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ABSTRACT: Morningness/eveningness (M/E) is a stable characteristic of individuals. Circadian rhythms are altered in episodes of mood disorder. Mood disorder patients were more evening-type than normal population. In this study, we compared the characteristics of M/E among the 257 patients with bipolar I disorder (BPD1), bipolar II disorder (BPD2) and major depressive disorder, recurrent (MDDR).
M/E was evaluated using the Korean version of the composite scale of morningness (CS). Factor analysis was done to extract specific elements of circadian rhythm (morning preference, morning alertness, and evening tiredness). The total score and scores for factors and individual items of CS were compared in order to evaluate differences among the three different diagnostic groups. Factor scores of CS were different among the diagnostic groups.
BPD1 subjects had a higher score for evening tiredness than BPD2 subjects (p=0.060), and BPD1 subjects had a significantly higher score for morning alertness than subjects with MDDR (p=0.034). This difference was even more profound for the representative item scores of each factor; item 2 of CS for evening tiredness (BPD1>BPD2, p=0.007) and item 5 of CS for morning alertness (BPD1>MDDR, p=0.002). Total score of CS were not different among 3 diagnostic groups.
Circadian rhythm characteristics measured by CS were different among BPD1, BPD2, and MDDR. BPD2 showed more eveningness than BPD1. MDDR showed less morningness than BPD1. CS would be a reasonable endophenotype associated with mood disorders. More studies with large sample size of mood disorders on M/E are warranted.
Clinical Psychopharmacology and Neuroscience 08/2012; 10(2):110-6.
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ABSTRACT: To compare the effectiveness of amisulpride in acute (up to 8 weeks) and maintenance (week 8 to 12 months) phases of a 12-month course of treatment in a heterogeneous group of patients with schizophrenia.
We conducted a 12-month, open-label clinical trial with flexible doses of amisulpride among 129 Korean patients with schizophrenia. The Positive and Negative Symptom Scale (PANSS) and several other scales measuring efficacy and tolerability were analyzed during the acute and maintenance phases.
The completion rates were 78.3% by week 8 and 55.8% by month 12. Total PANSS scores and scores on the negative-symptom and general-symptom subscales improved significantly during both acute and maintenance periods, but scores on the positive-symptom subscale improved only during the acute phase. Improvement during both treatment phases was significant in all other scales except for the Drug Attitude Inventory. The negative-symptom and mixed-symptom groups showed significant improvement in the PANSS negative subscale, the Clinical Global Impression scale, and the Global Assessment of Functioning during the maintenance period. Hyperprolactinemia and related events were commonly reported.
This study demonstrated the significant effectiveness and a good safety profile of amisulpride for treating acute and 12-month phases of schizophrenia under natural conditions.
Human Psychopharmacology Clinical and Experimental 12/2011; 26(8):568-77. · 2.48 Impact Factor
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ABSTRACT: The dual-specificity phosphatase 6 (DUSP6) gene resides at chromosome location 12q22-23, which is one of the candidate loci for susceptibility to bipolar disorder and which encodes a phosphatase selective for extracellular signal-regulated kinase (ERK). Previously, we reported a positive association between the functional Leu114Val polymorphism (rs2279574) in DUSP6 and bipolar disorder. Given that the association between DUSP6 and the reported down-regulation of DUSP6 transcript in bipolar postmortem brains were sex-dimorphic, showing significance in women but not men, we performed two independent analyses in homogenous samples of male and female Korean patients with bipolar disorder or schizophrenia using samples enlarged from our previous report. Among the examined DUSP6 SNPs, five (rs769700, rs704076, rs770087, rs808820, and rs2279574) showed positive allelic associations, with the frequency of minor alleles (C, T, G, G, and G) in each SNP significantly increased in women with BD. Consequently, the "C-T-G-G-G" haplotype was significantly over-represented (P=0.016; OR=3.242), whereas the "T-G-T-A-T" haplotype was significantly under-represented (P=0.014; OR=0.697). We found no significant associations with DUSP6 SNPs in men with bipolar disorder or schizophrenia. We also investigated the functions of the functional SNPs' positive associations and found that Leu114Val (rs2279574; T/G) and Ser144Ala (rs770087; T/G) mutations in DUSP6 proteins reduced lithium-induced ERK1/2 phosphorylation in vitro, implicating the dominant active functions. Thus, DUSP6 may not only play important roles in the pathogenesis of bipolar disorder, particularly in women, but also affect the therapeutic response to lithium through modulating lithium's effects on intracellular signaling.
