Linkage and Association Analyses of Schizophrenia with Genetic Variations on Chromosome 22q11 in Koreans

OBJECTIVE: Chromosome 22q11 has been implicated as a susceptibility locus of schizophrenia. It also contains various candidate genes for which evidence of association with schizophrenia has been reported. To determine whether genetic variations in chromosome 22q11 are associated with schizophrenia in Koreans, we performed a linkage analysis and case-control association study. METHODS: Three microsatellite markers within a region of 4.35 Mb on 22q11 were genotyped for 47 multiplex schizophrenia families, and a non-parametric linkage analysis was applied. The association analysis was done with 227 unrelated patients and 292 normal controls. For 39 single nucleotide polymorphisms (SNPs) spanning a 1.4 Mb region (33 kb interval) containing four candidate schizophrenia genes (DGCR, COMT, PRODH and ZDHHC8), allele frequencies were estimated in pooled DNA samples. RESULTS: No significant linkage was found at any of the three microsatellite markers in single and multi-point analyses. Five SNPs showed suggestive evidence of association (p<0.05) and two more SNPs showed a trend for association (p<0.1) in pooled DNA association analysis. Individual genotyping was performed for those seven SNPs and four more intragenic SNPs. In this second analysis, all of the 11 SNPs individually genotyped did not show significant association. CONCLUSION: The present study suggests that genetic variations on chromosome 22q11 may not play a major role in Korean schizophrenia patients. Inadequate sample size, densities of genetic markers and differences between location of genetic markers of linkage and association can contribute to an explanation of the negative results of this study.

Tardive Dyskinesia and Tardive Dystonia with Second-Generation Antipsychotics in Bipolar Disorder Patients Unexposed to First-Generation Antipsychotics

OBJECTIVES: Second-generation antipsychotics (SGAs) are frequently used in the treatment of bipolar disorder. However, there is still no consensus on their risk of tardive movement syndromes especially for first-generation antipsychotics (FGAs)-naive patients. This study aimed to investigate the prevalence and associated factors of SGAs-related tardive dyskinesia and tardive dystonia in patients with bipolar disorder, in a naturalistic out-patient clinical setting. METHODS: The authors assessed 78 non-elderly patients with bipolar (n = 71) or schizoaffective disorder (n = 7) who received SGAs with a combined use of mood stabilizers for more than three months without previous exposure to FGAs. Multiple direct assessments were performed and hospital records longer than one recent year describing any observed tardive movement symptoms were also reviewed. RESULTS: The prevalence rates of tardive dyskinesia and tardive dystonia were 7.7% and 6.4%, respectively. These patients were being treated with ziprasidone, risperidone, olanzapine, quetiapine, or paliperidone at the time of the onset of the movement symptoms. Tardive dyskinesia was mostly observed in the orolingual area, and tardive dystonia was most frequently detected in oromandibular area. A past history of acute dystonia was significantly associated with presence of both tardive movement syndromes. CONCLUSIONS: Our findings suggest that SGAs-related tardive movement syndromes occur in a substantial portion of bipolar disorder patients. Acute dystonia, a reported risk factor of tardive movement syndromes in the era of FGAs is confirmed as a risk factor of both tardive dyskinesia and tardive dystonia that were induced-by SGAs.

Correlation of Lifetime Symptom Dimensions with Cognitive Function and Other Clinical Characteristics in Schizophrenia Patients / 대한정신분열병학회지

