Comparison of MMSE Profiles Between Dementia, Psychotic Disorders, and Mood Disorders

Objective@#Cognitive impairment has been an area of interest for psychiatrists. Not only do patients with dementia exhibit symptoms associated with cognitive impairment, but those with some mental disorders such as psychotic and mood disorders as well. However, differences in cognitive impairment between these disorders remain unclear. In this study, we used the Korean Mini-Mental State Examination (K-MMSE), a tool that can be easily administered to patients, to compare cognitive impairment profiles among patients with dementia, psychotic disorders, and mood disorders. @*Methods@#We collected demographic and clinical characteristics of 59 patients who were over 50 years old. Cognitive func-tion was assessed using the K-MMSE. Patients were divided into three groups based on International Classification of Diseases 10th revision diagnosis codes: 1) F00-F01 Dementia, 2) F20-F29 Psychotic disorders, and 3) F30-F39 Mood disorders. We compared K-MMSE subscale scores between the three groups using one-way analysis of variance. @*Results@#The three groups did not differ in demographic data. The dementia group showed the lowest scores in orientation to time (standard deviation [SD]=1.45, F=3.233, p<0.05) and place (SD=1.25, F=3.388, p<0.05), as well as registration (SD=1.00, F=4.425, p<0.05) and recall (SD=0.91, F=3.364, p<0.05) of memory compared to the groups with psychotic and mood disorders. The psychotic disorder group showed significant impairment in language (SD=1.34, F=3.348, p<0.05) compared to the other groups. No significant differences were observed in calculation and drawing. @*Conclusion@#This study suggests that certain K-MMSE subscale scores could indicate an illness that causes cognitive impairment, especially in dementia, psychotic disorders, and mood disorders. By using K-MMSE profiles, we could provide better in-terventions for patients with cognitive impairment.

Worsening of Psychotic Symptoms in Patients with Chronic Schizophrenia after Switching to or Combining Aripiprazole and Aripiprazole Monthly (Abilify Maintena) / 신경정신의학

Objectives@#Aripiprazole is an antipsychotic that functions as a partial agonist in hypodopaminergic states and a dopamine antagonist in hyperdopaminergic states. @*Methods@#This paper reports a series of five clinical cases of worsening psychotic symptoms in schizophrenic patients related to the initiation of aripiprazole, oral and injection, as combination therapy. @*Results@#In all five cases, the switching of aripiprazole improved the psychotic symptoms. @*Conclusion@#Even with the suggestive relationship between aripiprazole therapy and the worsening of psychotic symptoms, further research is needed.

Obsessive-Compulsive Symptoms in Relation to Duration of Schizophrenia

OBJECTIVES: The aim of this study was to evaluate the psychopathological features such as depression and anxiety in schizophrenics with obsessive-compulsive symptoms (OCS) as well as the severity of OCS according to duration of schizophrenia. METHODS: We randomly selected sixty four inpatients with schizophrenia. We classified the patients into two groups (OCS group, non-OCS group) according to the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS). Clinical and demographic features were evaluated. To assess OCS, Y-BOCS were performed. The Korean version of the Positive and Negative Syndrome Scale(K-PANSS), the Brief Psychiatric Rating Scale (BPRS), the Korean version of the Calgary Depression Scale for Schizophrenia (K-CDSS), the Beck Anxiety Inventory (BAI) and the Satisfaction With Life Scale (SWLS) were conducted. Independent t-test and chi-square test were conducted to compare the two groups. Pearson correlation analysis was performed to examine the relationship between the duration of schizophrenia and the Y-BOCS score. RESULTS: The Y-BOCS, K-CDSS, and BAI scores were higher in the OCS group. There was a significant correlation between the duration of schizophrenia and the Y-BOCS score. CONCLUSIONS: Anxiety and depression symptoms were severe in the OCS group. In addition, the results of this study indicate that the longer duration of schizophrenia, the more severe the OCS. Therefore, the evaluation of OCS in schizophrenics should be accompanied by treatment intervention.