Progress in Neuro-Psychopharmacology and Biological Psychiatry 12/2011; 37(1):41-9. · 3.25 Impact Factor
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ABSTRACT: The early growth response gene 2 (EGR2) is located at chromosome 10q21, one of the susceptibility loci in bipolar disorder (BD). EGR2 is involved in cognitive function, myelination, and signal transduction related to neuregulin-ErbB receptor, Bcl-2 family proteins, and brain-derived neurotrophic factor. This study investigated the genetic association of the EGR2 gene with BD and schizophrenia (SPR) in Korea. In 946 subjects (350 healthy controls, 352 patients with BD, and 244 with SPR), nine single nucleotide polymorphisms (SNPs) in the EGR2 gene region were genotyped. Five SNPs showed nominally significant allelic associations with BD (rs2295814, rs61865882, rs10995315, rs2297488, and rs2297489), and the positive associations of all except rs2297488 remained significant after multiple testing correction. Linkage disequilibrium structure analysis revealed two haplotype blocks. Among the common identified haplotypes (frequency > 5%), 'T-G-A-C-T (block 1)' and 'A-A-G-C (block 2)' haplotypes were over-represented, while 'C-G-G-T-T (block 1)' haplotype was under-represented in BD. In contrast, no significant associations were found with SPR. Although an extended analysis with a larger sample size or independent replication is required, these findings suggest a genetic association of EGR2 with BD. Combined with a plausible biological function of EGR2, the EGR2 gene is a possible susceptibility gene in BD.
Experimental and Molecular Medicine 11/2011; 44(2):121-9. · 2.48 Impact Factor
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ABSTRACT: 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.
Journal of Korean medical science 10/2011; 26(10):1356-63. · 0.84 Impact Factor
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ABSTRACT: A significant overlap between childhood mood disorders and many aspects of attention deficit hyperactivity disorder (ADHD) has been established. High rates of co-occurrence, familial aggregation, and more severe clinical manifestations of the illnesses when they are comorbid suggest that common genetic and environmental factors may contribute to the development of both disorders. Research on the co-occurrence of childhood ADHD and mood disorders in childhood has been conducted. We retrospectively investigated childhood ADHD features in adults with mood disorders. Childhood ADHD features were measured with the Korean version of the Wender Utah Rating Scale (WURS). The sample consisted of 1305 subjects: 108 subjects were diagnosed with bipolar disorder type I, 41 with bipolar disorder type II, 101 with major depressive disorder, and 1055 served as normal controls. We compared total WURS scores as well as scores on 3 factors (impulsivity, inattention, and mood instability and anxiety) among the 4 different diagnostic groups. The 4 groups differed significantly from one another on all scores. The group with bipolar disorder type II obtained the highest total scores on the WURS. The impulsivity and inattention associated with childhood ADHD were more significantly related to bipolar disorder type II than with bipolar disorder type I. The mood instability and anxiety associated with childhood ADHD seem to be significantly related to major depressive disorder in adulthood. In conclusion, multifactorial childhood ADHD features were associated with mood disorders of adulthood.