OBJECTIVES: Considering large diversity of clinical presentation of schizophrenia, it is important to identify valid clinical subtypes or dimensions that might have homogeneous biological underpinning. The current study aimed to explore lifetime symptom-based dimensional phenotypes in patients with chronic schizophrenia, and to investigate their correlation with cognitive functions and other clinical characteristics. METHODS: Lifetime-based symptoms and additional clinical variables were measured using the Diagnostic Interview for Genetic Studies and the Schedule for the Deficit Syndrome in 315 clinically stable patients with chronic schizophrenia. Through principal components factor analysis, eight dimensional phenotypes were obtained. Comprehensive neuropsychological tests were administered for 103 out of 315 patients, and domain scores were calculated for cognitive domains defined in the MATRICS consensus battery. RESULTS: 'Non-paranoid delusion factor' including delusions of grandiose or religious nature, showed significant negative correlation with processing speed, working memory, attention/vigilance, and general cognitive ability, and positive correlation with intra-individual variability. 'Negative symptom factor' showed significant negative correlation only with general cognitive ability. Those two factors were also negatively correlated with function levels measured by Global Assessment Scale (GAS), and associated with poor treatment responses. CONCLUSION: Symptom-based dimensional phenotypes of schizophrenia measured on a lifetime basis showed discriminative correlation with cognitive function domains, global functioning level, and overall treatment responses, indicating their possibility as valid phenotype axes of schizophrenia having homogeneous biologic basis.

Clinical Case Conference / 신경정신의학

No abstract available.

Uncontrolled Self-Medication with Venlafaxine in a Patient with Major Depressive Disorder

Antidepressants are known to have no significant ability to cause addiction. However, a recent study showed many individuals with mood disorders self-medicated with antidepressants to relieve symptoms. We report here a male physician, diagnosed five years ago with major depressive disorder, with insomnia, anxiousness, and chest heaviness. He began self-medicating with 150 mg of venlafaxine daily, without any monitoring. During his most recent severe depressive episode, he was taking up to 1,500 mg of venlafaxine daily. Without this medication, he experienced discontinuation syndrome, which included severe anxiety, chest heaviness, and breathing difficulty, and which he judged as indicating a more severely depressed state. He also experienced overdose symptoms, such as hypertension and tachycardia. He attempted suicide with drugs that he possessed. In conclusion, careful monitoring is needed when treating patients with venlafaxine, because its discontinuation syndrome is similar to symptoms of major depressive disorder, and suicidality may result from an overdose.

Altered Cell Viability and Proliferation Activity of Peripheral Lymphocytes in Patients with Alzheimer's Disease

OBJECTIVE: We evaluated cell viability and proliferation activity of peripheral lymphocytes as potential models of neuronal death in Alzheimer's disease (AD). METHODS: We analyzed the cell viability and proliferation activity of phytohemagglutinin (PHA)-activated lymphocytes from 68 AD patients and 33 normal controls. The cellular measures were made at baseline (0 hr), 24 hrs, 48 hrs, 72 hrs, and 96 hrs after PHA stimulation. RESULTS: Cell viability in the AD patients was significantly decreased at 72 hrs and 96 hrs, compared with the normal controls. The declining ramp of the proliferation activity from 48 hrs to 72 hrs after PHA stimulation was significantly related to cell viability at 72 hrs and at 96 hrs in the AD patients. CONCLUSION: Lymphocytes from patients with AD have altered viability and proliferation characteristics in culture following PHA stimulation. These findings suggest that lymphocytes may be used as a peripheral tissue model of cell cycle dysregulation in AD.

Factor Structure of the Neurocognitive Tests: An Application of the Confirmative Factor Analysis in Stabilized Schizophrenia Patients

The purpose of the present study was to identify the factor structure of neurocognitive tests used on schizophrenia patients by using the confirmative factor analysis, and to assess the factor score differences of schizophrenia patients and healthy controls. Comprehensive neurocognitive tests were administered to stabilized schizophrenia patients (N=114) and healthy controls (N=120). In the results of factor analyses on patients, the multifactorial-6-factor model, which included the speed of processing, working memory, verbal learning and memory, visual learning and memory, attention/vigilance, and reasoning/problem solving as suggested by the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS), showed the better goodness of fit than any of the other models tested. And assessing the group differences of factor scores, we found the patients performed worse than the controls in all factors, but the result showed meaningful variations of impairments across the cognitive factors. Our study identifies the six major domains with multifactorial structure of cognitive abilities in schizophrenia patients and confirms the distinctive impairment patterns of each cognitive domain. These results may have utility in better understanding the pathology of schizophrenia as well as in genetic studies.

