Benzodiazepines: Pharmacology Up-to-Date and Practical Issues / 신경정신의학

Benzodiazepines have been widely used as anxiolytics, sedatives, hypnotics, anticonvulsants, or central muscle relaxants since the 1960s despite significant adverse effects, the potential for misuse, and consequent overdose. Benzodiazepines exert their pharmacological action by binding to gamma-aminobutyric acid type A (GABA-A) receptors in the brain and facilitateing the inhibitory actions of the neurotransmitter GABA. Recent findings have also elucidated the effects of benzodiazepines on the allosteric modulation of GABA-A receptors, including receptor subtypes and transmembrane proteins, which is a significant step in our understanding of GABA pharmacology. In clinical practice, the use of benzodiazepines to treat psychiatric disorders has been limited due to the challenges associated with the long-term use, namely the risks of abuse, misuse, and overdose, as well as withdrawal effects. Furthermore, the approval of selective serotonin reuptake inhibitors for anxiety disorders has led to their extensive use as a first-line pharmacological option and they have also been promoted in various practice guidelines for the treatment of anxiety disorders. However, although recent systematic reviews and meta-analyses have shown that benzodiazepines are useful and effective drugs for the treatment of various neuropsychiatric disorders, including anxiety, debates over the clinical use of benzodiazepines continue. More than 60 years after the introduction of benzodiazepines in clinical practice, it is necessary to revisit the controversies associated with benzodiazepine use and to update the discussion current approach to practice with thethrough an understanding of the new data on their pharmacological actions and to identify appropriate indications according to the new diagnostic systems of psychiatric disorders through an extensive literature review.

Satisfaction Survey of Patients Toward Electroconvulsive Therapy / 신경정신의학

Objectives@#This study examined the satisfaction of patients who had undergone electroconvulsive therapy to provide important information for improving the social misunderstanding about electroconvulsive therapy, to increase the effectiveness of treatment, and make a decision of effective treatment. @*Methods@#A questionnaire survey was conducted to determine the satisfaction, adverse effects, attitudes, and experiences toward electroconvulsive therapy in patients at 2 to 4 weeks after finishing an acute course of electroconvulsive therapy in three psychiatric hospitals. @*Results@#There were 85 respondents (38 males), whose average age was 42.0±13.6 years and average illness duration was 12.8±8.9 years. Fifty-two patients (61.2%), 19 (22.4%), 8 (9.4%), and 6 (7.1%) were diagnosed with schizophrenia, major depressive disorder, bipolar disorder, and other mental disorders, respectively. The average session number for acute electroconvulsive therapy was 12.6±6.0 sessions, and 61 patients (71.8%) had received maintenance electroconvulsive therapy. Among the respondents, 60.0% reported that they were satisfied with the electroconvulsive therapy. Satisfaction was similar according to sex, age, diagnosis, electrode placement, and use of anesthetic agents. Forty-three (53.8%) patients experienced memory impairment during acute electroconvulsive therapy. @*Conclusion@#This study showed that patients who received electroconvulsive therapy were generally satisfied with the treatment and that memory impairment should be detected early and managed promptly. Follow-up studies with a large number of subjects and variables will be needed to determine the predictive factors affecting satisfaction toward electroconvulsive therapy.

Satisfaction Survey of Patients Toward Electroconvulsive Therapy / 신경정신의학

Objectives@#This study examined the satisfaction of patients who had undergone electroconvulsive therapy to provide important information for improving the social misunderstanding about electroconvulsive therapy, to increase the effectiveness of treatment, and make a decision of effective treatment. @*Methods@#A questionnaire survey was conducted to determine the satisfaction, adverse effects, attitudes, and experiences toward electroconvulsive therapy in patients at 2 to 4 weeks after finishing an acute course of electroconvulsive therapy in three psychiatric hospitals. @*Results@#There were 85 respondents (38 males), whose average age was 42.0±13.6 years and average illness duration was 12.8±8.9 years. Fifty-two patients (61.2%), 19 (22.4%), 8 (9.4%), and 6 (7.1%) were diagnosed with schizophrenia, major depressive disorder, bipolar disorder, and other mental disorders, respectively. The average session number for acute electroconvulsive therapy was 12.6±6.0 sessions, and 61 patients (71.8%) had received maintenance electroconvulsive therapy. Among the respondents, 60.0% reported that they were satisfied with the electroconvulsive therapy. Satisfaction was similar according to sex, age, diagnosis, electrode placement, and use of anesthetic agents. Forty-three (53.8%) patients experienced memory impairment during acute electroconvulsive therapy. @*Conclusion@#This study showed that patients who received electroconvulsive therapy were generally satisfied with the treatment and that memory impairment should be detected early and managed promptly. Follow-up studies with a large number of subjects and variables will be needed to determine the predictive factors affecting satisfaction toward electroconvulsive therapy.