Comprehensive psychiatry 06/2011; 53(3):217-23. · 2.08 Impact Factor
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Kyu Young Lee,
Eun-Jeong Joo,
Yong Ick Ji,
Duk-Hwan Kim,
Joo Bae Park,
In-Won Chung,
Sang Ick Lee,
Yeon Ho Joo,
Yong Min Ahn,
Joo Yun Song,
Yong Sik Kim
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ABSTRACT: The dysregulation of the dopaminergic system has been implicated in the pathophysiology of major psychosis, including schizophrenia, with dopamine receptor genes (DRDs) presently targeted as the most promising candidate genes. We investigated DRD1-5 for association with schizophrenia using a multi-stage approach in a Korean sample. One hundred forty-two SNPs in DRD1-5 were selected from the dbSNP, and the associations of each SNP were then screened and typed by MALDI-TOF mass spectrometry using pooled DNA samples from 150 patients with major psychosis and 150 controls. Each of the suggested SNPs was then genotyped and tested for an association within the individual samples comprising each pool. Finally, the positively associated SNPs were genotyped in an extended sample of 270 patients with schizophrenia and 350 controls. Among the 142 SNPs, 88 (62%) SNPs in our Korean population were polymorphic. At the pooling stage, 10 SNPs (DRD1: 2, DRD2: 3, and DRD4: 5) were identified (P<0.05). SNPs rs1799914 of DRD1 (P=0.046) and rs752306 of DRD4 (P=0.017) had significantly different allele frequencies in the individually genotyped samples comprising the pool. In the final stage, with the extended sample, the suggestive association of DRD4 with rs752306 was lost, but the association of DRD1 with rs1799914 gained greater significance (P=0.017). In these large-scale multi-stage analyses, we were able to find a possible association between DRD1 and schizophrenia. These findings suggested the potential contribution of a multi-step strategy for finding genes related to schizophrenia.
Experimental and Molecular Medicine 01/2011; 43(1):44-52. · 2.48 Impact Factor
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ABSTRACT: Early growth response (EGR) genes play critical roles in signal transduction in the brain, which is involved in neuronal activation, brain development, and synaptic plasticity. EGR genes, including EGR2, EGR3, and EGR4, showed significant association with schizophrenia in Japanese schizophrenic pedigrees. In particular, EGR3, which resides at the chromosomal location 8p21.3, was suggested to be a potential susceptibility gene in schizophrenia based on a study of Japanese cases. However, this requires further replication with an independent sample set. We investigated the association of the EGR3 and EGR2 genes, which were suggested as potential susceptibility genes for schizophrenia supported by both genetic association and postmortem brain expression studies, with schizophrenia in Korean patients. Along with 350 healthy individuals, 244 schizophrenic patients were analyzed. Among the four examined single-nucleotide polymorphisms (SNPs) of EGR3 (rs1008949, rs7009708, rs35201266, and rs3750192), SNP rs35201266 in intron 1 of the EGR3 gene showed a significant association with schizophrenia (P = 0.0008, χ(2) = 11.156, OR = 1.493), which withstands multiple testing correction. In addition, the "T-G-C-G" haplotype of EGR3 was under-represented in the patients with schizophrenia (P = 0.0073, χ(2) = 7.188, OR = 0.697). However, an association between the SNPs of EGR2 (rs2295814 and rs2297488) and schizophrenia was not found. These findings are consistent with the previous genetic association of the EGR3 gene in Japanese cohorts, which is the first replication concerning the association of EGR3 with schizophrenia in an independent cohort. Taken together, EGR3 could be suggested as a compelling susceptibility gene in schizophrenia.
American Journal of Medical Genetics Part B Neuropsychiatric Genetics 10/2010; 153B(7):1355-60. · 3.70 Impact Factor
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ABSTRACT: Genes associated with circadian rhythms have been suggested to play an important role in the pathophysiology of bipolar disorder. A single nucleotide polymorphism (SNP) in the 3'-flanking region of CLOCK (3111T/C; rs1801260) has been reported to be associated with sleep disturbances and an increased recurrence rate in patients with bipolar disorder. We examined the association of CLOCK 3111T/C with bipolar disorder in 260 patients and 350 controls in a Korean population. CLOCK 3111T/C showed significant allelic and genotypic associations with bipolar disorder (P=0.012, P=0.033, respectively). Morningness/eveningness (M/E) was evaluated using the Composite Scale of Morningness (CSM) in 108 patients with bipolar disorder. In the subgroup analysis of the highest and lowest 25th percentile of M/E scores, significantly more C allele carriers were found among extreme evening types than among extreme morning types (P=0.041). After correcting for age, C allele carriers had lower M/E scores than those carrying the T/T genotype, but the association was not statistically significant. We also analyzed the association between age at onset (AAO) and CLOCK 3111T/C in the bipolar disorder group, and no association was found. Despite the relatively small sample sizes, these results support a possible role of the CLOCK 3111T/C SNP in bipolar disorder. Further studies with larger samples and more polymorphisms are necessary.
