The Newer Assessment Tools for Functionings and the Personal and Social Performance Scale in Patients with Schizophrenia / 대한정신약물학회지

Personal and Social Performance scale (PSP) is the new measurement scale of patient functioning. PSP is simple and useful questionnaire for psychiatrist and medical personnel, especially for rehabilitation center workers. Compared with GAF (Global Assessment of functioning Scale), PSP has relatively good covariance with social and occupational and psychological symptoms. In clinical practice, PSP can be adopted for treatment planning and the evaluation of treatment effect, especially for the patients with schizophrenia.

Effects of Quetiapine on the Immobilization Stress-induced BDNF and CRF Expression in Rat Brain / 대한정신약물학회지

OBJECTIVE: In this study we examined the effects of quetiapine on the immobilization stress-induced brain-derived neurotrophic factor (BDNF) and corticotropin-releasing factor (CRF) expression in rat brain. We also assessed the antidepressant activity of quetiapine. METHOD: We used in situ hybridization to examine the effects of chronic administration of quetiapine in gene transcription. This study also examined the influence of quetiapine in an animal model of depression, the forced swimming test (FST). RESULTS: 1) Repeated immobilization stress (2 hr daily for 3 weeks) decreased mRNA levels of BDNF in the hippocampus (p<0.01), parietal cortex (p<0.01) and pyriform cortex (p<0.05). 2) Repeated immobilization stress increased mRNA levels of CRF in the hypothalamic paraventricular nucleus (PVN)(p<0.01). 3) Chronic quetiapine (10 mg/kg) treatment (daily for 3 weeks) alone significantly increased BDNF mRNA expression in the dentate gyrus of hippocampus when compared to controls under basal conditions (p<0.01), whereas no such effect was observed in the neocortex. 4) Chronic pretreatment of quetiapine also markedly increased the stress-induced decrease of BDNF mRNA expression in the hippocampus (p<0.01) and neocortex (p<0.01). 5) Moreover, the stress-induced elevation of CRF mRNA expression was blocked by chronic quetiapine pretreatment in PVN (p<0.01) although chronic quetiapine treatment alone did not significantly reduce CRF mRNA levels in comparison to controls under basal condition. 6) When rats received acutely quetiapine, quetiapine did reduce the immobility time at 10 mg/kg, as compared with the control group (p<0.05). CONCLUSION : These results suggest that quetiapine has not only potentially an antidepressant effect but also a neuroprotective action in schizophrenia and this effect may be related to its antipsychotic effect in patients with schizophrenia.

Strategies for Switching Antipsychotics / 대한정신약물학회지

As novel antipsychotic agents are introduced, the needs for practical guidelines on switching medications is becoming increasingly important. Cross-tapering is generally the most acceptable methods of switching, although abrupt change may be used in some cases. The important goal of antipsychotic agents witching guidelines is to reduce adverse effect of antipsychotic agents and to minimize the aggravation of the psychiatric symptoms during the switching periods. Recently, drug switching to novel antipsychotics is increased. In this article authors reviewed previous clinical studies on the antipsychotic medications switching.

Association between Changes in Serum Prolactin Levels after the Administration of Antipsychotics and 5-HT Transporter Polymorphism in Schizophrenic Patients / 대한정신약물학회지

OBJECTIVE: 1) To compare prolactin responses to (and related clinical manifestations of) haloperidol, risperidone, and other atypical antipsychotics (clozapine, olanzapine, quetiapine, zotepine) with data from previous reports. 2) To investigate the association between changes in serum prolactin levels after the administration of antipsychotics and 44-bp insertion/deletion polymorphism in 5-HT transporter-linked polymorphic region (5-HTTLPR) in Korean schizophrenics. METHODS: The subjects were 136 patients diagnosed schizophrenic according to the DSM-IV criteria for schizophrenia who had taken antipsychotics for at least 3 months. The 136 patients consisted of the following 82 taking haloperidol (48 males and 34 females), 25 taking risperidone (14 males and 11 females), and 29 taking other atypical antipsychotics (18 males and 11 females). We measured serum prolactin concentrations by radioimmunoassay and investigated the clinical manifestations. We examined the genotype distribution and allele frequency of the 5-HTTLPR in all subjects by polymerase chain reaction of genomic DNA with primers flanking the promoter regions of the 5-HTT gene. Chi-square test, ANOVA and tukey test were used for statistical analysis with SAS 8.1 and p values of 0.05 or less were regarded as significant difference. RESULTS: Serum prolactin levels of patients taking haloperidol and risperidone were significantly higher than those taking other atypical antipsychotics (p<0.05). Females showed significantly higher prolactin levels than males (p<0.05). There was no significant difference in the genotype distribution and allele frequency of 5-HTTLPR among groups taking haloperidol, risperidone, and other atypicals. There was also no significant difference in genotype distribution and allele frequency of 5-HTTLPR between male and female schizophrenic patients. CONCLUSIONS: These results suggest that there was no association between serum prolactin levels after the administration of antipsychotics and 5-HTTLPR polymorphism in Korean schizophrenics.