Association between Painful Physical Symptoms and Clinical Outcomes in Korean Patients with Major Depressive Disorder: A Three-Month Observational Study

OBJECTIVE: This paper aims to examine the association between painful physical symptoms (PPS) and major depressive disorder (MDD) in a naturalistic clinical practice setting within a Korean population. METHODS: Patients with acute MDD that joined a multicountry, observational, three-month study in six Asian countries and regions were classified as PPS+ (mean score > or =2) and PPS- (mean score <2) using the modified Somatic Symptom Inventory. In this analysis, we report the results from the Korean subset, where depression severity was assessed using the Clinical Global Impression of Severity (CGI-S) scale and 17-item Hamilton Depression Rating Scale (HAMD(17)). Pain severity was measured using a visual analogue scale (VAS), while the EuroQoL (EQ-5D) assessed patient well-being. RESULTS: Of 198 patients, 45.96% (91/198) of patients were classified as PPS+, of which 78.02% (71/91) were women. PPS+ patients had significantly more severe depression at baseline {CGI-S score, mean [standard deviation (SD)], PPS+: 5.09 [0.79]; PPS-: 4.63 [0.76]; p<0.001; HAMD(17) total score, mean [SD], PPS+: 24.34 [5.24]; PPS-: 20.76 [5.12]; p<0.001} and poorer quality of life [EQ-5D overall health state, mean (SD), PPS+: 39.37 (20.52); PPS-: 51.27 [20.78]; p<0.001] than PPS- patients. Both groups improved significantly (p<0.001) in depression and pain severity outcomes, as well as quality of life by endpoint, but no significant within-group baseline-to-endpoint change wase observed. CONCLUSION: The frequency of PPS was common in Korean patients with MDD, and was associated with more severe depression, poorer quality of life, and a trend towards poorer clinical outcome.

Association between Painful Physical Symptoms and Clinical Outcomes in Korean Patients with Major Depressive Disorder: A Three-Month Observational Study

OBJECTIVE: This paper aims to examine the association between painful physical symptoms (PPS) and major depressive disorder (MDD) in a naturalistic clinical practice setting within a Korean population. METHODS: Patients with acute MDD that joined a multicountry, observational, three-month study in six Asian countries and regions were classified as PPS+ (mean score > or =2) and PPS- (mean score <2) using the modified Somatic Symptom Inventory. In this analysis, we report the results from the Korean subset, where depression severity was assessed using the Clinical Global Impression of Severity (CGI-S) scale and 17-item Hamilton Depression Rating Scale (HAMD(17)). Pain severity was measured using a visual analogue scale (VAS), while the EuroQoL (EQ-5D) assessed patient well-being. RESULTS: Of 198 patients, 45.96% (91/198) of patients were classified as PPS+, of which 78.02% (71/91) were women. PPS+ patients had significantly more severe depression at baseline {CGI-S score, mean [standard deviation (SD)], PPS+: 5.09 [0.79]; PPS-: 4.63 [0.76]; p<0.001; HAMD(17) total score, mean [SD], PPS+: 24.34 [5.24]; PPS-: 20.76 [5.12]; p<0.001} and poorer quality of life [EQ-5D overall health state, mean (SD), PPS+: 39.37 (20.52); PPS-: 51.27 [20.78]; p<0.001] than PPS- patients. Both groups improved significantly (p<0.001) in depression and pain severity outcomes, as well as quality of life by endpoint, but no significant within-group baseline-to-endpoint change wase observed. CONCLUSION: The frequency of PPS was common in Korean patients with MDD, and was associated with more severe depression, poorer quality of life, and a trend towards poorer clinical outcome.

