Sook Haeng Joe

Topiramate as an Adjuvant Treatment With Atypical Antipsychotics in Schizophrenic Patients Experiencing Weight Gain

Schizophrenic patients commonly suffer weight gain, which is often associated with widely prescribed antipsychotic medicines. It is distressing to most patients who experience it and may affect their response to treatment of schizophrenia. Weight gain is also associated with treatment noncompliance and several medical conditions. This study explored the efficacy and tolerability of topiramate as an adjuvant treatment of patients with schizophrenia who were carrying excess weight. In this 12-week, randomized, placebo-controlled prospective study, 66 hospitalized patients with schizophrenia who were carrying excess weight were given topiramate at doses of 100 mg/day or 200 mg/day, or a placebo. The primary measures made were body weight, body mass index, waist measurement, hip measurement, and waist-to-hip ratio. Safety measures included physical examinations and the monitoring of adverse effects, clinical laboratory data, and vital signs. The Clinical Global Impression-Severity of Illness scale (CGI-S) and the Brief Psychiatric Rating Scale (BPRS) were used to quantify changes in schizophrenic symptoms and signs. In the 200-mg/day topiramate group, body weight, body mass index, waist measurement, and hip measurement decreased significantly compared with the 100-mg/day topiramate and placebo groups over 12 weeks. However, the waist-to-hip ratio did not change in any group. Scores on the CGI-S and BPRS decreased significantly over the 12-week period in both topiramate groups, but the decrease was not clinically meaningful. These results suggest that a higher dose of topiramate is efficacious as an adjuvant treatment of patients with schizophrenia experiencing excess weight gain. Further clinical research is required to establish guidelines for the use of topiramate as an antiobesity agent in schizophrenic patients.

Symptom severity and attitudes toward medication: Impacts on adherence in outpatients with schizophrenia

OBJECTIVE The primary aim of this study was to compare electronic monitoring with other measures of adherence to antipsychotic medication in outpatients with schizophrenia. The secondary aim of the study was to analyze the relationships between adherence and other clinical parameters. METHOD Fifty-one patients diagnosed with schizophrenia were monitored over an eight-week period. Medication adherence was assessed using the Medication Event Monitoring System (MEMS), which is a bottle cap with a microprocessor that records the occurrence and times of bottle opening, patient self-reports, a clinician rating scale, and pill counts. Agreements among adherence measures and the relationships between adherence and other clinical factors were assessed. RESULTS The rate of non-adherence according to the MEMS was 41.2%, considerably higher than those of pill counting (7.8%), clinician rating scale (7.8%), or self-reporting (25.5%). Excitement, impulse control, and preoccupation symptoms on the Positive and Negative Syndrome Scale (PANSS) were higher in the non-adherent patients than in the adherent patients. The full Drug Attitude Inventory (DAI) score was higher in adherent versus non-adherent patients and the significant other subscale of the Multidimensional Scale of Perceived Social Support score was lower in the adherent patients. The Clinical Global Impression-Severity score was negatively correlated with adherence as measured by the MEMS (r=-0.426, p<0.05) and DAI scores were positively correlated with adherence according to the MEMS and the clinician rating scale (r=0.498, p<0.01 and r=0.387, p<0.05). Multivariate analysis showed that PANSS and DAI scores significantly contributed to MEMS adherence. CONCLUSION Adherence as measured by the MEMS showed a discrepancy with other measures of adherence in patients with schizophrenia. The severity of disease and attitudes toward medication were related to adherence. Further studies are needed to evaluate the impacts of medication adherence in schizophrenia.

Association between glucocorticoid receptor methylation and hippocampal subfields in major depressive disorder.

Background DNA methylation in the promoter region of the glucocorticoid receptor gene (NR3C1) is closely associated with childhood adversity and suicide. However, few studies have examined NR3C1 methylation in relation to major depressive disorder (MDD) and hippocampal subfield volumes. We investigated the possible association between NR3C1 methylation and structural brain alterations in MDD in comparison with healthy controls. Methods We compared the degree of NR3C1 promoter methylation in the peripheral blood of non-psychotic outpatients with MDD and that of healthy controls. Correlations among NR3C1 promoter methylation, structural abnormalities in hippocampal subfield volumes and whole-brain cortical thickness, and clinical variables were also analyzed. Results In total, 117 participants (45 with MDD and 72 healthy controls) were recruited. Patients with MDD had significantly lower methylation than healthy controls at 2 CpG sites. In MDD, methylations had positive correlations with the bilateral cornu ammonis (CA) 2–3 and CA4-dentate gyrus (DG) subfields. However, in healthy controls, methylations had positive correlation with the subiculum and presubiculum. There were no differences in total and subfield volumes of the hippocampus between patients with MDD and healthy controls. Compared with healthy controls, patients with MDD had a significantly thinner cortex in the left rostromiddle frontal, right lateral orbitofrontal, and right pars triangularis areas. Conclusions Lower methylation in the NR3C1 promoter, which might have compensatory effects relating to CA2-3 and CA4-DG, is a distinct epigenetic characteristic in non-psychotic outpatients with MDD. Future studies with a longitudinal design and a comprehensive neurobiological approach are warranted in order to elucidate the effects of NR3C1 methylation.