Electroconvulsive Therapy for Psychiatric Disorders in Elderly Adults

Electroconvulsive therapy (ECT) is indicated for various mental disorders (e.g., major depressive disorder, schizophrenia, and bipolar disorder) and the behavioral and psychological symptoms of dementia in elderly patients. Furthermore, ECT is a useful first-line treatment in emergency and crisis situations such as suicide risk, violent behavior, catatonia, and food refusal, which are more frequent in elderly patients. ECT is also effective in the treatment of the motor symptoms of neurological disorders, such as Parkinson’s disease and Huntington’s disease. Due to the high risk of various physical diseases, the comorbid physical conditions of elderly patients should be individually controlled to optimize ECT treatment. Compared to young adults, in elderly patients the seizure threshold is higher, the seizure duration is shorter, and the anesthetic dose is lower. On the contrary, the response rate in the elderly is both faster and higher. Considering potential cognitive decline and the prevention of further deterioration of cognitive function in elderly patients, in the absence of significant comorbidities, twice weekly sessions and right unilateral electrode placement with a lower seizure threshold and less cognitive effect are preferred to bilateral electrode placement, which has a high risk of adverse cognitive effects. After an acute course of ECT, continuation and maintenance of ECT, combined with prescription of therapeutic drugs, may prevent possible relapse or recurrence of mental disorders. In conclusion, ECT can be used to treat mental disorders in elderly adults, with safety and effectiveness comparable to that in young adults.

Electroconvulsive Therapy for Psychiatric Disorders in Elderly Adults

Electroconvulsive therapy (ECT) is indicated for various mental disorders (e.g., major depressive disorder, schizophrenia, and bipolar disorder) and the behavioral and psychological symptoms of dementia in elderly patients. Furthermore, ECT is a useful first-line treatment in emergency and crisis situations such as suicide risk, violent behavior, catatonia, and food refusal, which are more frequent in elderly patients. ECT is also effective in the treatment of the motor symptoms of neurological disorders, such as Parkinson’s disease and Huntington’s disease. Due to the high risk of various physical diseases, the comorbid physical conditions of elderly patients should be individually controlled to optimize ECT treatment. Compared to young adults, in elderly patients the seizure threshold is higher, the seizure duration is shorter, and the anesthetic dose is lower. On the contrary, the response rate in the elderly is both faster and higher. Considering potential cognitive decline and the prevention of further deterioration of cognitive function in elderly patients, in the absence of significant comorbidities, twice weekly sessions and right unilateral electrode placement with a lower seizure threshold and less cognitive effect are preferred to bilateral electrode placement, which has a high risk of adverse cognitive effects. After an acute course of ECT, continuation and maintenance of ECT, combined with prescription of therapeutic drugs, may prevent possible relapse or recurrence of mental disorders. In conclusion, ECT can be used to treat mental disorders in elderly adults, with safety and effectiveness comparable to that in young adults.

Reliability and Validity of the Korean Version of the Birchwood Insight Scale / 신경정신의학