Association of Genetic Variations within 5' end of Neuregulin 1 with Schizophrenia in Korean Population / 신경정신의학

OBJECTIVES: The authors recently found a suggestive evidence of linkage of chromosome 8p21-12 to schizophrenia in Korean multiplex families. Neuregulin 1 (NRG1) was identified in this locus as a positional and functional candidate gene for schizophrenia, through several independent studies with European and Chinese populations. The purpose of this study is to determine whether NRG1 is associated with schizophrenia in Korean population. METHODS: Three SNPs (SNP8NRG221533, SNP8NRG241930, SNP8NRG243177) and two microsatellites markers (478B14-848, 420M9-1395) located at the 5' end of NRG1 were genotyped for 242 unrelated schizophrenia patients and the same number of normal controls. Genetic association was tested by chi2-test (df=1). Not only for the whole patients group but also for a subgroup of patients with auditory hallucination. This subtype showed stronger linkage with chromosome 8p12 in the prior study of the authors with multiplex families. RESULTS: G allele of SNP8NRG241930 was significantly in excess in the subgroup of patients with auditory hallucination compared to the control group (p=0.03, OR=1.76). We also found that 3 SNPs haplotype TTC (p=0.04, OR=0.58) and five markers haplotype TTC53 (p=0.01, OR=0.49) were associated with schziophrenia with a protective effect. Three SNPs haplotype CGT which is a part of the at-risk haplotype of the Icelandic schizophrenia families was found in excess in the patients group but no significant association was observed. CONCLUSION: NRG1 might either play a role in the predisposition to schizophrenia or be in linkage disequilibrium with a causal locus of this illness.

Fever Associated with Clozapine Administration: Incidence, Clinical Characteristics, and Related Factors / 대한정신약물학회지

OBJECTIVE: This study aims at investigating the incidence, clinical nature and associated clinical characteristics of the clozapine-induced fever. METHODS: Retrospective review of hospital records was performed for 56 inpatients who had started to take clozapine and stayed at the hospital for four or more weeks after the initiation of clozapine treatment. RESULTS AND CONCLUSION: Clozapine-induced fever was developed in 31% of the patients. The mean peak temperature was 39degrees C and the mean duration of the fever was 3 days. Fever was developed average of 11 days after the initiation of clozapine treatment. All the patients were recovered without discontinuation of clozapine. Demographic variables, the clinical response to clozapine, other drugs administered with clozapine, and the presence of other adverse effects of clozapine were not associated with the clozapine-induced fever.

Polymorphisms and Serotonin Dopamine Antagonist-Induced Weight Gain in Patients with Schizophrenia / 대한정신약물학회지

OBJECTIVE: Several lines of pharmacological evidences including the data of animal studies indicate that serotonin 2C receptor (5HT2C) is involved in the pharmacodynamic process of serotonin dopamine antagonists (SDA)-induced weight gain. Controversial data have been reported on the association between the polymorphisms of 5HT2C receptor gene and antipsychotics-induced weight gain. This study aims at investigating the association between the polymorphisms of 5HT2C receptor gene and SDA-induced weight gain in korean schizophrenic patients. METHODS: Seventy-seven schizophrenia patients in their first episode or patients who did not take any antipsychotics for the previous two months were recruited. All the patients were administered with one of the SDAs (risperidone, olanzapine, quetiapine, clozapine) for 8weeks. Body mass index (BMI) were measured weekly during the 8weeks. The subjects were genotyped for the -759 C/T and -697 G/C polymorphism of the 5HT2C receptor gene. RESULTS: The degree of linkage disequilibrium between the two polymorphic loci genotyped are almost 100%. Significant association was not observed between polymorphisms of the 5HT2C receptor gene (-759 C/T and -697 G/C) and SDA-induced weight gain after 8 weeks of treatment. CONCLUSION: Our data do not support the involvement of the polymorphisms of 5HT2C receptor gene (-759 C/T and -697 G/C) in SDA- induced weight gain. Further studies with sufficient sample size are warranted to follow up on the trend of high weight gain in the male patients having -759 T (-697 C) allele.

