Multicenter Clinical Trials for Efficacy and Safety of Mirtazapine in Moderate-to-Severe Major Depressive Patients / 대한정신약물학회지

OBJECTIVE: The purpose of this study is to evaluate the efficacy and safety of mirtazapine treatment in multicenter population consisting of Korean patients suffering from moderate-to-severe depression. METHODS: Total 163 of in and outpatients with a diagnosis of major depressive disorder (DSM-IV) and 18 or over scores of 17-items Hamilton Rating Scale for Depression (HAMD) received treatment with mirtazapine (15-45 mg/day) for 6 weeks. Efficacy was assessed by HAMD, Montgomery and Asberg Depression Rating Scale (MADRS), Beck's Depression Inventory (BDI), and Clinical Global Impression (CGI) scales and statistical analyses were performed on the intent-to-treat sample (143 patients) using the last-observation-carried-forward method. In addition, reported adverse events, routine laboratory parameters, and vital signs were investigated to evaluate the safety of mirtazapine. RESULTS: Mean daily dose of mirtazapine was 28.4 mg. At the end of the study, the response rate (50% or more reduction from baseline in HAMD scores) was 75.5% and the remission rate (7 or less in HAMD score) was 42.7%. Mirtazapine treatment induced significant reduction in depressive symptoms at the 4(th) day and substantial reduction along the treatment period, as assessed by changes in HAMD, MADRS, BDI, and CGI scales. At the 4(th) day and first week of mirtazapine treatment, the mean HAMD-17 total score was significantly reduced compared that of the baseline and the response rates were 11.9% and 28.7%, respectively. Mirtazapine was well tolerated in general, and somnolence and sedation were the most common adverse events reported. In addition, there were no clinically relevant changes in laboratory parameters and vital signs, although body weight was increased. CONCLUSION: Although this trial had many limitations of open non-comparative study, mirtazapine was demonstrated to an effective treatment for moderate to severe major depressive disorder and was well tolerated. A potentially rapid onset of overall therapeutic efficacy of mirtazapine was suggested by significant changes in all major variables of efficacy after 4(th) day of treatment.

Korean Epidemiologic Catchment Area(KECA) Study for Psychiatric Disorderscc: Prevalence of Specific Psychiatric Disorders / 신경정신의학

OBJECTIVES: This study aims to estimate the prevalence of the DSM-IV psychiatric disorders in Korean population using the Korean version of Composite International Diagnostic Interview (K-CIDI). METHODS: Subjects were selected by taking multi-stage, cluster samples of 7,867 adult household residents, 18 to 64 years of age, in ten catchment areas. Total 78 trained interviewers administered the K-CIDI to the selected respondents, from June 1 to November 30, 2001. RESULTS: Total 6,275 respondents completed the interview. Some 33.5% of respondents reported at least one lifetime disorder, 20.6% reported at least one-year disorder, and 16.7% reported at least one-month disorder. The most common lifetime disorders were alcohol abuse/dependence (17.24%), nicotine dependence/withdrawal (11.19%), specific phobia (5.16%), and major depressive disorder (4.25%). The lifetime prevalence of substance abuse/dependence (0.25%) and schizophrenia (0.16%) was very low. Nicotine and alcohol use disorder showed very high male/female ratio. Mood disorder and anxiety disorder were more prevalent among female than male. CONCLUSION: The prevalence of psychiatric disorders was high. In comparison with other studies, remarkable differences in distributions of psychiatric disorders across the areas and times were observed.

A Preliminary Study for the Development and the Standardization of Korean Version of the Intrinsic/Extrinsic Religious Orientation Scale / 신경정신의학

OBJECTIVES: This study was designed and conducted to develop and standardized Korean version of intrinsic and extrinsic religious orientation scale. METHODS: The sample consisted of 209 Christians living in Seoul and Kyungkido. The 26 items were collected from religious orientation scale of Allport and Ross, Feign, Hoge, and Gorsuch and McPherson. The reliability and validity were tested. RESULTS: The Korean version of intrinsic and extrinsic religious orientation scale of this study showed high internal consistency, test-retest reliability. The exploratory factor analysis revealed eight factors, but confirmatory factor analysis showed all items were fallen under intrinsic and extrinsic categories. The correlation between intrinsic religiosity and Spiritual well-being scale was statistically significant, but the correlation between extrinsic religiosity and Spiritual well-being scale was statistically insignificant. And intrinsic religiosity positively correlated with depression and trait-anxiety, but extrinsic religiosity showed no statistically significant correlation with depression and trait-anxiety. CONCLUSION: This is a preliminary study. The Korean version of intrinsic and extrinsic religious orientation scale was found to be a reliable and valid instrument for screening religious orientation. More refining of the items should be necessary.