OBJECTIVES: In the treatment of schizophrenia, treatment compliance is an important prognostic factor. As insight has a significant impact on treatment compliance, an appropriate assessment of insight is essential in the treatment of schizophrenia. This study examined the reliability and validity of the Korean version of Birchwood Insight Scale (BIS). METHODS: Fifty seven adult patients diagnosed with schizophrenia according to DSM-5 were recruited from a university hospital. They were evaluated using the Positive and Negative Syndrome Scale (PANSS), The Scale to Assessment Unawareness of Mental Disorder (SUMD) and BIS. Explorative factor analysis was performed to examine the construct validity of the Korean version of BIS. Concurrent validity was evaluated by a comparison with the PANSS G12 item and SUMD. The test-retest correlation was evaluated to examine the test-retest reliability. Multiple regression analysis was performed to examine the variables affecting insight. RESULTS: Explorative factor analysis showed that the Korean version of BIS was composed of 2 factors, which are ‘Awareness of symptoms’ and ‘Awareness of illness and need for treatment.’ The Korean version of BIS was reliable in terms of the internal consistency. Concurrent validity with the PANSS G 12 item and SUMD was statistically significant. The test-retest reliability was also statistically significant. Multiple regression analysis showed that the PANSS negative factor affects the BIS score, indicating that negative symptoms of schizophrenia may impair insight of the illness. CONCLUSION: This study suggests that the Korean version of BIS is a valid and reliable tool for assessing the insight of patients with schizophrenia.

Long-Term Evolution of Metabolic Status in Patients with Schizophrenia Stably Maintained on Second-Generation Antipsychotics

OBJECTIVE: Second-generation antipsychotics (SGAs) increase the risk of metabolic syndrome (MetS). Despite the risk of MetS, SGAs may have to be continued with change in some patients. The aim of this study was to trace the evolution of MetS in these patients. METHODS: Patients with schizophrenia who had been maintained on a fixed SGA regimen for more than a year were followed-up without changing the regimen. Metabolic indicators were evaluated at baseline and at follow-up. Prevalence, incidence and spontaneous normalization rate of MetS were estimated. Risk factors that might have influenced the evolution were scrutinized. RESULTS: A total of 151 subjects were included. During the mean observation period of 389.9±162.4 days, the prevalence of MetS was increased from 35.1 to 45.0%. The incidence rate was 29.6%, while the normalization rate was 26.4%, risk factors affecting incidence were age (OR=1.09, 95% CI: 1.03–1.17), baseline continuous values of metabolic syndrome risk scores (cMetS, OR=1.77, 95% CI:1.29–2.55) and baseline body weight (OR=1.06, 95% CI: 1.01–1.13). Normalization was influenced by age (OR=0.74, 95% CI: 0.57–0.89) and baseline body weight (OR=0.85, 95% CI: 0.72–0.95). CONCLUSION: The prevalence of MetS steadily increased with the continuous use of SGAs. However, individual difference was extensive and about a quarter of the patients were able to recover naturally without specific measurements.

Practical Considerations in Anesthesia for Electroconvulsive Therapy

Electroconvulsive therapy (ECT) has been recognized effective as primary or secondary treatments for major psychiatric disorders including depression and schizophrenia, as well as psychiatric emergency such as suicide, food refusal and catatonia, and so on. Medicines used in anesthetic induction for ECT, cause various reactions in autonomous, hemodynamic, and neuromuscular systems. The anesthetics also affect the duration, threshold, and intensity of seizures evoked with electric stimuli, and thus modify the seizure quality in ECT. Individual characteristics of age, sex, weight, comorbid physical disorders, and medications should also be considered for optimal clinical response after ECT. When preparing for anesthesia, adequate anesthetic agents and muscle relaxants, and rapid recovery should be carefully considered. We conducted a case-series study to address practical issues that are frequently encountered during ECT anesthesia with reviews of updated journals in order to provide practical helps to clinicians who are preparing ECT for their patients.

Psychotic Disorder Induced by Appetite Suppressants, Phentermine or Phendimetrazine: A Case Series Study

OBJECTIVES: A retrospective case series study was conducted to investigate the clinical characteristics of psychotic disorders induced by appetite suppressants, phentermine and phendimetrazine. METHODS: A retrospective electronic medical record review identified 5 admitted patients who had psychotic symptoms after taking phentermine or phendimetrazine. Clinical information was reviewed and summarized in each case. RESULTS: Hallucinations were reported in all cases, including auditory, visual, olfactory and somatic hallucinations. After discontinuation of phentermine or phendimetrazine, the symptoms rapidly improved with low dose of antipsychotics. Patients tended to have less prominent negative symptoms and higher insight into illness, and often showed depressive mood. These clinical characteristics were similar to psychosis induced by amphetamines. Two patients developed stimulant use disorder while using phentermine. CONCLUSIONS: These findings call for awareness of the risks associated with use of appetite suppressants. Prescription of phentermine or phendimetrazine should be accompanied by close monitoring of mental status, and suspicion for substance/medication-induced psychotic disorder.