Characteristics and clinical correlates of restless legs syndrome in schizophrenia

OBJECTIVE The cause of restless legs syndrome (RLS) has not yet been ascertained, but one of the most promising theories involves dopaminergic deficiency. In accordance with this theory, we assumed that the prevalence of RLS would be higher among schizophrenics treated with antipsychotics than in the normal population. The purpose of this study was to establish the prevalence, characteristics, and clinical correlates of RLS in schizophrenic patients undergoing treatment with antipsychotics. METHODS A total of 182 hospitalized schizophrenic patients and 108 age- and sex-matched normal controls were enrolled. The presence of RLS and its severity were assessed using the International Restless Legs Syndrome Study Group (IRLSSG) diagnostic criteria and the IRLSSG rating scale, respectively. The Athens Insomnia Scale (AIS), Brief Psychiatric Rating Scale (BPRS), and Barnes Akathisia Rating Scale (BARS) were used to evaluate insomnia, global psychiatric symptoms, and akathisia, respectively, in schizophrenic patients. RESULTS Of the 182 schizophrenic patients, 39 (21.4%) were found to have RLS and 87 (47.8%) met at least one of the RLS diagnostic criteria. The prevalence of RLS was significantly higher in the schizophrenia group than in the control group (p=0.009), as were the RLS scores (p<0.001). The BPRS (p=0.001) and the AIS (p<0.001) scores were higher in the RLS group than in the group with no RLS symptoms. CONCLUSION We conclude that it is important to consider the diagnosis of RLS when schizophrenic patients complain of insomnia, and that RLS symptoms could be associated with more severe psychiatric symptoms and insomnia.

Factors Influencing the Severity of Menopause Symptoms in Korean Post-menopausal Women

We have relatively limited knowledge of symptomatic aspects of the postmenopause, rather than perimenopause. We tried to determine the factors associated with experiencing menopausal symptoms by Korean postmenopausal women. A total of 657 Korean women who underwent a natural menopause completed multiple questionnaires, which included questions regarding their attitudes to menopause, depressive symptoms, state anxiety, self-esteem, dyadic relationships, sociodemographic variables, and 11-item Menopause Rating Scale (MRS). Multiple regression analyses were performed to collectively examine the relative impact of each independent variable on the quality of life, as determined by the MRS. Decreased severity of menopausal symptoms was associated with more time spent in education, an employed status, a history of pregnancy, longer postmenopausal duration, positive attitudes to menopause, higher state anxiety, heightened self-esteem, and higher dyadic consensus. Increased severity of menopausal symptoms was also associated with absence of a partner, alcohol consumption, a history of hormone replacement therapy, a history of probable premenstrual dysphoric disorder, and increased severity of depressive symptoms. Sociodemographic characteristics, lifestyle factors, premenstrual dysphoric disorder, attitudes to menopause, a dyadic relationship with a partner, and the inner psychological status can be associated with the severity of menopause symptoms specifically in Korean postmenopausal women.

Short-term testosterone augmentation in male schizophrenics: A randomized, double-blind, placebo-controlled trial

Abstract Although there are few studies on the treatment of schizophrenia with testosterone, several indirect findings have suggested testosterone as a possible treatment modality for schizophrenia. To explore the therapeutic effect of testosterone augmentation of antipsychotic medication on symptoms in male patients with schizophrenia, the authors performed a placebo-controlled, double-blind trial on 30 schizophrenic men, using either 5 g of 1% testosterone gel (Testogel; Besins Iscovesco, Paris, France) or a placebo added to a fixed dosage of antipsychotic medication over a period of 4 weeks with a 2-week washout period. In addition, to get additional information about the involvement of these reproductive hormones after testosterone augmentation, the authors evaluated several hormones such as total testosterone, free testosterone, dehydroepiandrosterone sulfate, estradiol, and prolactin. Results indicated a significant improvement of negative symptoms in both the last observation carried forward and the completer analyses and a nonsignificant trend for the improvement of depressive symptoms in completers. There were no significant changes in serum hormone levels except total and free testosterone. The findings of this study suggest that testosterone augmentation may be a potential therapeutic strategy in patients with schizophrenia.