Efficacy and Safety of Olanzapine in the Treatment of Korean Patients with Schizophrenia and Schizophreniform Disorder: Open Multicenter Clinical Trial / 신경정신의학

OBJECTIVE: This multicenter clinical trial was carried out to investigate the efficacy and the safety of olanzapine for the treatment of Korean patients. METHOD: 105 patients with schizophrenia and schizophreniform disorder, visited at 10 mental or university hospitals, had received an open and non-comparative treatment with olanzapine for 8 weeks. Patients had psychotic or depressive symptoms with the severity above moderate degree or intolerable side effects to previous antipsychotics. After a wash-out period of 2-7 days, 10mg olanzapine was prescribed initially to all the patients, and then the dosage could be adjusted within the range of 5-20mg/day of olanzapine by 3-7 days. RESULTS: 90(85.7%) of 105 patients completed the 8-weeks trial and the mean modal dose of olanzapine was 16.1(+/-4.7)mg/day. At the end of the trial, 73 patients(69.5%) were classified as responder, which was defined as 40% or more improvement in BPRS(Brief Psychiatric Rating Scale) score comparing to baseline. There was a significant reduction in the scores of PANSS(Positive and Negative Syndrome Scale) and subscales including negative symptom scores and CGI. Also weekly analysis showed that the reductions in scores were kept on for the whole period of the trial. 43.8% of all the patients had depressive symptoms at the baseline and total scores of MADRS(Montgomery-sberg Depression Rating Scale) and HAM-A(Hamilton Rating Scale for Anxiety) were also reduced after the trials. Vital signs revealed no clinically significant changes but continuous weight gain was observed during the treatment with olanzapine. The scores of SAS(Simpson-Angus Scale) and AIMS(Abnormal Involuntary Movement Scale) for assessing the EPS(extrapyramidal symptoms) and tardive dyskinesia respectively were significantly decreased and only a few patients reported EPS as adverse events. Although mild and clinically non-significant elevation of ALT/SGPT was observed, most laboratory parameters including plasma prolactin level showed no significant changes during the trial. CONCLUSIONS: Although this trial had many limitations because it was a non-comparative and open study, olanzapine showed high efficacy on the positive, negative and depressive symptoms in schizophrenia and schizophreniform disorder. In addition to that, olanzapine showed a substantially favorable safety profile, such as low incidence of EPS and hyperprolactinemia.

Effects of Naltrexone on the Tyrosine Hydroxylase Expression in the Hypothalamic Areas in Rats with Chronic Ingestion of 5% Ethanol / 대한정신약물학회지

