST and NRC. Sixteen RECIST nonresponding patients achieved a designation of partial response according to NRC. In the validation arm (n=75), patients of optimal response (partial response) with the new criteria had median overall survival of 18.4 months compared with 8.5 months in patients with poor response (P=.04). However, RECIST failed to show survival difference between the two response groups. In NSCLC patients treated with EGFR-TKIs, new CT criteria reflecting additional morphological characteristics of target lesions are reproducible and have statistically significant association with overall survival.