Association between Global Cortical Atrophy, Medial Temporal Atrophy, White Matter Hyperintensities and Cognitive Functions in Korean Alzheimer's Disease Patients

OBJECTIVES: The aim of this study is to investigate the correlation between degenerative changes in brain [i.e., global cortical atrophy (GCA), medial temporal atrophy (MTA), white matter hyperintensities (WMH)] and neurocognitive dysfunction in Korean patients with Alzheimer's disease. METHODS: A total of 62 elderly subjects diagnosed with Alzheimer's disease were included in this study. The degenerative changes in brain MRI were rated with standardized visual rating scales (GCA or global cortical atrophy, MTA or medial temporal atrophy, and Fazekas scales) and the subjects were divided into two groups according to the degree of degeneration for each scale. Cognitive function was evaluated with Korean version of the Consortium to Establish a Registry for Alzheimer's Disease (CERAD-K) and several clinical features, including apolipoprotein E epsilon4 status, lipid profile and thyroid hormones, were also examined. Chi-square test and Fisher's exact test were performed to analyze the relationship between the degree of cerebral degeneration and neurocognitive functions. RESULTS: Demographic and clinical features, except for the age, did not show any significant difference between the two groups divided according to the degree of cerebral degenerative changes. However, higher degree of GCA was shown to be associated with poorer performance in verbal fluency test, word list recall test, and word list recognition test. Higher degree of MTA was shown to be associated with poorer performance in Mini-Mental State Examination in the Korean Version of CERAD Assessment Packet (MMSE-KC), word list recognition test and construction praxis recall test. Higher degree of white matter hyperintensities was shown to be associated with poorer performance in MMSE-KC. CONCLUSIONS: Our results suggest that severe brain degeneration shown in MRI is associated with significantly poorer performance in neurocognitive tests in patients with Alzheimer's disease. Moreover, the degree of GCA, MTA and white matter hyperintensities, represented by scores from different visual rating scales, seems to affect certain neurocognitive domains each, which would provide useful information in clinical settings.

Obesity and Psychopathology of Inpatients with Schizophrenia / 신경정신의학

OBJECTIVES: The aims of this study were to examine the relationship between obesity and psychopathology of inpatients with schizophrenia. METHODS: Eighty four inpatients with schizophrenia and 81 control subjects were recruited. Height and weight were measured for calculation of body mass index (BMI). Symptom severity scales [Positive and Negative Syndrome Scale (PANSS), Brief Psychiatric Rating Scale] and Global Assessment of Functioning Scale (GAF) were conducted in all patients. Comorbid medical conditions, years of education, smoking status, age of onset, duration of illness, and medication history were collected. RESULTS: Patients with schizophrenia had significantly higher BMI and ratio of obesity than control subjects. Among patients, obese patients scored lower on symptom severity scales and better on functional assessment than not obese patients. Multiple regression analysis revealed an association of late onset and being obese with lower PANSS total score and better GAF score in patients. Late onset and being female were inversely related with negative symptom score. The type and dose of antipsychotics showed no association with obesity. CONCLUSION: The results of this study indicate that patients with schizophrenia are likely to be more obese. Some characteristics of patients with less severe psychopathology, such as late onset, being obese, were coincident with the result of previous studies. In addition, the result showing that the heavier the weight of patients, the lower severity of symptoms was repeatedly reported in previous studies. The type and dose of antipsychotics were not associated with obesity. These results prompt further investigation of the relationship among schizophrenia, antipsychotics, and weight gain.

Safety and Effectiveness of Long Acting Injectable Antipsychotic Paliperidone Palmitate Treatment in Schizophrenics : A 24-Week Open-Label Study

OBJECTIVES: We investigated the effectiveness and safety when treated in schizophrenics with paliperidone palmitate, a long acting injectable antipsychotic. METHODS: This was a 24-week open-label study, performed at one center in Korea. The eligible patients with schizophrenia diagnosed by Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) criteria were enrolled. Patients received long-acting paliperidone palmitate injection (234 mg, baseline; 156 mg, week 1 ; then once 4 weeks flexible dosing). Effectiveness assessments were measured by the Positive and Negative Syndrome Scale (PANSS), The Clinical Global Impression Severity Scale (CGI-S), The Personal and Social Performance (PSP) at baseline, week 1, every 4 weeks untill 24 weeks or endpoint. Safety assessments were measured by The Extrapyramidal Symptom Rating Scale (ESRS), body weight (BW) and incidence of adverse events. Oral antipsychotics were stopped or tapered off within next 14 days. RESULTS: Of 20 patients recruited, 9 patients (45%) completed the study. Paliperidone palmitate produced a significant improvement in PANSS total score from baseline to endpoint. The response rate was 75% [mean change (+/- SD) -25.9 +/- 14.4, all p or = 10%) in paliperidone palmitate were anticholinergic adverse event, extrapyramidal symptoms, weight gain, akathisia, insomnia, headache, agitation, anxiety and GI trouble. ESRS score is not statistically significant, but tends to get better at the end of the study when compared to baseline. CONCLUSIONS: Our study results demonstrated maintained effectiveness and safety of paliperidone palmitate treatment in schizophrenics. And provides both clinicians and patients with a new choice of treatment that can improve the outcome of long term therapy. Their potential effectiveness and safety should be better addressed by future randomized-controlled trials.