Progress in Neuro-Psychopharmacology and Biological Psychiatry 10/2010; 34(7):1196-201. · 3.25 Impact Factor
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ABSTRACT: CHRNA7 has been shown to be a strong candidate gene for schizophrenia and bipolar disorder. It is located on chromosome 15q13-q14, which is one of the replicated linkage spots for schizophrenia and bipolar disorder.
We conducted an association study to determine whether previous positive association is replicable in the Korean population. We included 254 patients with schizophrenia, 193 patients with bipolar disorder type I, 38 patients with bipolar disorder type II, 64 schizoaffective disorder patients, and 349 controls. All subjects were ethnically Korean. A total of 898 subjects were included, and genotyping was done for three single nucleotide polymorphisms (SNPs) of CHRNA7. These three intronic SNPs were rs2337506 (A/G), rs6494223 (C/T), and rs12916879 (A/G).
There was only one marginally significant association; this association was between rs12916879 and bipolar disorder type I in the male subgroup. In both the allele and genotype distributions, we found a weak signal (Chi-squared=3.57, df=1, p=0.06 for allele, Chi-squared=7.50, df=2, p=0.02 for genotype) only. Unphased haplotype analysis could not provide additional support for this finding. No SNP was associated with schizophrenia or any other affected groups in this Korean sample. The associative finding is marginal and inconclusive.
We could not replicate positive association in other ethnic groups previously studied. This suggests possible heterogeneity in the genes associated with schizophrenia and bipolar disorders. Because of structural complexity of the CHRNA7 gene and the limited statistical power of this study, further genetic studies with more SNPs and larger samples covering various populations, along with more fine molecular exploration of the CHRNA7 gene structure, are required.
Psychiatry investigation 09/2010; 7(3):196-201. · 0.99 Impact Factor
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ABSTRACT: The percentage of successive normal cardiac interbeat intervals greater than 50 msec (pNN50) is a widely used heart rate variability measure, which is useful in identifying the neuroautonomic dysfunction of psychiatric disorders. However, pNN50 is only one member of a larger family of pNNx statistics, where x is greater than 0 msec. The potential application of the general pNNx statistics has not yet been explored in the psychiatric field. The authors examined the pNNx statistics in clozapine-treated subjects and normal controls to evaluate the usefulness of the general pNNx statistics.
Sixty-one schizophrenic patients treated with clozapine and fifty-nine normal controls were evaluated. Probability values for the differences between the groups at each pNN value (range: pNN1-pNN100) were calculated using data obtained from a 30-minute electrocardiogram.
The conventional pNN50 and pNNx values with x<50 msec were all significantly lower in the patient group (p<0.05). The distinction between the two groups was more prominent at pNN values less than 50 msec than that observed at pNN50. The maximum separation between groups occurred at pNN5 (68.2+/-19.1 vs. 22.5+/-20.5, p<10(-22)).
The pNNx with x<50 msec provided more robust discrimination between the groups than the conventional pNN50, suggesting the importance of analyzing very small variations of interbeat interval in discriminating normal and pathological heart rate patterns. The results also suggest that the general pNNx statistics may be applied and useful in evaluating the neuroautonomic dysfunction in patients treated with clozapine, complementing the traditionally computed pNN50 value.