OBJECTIVE: This study was designed to evaluate the effects of nonselective opioid antagonist naltrexone on the expression of tyrosine hydroxylase (TH) in variable areas of hypothalamus in rats with chronic ingestion of 5% ethanol using immunohistochemical measures. METHODS: To induce polydipsia with 5% ethanol, Spraque-Dawley rats were placed in automatic cage where a pellet dispenser automatically dispensed 90 mg pellets at fixed time 60 seconds (FT 60s) feeding schedule over 150-minute test session. After 4 weeks of daily exposure to the FT 60s feeding schedule, experimental rats were administered naltrexone (0.25 mg/kg, i.p), vehicle (1 cc/kg, i.p) for 3 weeks. After completing the 3 weeks of naltrexone and vehicle injections, the polydipsic rats were sacrificed. The brains were removed and postfixed in the same overnight fixation, then frozen sections of 40microM thickness were made in the coronal plane. Sections were stained for detection of tyrosine hydroxylase (H) according to the immunohistochemical method. RESULTS: 1) Both experimental animals with schedule-induced polydipsia (IP) and the bolus with 5% ethanol control showed significant increase in the amounts of 5% ethanol ingestion as compared with their baseline. The naltrexone treated group showed significant decrease in the amount of 5% ethanol ingestion at 2nd and 3rd week as compared with their baseline. Meanwhile, the vehicle control showed no changes in the amount of 5% ethanol ingestion for 3 weeks as compared with their baseline. 2) There was diffused and definite decreases in the TH immunoreactive cells in the bolus control with chronic ingestion of 5% ethanol. The SIP with water group showed marked increase in TH immunoreactive cells in the paraventricular nucleus and the periventricular hypothalamic nucleus. The SIP with 5% ethanol group showed definite decrease of TH immunoreactive cells in the paraventricular nucleus and the periventricular hypothalamic nucleus. The naltrexone treated group showed significant increase of TH immunoreactive cells in the paraventricular nucleus but no changes in the periventricular hypothalamic nucleus. CONCLUSION: These results suggest that the fixed time feeding procedure for schedule induced polydipsia as an animal model of alcoholism was not suitable. The author identified that naltrexone has suppressed the ingestion of ethanol. The chronic ingestion of 5% ethanol suppress the TH immunoreactive cells in the paraventricular nucleus and the periventricular hypothalamic nucleus. Naltrexone increases the TH immunoreactive cells which was suppressed by chronic ingestion of 5% ethanol in the paraventricular nucleus.

Effects of Fluoxetine on Tyrosine Hydroxylase Expression in Schedule-Induced Polydipsia Rats / 신경정신의학

OBJECTIVE: It has been suggested that fluoxetine inhibits the dopaminergic neurotransmission by serotonergic mediation. And also, it has been shown to inhibit synthesis of DOPA in dopamine-rich areas of the rat forebrain. These dopamine-antagonistic capacity of fluoxetine is only supported by anecdotal report that the increased amount of motor disability in patients with idiopathic Parkinson's disease after exposure to fluoxetine. However, there is still no evidence of the direct effect of fluoxetine on dopaminergic neuronal cell body in the substantia nigra, VTA, caudate & putamen. This study was designed to evaluate the effects of fluoxetine in rat brain which showed decreased numbers of dopaminergic neuronal cell body induced by schedule-induced polydipsia(SIP). METHODS: We incidentally found that 4 weeks of schedule-induced polydipsic rats revealed the suppression of tyrosine hydroxylase expression in the substantia nigra, VTA, caudate & putamen with the immunohistochemistric measures. After 3 weeks of intraperitoneal injection of 10mg/kg of fluoxetine to the schedule induced polydipsic rats, the tyrosine hydroxylase expression was also measured with immunohistochemistry. We compared the tyrosine hydroxylase expression among the normal control, the polydipsic rats, and the rats with fluoxetine treatment. RESULTS: 1) By contrast with the control, the polydipsic rats revealed the evidence of decreased tyrosine hydroxylase expression in the substantia nigra, VTA, caudate & putamen. 2) After daily injection of fluoxetine for 3 weeks, the polydipsic rats showed increment of tyrosine hydroxylase expression in those areas. CONCLULSION: In previous studies, a great deal of results suggest that fluoxetine negatively influence the dopaminergic systems indirectly via serotonergic activation such as inhibition of dopamine synthesis or transport system. Although our results are obtained from rodents, we suggest that fluoxetine directly and positively enhance the dopamine system in the substantia nigra, VTA, caudate & putamen. The chronic adminstration of fluoxetine may be helpful to dopamine-depleted condition in clinical situations. We anticipate the replication studies of our findings and well-controlled clinical trial.