The Changes of Blood Glucose Control and Lipid Profiles after Short-Term Smoking Cessation in Healthy Males

OBJECTIVE: Our aim was to evaluate the changes in blood glucose control and lipid profiles after 2-months of smoking cessation in healthy males. METHODS: Smoking abstinence was evaluated through self-report and urine cotinine levels. 12 individuals who succeeded in quitting smoking were analyzed. Fasting values of glucose and insulin were used to estimate the beta-cell activity and insulin resistance was evaluated using the Homeostasis Model Assessment (HOMA) and Quantitative Insulin Sensitivity Check Index (QUICKI). RESULTS: The data showed that the subjects had a significant increase in weight, body mass index and fasting plasma glucose levels after smoking cessation. The HOMA-Insulin Resistance and the HOMA beta-cell function increased significantly (p=0.005, p=0.047 respectively). The QUICKI showed a significant decrease (p=0.005). In addition, the low-density lipoprotein cholesterol levels decreased significantly (p=0.028); however, changes in the high-density lipoprotein cholesterol, the triglyceride and total cholesterol levels were not significant (p=0.284, p=0.445 respectively). CONCLUSION: During the initial stage of smoking abstinence, insulin resistance increased and insulin sensitivity decreased due to elevated body weight and fat composition. Therefore, it is important to educate individuals that stop smoking about the necessity of weight control during smoking cessation programs.

Association between Estrogen Receptor Gene Polymorphisms and Depression in Post-Menopausal Women: A Preliminary Study

Post-menopausal women experience variable biological and psychological changes. The effect of reduced levels of estrogen can effect on post-menopausal depression. Estrogen triggers physiological responses by binding to the estrogen receptor (ER). Two subtypes of ER, ERa and ERb are now known. We investigated the significance of ERa and ERb polymorphisms and post-menopasal depression in this study. Forty three women with post-menopausal depression and 63 post-menopausal women without depression as normal controls were recruited. Polymerase chain reaction-restriction fragment length polymorphism method was used to investigate genotypes of ERa and ERb polymorphisms. Genotypes of PvuII and XbaI polymorphism of ERa receptor were significantly different in patients with post-menopausal depression comparing with controls. Genotypes of ERb did not show association with post-menopausal depression. Our study showed that ERa receptor polymorphism had an association with depression in post-menopausal women. It suggests that investigation of ER genes and their functions might be important for understanding pathophysilogical mechanism of post-menopausal depression.

Effect of the Dysbindin Gene on Antimanic Agents in Patients with Bipolar I Disorder

OBJECTIVE: We previously reported an association between dysbindin gene (DTNBP1) variants and bipolar I disorder (BID). This paper expands upon previous findings suggesting that DTNBP1 variants may play a role in the response to acute mood stabilizer treatment. METHODS: A total of 45 BID patients were treated with antimanic agents (lithium, valproate, or carbamazepine) for an average of 36.52 (+/-19.87) days. After treatment, the patients were evaluated using the Clinical Global Impression (CGI) scale and the Young Mania Rating Scale (YMRS) and genotyped for their DTNBP1 variants (rs3213207 A/G, rs1011313 C/T, rs2005976 G/A, rs760761 C/T and rs2619522 A/C). RESULTS: There was no association between the variants investigated and response to mood stabilizer treatment, even after considering possible stratification factors. CONCLUSION: Although the small number of subjects is an important limitation in our study, DTNBP1 does not seem to be involved in acute antimanic efficacy.