Estrogen, Cognitive Function and Negative Symptoms in Female Schizophrenia

The aim of this study was to evaluate the relationship of serum reproductive hormone levels with cognitive function and negative symptoms in schizophrenic women during the follicular phase of the menstrual cycle. Thirty-five women with chronic schizophrenia who had minimal positive symptoms participated in this study. We evaluated the correlation of serum reproductive hormone levels with the Scale for the Assessment of Negative Symptoms (SANS) and cognitive function tests such as the Immediate Visual Recognition Scale, Oral Fluency Test, List Recall Scale with List Acquisition Scale, Trail Making Tests A and B, and Digit Symbol Test. The patients were divided into two subgroups (low estradiol group and normal estradiol group) using the normal serum reference range for estradiol. Significant correlation between SANS subcategories, such as Alogia and Attention Impairment, and estradiol were found. Moreover, significant relationships between the estradiol level and the Oral Fluency Test, List Recall Scale with List Acquisition Scale, Trail Making Test B and Digit Symbol Test were observed. In the low estradiol group, the SANS scores, except for Anhedonia-Asociality and Avolition-Apathy, were significantly higher than those in the normal estradiol group. Patients in the low estradiol group had a significantly lower performance in the cognitive function tests, except Visual Recognition Scale, when compared to patients in the normal estradiol group. These results suggest that for schizophrenic women of reproductive age, lower levels of estrogen are associated with more severe negative symptomatology as well as reduced performance in cognitive function, especially verbal performance and executive functioning.

Allelic Variants Interaction of Dopamine Receptor D4 Polymorphism Correlate With Personality Traits in Young Korean Female Population

Polymorphism in exon III of the dopamine D4 receptor (DRD4) gene has been implicated to be associated with the human personality trait of novelty seeking (NS). For this study, we have investigated the possible association between 48‐bp VNTR in exon III and −521 C/T SNP of the DRD4 and personality traits among young (≈14 years of age) Korean female population. We found that the interaction between the two alleles of DRD4 polymorphism, 48‐bp VNTR and −521 C/T, were significantly high on NS (F = 4.88, P = 0.029) and persistence (P) (F = 5.05, P = 0.027) personality scores, suggesting that the variants of DRD4 gene influence the NS and P (persistent) personality traits. When analyzed independently, however, the two different alleles of DRD4 polymorphisms, 48‐bp VNTR and −521 C/T, there was no direct correlation with the personality traits.

Effects of season and climate on the first manic episode of bipolar affective disorder in Korea

The purpose of this study was to determine if a seasonal pattern existed for the first manic episodes in Korea. The first manic episodes out of 152 bipolar disorder patients were investigated, in subjects who were admitted in two hospitals in Seoul between 1996 and 1999. Correlations between the monthly climate variables and the first monthly manic episodes indicated that the first manic episodes peaked in 25 cases during March. The mean monthly hours of sunshine and sunlight radiation correlated significantly with manic episodes. Separating the patients into two groups, namely, with and without major depressive episode, only the occurrence of manic episodes with major depressive episode was significantly correlated with mean monthly hours of sunshine. Separating the subjects by gender, the monthly first manic episodes was significantly correlated with the intensity of sunlight radiation in female patients only. These findings suggested that increasing the duration and intensity of sunlight could facilitate breakdown into the manic episodes.

Manganese superoxide dismutase gene Ala–9Val polymorphism might be related to the severity of abnormal involuntary movements in Korean schizophrenic patients

OBJECTIVE This study examined whether the manganese superoxide dismutase (MnSOD) gene Ala-9Val single-nucleotide polymorphism (SNP) is associated with neuroleptic-induced tardive dyskinesia (TD) and the severity of the abnormal involuntary movements in Korean schizophrenic patients. METHOD We investigated whether the MnSOD gene Ala-9Val SNP is associated with TD in Korean schizophrenic patients with (n=83) and without (n=126) TD who were matched for exposure to antipsychotics and other relevant variables. RESULTS Logistic regression analysis revealed that being older (p=0.026) was a risk factor for TD, but that there was no significant association between MnSOD gene and TD. Abnormal involuntary movements were more severe in carriers of the Ala allele than in noncarriers (p=0.044). CONCLUSION These findings do not support that the MnSOD gene Ala-9Val SNP is associated with TD in Korean schizophrenic patients. However, this polymorphism might be related to the severity of abnormal involuntary movements in this population.