Prevalence of Tardive Dyskinesia among the Hospitalized Schizophrenic Patients

OBJECT: This cross-sectional study was performed in order to evaluate the prevalence of tardive dyskinesia among the hospitalized schizophrenic patients. METHODS: Four hundred nineteen hospitalized schizophrenic patients(male=263, female=156) were recruited for this study. They were treated with antipsychotics for more than 3 months. The prevalence of tardive dyskinesia was assessed by the Abnormal Involuntary Movement Scale. RESULTS: The prevalence of tardive dyskinesia was 35.6%(Male=36.9%, Female 33.3%). There were no significant differences in the prevalence of tardive dyskinesia among male and female schizophrenic patients. The prevalence of tardive dyskinesia among the patients over 30years old was much higher than those below 30years old. There were no significant correlations between the prevalence of tardive dyskinesia and the duration of hospitalization, the total amount of antipsychotics. The frequently involved parts of the body in the schizophrenic patients who have tardive dyskinesia were tongue, upper extremity, lips and perioral area, jaw, lower extremity, muscles of facial expression trunk, respectively. CONCLUSIONS: There was significant correlation between the age and the prevalence of tardive dyskinesia in the antipsychotic-treated schizophrenic patients.

Tardive Dyskinesia and CAG Repeat Expansions / 신경정신의학

OBJECTIVES: Much interest has recently been focused on the possibility of the involvement of unstable DNA in the etiology of schizophrenia following several publications that reported increases in frequency of large CAG repeats in affected individuals. Tardive dyskinesia(TD), an involuntary movement disorder following pharmacological treatment of schizophrenia, shares a great deal of common clinical and biological features with Huntington's disease, a representative movement disorder with CAG repeat expansions. The authors studied for a possible CAG repeat expansions in patients with schizophrenia and TD. METHODS: TD was diagnosed by the Abnormal Involuntary Movement Scale. Using repeat expansion detection(RED), a method in which a thermostable ligase is used to detect repeat expansions directly from genomic DNA, subjects with schizophrenia with/without TD(n=79/n=75) and normal controls (n=72) were studied for the presence of the CAG repeat expansions were analyzed. RESULTS: No significant size differences were detected in the(CTG)17 ligation products between schizophrenic cases and controls using RED(X(2)=2.907, df=2, p=0.234). CONCLUSIONS: This finding does not support the hypothesis that CAG repeat expansions contributes to the susceptibility for schizophrenia and TD.

The Relationship between Tardive Dyskinesia and both Negative Symptoms and Cognitive Dysfunctions in Chronic Schizophrenic In-patients / 신경정신의학

OBJECTIVES: The purpose of present study was to determine the prevalence rate of tardive dyskinesia and to search for its risk factors in chronically institutionalized schizophrenic subjects. We also examined the relationship between tardive dyskinesia and both negative symptoms and cognitive impairments in the same subjects. METHODS: Subjects were 271 in-patients (174 males, 97 females) at Masan Dongsuh Hospital. They met DSM-IV criteria for schizophrenia and had been taking fixed doses of antipsychotics for at least 3 months. Tardive dyskinesia was assessed by Abnormal Involuntary Movement Scale (AIMS). Cases of tardive dyskinesia were ascertained by the criteria of Schooler and Kane (1982) and DSM-IV. The rating of psychopathology was acquired using Brief Psychiatric Rating Scale (BPRS) and Schedule for the Deficit Syndrome (SDS) and the assessment of cognitive function using Mini-Mental State Examination (MMSE). RESULTS: The prevalence of tardive dyskinesia is 50.9% and the frequency of tardive dyskinesia was high est in male above the age of fifty. But there was no statistically significant relationship between the frequency of tardive dyskinesia and both the length of hospitalization and the daily dose of antipsychotics. The frequency order of abnormal movement in the patients with tardive dyskinesia was as follows: tongue, upper extremities, lips and perioral area. We couldn't find any significant difference in the total and subscale scores of BPRS between the groups with and without tardive dyskinesia. There were no differences in MMSE scores between the groups with and without tardive dyskinesia. CONCLUSION: This study gave us that the prevalence of tardive dyskinesia was high in chronically institutionalized schizophrenic inpatients and that age was the most significant risk factor of tardive dyskinesia. The relationship between tardive dyskinesia and both negative symptoms and cognitive impairment, however, was not revealed.