Effects of Risperidone on the Schedule-Induced Polydipsia in Rats / 신경정신의학

OBJECTIVES: This study was designed to evaluate the effects of risperidone on the schedule-induced polydipsia (SIP) which is one of animal model of obsessive-compulsive disorder in rats. We administered risperidone as a serotonin and dopamine blocking agent, fluoxetine as a selective serotonin reuptake inhibitor, and haloperidol as a dopamine antagonist to rats which showed schedule-induced polydipsic behaviour. METHODS: Sprage-Dawley rats weighing 200 - 250gm were individually housed and main-tained and allowed free access to water. The rats were placed on a restricted diet. To induce polydipsia, rats were placed in the cage where a pellet dispenser automatically dispensed 90mg pellets on a fixed-time 60 seconds (FT 60s) feeding schedule over 150 minute test session per day. Water was available at all times in the cage. After 4 weeks of daily exposure to the FT 60s feeding schedule, experimental rats met a predetermined criterion for polydipsic behavior (greater than 3 times of water per session on average). 5 groups of rats were administered risperidone (0.1mg/kg, i.p), risperidone (0.5mg/kg, i.p), fluoxetine (5mg/kg, i.p.), haloperidol (0.1mg/kg, i.p.), and vehicle (1cc/kg, i.p. ) for 3 weeks. The rats were tested once a week to access schedule induced polydipsic behavior. Water bottles were weighed before and after the 150-minute test session. The chronic effects of administration of experimental drugs on schedule induced polydipsic behavior were analyzed with ANOVA and Scheffe test as a posthoc comparison. In order to measure water consumption in non-polydipsic food-deprived rats, a separate group of rats (N=8) was individually housed and given a single bolus (14.5gm) of food per day which maintained them at their average body weight. RESULTS: The results were as follows; 1) After 4 weeks of scheduled feeding procedure, the experimental group showed significant differences than the bolus control in the amount of water consumption as compared with their average water intakes for 4 weeks. At the same periods, there were no differences between the experimental group and the bolus control in the body weight. 2) The fluoxetine group showed significant decrease in the amount of water intake at 1st, 2nd, and 3rd weeks of drug treatment as compared with their average amount of polydipsic water intakes. The risperidone 0.1mg group and the risperidone 0.5mg group showed significant decrease in the amount of water intake at the 3rd weeks of drug treatment as compared with their baseline of polydipsic water intakes. However, the haloperidol group and the vehicle control group showed no changes of amounts of water intake for 3 weeks of treatment as compared with their baseline of polydipsic water intakes. 3) The fluoxetine group (22.5+/-10.4ml) showed significantly lower amounts of water intake than haloperidol group (41.3+/-7.1ml) at 2nd weeks of drug treatment. And also the fluoxetine group (18.8+/-3.5ml) showed significantly lower amounts of water intake than the haloperidol group (35.0+/-11.7ml) and the vehicle control (34.4+/-6.8ml) at 3rd weeks of drug treatment. The risperidone 0.1mg group and the risperidone 0.5mg group showed significantly lower amounts of water intake than the haloperidol group (35.0+/-11.7ml) at 2nd weeks and the vehicle control (37.5+/-12.5 , 34.4+/-6.8ml) at 2nd and 3rd weeks of drug treatment. CONCLUSIONS: Above findings suggest that the fixed time feeding procedure for schedule induced polydipsia could be applied as an effective animal model of obsessive compulsive disorder for the evaluation of pharmacological challenge study. We confirmed that chronic treatment with risperidone revealed antipolydipsic effect as effective as fluoxetine on the schedule-induced polydipsic behaviour but the onset of effect was later than fluoxetine.

Effects of Opioid Agonists on the Suppressed Spontaneous Alternation Behaviour in Rats