Genetic Association between Single Nucleotide Polymorphisms on COMT Gene and Schizophrenia in Korean Population / 대한정신약물학회지

OBJECTIVE: This study aimed to explore genetic relation between schizophrenia and COMT gene which plays an important role in metabolizing dopamine, one of the most intriguing neuro-transmitters for schizophrenia. METHODS: 1) Single Nucleotide Polymorphism (SNP) on exons of COMT gene was searched by F-CSGE (Fluorescent-Conformation Sensitive Gel Electrophoresis) method with 50 patients with schizophrenia to look for any SNP unique to Korean patients with schizophrenia. 2) Genotyping was done for five SNPs on COMT gene for 218 patients with schizophrenia and 199 normal controls by SNaPShot method. Allele frequencies, genotype frequencies and simulated haplotype frequencies were compared between patients with schizophrenia and normal controls. RESULTS: 1) No unique SNPs for Koreans was found on exons of COMT gene and seven SNPs were found, all of them are already reported to be found in other ethnic groups. 2) No significant difference between patients with schizophrenia and normal controls in terms of allele frequencies, genotype frequencies and haplotype frequencies was found in our sample. CONCLUSION: Genetic association between five SNPs on COMT gene and DSM-IV diagnosis of schizophrenia among Koreans was not able to be found in this study.

Subjective Quality of Life in Schizophrenic Patients Receiving Atypical Antipsychotics: Relationship to Psychopathology, Adverse Drug Effects and Subjective Response to Drug / 신경정신의학

OBJECTIVES: The purpose of this study was to evaluate the characteristics of psychopathology, adverse drug effects, and subjective response to drugs that have a significant impact on the subjective quality of life in schizophrenic patients receiving atypical antipsychotics. METHODS: One hundred and one schizophrenic patients, who were receiving maintenance treatment with atypical antipsychotics, were evaluated. Subjective quality of life was assessed using the standardized Korean modification of a self-rating scale to measure subjective well-being under neuroleptics (KmSWN). Patients' psychopathology was evaluated using the Positive and Negative Syndrome Scale. Adverse effects and subjective response to drug were evaluated using the Liverpool University Neuroleptic Side Effect Rating Scale and the Drug Attitude Inventory-10, respectively. Correlation analysis and stepwise multiple regression analysis were conducted. RESULTS: In psychopathology, the severity of depression and anxiety showed the most significant correlation with the score of KmSWN. In adverse drug effects, the severity of psychic side effect and extrapyramidal side effect showed the most significant correlation with the score of KmSWN. Regarding subjective response to drug, significant correlation was observed between the severity of subjective negative response and the score of KmSWN. Stepwise multiple regression analysis revealed that psychic side effect, extrapyramidal side effect, and depression contributed significantly to the total score of KmSWN. These variables accounted for 59.7% of the total variance. CONCLUSION: The results of the present study suggest that psychic side effect, extrapyramidal side effect and depressive symptom are the clinical characteristics that are significantly associated with the subjective quality of life. An effective management strategy for these variables should be established in developing a treatment program to enhance the quality of life of patients with schizophrenia.

Search of Altered Gene Expression after Chronic Administration of Olanzapine in the Rat Frontal Cortex using cDNA Microarray / 대한정신약물학회지

OBJECTIVE: cDNA microarray is a convenient molecular technology that enables to search for gene expression in large scale. To explore the effect of antipsychotics on the gene expression in the brain, we applied cDNA microarray and searched for differentially expressed genes in the olanzapine-treated rat frontal cortex. METHODS: We administered olanzapine (4 mg/kg/day, IP) to S-D rats for 14days, and dissected the frontal cortex to examine. We analyzed altered gene expression from microarray, and screened up- or down-regulated genes. Their changes were confirmed by RT-PCR. RESULTS: Three down-regulated and one up-regulated genes were screened by triplicate cDNA microarray analysis. Among them, translocase of the inner mitochondrial membrane 23 (TIM23) was confirmed in RT-PCR. The expression of TIM23 mRNA was significantly increased in olanzapine-treated rat frontal cortex. CONCLUSION: This is the first report of up-regulated gene expression of TIM23 by antipsychotics in the rat brain. TIM23 is the essential component of mitochondrial biogenesis. From this result, we suggest that antipsychotic effect may be related to the improvement of mitochondrial dysfunction in the brain.

