Se Hoon Shim

Differences in cytokines between non-suicidal patients and suicidal patients in major depression.

Several studies have shown that there is an imbalance between pro-inflammatory and anti-inflammatory cytokines in major depressive disorder (MDD). However, little is known about the role of cytokines in suicide. In the present study, amounts of IL-6, IL-2, IFN-gamma, IL-4, and TGF-beta1 produced by mitogen-stimulated whole blood were measured in 36 MDD patients who had recently attempted suicide, 33 non-suicidal MDD patients, and 40 normal controls. The severity of depression symptoms and suicidal behaviors was evaluated using Hamiltons depression rating scale (HDRS), the Lethality Suicide Attempt Rating Scale (LSARS), and the Risk-Rescue Rating (RRR). Non-suicidal MDD patients had significantly higher IL-6 production than suicidal MDD patients and normal controls (p<0.001). Suicidal MDD patients had significantly lower IL-2 compared with non-suicidal patients and normal controls (p<0.001). Both MDD groups, with or without attempted suicide, had significantly lower IFN-gamma and IL-4 and higher TGF-beta1 production. HDRS scores had significant positive correlations with IL-6, IFN-gamma, and the Th1/Th2 ratio and significant negative correlations with IL-4 in non-suicidal depression patients (p<0.005); however, these correlations did not hold true for suicidal patients. Suicidal MDD patients had no significant correlations between the LSARS or RRR scores and cytokine release. Our findings suggest that the immune response has distinct differences between non-suicidal patients and suicidal patients. Non-suicidal MDD may be associated with increased IL-6 production and a Th1/Th2 imbalance with a shift to Th1, while suicidal MDD may be associated with decreased IL-2.

Increased levels of plasma brain-derived neurotrophic factor (BDNF) in children with attention deficit-hyperactivity disorder (ADHD)

BACKGROUND Recent reports have suggested a pathophysiological role of brain-derived neurotrophic factor (BDNF) in attention deficit-hyperactivity disorder (ADHD). We evaluated the plasma levels of BDNF in patients with ADHD. METHODS Plasma BDNF levels were measured in 41 drug naive ADHD patients and 107 normal controls. The severity of ADHD symptoms was determined by patient scores on the ADHD rating scale (ARS) and the computerized ADHD diagnostic system (ADS). RESULTS ANCOVA with age and gender as covariates showed that the mean plasma BDNF levels were significantly higher in ADHD patients than in normal controls (F=16.968, p<0.001). There were also significant differences in plasma BDNF levels of ADHD patients and those of normal controls for males and females (Mann-Whitney U-test, p=0.001 and 0.041, respectively). We also found a significant correlation between plasma BDNF levels and omission errors in ADS outcome-variable T-scores (p<0.001). CONCLUSIONS Our study suggests that there is an increase of plasma BDNF levels in untreated ADHD patients, and that plasma BDNF levels had a significant positive correlation with the severity of inattention symptoms. Further studies are required to elucidate the source and role of circulating BDNF in ADHD.

Increased plasma nitric oxide metabolites in suicide attempters.

Objective: To evaluate any correlation between plasma levels of nitric oxide metabolites (NOx) and suicide attempt. Method: Plasma NOx levels were measured in 53 patients who had recently attempted suicide, 58 nonsuicidal psychiatric patients, and 75 normal controls. The severity of suicidal behaviors was evaluated using Weisman and Worden’s Risk-Rescue Rating Scale. Results: Plasma NOx levels were significantly higher in suicidal patients than nonsuicidal psychiatric patients or normal control subjects (F = 11.029, d.f. = 2, 183, p < 0.001). Among the patients with a diagnosis of major depression, suicidal depressive patients had significantly higher plasma NOx levels than nonsuicidal depressive patients (t = –3.090, d.f. = 84, p = 0.003). Conclusion: Our study suggests that increased NO production in plasma is associated with suicide attempt, especially in depressive patients.

Association between Intracellular Infectious Agents and Schizophrenia.

Objective A number of studies have reported association between Toxoplasma gondii (T. gondii) and Chlamydia infection and the risk of schizophrenia. The aim of the present study was to compare the prevalence of T. gondii and Chlamydia infection between the schizophrenia and normal control subjects and to compare the clinical features between seropositive and seronegative schizophrenia patients. Methods The rate of serum reactivity to T. gondii, Chlamydia trachomatis (C. trachomatis), Chlamydia pneumonia in 96 schizophrenia and 50 control subjects was investigated using enzyme-linked immunosorbent assay and indirect fluorescent antibody technique. The clinical symptoms of the schizophrenia patients were scored with Positive and Negative Syndrome Scale and a comparative analysis was carried out. Results A significant positive association between immunoglobulin G (IgG) antibodies to T. gondii and C. trachomatis in schizophrenia was found, and the odds ratio of schizophrenia associated with IgG antibody was found to be 3.22 and 2.86, respectively. The Toxoplasma-seropositive schizophrenia patient had higher score on the negative subscale N1 and N7 and general psychopathology subscale G13, while C. trachomatis-seropositive schizophrenia patient had higher score on the general psychopathology subscale G10. Conclusion The results from the present study suggest significant association between T. gondii, C. trachomatis infection and schizophrenia. In future, further studies are needed to elucidate the correlation between the two types of infection and schizophrenia.