This study was designed to evaluated the effects of opioid receptor agonists on the spontaneous alternation behaviour in an animal model of obsessive-compulsive disorder in rats. According to the theory that dopamine is related to the biological etiology of obsessive-compulsive disorder, the effect of the nalbuphine(opioid kappa agonist) and the tramadol(opioid mu agonist), which act as manipulating agents on the inhibition or stimulation of dopamine release, in the spontaneous alternation behaviour were evaluated. 24 hours prior to the experiment, rats were food-deprived. These rats were put into the T-maze, in which white and black goal boxes were baited with small amounts of chocolate milk. Each rat was given 2 set of 7 trials during which it was placed in the start box and allowed to choose the one of the goal boxes for each time. After identifying the stable baseline of spontaneous alternation behaviour, nonselective 5-HT agonist 5-MeODMT(1.25mg/kg/IP) disrupted spontaneous alternation. Rats were stratified into fluoxetine(10mg/kg/IP), nalbuphine(10mg/kg/IP), tramadol(46.4mg/kg/IP), and saline(0.5cc/IP) injection group with experimental drug treatment for 21 days. The effects on the 5-M?DMT(1.25mg/kg/IP) induced disruption of spontaneous alternation behaviour were checked at the next day of discontinuation of drug treatment. The results were as follows : 1) At the day after 21 days of the drug treatment, the nalbuphine treated group and the fluoxetine treated group showed significant difference from the tramadol treated group and the saline treated group in the 5-MeODMT(1.25mg/kg/IP) induced suppression of spontaneous alternation behaviour. 2) Within each drug treatment group, the fluoxetine treated group showed significant difference between before and after the treatment of fluoxetine in the 5-MeODMT(1.25mg/kg/IP) induced suppression of spontaneous alternation behaviour. And also, the nalbuphine treated group showed significant difference between before and after the treatment of nalbuphine in the 5-MeODMT(1.25mg/kg/IP) induced suppression of spontaneous alternation behaviour. There was no difference between the baseline and after the treatment of nalbuphine in the 5-MeODMT(1.25mg/kg/IP) induced suppression of spontaneous alternation behaviour. We indentified that the opioid kappa agonist that act as dopamine release inhibitor affect the spontaneous alternation behaviour which is an animal model of obsessive-compulsive disorder in rat.

Effects of Olanzapine on the Schedule-Induced polydipsic Rats

OBJECT: This study was designed to evaluate the effects of olanzapine on the schedule-induced polydipsia(SIP) which is one of animal model of obsessive-compulsive disorder in rats. We administered olanzapine as a serotonin and dopamine blocking agent, fluoxetine as a selective serotonin reuptake inhibitor, and haloperidol for the dopamine antagonist to rats which showed schedule-induced polydipsic behavior. METHODS: Spraque-Dawley rats weighing 200-250gm were individually housed and maintained and allowed free access to water. The rats were placed on a restricted diet. To induce polydipsia, rats were placed in the cage where a pellet dispenser automatically dispensed 90mg pellets on a fixed-time 60 seconds(FT-60s) feeding schedule over 150 minute test session per day. Water was available at all times in the cage. After 4 weeks of daily exposure to the FT 60s feeding schedule, experimental rats met a predetermined criterion for polydipsic behavior(greater than 3 times of water per session on average). 5 groups of rats were administered olanzapine(3mg/kg, i.p), olanzapine(10mg/kg, i.p), fluoxetine(5mg/kg, i.p.), haloperidol(0.1mg/kg, i.o), and vehicle(1cc/kg, i.p) for 3 weeks. The rats were tested once a week to access schedule induced polydipsic behavior. Water bottles were weighted before and after the 150-minute test session. The chronic effects of administration of experimental drugs on schedule induced polydipsic behavior were analyzed with ANOVA and Scheffe test as a post-hoc comparison. In order to measure water consumption in non-polydipsic food-deprived rats, a separate group of rats(N=8) were individually housed and given a single bolus(14.5gm) of food per day which maintained them at their average body weight. RESULTS AND CONCLUSION: There results were as follows : 1) After 4 weeks of scheduled feeding procedure, the experimental group showed significant differences than the bolus control in the amount of water consumption as compared with their average water intakes for 4 weeks. At the same periods, there were no differences between the experimental group and the bolus control in the body weight. 2) The fluoxetine group showed significant decrease in the amount of water intake over the 3 weeks of drug treatment as compared with their average amount of polydipsic water intakes. The olanzapine 3mg group showed significant decrease in the amount of water intake at 3rd weeks of drug treatment as compared with their average amount of polydipsic water intakes. The olanzapine 10mg group showed significant decrease in the amount of water intake at 2nd and 3rd weeks of drug treatment as compared with their average amount of polydipsic water intakes. However, the haloperidol group and the vehicle control group showed no changes of amounts of water intake for 3 weeks of treatment as compared with their average amount of polydipsic water intakes. 3) The fluoxetine group showed significantly lower amounts of water intake than the haloperidol group at 2nd weeks of drug treatment. And also the fluoxetine group showed significantly lower amounts of water intake than the haloperidol group and the vehicle control at 3rd weeks of drug treatment. The olanzapine 3mg group and the olanzapine 10mg group showed significantly lower amounts of water intake than the haloperidol group and the vehicle control at 3rd weeks of drug treatment. Above findings suggest that the fixed time feeding procedure for schedule-induced polydipsia as an animal model of obsessive compulsive disorder was effective to the evaluation of pharmacological challenge study. The authors assume that the serotonin hypothesis and the serotonin-dopamine interaction hypothesis are preferred to the dopamine hypothesis in the biological etiology of obsessive-compulsive disorder.