Effectiveness of Electroconvulsive Therapy Augmentation on Clozapine-Resistant Schizophrenia

OBJECTIVE: This retrospective case series study of the effectiveness of electroconvulsive therapy (ECT) augmentation on clozapine-resistant schizophrenia was conducted by EMR review. METHODS: Clozapine-resistance was defined as persistent psychotic symptoms despite at least 12 weeks of clozapine administration with blood levels over 350 ng/mL in order to rule out pseudo-resistance. Seven in-patients who were taking clozapine and treated with ECT were selected. We analyzed the psychopathology and subscales changed by ECT. RESULTS: The average number of ECT sessions was 13.4 (±4.6). Total Positive and Negative Syndrome Scale (PANSS) score was significantly reduced by 17.9 (±12.8) points (p=0.0384) on average, which represented a reduction of 25.5% (±14.3). 71.4% (5/7) of patients were identified as clinical remission, with at least a 20% reduction in PANSS score. PANSS reduction was associated with number of ECT sessions, stimulus level in the final session, and blood clozapine levels before ECT. However, the negative subscale on the PANSS were not reduced by ECT in any patient. We did not observe any persistent adverse cognitive effects. CONCLUSION: This study supports that ECT augmentation on clozapine-resistant schizophrenia reveals clinically effective and safe. Further research should be done involving a larger number of patients to investigate the effectiveness of clozapine/ECT combination therapy.

Multidimensional Relationship between Auditory Verbal Hallucinations and PANSS Factors of Psychopathology in the Patients with Schizophrenia

OBJECTIVES: This study was aimed to examine the multidimensional relationship between auditory verbal hallucinations (AVHs) and Positive and Negative Syndrome Scale (PANSS) factors of psychopathology in the patients with schizophrenia. And we explored the differences between assessments to hallucination by the clinicians and patients. METHODS: 82 patients with schizophrenia who were assessed by the Hamilton Program for Schizophrenia Voices Questionnaire (HPSVQ), Psychotic Symptom Rating Scale-Auditory Hallucination (PSYRATS-AHS), and the PANSS were recruited. Hwang's five-factor model of PANSS, items and total scores of hallucination scales, Kim's and Haddock's factor models of hallucination were applied to examine the correlations between psychopathology and AVHs. AVH-positive patients was 50 in PANSS-HPSVQ group and 24 in PANSS-PSYRATS-AHS. These two groups were separately analyzed. RESULTS: Among the five factors of the PANSS, negative and depression/anxiety factors were correlated with the total scores of HPSVQ and PSYRATS-AHS, and positive and autistic preoccupation factors were correlated only with the total score of PSYRATS-AHS. The activation factor was correlated with none of the total scores of HPSVQ/PSYRATS-AHS. These correlation patterns of a total score of HPSVQ/PSYRATS-AHS were same in the emotional factor of HPSVQ and physical factor of PSYRATS-AHS respectively. In the items which showed significant correlations, correlation coefficients of PANSS-PSYRATS-AHS group ranged between 0.406-0.755 and those of PANSS-HPSVQ ranged between 0.283-0.420. CONCLUSIONS: This study suggested that the psychopathological domains of schizophrenia were differentially correlated with AVHs and the assessment of AVHs by clinicians and patients showed substantial differences which should be integrated into the therapeutic interventions.