Minor Physical Anomalies in Patients with Schizophrenia

OBJECT AND METHOD: Minor physical anomalies(MPAs) are frequently seen in patients with schizophrenia. MPAs are considered to arise from the anomalous development of ectoderm-originated tissues in the developing fetus. Since the central nervous system originates from ectoderm, MPAs can be regarded as externally observable and objective indicators of the aberrant development which might have taken place in the central nervous system. To investigate whether MPAs are more frequent in schizophrenic patients, the frequencies of MPAs were compared between schizophrenic patients and normal controls. Total 245 schizophrenic patients diagnosed with DSM-IV(male : 158, female : 87), and 418 normal control subjects(male : 216, female : 202) were included in this study. The MPAs were measured using the modified Waldrop scale with fifteen items in six bodily regions; head, eye, ear, mouth, hand, and foot. RESULT: The total scores of Waldrop scale were 4.40+/-1.93(mean+/-standard deviation) in patients and 3.43+/- 1.68 in controls for females, and for males, 4.58+/-1.75 in patients and 4.28+/-1.59 in controls. For females, the excess of MPAs in schizophrenic patients was statistically significant(t-test : p<0.001). For males, schizophrenic patients also showed more MPAs than normal controls, but this tendency did not reach statistical significance (t-test : p=0.094). When the modified Waldrop total scores excluding head circumference were compared, the total scores in schizophrenic patients were significantly higher for both male and female subjects(t-test : male p<0.001, female p=0.001). The individual anomaly items included in Waldrop scale were also investigated. The items of epicanthus, hypertelorism, malformed ears, syndactylia were significantly more frequent in schizophrenic patients. In contrast, the items of adherent ear lobes, asymmetric ears, furrowed tongue, curved fifth finger, single palmar crease and big gap between toes did not show any differences in frequency between schizophrenic patients and normal controls. Since a lot of statistical analyses showed different results between male and female subjects, it seems to be necessary to consider gender as an important controlling variable for the analysis, however only the item of head circumference showed statistically significant gender-related difference according to log-linear analysis. CONCLUSION: With a relatively large sample size, the frequencies of MPAs enlisted in Waldrop scale were compared between schizophrenic patients and normal controls in this study. MPAs were more frequently seen in schizophrenic patients and, especially, several specific items in the Waldrop scale showed prominent excess in schizophrenic patients. Although definite conclusions cannot be drawn due to the inherent limitation of the study using Waldrop scale, these results seem to support the possibility that aberrant neurodevelopmental process might be involved in the pathogenesis of schizophrenia in some of the patients.

Phosphorylation of glycogen synthase kinase-3beta at serine-9 by phospholipase Cgamma1 through protein kinase C in rat 3Y1 fibroblasts

Phospholipase Cgamma1 (PLCgamma1) plays an important role in controlling cellular proliferation and differentiation. PLCgamma1 is overexpressed in some tumors, and its overexpression induces solid tumors in nude mice. However, the regulatory mechanisms underlying PLCgamma1-induced cell proliferation are not fully understood. Here we show that overexpression of PLCgamma1 highly phosphorylated glycogen synthase kinase-3beta (GSK-3beta) at serine-9 in 3Y1 fibroblasts. Inhibition of protein kinase C (PKC)s with GF109203X abrogated GSK-3beta phosphorylation by PLCgamma1. We also found that steady-state level of cyclin D1 protein, but not cyclin D1 mRNA, was highly elevated in response to serum stimulation in PLCgamma1-transfected cells as compared with vector-transfected cells. Since GSK-3beta is involved in cyclin D1 proteolysis in response to mitogenic stimulation, PLCgamma1-mediated GSK-3beta phosphorylation may function as a regulation of cyclin D1 accumulation in PLCgamma1-overexpressing cells.