Prescription Pattern of Risperidone and Olanzapine for Elderly Psychiatric Inpatients in a Naturalistic Setting

Several studies have reported that either risperidone or olanzapine is effective and tolerable in the elderly patients with psychotic symptoms. However, there is a lack of clinical data of risperidone and olanzapine prescription for elderly patients in the Aisan population. We reviewed retrospectively the medical records of risperidone (n=112) and olanzapine (n=96) treated patients older than age 60 who were admitted to a university-affiliated hospital between October 2005 and August 2006. The mean daily dose of risperidone was 3.4+/-1.5 mg and olanzapine, 8.8+/-5.6 mg, respectively. The response rate on the CGI (much and very much improved) appeared to be 67.4% in the risperidone group and 70.8% in the olanzapine group, respectively. Adverse events were reported in 48.2% in the risperidone group and 46.9% in the olanzapine group, without serious adverse events, respectively. This study showed that either risperidone or olanzapine would be effective and tolerable in elderly patients with psychotic symptoms and that provides similar results to those reported from western countries.

Comparison of the Clinical Efficacy and Safety between Intramuscular Olanzapine and Intramuscular Haloperidol Injection in the Treatment of Delirium / 대한정신약물학회지

OBJECTIVE: The present study aimed to provide preliminary data on the effectiveness and tolerability of intramuscular (IM) olanzapine and IM haloperidol for patients with delirium. METHODS: Sixty-two patients with delirium were randomly assigned to either olanzapine IM or haloperidol IM groups, with a flexible dosing schedule for 7 days. The Delirium Rating Scale-revised-98 (DRS-R-98), clinical global impression-severity (CGI-S) were assessed daily. The Simpson-Angus Rating Scale (SAS), the Barnes Akathisia Rating Scale (BARS) and the Abnormal Involuntary Movement Scale (AIMS) were used for the assessments of side effects. RESULTS: The DRS-R-98 scores were significantly decreased over time (F=26.02, P<0.0001), without any significant group differences (F=0.048, P=0.829), and time by treatment group interaction (F=5.64, P=0.725). There were no serious adverse events in both groups. The scores on the SAS, BARS, and AIMS were not changed significantly during the study. CONCLUSIONS: This study showed that olanzapine IM did not show any superior efficay and safety compared with haloperidol IM in treatment delirium. However our study suggested that either olanzapine IM or haloperidol IM would be effective and tolerable. Adequately powered studies with a head-to-head comparison design will be mandatory to draw any definite conclusion.

Comparison of the Clinical Efficacy and Safety between Intramuscular Olanzapine and Intramuscular Haloperidol Injection in the Treatment of Delirium / 대한정신약물학회지

OBJECTIVE: The present study aimed to provide preliminary data on the effectiveness and tolerability of intramuscular (IM) olanzapine and IM haloperidol for patients with delirium. METHODS: Sixty-two patients with delirium were randomly assigned to either olanzapine IM or haloperidol IM groups, with a flexible dosing schedule for 7 days. The Delirium Rating Scale-revised-98 (DRS-R-98), clinical global impression-severity (CGI-S) were assessed daily. The Simpson-Angus Rating Scale (SAS), the Barnes Akathisia Rating Scale (BARS) and the Abnormal Involuntary Movement Scale (AIMS) were used for the assessments of side effects. RESULTS: The DRS-R-98 scores were significantly decreased over time (F=26.02, P<0.0001), without any significant group differences (F=0.048, P=0.829), and time by treatment group interaction (F=5.64, P=0.725). There were no serious adverse events in both groups. The scores on the SAS, BARS, and AIMS were not changed significantly during the study. CONCLUSIONS: This study showed that olanzapine IM did not show any superior efficay and safety compared with haloperidol IM in treatment delirium. However our study suggested that either olanzapine IM or haloperidol IM would be effective and tolerable. Adequately powered studies with a head-to-head comparison design will be mandatory to draw any definite conclusion.