Stenotrophomonas maltophilia and Ventilator-Associated Pneumonia in Critically Ill Pediatric Patients: a Retrospective Analysis at a Single Center

PURPOSE: Ventilator-associated pneumonia (VAP) is a serious threat in critically ill pediatric patients. Data regarding Stenotrophomonas maltophilia VAP in pediatric population is limited. We evaluated the clinical data of S. maltophilia associated VAP in critically ill pediatric patients. METHODS: A retrospective chart review was performed in pediatric patients 18 years old or younger who developed S. maltophilia associated VAP at Samsung Medical Center, Seoul Korea from January 2008 to December 2012. RESULTS: A total of 31 patients were identified S. maltophilia associated VAP. Median age was 8 months (range, 0.5 month to 16.6 years) and 13 patients were male (40.6%). Underlying illnesses were cardiologic diseases (n=11, 34.4%), hematologic oncologic malignancies (n=7, 25%), neurologic diseases (n=4, 12.5%), pulmonary diseases (n=3, 9.4%), and others (n=4, 12.5%). The median duration of ventilator use before S. maltophilia VAP diagnosis was 14 days (range, 4-256 days). Overall mortality at 30 days was 12.5% (4/32). CONCLUSIONS: S. maltophilia should be also considered as a possible pathogen for VAP in critically ill pediatric patients. Empiric antibiotic choice should include agents that are active against S. maltophilia in patients who are deteriorating on broad spectrum beta-lactam antimicrobial agents.

Tolerability, Safety and Effectiveness of Paliperidone ER in Patients with Schizophrenia : A 24-Week Interim Analysis of the 48-Week Open-Label, Prospective, Switch Study

OBJECTIVES: We investigated the tolerability, safety, and treatment response to flexible-dose paliperidone ER in patients with non-acute schizophrenia in whom previous antipsychotic drugs were ineffective. METHODS: This 24-week interim analysis of the 48-week multicenter, prospective, open-label study assessed effectiveness using the Positive and Negative Syndrome Scale (PANSS), Clinical Global Impression-Schizophrenia-Severity (CGI-SCH-S) Scale, Personal and Social Performance (PSP) and Drug Attitude Inventory (DAI). Safety and tolerability were assessed using the Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS) and Liverpool University Neuroleptic Side Effect Rating Scale (LUNSERS). RESULTS: Effectiveness was assessed in 169 patients. Significant improvement in the PANSS total score was observed by week-1 and continued until week-24. The response rate was 33%. The CGI-SCH-S and PSP total scores significantly improved during 24 weeks ; however, no change occurred in the total DAI. Fifty-nine percent of patients reported adverse events, of which extrapyramidal symptoms were the most frequent (19.0%). The DIEPSS and LUNSERS scores were improved after 24 week. CONCLUSIONS: Switching to the flexible-dose paliperidone ER from an ineffective antipsychotic drug was safe, tolerable, and showed a good treatment response in Korean patients with schizophrenia.

The Preference Survey for Long-Acting Injectable Antipsychotics of Community-Dwelling Patients with Schizophrenia and their Caregivers / 대한정신분열병학회지

OBJECTIVE: The prescription rates of long-acting injectable (LAI) antipsychotics are very low around 1% in Korea. This study was aimed to explore the preference of LAIs in patients with schizophrenia, who are currently living in community, and their caregivers. METHODS: The patients, diagnosed with schizophrenia by DSM-IV TR and were registered in the 31 mental health centers of Gyeonggi province and their caregivers were inquired the knowledge of the LAIs. The questionnaires contained information such as demographic characteristics, history of psychiatric treatment, and so on. RESULTS: About 5,318 were registered in 31 community mental health centers of Gyeonggi province in February 2012. The questionnaires of 614 patients and 365 caregivers were gathered from 20 community mental health centers. The mean ages (+/-SD) of patients and caregivers were 41.9 (+/-10.2) and 62.2 (+/-13.4) years old, respectively. 272 patients (44.6%) had experienced the discontinuation of medications without doctor's consent. 217 patients (35.9%) and 97 caregivers (27.1%) knew about the LAIs. The preference rates for LAIs were 35.2% and 46.8% for the patients and caregivers, respectively. CONCLUSION: There is still huge discrepancy between the preference and the real prescriptions of LAIs in community-dwelling patients and their caregivers, much higher than in those of hospital settings. This study suggests that both patients and caregivers registered in the community mental health centers have a strong commitment to live in the community. The obstacles against the benefits of LAIs need to be resolved.