Effects of the Clozapine on the Suppressed Spontaneous Alternation Behaviour in Rats / 신경정신의학

OBJECTIVES: The study was designed to evaluate the role of the 5-HT2 and dopanmine D2 antagonist on spontaneous alternation behaviour which is an animal model of obsessive compulsive disorder in rat. On the basis of serotonin-dopamine interaction hypothesis, the effect of clozapine was evaluated by applying the suppressed spontaneous alternation behaviour model. METHODS: The apparatus for spontaneous alternation behaviour was a black plexiglas T-maze with distinctive black and white goal boxes. Black guillotine doors separated the start box and the goal boxes from the main body of the T-maze. Small cups of chocolate milk were placed in the corners of both goal boxes. At 24 hours prior to experiment, rats(spraque-Dawley) were food-deprived. The food-deprived rate were put into T-maze, in which both goal during which it was placed in the start box and allowed to choose one of the goal boxes for each time. The mean number of choices until the occurrence of spontaneous altemation behaviour were checked. After baseline of the number of choices of spontaneous altemation behaviour was stabilized, the spontaneous altemation was disrupted by nonselective 5-HT agonist, 5-MeODMT(1.25mg/kg/IP). The experimental animals were stratified nito 5 groups : clomipramine(5mg/kg/IP), clozapine(10mg/kg/IP), clozapine(20mg/kg/IP), haloperidol(0.1mg/kg/IP), and saline(0.2cc/IP) control groups. They all went through 21 days fo treatment(intraperitoneal). The protective effects against the 5-McODMT-induced disruption of spontaneous alternation behaviour were evaluated on the next day of drug treatment in each group. RESULTS: 1) SAB was supressed by 5-McODMT injection. 2) After 21 days of the drug treatment, the clozapine and the clomipramine groups showed significant difference from the haloperidol and the saline control groups in the reversal of 5-McODMT-induced from the haloperidol and the saline control groups in the reversal of 5-MeODMT-induced suppression of spontaneous altermation behaviour. 3) The clozapine(20mg/kg/IP) group was superior to the clomipramine group in the protective effect of 5-MeODMT-induced suppression of spontaneous alternation behaviour. CONCLUSION: In clinical situation, the we think that atypical antipsychotic drugs those acting as serotonin and dopamine receptor antagonist with no extrapyramidal side effect can be beneficial to improve the symptoms of obsessive-compulsive disorder.

Effects of Sertraline on the 1% Sucrose Consumption and the Body Weight Following Chronic Unpredictable Mild Stress in Rats / 신경정신의학