Working Memory Deficits in Patients with Schizophrenia: fMRI Investigation

OBJECTIVE: Impaired processing of working memory is one of the cognitive deficits seen in patients with schizophrenia. This aimed at corroborating the differences in the brain activities involved in the process of working memory between patients with schizophrenia and the control subjects. METHOD: Fourteen patients with schizophrenia and 12 healthy volunteers were recruited in this study. Functional magnetic resonance imaging(fMRI) was used to assess cortical activities during the performance of a 2-back visual working memory paradigm using the Korean alphabet as mnemonic content. RESULTS: Group analysis revealed that left lateral prefrontal cortex and right parietal lobule showed decreased cortical activities in the patient group. On the other hand, an increased activation in left superior and middle frontal gyrus, left middle temporal gyrus, right cuneus, both occipital lobes, right fusiform gyrus and right cingulate gyrus. The activation in left anterior lobe and both declive of cerebellum was also increased. CONCLUSIONS: This study showed a decreased activation in left lateral prefrontal and right parietal neural networks from the patient group and confirmed the earlier findings on the impaired working memory of patients with schizophrenia using fMRI investigation. The regions implicated in our study suggest an abnormal functioning of the fronto-parietal cortical areas that are critical to the information processing stream, which might be correspondent to common pathophysiology rather than a common etiology in schizophrenia.

Changes of Cholesterol Level after Treatment in Bipolar Patients / 대한정신약물학회지

OBJECTIVES: Cholesterol interacts with serotonin and it has been found to be associated with some clinical symptoms of mood disorders. There is a paucity of data on first onset bipolar patients and from Asian population. In this study, we compared the total choelsterol (TC) level between the bipolar I patients with a single manic episode (BPSM) and the normal controls, and investigated the relationship between the TC level and treatment response in the BPSM. METHODS: Twenty-five BPSM and thirty normal controls were enrolled in this study. The pretreatment and posttreatment TC levels in the BPSM were measured and comapred to that of normal controls. Young Mania Rating Scale (YMRS) was used for assessing symptom severity in the BPSM. RESULTS: The TC level was significantly lower in the BPSM than in the controls. There were negative correlations between the YMRS scores and the pretreatment TC level in the BPSM. The posttreatment TC level was significantly higher than the pretreatment TC level in the BPSM. CONCLUSION: This study suggests that the TC level can be changed after treatment in bipolar manic patients, although more studies involving different ethnic groups will be needed. Further longitudinal studies will be needed to examine the change of total cholesterol level according to the clinical course of bipolar disorder.

Add-On Therapy of Quetiapine for Bipolar Disorder: A 6 Month, Prospective Trial / 대한정신약물학회지

OBJECTIVES: This study was conducted to evaluate the overall effectiveness and tolerability of adjunctive quetiapine in the long-term treatment of bipolar disorder as a continuation therapy. METHODS: Twenty-three bipolar I patients participated and required to have quetiapine add-on treatment in combination with existing or new mood stabilizers. Clinical assessment was carried out using Young Mania Rating Scale (YMRS), Clinical Global Impression (CGI), Hamilton Depression Rating Scale-17 item, Simpson-Angus Rating Scale and Barnes Akathisia Rating Scale at baseline, 1, 4, 12 and 24 weeks. RESULTS: The YMRS and CGI decreased significantly from baseline to endpoint by 89.7% and 78.3%, respectively (p<0.0001 ; p<0.0001). Twenty-two patients exhibited at least 50% improvement on YMRS score by the end of the study. CONCLUSION: This study suggests that quetiapine may hold a promise as an adjunct in the long-term treatment of bipolar disorder.

A Case Report: Effect of Aripiprazole for a Patient with Psychotic Symptoms and Parkinsonism Associated with Carbon Monoxide Poisoning / 대한정신약물학회지

A newer atypical antipsychotic, aripiprazole has been shown to be effective in the treatment of schizophrenia and other psychotic disorders. A 44-year-old woman who developed psychotic symptoms and parkinsonism a month after carbon monoxide poisoning and did not respond to other atypical antipsychotics, was successfully treated with aripiprazole. This case suggests that aripiprazole may be helpful to those developed psychotic symptoms and movement disorders associated with toxic brain injury such as carbon monoxide poisoning.