Psychiatry investigation 12/2009; 6(4):294-8. · 0.99 Impact Factor
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Kyu Young Lee,
Eun-Jeong Joo,
Seong Hoon Jeong,
Ung Gu Kang,
Myoung-Sun Roh,
Se Hyun Kim,
Joo Yun Song,
Jae Yeon Hwang,
Su-Gyeong Kim,
Namyoung Lee,
Yong Min Ahn,
Yong Sik Kim
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ABSTRACT: V-akt murine thymoma viral oncogene homolog 1 (AKT1) has been suggested to be involved in the pathophysiology of schizophrenia. Recent, independent studies in Caucasian, Japanese, Iranian, and Chinese populations have reported that the AKT1 gene may be associated with schizophrenia, but these results have yet to be replicated in other populations. In the present study, we performed a case-control association study between AKT1 and schizophrenia in a Korean population. We genotyped six single nucleotide polymorphisms (SNP1 (rs3803300), SNP2 (rs1130214), SNP3 (rs3730358), SNP4 (rs1130233), SNP5 (rs2494732), SNP A (rs2498804)) of AKT1, selected from previous reports, in a sample of 283 subjects with schizophrenia and 350 controls. No significant difference in single marker polymorphisms or haplotype frequencies of the six SNPs in the AKT1 gene was observed between controls and subjects with schizophrenia. In addition, we carried out an updated meta-analysis of the six SNPs, and found no evidence for an association between the six SNPs and schizophrenia. Taken together, our results do not support the hypothesis that AKT1 is a susceptibility gene for schizophrenia.
Neuroscience Research 11/2009; 66(3):238-45. · 2.25 Impact Factor
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ABSTRACT: Due to its pleomorphic phenomenology, the clinical features of bipolar depression are difficult to assess. The objective of the present study was therefore to explore the internal structure of the Bipolar Depression Rating Scale (BDRS) in terms of the phenomenological characteristics of bipolar depression.
Sixty patients with DSM-IV bipolar depression completed the BDRS, depression and excitement subscales of the Positive and Negative Syndrome Scale (PANSS-D and PANSS-E), 17-item Hamilton Depression Rating Scale, Montgomery-Asberg Depression Rating Scale, Young Mania Rating Scale (YMRS), and the Drug-Induced Extrapyramidal Symptoms Scale. The internal structure of the BDRS was explored through hierarchical cluster analysis (HCA) using Ward's method and multidimensional scaling (MDS).
From 20-item BDRS data, the HCA yielded two symptom clusters. The first cluster included 12 items of conventional depressive symptoms. The second cluster included eight items of mixed symptoms. The MDS identified a depressive-mixed dimension. The depressive symptom cluster showed a more cohesive and conglomerate cluster structure on the MDS map compared to the mixed symptom cluster. After controlling for the effects of treatment-emergent extrapyramidal symptoms, strong positive correlations were observed between the BDRS and other depression rating scales, and the BDRS also weakly correlated with the YMRS and the PANSS-E.
The internal structure of BDRS appears to be sensitive to complex features of bipolar depression. Hence, the BDRS may have an advantage in evaluating clinical changes in patients with bipolar depression within the therapeutic process.
Australian and New Zealand Journal of Psychiatry 10/2009; 43(9):830-7. · 2.93 Impact Factor
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ABSTRACT: This study presents results of a 1-year follow-up investigation of the causal model of insight in schizophrenia using a subsample of acute patients starting or switching to amisulpride included in an earlier study. Our causal model of insight based on the Positive and Negative Syndrome Scale factors, with the positive, negative, and autistic preoccupation factors designated as the primary predictors, and the activation factor as a mediating variable of insight, was examined for fitness at the stabilized stage (8 week) and at the chronic stage (1 year) using the structural equation modeling method. Results showed that the intercorrelations among the factors and regression coefficients toward insight changed in their magnitudes, but the validity of our hypothesized model of insight was still confirmed for both the stages with nearly perfect goodness-of-fitness indices. The fitness of the model was also confirmed for the longitudinal changes in the scores of insight and psychopathology. An alternative model, which included the anxiety/depressive factor as a second mediating variable between insight and the positive and negative factors, was also found to be valid for both the stages. A post-hoc causal model with anxiety/depressive factor showed tentative evidence favoring anxiety/depressive variable predicting insight than the other way around.
International clinical psychopharmacology 08/2009; 24(4):189-98. · 3.35 Impact Factor
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ABSTRACT: We performed a genetic association study with schizophrenic patients to investigate whether the V-akt murine thymoma viral oncogene homolog 1 (AKT1) gene plays a role in obstetric complications.