The study was designed to evaluate the effects of sertraline on l% sucrose intake and weight change in rats with chronic unpredictable mild stress and normal controls. We applied 11 types of stress regimens and identified depressive behaviours in 18 Spraque-Dawley rats for 8 weeks. After 4 weeks of chronic unpredictable mild stress procedure, those 18 rats were stratified into a sertraline-treated subgroup and a saline subgroup. Also nonstressed 18 rats were stratified into the sertraline-treated subgroup and the saline subgroup and were started intraperitoneal injections of sertraline(4.29mg/Kg) or saline for rest of 4 weeks. The 1% sucrose intake and the body weight were checked on the 4th day of every week, over the 8 weeks of experiment. The results were as follows: 1) The sertraline-treated subgroup of chronic unpredictable mild stressed rats showed significant increase of 1% sucrose intake between the 1st week and the 2nd, the 3rd and 4th week, while the sertraline-treated subgroup of non-stressed rats showed decreasing trend for 1% sucrose intake. 2) The sertraline-treated subgroup of chronic unpredictable mild-stressed rats showed a sustained decrease of body weight, while the sertraline-treated subgroup of non-stressed rats showed a non-significant increase of body weight. 3) In the group subjected to chronic unpredictable mild stress, there were no significant correlations between 1% sucrose intake and body weight and also no correlations in the nonstressed group. In summary, sertraline had an effect on restoring the decreased 1% sucrose intake to normal condition but no effect on regaining the body weight in the chronic unpredictable mild stresstreated rats. Sertraline resulted in a decrease of l% sucrose intake and no effect on body weight in the non-stressed rats.

A Cabe of Clozapine-Induced Agranulocytosis / 신경정신의학

We report a 20-year-old female patient who developed clozapine-induced agranulocytosis on the 29th day of clozapine treatment. She recovered from the agranulocytosis on the 8th day of progression after treatment with G-CSE, GM-CSF, antibiotics and associated aseptic procedures. The cause of clozapine-induced agranulocytosis is still un known and it is proposed that the dominant gene of major histocompatibility complex region and the reactive metabolites which suppress the myeloid system may be responsible. We recommend that careful attentions such as the selection of patient, evaluation of the risk factors, and the thorough control of CPMS should be paid. If the agranulocytosis happens, it is helpful to consult to the department of medicine immediately.

Influences of Christian Belief on the Treatment of Schizophrenic Outpatients / 신경정신의학

OBJECTIVES: Many psychiatrists ignore the behavioral and attitudinal aspects of religious beliefs of patients with schizophrenia. Therefore, how the Christian belief affects the treatment of schizophrenia was investigated. METHODS: The subjects of the study were 13 schizophrenic outpatients with protestant belief having partial or full insight. GAF score of each of the patients was above 41. RESULTS: A. Positive effects; 1) Taking the patient's belief seriously without prejudice was helpful to therapeutic relation. 2) Faith fulfilled it's function of silencing the anxiety of the patients. 3) The factors which make schizophrenic patients develop self-identity and self-concept in their religious lives were as follows; social identity as a Christian, religious identity as a child of God, experiences of safe dyadic relationship with God, feelings of being always accepted by God, and experiences of being accepted safely by the church. 4) Faith experiences and spiritual enlightenment itself had a therapeutic impact on the patients as a guiding principle of their lives and blueprints for their actions. 5) Experiences of a safe dyadic relationship with God, feelings of being accepted by God, faith experiences, and spiritual enlightenment provided peculiar religious experiences which can not be found in everyday life. And these peculiar religious experiences seemed to have healing power. B. Negative effects; 1) The clergymen and the members of the church put the patients and their families into the confusion by compelling or recommending religious treatment methods like prayer retreats. 2) They interfered with patients getting insights by interpreting their symptoms religiously. 3) There was a risk of cognitive defect of grasping faith literally. 4) There was a tendency to direct punishment and blame inwards, on to the self with guilty feelings. CONCLUSIONS: Christian belief exerted many influences both good and bad, on the treatment of the schizophrenic outpatients. We suggest that psychiatrists should consider the influence of the patient's faith upon the treatment.

Effects of Combined Treatment with Fluoxetine and Choline on the Retention of Passive Avoidance Learning after Chronic Mild Stress in Rat / 신경정신의학

This study was performed to evaluate the effects of serotonin and choline on the memory function in rat model of depression. Chronic exposure to mild unpredictable stress was found to depress the consumption of sweet 1% sucrose solution in the Sprague-Dawley rats. We identified depressive behaviours in 27 Sprague-Dawley rats. Rats in experiments were stratified into 3 groups, ie, fluoxetine with choline, choline, and saline control. Memory function was evaluated by passive avoidance learning and retention tests. We evaluated how long memory retention would remain improved at training-testing intervals of 1 day, 1 week, 2 week, 3 week, and 4 week in depressive state of the Sprague-Dawley rats during 4 weeks of experimental drugs treatment. The results were as follows: 1) The fluoxetine with choline-treated group showed significant differences in the maintenance of retention from the saline control at 1, 2, 3, and 4 week training-testing interval. 2) The choline-treated group showed significant differences in the maintenance of retention from the saline control at 3 and 4 week training-testing interval. In summary, the combined treatment of fluoxetine with choline showed earlier effects on memory function compared with choline alone in the passive avoidance retention test in the animal model of depression. We suggest that there are synergistic interaction between serotonin and choline in the long term memory function in rat model of depression.