Nonlinear Analysis of Electroencephalogram during the Course of Electroconvulsive Therapy: A Single Case Study / 신경정신의학

OBJECTIVES: In order to search for new parameters for the evaluation of the adequacy of electroconvulsive therapy (ECT) the authors performed a non-linear analysis of electroencepha-logram(EEG)recorded during the course of electroconvulsive therapy(ECT)in a single female patient with depression. METHODS: Digitized EEG recordings from two ECT sessions spaced one week were analyzed at five different stages; pretreatment stable, postanesthetic-preictal, ictal, postictal suppression and posttreatment stable stages. RESULTS: Our analysis showed that 1)EEG signals had low dimensional (below 10 dimensions) deterministic characteristics 2) although EEG was nonstationary signal, non-linear parameters could reliably differentiate between various stages we examined. 3)the deterministic property of ictal EEG increased according to the progression of sessions and 4)the primary Lyapunov exponent(PLE)and correlation dimension of pre- and post-treatment stable stage EEG increased according to the progression of sessions. CONCLUSION: In this single case study, results of various non-linear analyses suggested that non-linear variables extracted from EEG recordings during ECT may have utilities as tools for the quantitative evaluation of ECT.

A Study of Obstetric Complications and Minor Physical Anomalies in Sibling and Sporadic Schizophrenics / 신경정신의학

The authors hypothesized that sporadic schziophrenic patients had more chances of receiving environmental insults during the fetal neural development compared with familial schizophrenics. We tested our hypothesis by comparing obstetric complications(OCs), minor physical anomalies(MPAs) and other clinical features, and examining the correlation between OCs and MPAs in schziophrenic patients who had one or more sibling with schizophrenia(sibling group) and sporadic schizophrenics(sporadic group) and normal controls. OCs were evaluated by the scale of Lewis, and MPAs were measured by the Waldrop scale. There were no significant differences in OCs and MPAs between schizophrenic and control groups. Sporadic group had significantly higher fetal distress, total Waldrop score and Waldrop score for mouth than sibling group. And there was a tendency that the number of subjects having the Waldrop score over 4 points was greater in the sporadic group. No significant correlation was observed between OCs and MPAs. The scores of initial psychopathology and post-treatment functioning were much higher in the sporadic group, but the other clinical features showed no differences. Although male patients had more OCs than female patients in sibling group, no sex differences were observed as a whole. Our results suggest that, if the methodological weakness were complemented, OCs and MPAs would be useful tools in the search for the cause of schizophrenia.

Effect of Clonazepam in the Chronic Schizophrenics with Treatment-Refractory Hallucinations: A Preliminary Report / 대한정신약물학회지

OBJECTIVES: Many chronic schizophrenics are suffered from treatment-refractory hallucinations. As a countermeasure, the combined use of neuroleptics and benzodiazepines has been studied. In this context, the authors tried to evaluate the anti-hallucinatory effect of neuroleptics-clonazepam combination therapy. METHODS: At first, the authors described 3 cases of chronic schizophrenics who reported alleviation of hallucinations, which are resistant to neuroleptic treatment, after adding clonazepam. And then, prospective open study including 6 female chronic schizophrenic inpatients having neuroleptic-refractory hallucinations was done. In addition to existing psychiatric medication, these patients were treated with clonazepam 1.5 mg for 6weeks and evaluated at 5 points ; at baseline, and 1, 2, 4 and 6 weeks of treatment. The psychopathology was assessed by the items of hallucinatory behavior and anxiety/tension of PANSS and BPRS. Clinical improvement was defined by fall-off of the hallucinatory behavior below the moderate level. The side effects were assessed by UKU Side Effect Rating Scale. RESULTS: All patients completed 6 weeks' trial. At the end of 6 weeks, 2 (33.3%) of 6 patients showed decrement of the hallucinatory behavior below the moderate level, when evaluated by PANSS and BPRS. However, the courses of anti-hallucinatory effect were different in these 2 patients. Another one patient showed that the hallucinatory behavior assessed by BPRS fell to the moderate level, but not when assessed by PANSS. The item of anxiety/tension was unchanged in all 6 patients. Except very mild sedation in one patient, there was no side effect. CONCLUSION: This study suggests that neuroleptics-clonazepam combination therapy is effective against treatment-refractory hallucinations in some schizophrenics and generally safe.