Working Memory Deficits of Facial Images in Patients with Schizophrenia: fMRI Investigation / 신경정신의학

OBJECTIVES: Impaired processing of facial information is one of the broad ranges of cognitive deficits seen in patients with schizophrenia. We aimed to elucidate the differences in brain activities involved in the process of facial working memory between schizophrenic patients and healthy comparison subjects. METHODS: Twelve patients with schizophrenia were recruited along with twelve demographically matched healthy volunteers as a comparison group. Functional magnetic resonance imaging (fMRI) was used to assess cortical activities during the performance of a 2-back working memory paradigm using images of neutral faces as mnemonic content. RESULTS: The patient group performed the tasks with reduced accuracy. Group analysis revealed that the left fusiform gyrus, the right superior frontal gyrus, the bilateral middle frontal gyri/insula, the left middle temporal gyrus, the precuneus, the quadrangular lobules and the vermis of cerebellum showed decreased cortical activities in the patient group. On the other hand, an increased level of activation in the lateral prefrontal cortex and the parietal lobule was observed from the patient group, all in the right hemisphere. CONCLUSION: A decreased level of activity in the left fusiform gyrus among the patient group implicates inefficient processing of facial information. An increased level of activation in prefrontal and parietal neural networks from the patient group confirms earlier findings on the impaired working memory of patients with schizophrenia.

Glutathione S-Transferase M1 Polymorphism and Schizophrenia / 신경정신의학

OBJECTIVES: This study aimed to test the possible association between Glutathione S-Transferase M1 gene (GSTM1) variants and schizophrenia. METHODS: One hundred and eleven inpatients with schizophrenia and 130 healthy controls were recruited. Genotyping was performed by polymerase chain reaction-based method. RESULTS: The GSTM1 null genotype was significantly more frequent in patients with schizophrenia than in controls (p=0.014, odd ratio=1.93, 95% confidence interval=1.115-3.351), while GSTM1 genotype variants were not associated with either tardive dyskinesia (TD) or total Abnormal Involuntary Movement Scale (AIMS) scores. CONCLUSION: The present study suggests that the GSTM1 polymorphism may confer susceptibility to the development of schizophrenia but not to TD, at least in Korean population.

Monocyte Chemoattractant Protein-1(MCP1) -2518 Polymorphism and Bipolar I Disorder / 신경정신의학

OBJECTIVES: Several studies suggested that cytokines could be involved in the pathogenesis of mood disorders, while data for bipolar disorder is relatively deficient (BD). BD, Knowned to have a inherited tendency, has been considered to be related with T-helper cell system. This study was designed to investigate the association between polymorphism of monocyte chemoattractant protein-1 (MCP1) gene at promoter -2518 and BD. METHODS: Patients with BD (n=92) in accordance with DSM-IV criteria and control subjects (n=114) participated in this study. DNA was extracted from whole blood and the MCP-1 gene promoter region was amplified by polymerase chain reaction-based method. RESULTS: Genotype and allele distributions in patients with BD were not different from those of control subjects (p=0.587; p=0.384). Genotype and allele distributions in accordance to presence or absence of suicide attempt (p=0.423), family history (p=0.733) and psychotic feature (p=0.436) were not different between the two groups. CONCLUSION: Present study suggests that the MCP1 promoter -2518 polymorphism may not affect the susceptibility and clinical diversity of the development of BD.

Effectiveness and Tolerability of Topiramate Versus Divalproex in Bipolar Mania / 대한정신약물학회지

Mood stabilizers and atypical antipsychotics are commonly combined for the treatment of bipolar mania. The aim of this study was to compare the effectiveness and tolerability of topiramate and divalproex in combination with risperidone for treating acute mania patients in a naturalistic treatment setting. Seventy-four patients who met the DSM-IV criteria for bipolar mania were enrolled in this study. In order to assess the efficacy and the extrapyramidal symptoms, the Young Mania Rating Scale (YMRS), Clinical Global Impression (CGI) and Simpson-Angus Rating Scale were measured at the baseline and at weeks 1, 3 and 6. From the baseline to the endpoint, the YMRS and CGI scores were reduced by 67.9% and 56.6% in the topiramate group. The YMRS and CGI scores were also reduced by 63.7% and 58.2% in the divalproex group. The weight and BMI increased significantly by 3.6% and 3.3% from the baseline to the endpoint in the divalproex group, while they decreased by 0.4% and 0.5%, respectively, with no significant difference in the topiramate group. There were no serious adverse events in either group. Topiramate is effective and tolerable for treating acute mania, and may also be a promising alternative to a weightgain liable mood stabilizer such as divalproex.