The Relationship between Insight and Psychopathology in the Treatment of Schizophrenia with Acute Psychotic Episode / 신경정신의학

OBJECTIVES: Lack of insight has been regarded as the key feature of schizophrenia since the era of Kraepelin. The relationship between insight and psychopathology has been known to be statistically modest and non-linear. The aim of this study was to investigate psychopathological factors influencing insight achievement during treatment of acute psychotic episodes in schizophrenia, using the Korean version of the Scale to Assess Unawareness of Mental Disorder (SUMD-K) and the Positive and Negative Syndrome Scale (PANSS). METHODS: Information on demographic characteristics, SUMD-K, and PANSS were collected from the medical records of patients who were admitted to the psychiatric ward of Dongguk University International Hospital from March 1, 2009 to February 28 and were diagnosed as schizophrenia by the DSM-IV TR 2010. A total of 29 patients met the inclusion criteria. The scores of total and sub-items of SUMD-K for both current and past illnesses were assessed at five weeks after hospitalization and the scores of total and five factors of PANSS were assessed on hospitalization and at five weeks after hospitalization, respectively, and the changes in score between two time points were calculated. Statistical analysis of the relationships between the various items of the SUMD-K and the clinical characteristics, the total and sub-scores of PANSS was performed using the Pearson correlation test and multiple regression analysis with stepwise variable selection. RESULTS: Total score and five factor scores of PANSS for hospitalization and PANSS changes did not show statistical correlation with SUMD-K. The total score of general items and awareness of mental disorder of SUMD-K at five weeks after hospitalization showed significant associations with duration of education, depressed and cognitive factors for current illness of PANSS at five weeks after hospitalization, respectively. In addition, depressed factor and cognitive factor of PANSS showed a significant association with awareness of social consequences and awareness of the achieved affect of medication, respectively. CONCLUSION: During treatment of acute psychotic episodes in patients with schizophrenia, various domains of psychopathology were differentially correlated with insight, which implied the multidimensional construct on a continuum. Conduct of further studies of neurobiological approaches underlying factors showing correlation with insight is needed.

Factors Influencing the Subjective Sexual Function in Patients with Schizophrenia Switched to Olanzapine / 대한정신약물학회지

OBJECTIVE: Sexual dysfunction is highly prevalent in both untreated and treated patients with schizophrenia. Sexual dysfunction is a major cause of poor quality of life, negative attitude to therapy and treatment non-compliance. We thereby conducted this study to better understand the predictors of subjective sexual dysfunction. METHODS: The subjects consisted of 83 patients (46 men; 37 women) who participated in an open label study on switching antipsychotics to olanzapine. All subjects met the Tenth Revision of International Classification of Diseases diagnostic criteria for schizophrenia. To better understand the predictors of subjective sexual dysfunction, we used the Liverpool University Neuroleptic Side-effect Rating scale (LUNSERS), a comprehensive self-rating instrument for assessing and quantifying the subjective adverse events during antipsychotic treatment. All patients were taking antipsychotics at the initiation of the study and were assessed using LUNSERS, the Simpson-Angus Scale (SAS), the Barnes Akathisia Rating scale (BARS), Abnormal Involuntary Movement Scale (AIMS), Clinical Global Impression (CGI), and the Positive and Negative Syndrome Scale (PANSS). They were also checked for their serum prolactin levels and vital signs before and after a 6-week treatment with olanzapine. In order to identify the cross-sectional and longitudinal predictors of LUNSERS hormonal side effect, we carried out multiple regression analyses. RESULTS: Prolactin levels, LUNSERS hormonal side effect, CGI, PANSS, SAS, AIMS, and BARS decreased after a 6-week treatment with olanzapine. At initial evaluation, cross-sectional predictors of LUNSERS hormonal side effect were red herring and allergic reaction subscale, but after the 6-week treatment with olanzapine, none of the variables were found to significantly predict LUNSERS hormonal side effect. Longitudinal predictors of LUNSERS hormonal side effect were LUNSERS extrapyramidal system side effect and prolactin levels. CONCLUSION: These findings suggested relationships among prolactin, extrapyramidal symptom, motor function and sexual dysfunction. After switching to olanzapine, sexual function of the patients improved subjectively. More studies are warranted as these results have significant implications for quality of life and treatment adherence.