Gender Differences in Suicidal Behavior in Korea

Objective To examine gender differences in the characteristics of suicidal behavior in South Korea. Methods Between August 2003 and December 2006, 344 suicide attempters (116 men, 228 women) participated in this study. The attempters were interviewed using the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I), and the lethality of the attempt was measured using the Lethality Suicide Attempt Rating Scale-II (LSARS-II) and Risk-Rescue Rating Scale (RRRS). Results Significantly more women than men were admitted to emergency rooms due to attempted suicide during the study period. The male attempters were older and had a higher rate of employment than the females. Depression was the most common psychiatric disorder in both genders. The lesion/toxicity scores of the RRRS indicated that the male suicide attempters used higher doses or more toxic agents than the female attempters. The most common methods of suicide were ingestion and cutting in both sexes. Although there were significant gender differences in the RRRS risk score and RRRS total scores, there was no gender difference in the LSARS-II scores, which suggests that patients of both sexes share a similar ambivalence regarding suicide completion or death. Conclusion Our study should be understood within the context of the specific cultural background of South Korea. We found that males and females use similar methods when attempting suicide and share a similar ambivalence regarding the outcome of the attempt; however, there was a difference in severity of the attempt between the two groups. Our findings may aid in the identification of more effective methods of intervention to prevent suicide.

Effect of osmotic-release oral system methylphenidate on learning skills in adolescents with attention-deficit/hyperactivity disorder: an open-label study.

We evaluated the effect of osmotic-release oral system (OROS) methylphenidate on learning skills in adolescents with attention-deficit/hyperactivity disorder (ADHD). In an open-label study, 121 adolescents with ADHD were administered flexible doses of OROS methylphenidate for 12 weeks. The efficacy of methylphenidate on ADHD symptoms was evaluated by ADHD Rating Scale (ARS) and Clinical Global Impression Scale (CGI). Learning Skills Test (LST) was used to measure the learning skills of the participants at the baseline and the endpoint. Continuous performance test, visuospatial and verbal working memory, verbal fluency, and inhibition were evaluated before and after the 12 weeks of treatment. The mean total and subscores of LST were significantly increased after the 12-week treatment with OROS methylphenidate. Executive functions were also improved during the trial, with the exception of inhibition measured by the Stroop Test. To the best of our knowledge, this is the first study to examine the influence of OROS methylphenidate on learning skill. As a result, OROS methylphenidate was effective in enhancing learning skills in adolescents with ADHD.

Clinical and neurobiological factors in the management of treatment refractory attention-deficit hyperactivity disorder

Attention-deficit/hyperactivity disorder (ADHD) is a highly prevalent mental disorder of childhood, which often continues into adolescence and adulthood. Stimulants such as methylphenidate (MPH) and non-stimulants such as atomoxetine are effective medications for the treatment of ADHD. However, about 30% of patients do not respond to these medications. Pharmacological treatment for ADHD, although highly effective, is associated with marked variabilities in clinical response, optimal dosage needed and tolerability. This article provides an overview of up-to-date knowledge regarding the clinical and neurobiological factors which contribute to and help predict treatment-refractory ADHD. Pharmacogenetic, pharmacogenomics and neuroimaging studies are still controversial with respect to determining the associations between response to medication and genetic factors, thereby resulting in hypotheses that differences in the genetic factors and neuroimaging findings contribute to treatment outcome. Much research on the potential role of genotype in pharmacological effects has focused on the catecholaminergic gene related to executive functions. Many neuroimaging studies have also reported a relationship between treatment response and common patterns of brain structure or activity according to various genetic polymorphisms. When children, adolescents and adults with ADHD do not respond to MPH, we should consider additional pharmacological options, including other classes of psychostimulants, the nonstimulant atomoxetine, bupropion, tricyclic antidepressant, clonidine, guanfacine and lisdexamphetamine. Prudent choice of an appropriate medication and active engagement of children, parents, and teachers in daily management may help to ensure long-term adherence. Therefore, additional research might help to optimize the treatment of children, adolescents and adults with ADHD and to find new options for the treatment of patients who do not respond to stimulants and the other medications. Because these findings should be interpreted cautiously, further studies are needed to elucidate these issues more clearly.

No Association between Serotonin Receptor 2C-759C/T Polymorphism and Weight Change or Treatment Response to Mirtazapine in Korean Depressive Patients

Objective 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. Methods 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. Results 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. Conclusion 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.

Comparison of Baseline Characteristics between Community-based and Hospital-based Suicidal Ideators and Its Implications for Tailoring Strategies for Suicide Prevention: Korean Cohort for the Model Predicting a Suicide and Suicide-related Behavior

In this cross-sectional study, we aimed to identify distinguishing factors between populations with suicidal ideation recruited from hospitals and communities to make an efficient allocation of limited anti-suicidal resources according to group differences. We analyzed the baseline data from 120 individuals in a community-based cohort (CC) and 137 individuals in a hospital-based cohort (HC) with suicidal ideation obtained from the Korean Cohort for the Model Predicting a Suicide and Suicide-related Behavior (K-COMPASS) study. First, their sociodemographic factors, histories of medical and psychiatric illnesses, and suicidal behaviors were compared. Second, diagnosis by the Korean version of the Mini International Neuropsychiatric Interview, scores of psychometric scales were used to assess differences in clinical severity between the groups. The results revealed that the HC had more severe clinical features: more psychiatric diagnosis including current and recurrent major depressive episodes (odds ratio [OR], 4.054; P < 0.001 and OR, 11.432; P < 0.001, respectively), current suicide risk (OR, 4.817; P < 0.001), past manic episodes (OR, 9.500; P < 0.001), past hypomanic episodes (OR, 4.108; P = 0.008), current alcohol abuse (OR, 3.566; P = 0.020), and current mood disorder with psychotic features (OR, 20.342; P < 0.001) besides significantly higher scores in depression, anxiety, alcohol problems, impulsivity, and stress. By comparison, old age, single households, and low socioeconomic status were significantly associated with the CC. These findings indicate the necessity of more clinically oriented support for hospital visitors and more socioeconomic aid for community-dwellers with suicidality.