One-hundred-eighty patients with schizophrenia (male, 113; female, 67) were included. All patients fulfilled DSM-IV criteria for schizophrenia. Obstetric complications were measured by the Lewis scale. Prenatal and perinatal information was retrospectively collected from the patients' mothers. We selected six single nucleotide polymorphisms (SNPs) for the AKT1 gene: SNP1 (rs3803300), SNP2 (rs1130214), SNP3 (rs3730358), SNP4 (rs 1130233), SNP5 (rs2494732), and SNPA (rs2498804). The genotype data were analyzed for an association with the Lewis total score in terms of allele, genotype, and haplotype distribution.
The mean total Lewis scores were 1.30+/-1.61 for males and 1.54+/-1.87 for females. Higher total score tended to be correlated with an earlier age of onset of schizophrenia in females. In the total sample, no SNP was associated with obstetric complications. However, the additional analyses for male and female subgroups found a significant association between SNPA and SNP4 and Lewis score in females (p=0.02 for SNPA, p=0.04 for SNP4). The SNP5-SNPA haplotype showed a positive association with obstetric complications (p=0.03) in the female patient group.
We found an association between SNPs in the AKT1 gene and total Lewis score measuring obstetric complications in female patients with schizophrenia. Because these findings did not survive a correction for multiple testing, the significance should be interpreted carefully and replication studies are required.
Psychiatry investigation 06/2009; 6(2):102-7. · 0.99 Impact Factor
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Yong Min Ahn, Kyu Young Lee,
Chul-Eung Kim,
Jae-Jin Kim,
Dae-Yeob Kang,
Tae-Youn Jun,
Jin Sook Choi,
In-Won Chung,
Se Hyun Kim,
Samuel S-H Hwang,
Yong Sik Kim
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ABSTRACT: We examined short- and long-term changes in neurocognitive functions in patients with schizophrenia who were either started or switched to amisulpride in comparison with the normal controls. Fifty-seven patients treated with amisulpride and 60 normal controls completed a comprehensive neurocognitive function test battery at the baseline, the 8-week, and the 1-year follow-up. We conducted and compared the results of both intention-to-treat (ITT) and per-protocol (PP) analyses to account for the follow-up loss. Three general results obtained were as follows: (1) the degree of the improvements in neurocognitive function was comparable to those of other second-generation antipsychotics in both ITT and PP analysis; (2) in light of the relative effect size, the composite effect size and the effect size in most measures in both ITT and PP analyses were smaller for the patient group than those of the control group, signifying that improvement in performance may be largely attributable to practice effects; and (3) nonetheless, there were evidences of both short- and long-term improvements in some cognitive tasks, such as in the Korean-Wechsler Adult Intelligence Scale vocabulary subtest and the Trail Making Test, that may not be accounted by practice effect. These results suggest the need to include a healthy control group to validate the medication effect of cognitive improvements in patients with schizophrenia and to consider practice effect in interpreting the results of repeated administration of neurocognitive function tests.
Journal of clinical psychopharmacology 05/2009; 29(2):117-23. · 5.09 Impact Factor
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ABSTRACT: We used structural equation modeling to formulate a causal model of insight in schizophrenia patients that explains the inconsistent results of the studies on the relationship between insight and psychopathology. The Positive and Negative Syndrome Scale was used to assess 342 patients with acute stage schizophrenia and 5 factors were identified through factor analysis with which a causal model of insight was constructed. Our model, where positive, negative, and autistic preoccupation (cognitive) factors were the primary predictors of insight with the activation factor mediating between positive and autistic preoccupation factors and insight, was found to show a perfect fit by most goodness-of-fit indices and to be superior to other alternative models. Specifically, positive, negative, and autistic preoccupation factors each had some predictive power for insight and the activation factor played a partial mediating role for the positive factor and a moderating role for the autistic preoccupation factor.