No Association of Functional Polymorphisms in Methlylenetetrahydrofolate Reductase and the Risk and Minor Physical Anomalies of Schizophrenia in Korean Population

Methylenetetrahydrofolate reductase (MTHFR), a critical enzyme in folate metabolism, plays an important role in DNA methylation. It has been suggested that abnormal DNA methylation contributes to the pathogenesis of schizophrenia and congenital anomalies. The previous findings regarding the genetic relationship between MTHFR and schizophrenia are controversial. This study investigated the association of the two functional polymorphisms of MTHFR, C677T and A1298C, with the risk for schizophrenia. Furthermore, we conducted an updated meta-analysis on the two polymorphisms. In addition, we investigated the relationship between the polymorphisms and minor physical anomaly (MPA), which may represent neurodevelopmental aberrations in 201 schizophrenia patients and 350 normal control subjects. There was no significant association between either of the two polymorphisms and the risk of schizophrenia (chi-square = 0.001, df = 1, P = 0.971 for C677T; chi-square = 1.319, df = 1, P = 0.251 for A1298C). However, in meta-analysis, the C677T polymorphism showed a significant association in the combined and Asian populations (OR = 1.13, P = 0.005; OR = 1.21, P = 0.011, respectively) but not in the Korean and Caucasian populations alone. Neither polymorphism was associated with MPAs measured by the Waldrop scale (chi-square = 2.513, df = 2, P = 0.285). In conclusion, the present findings suggest that in the Korean population, the MTHFR polymorphisms are unlikely to be associated with the risk for schizophrenia and neurodevelopmental abnormalities related to schizophrenia.

Study on the P50 Auditory Evoked Potential in Mood Disorder Subjects / 신경정신의학

OBJECTIVES: Diminished suppression of the P50 response, a consistent finding in schizophrenia, has also been reported in patients with bipolar disorder. It is a promising endophenotype for schizophrenia, but its relationship to genetic liability in mood disorder is controversial. The present study investigated event-related brain potential (ERP) indices of auditory processing and sensory gating in mood disorder and subgroups of patients with bipolar disorder with or without a history of psychosis using the P50 dual-click procedure. METHODS: The P50 auditory evoked potential response to paired stimuli was measured in 77 subjects with mood disorder (58 with bipolar disorder and 19 with major depressive disorder) and 28 healthy controls. P50 parameters were compared between groups. RESULTS: P50 suppression in patients with mood disorder did not differ from that in the healthy subjects. Except for S1 latency, there were no significant differences in P50 parameters between the diagnosis groups. In patients with bipolar disorder, a history of psychosis made no difference to P50 parameters. CONCLUSION: P50 was not significantly impaired in patients with mood disorder. There has been much debate on the meaning of P50, and more studies including longitudinal within-subjects studies are warranted to clarify the meaning and mechanisms of P50.

Spontaneous Bacterial Peritonitis due to Ochrobactrum anthropi: A Case Report

We report a case of spontaneous bacterial peritonitis from Ochrobactrum anthropi. O. anthropi is recognized as an emerging pathogen in immunocompromised patients. In contrast to most previously described cases, the patient reported here had no indwelling catheter. To our knowledge, no case of O. anthropi spontaneous bacterial peritonitis has been reported in the medical literature until now.

Image Standardization and Determination of Gray Level Threshold in the Assessment of the Myocardial Fibrosis by the Computerized Image Analysis

The computerized image analysis is a useful tool for the quantitative assessment of histopathologic findings. In contrast to the usual microscopic examination by pathologists, the computerization should be accompanied with the standardization process of the image. We developed an algorithm to standardize images and to determine the optimal gray level threshold, using a myocardial fibrosis model. Sirius red staining was more convenient for the image analysis than Masson's trichrome staining because of a better contrast with the surrounding structures. To get an optimal measurement, light intensity was standardized at each of the fibrosis, myocardium and background. In this study, the most promising method to determine the degree of fibrosis was that of revising the background without tissue to a gray level of 200, obtaining a green component of the color image, revising the myocardial fiber to 163, and defining a partial ratio as fibrosis index when the gray level threshold was 120. These threshold levels and parameters were determined after drawing the binarization index curves according to the change of the gray level threshold and by the morphological examination of the actual binarization figures overlaid to the original color image. Through these processes we could get a consistent result on the myocardial fibrosis and we expect a similar principle applies when we analyze color images in the histopathologic quantitation by computerized image analysis.