Neurobiology of Depression

At the beginning, researches on the biology of depression or affective illness have focused mainly on the receptor functions and neuroendocrine activities. And the studies of the past years did not break new theoretical background, but the recent advances in the research on the molecular mechanisms underlying neural communication and signal transduction do add some insights to many established ideas. This article will overview some of the more recent advances in the clinical researches of depression. Our major concerns to be presented here include the following : (1) alterations in the post-synaptic neural transduction ; (2) changes in the neurons of hypothalamic neuropeptides ; (3) decreased peptidase enzyme activities : (4) associations of hypothalamic-pituitary-adrenal axis abnormalities with serotonin neurotransmission ; (5) role of serotonin transporter ; (6) changes in the responsiveness of intracellular calcium ion levels ; (7) the inositol deficiency theory of lithium and depression ; (8) the transcription factors including immediate early genes ; (9) recent genetic studies in some families. This brief overview will suggest that changes in DNA occur during antidepressant therapy. These changes at the DNA level initiating a cascade of events underlying antidepressant modality will give us the insight on the molecular biological basis of the pathogenesis of depression and cues for a new class of antidepressants.

Molecular Neurobiology of Alzheimer's Disease

Alzheimer's disease (AD), the most common dementia in the elderly, is associated with a characteristic neuropathology:extracellular neuritic plaques (NPs) and intraneuronal neurofibrillary tangles (NFTs). AD is diagnosed clinically on the basis of progressive cognitive impairment. However, the diagnosis of AD is only reliable if a histopathological examination at autopsy shows high numbers of NPs and NFTs particularly in the hippocampus and cerebral cortex. The major component of NP is beta-amyloid protein (Abeta), a fragment of the amyloid precursor protein (APP). NFTs are largely composed of paired helical filaments (PHFs) containing abnormally phospholylated form of the microtubule-associated protein (MAP), tau. A genetic etiology for AD has been established based on population survey. It is revealed that 25-40% of the AD patients are familial and the disease is inherited as an autosomal-dominant trait in most families. Age at onset patterns of AD patients in affected families had indicated that its distribution is bimodal with a cut-off age 58 years. Several mutations in the APP gene, located on chromosome 21, are linked to early-onset AD (EOAD). However, these account for only a small fraction of cases of EOAD. The remaining cases are associated with mutations in two other genes:one on chromosome 14 that encodes S182 (presenilin 1) and the other on chromosome 1 that encodes STM2 (presenilin 2). It is also known that inheritance of specific apolipoprotein E (apoE) alleles, located on chromosome 19, determines the risk and mean age of onset of late-onset AD (LOAD). In this review, we will briefly discuss the biology and hypothetical mechanisms of Abeta, presenilins, apoE and tau protein, those involved in the pathogenesis of AD.

Molecular Neurobiology of Alzheimer's Disease

Alzheimer's disease (AD), the most common dementia in the elderly, is associated with a characteristic neuropathology:extracellular neuritic plaques (NPs) and intraneuronal neurofibrillary tangles (NFTs). AD is diagnosed clinically on the basis of progressive cognitive impairment. However, the diagnosis of AD is only reliable if a histopathological examination at autopsy shows high numbers of NPs and NFTs particularly in the hippocampus and cerebral cortex. The major component of NP is beta-amyloid protein (Abeta), a fragment of the amyloid precursor protein (APP). NFTs are largely composed of paired helical filaments (PHFs) containing abnormally phospholylated form of the microtubule-associated protein (MAP), tau. A genetic etiology for AD has been established based on population survey. It is revealed that 25-40% of the AD patients are familial and the disease is inherited as an autosomal-dominant trait in most families. Age at onset patterns of AD patients in affected families had indicated that its distribution is bimodal with a cut-off age 58 years. Several mutations in the APP gene, located on chromosome 21, are linked to early-onset AD (EOAD). However, these account for only a small fraction of cases of EOAD. The remaining cases are associated with mutations in two other genes:one on chromosome 14 that encodes S182 (presenilin 1) and the other on chromosome 1 that encodes STM2 (presenilin 2). It is also known that inheritance of specific apolipoprotein E (apoE) alleles, located on chromosome 19, determines the risk and mean age of onset of late-onset AD (LOAD). In this review, we will briefly discuss the biology and hypothetical mechanisms of Abeta, presenilins, apoE and tau protein, those involved in the pathogenesis of AD.