The Journal of nervous and mental disease 03/2009; 197(2):79-84. · 1.77 Impact Factor
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ABSTRACT: Urinary incontinence and enuresis are well-known side effects of clozapine. However, clinical experience has shown that patients also suffer from diverse lower urinary tract symptoms (LUTS). The natural course of clozapine-related LUTS is unclear. Thus, a longitudinal follow-up study is needed. A total of 101 subjects who were taking clozapine initially participated. Their LUTS were evaluated using the International Prostate Symptom Score (IPSS), other questionnaires, and a medical records review. After 2 years, 87 of the original subjects could be contacted, and the status of their LUTS was re-evaluated. The average IPSS total was 7.4 +/- 5.9 at the initial evaluation. Although only 11 subjects (10.9%) reported actual incontinence, 42 subjects (41.6%) were found to have clinically significant LUTS (IPSS total score > or =8). No influencing factors could be found among the demographic and clinical variables. At the follow-up, the average IPSS total (7.9 +/- 6.0) and the percentage of subjects with clinically significant LUTS (43.7%) had both increased, although the change was not statistically significant. The prevalence of LUTS in clozapine-medicated patients was higher than in the general population of the same age. However, the prevalence of incontinence was only a quarter of that of LUTS. If clinicians focus only on incontinence, distress from LUTS will not receive appropriate attention. Furthermore, contrary to literature observations, clozapine-related LUTS did not remit easily but rather persisted even into the long-term maintenance phase. More concern should be directed at these troublesome and often neglected side effects.
Journal of clinical psychopharmacology 12/2008; 28(6):618-24. · 5.09 Impact Factor
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ABSTRACT: Objectives: Although a broad range of circadian rhythm variations have been reported, analyses of chronotypes in bipolar I disorder (BDI) and schizophrenia are rare. The present study aimed to investigate specific chronotype patterns in BDI and schizophrenia compared with healthy subjects.
All patients were clinically stable and recruited from the outpatient clinics of Seoul National University Hospital. They were diagnosed according to DSM-IV criteria. 'Morningness/eveningness', a chronotype correlated with circadian phase, was evaluated using the Composite Scale of Morningness (CSM) among 92 patients with BDI, 113 patients with schizophrenia (SZ), and 95 control individuals.
The CSM scores were significantly correlated with age in the control group, but a significant correlation with age was not observed in the schizophrenia or BDI groups. After controlling for age, there were significant differences between the BDI and control groups. The SZ patients did not differ from the BDI or control groups.
In this Korean sample, patients with BDI showed a significantly greater preference for 'eveningness' (including delayed sleep timing) than control individuals. The influences of pharmacotherapy or clinical status on CSM scores need to be clarified.
Bipolar Disorders 04/2008; 10(2):271-5. · 5.29 Impact Factor
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ABSTRACT: Inadequate response to clozapine poses a substantial problem in the pharmaco-therapy of refractory schizophrenia. This randomized, double-blind, placebo-controlled study evaluated the efficacy and safety of aripiprazole augmentation in clozapine-treated patients with refractory schizophrenia.
Patients with DSM-IV schizophrenia who had a history of treatment failure or partial response to long-term clozapine treatment were recruited. A total of 62 patients with either a baseline Brief Psychiatric Rating Scale (BPRS) score of at least 35 or more than 2 Schedule for Assessment of Negative Symptoms (SANS) global rating item scores of at least 3 were randomly assigned to double-blind augmentation treatment with either aripiprazole (5-30 mg/day) or placebo over 8 weeks. The primary outcome measure was change in BPRS total score from baseline. The study was conducted between December 1, 2005, and December 10, 2006.
There was no significant difference in the primary outcome measure between the 2 groups. In secondary analyses, improvement was significantly greater with aripiprazole treatment than with placebo for negative symptoms assessed by both the BPRS negative symptom sub-scale and the SANS total score but not for positive symptoms. Prolactin and triglyceride levels were significantly lower in the aripiprazole group than in the placebo group. No significant differences between the 2 groups were observed in adverse effects, including extrapyramidal symptoms and serum glucose levels.
Although aripiprazole augmentation of clozapine did not lead to a significant improvement of total symptom severity in schizophrenia, a favorable change in the negative symptom domain was observed.
The Journal of Clinical Psychiatry 04/2008; 69(5):720-31. · 5.80 Impact Factor