The Relationship between Depressive Tendency in Postpartum Women and Factors such as Infant Temperament, Parentiong Stress and Coping Style / 신경정신의학

OBJECTIVES: This Study examined the relationship of depressive tendency in postpartum women with psychosocial factors such as infant temperament, parental stress and coping style. METHODS: The subjects consisted of 105 postpartum women, each of whom had an infant aged 4 to 12 months. They were assessed on demographic variables and on measures of the depressive symptomatology, infant temperament, parental stress and the coping style using Beck Depression Inventory(BDI), the EAS temperamental survey, Parenting Stress Index(PSI), the Way of Coping Checklist(WCC). And then we assessed the relationship of depressive tendency in postpartum women with psychosocial factors. RESULTS: The results were as follows: 1) Depressive tendency in postpartum women had significant relationship with emotionality(r=.26 p<0.05) and activity(r=.22 p<0.05) of infant temperament. 2) Depressive tendency in postpartum women had significant relationship with parenting stress(r=.44 p<0.001). 3) Depressive tendency in postpartum women had no significant relationship with coping style. 4) Parental stress had significant relationship with emotionality(r=.49 p<0.001) but did not have any relationship with sociability and activity of infant temperament. Parenting stress had no significant relationship with coping style. CONCLUSION: These results suggest that depressive tendency in postpartum women correlated with emotionality and activity of infant temperament correlated with parenting stress but not correlated with coping style. Infant temperament and parenting stress to child rearing are more significantly correlated with depressive tendency in postpartum women than coping style of postpartum women.

There Cases of Extrapyramidal Symptoms Following Fluoxetine / 신경정신의학

The selective serotonin reuptake inhibitor fluoxetine is one of the most frequently prescribed drugs for the treatment of depression and other psychiatric disorders. In the few years, there have been several reports of adverse effects encountered during coadministration of fluoxetine with or without other psychotropic drugs. We experienced three cases of extrapyamidal symptoms were developed when administered fluoxetine alone and with neuroleptics. We conclude that there is a probable or possible causal relationship between fluoxetine and extrapyramidal side effects. The pathogenesis of such adverse reactions, which may be hetero-geneous, is unknown, but it has been suggested that they might be caused by serotonergically mediated inhibition of dopaminergic transmission. From reports in those cases, it appears that fluoxetine alone may be associated with extrapyramidal side reactions. Furthermore the potential for increased levels of concomitant psychotropic medicines and increased side effects, should be borne in mind.

Effects of Selective Serotonin Reuptake Inhibitors on the Retention of Passive Avoidance Learning after Chronic Mild Stress in Rats

The study was designed to evaluate the significant roles of SSRI in rat of depression model. Chronic exposure to mild unpredictable stress has been found to depress the consumption of sweet 1% sucrose solutions in the Sprague-Dawley rats. We applied the variety of 11 types of stress regimens and identified depressive behavious(developed by Willner) in 70 Sprague-Dawley rats. Rats in experiments were stratified into 6 groups, i.e.; 3 kinds of SSRI(paroxetine, fluoxetine, sertraline), clomipramine, choline and saline control. Memory function was evaluated by passive avoidance learning and retention test. The authors determined how long memory retention would remain improved with 24 hour, 1 week, 2 weeks, 3 weeks, and 4 weeks at training-testing interval in depressive states of the Sprague-Dowley rats. The results were as follows; 1) There were to significant differences between the 6 groups at the 24 hour training-testing interval. 2) The paroxetine treated group showed significant differences from the control group at the 1 week and 2 weeks training-testing interval. 3) The paroxetine and the fluoxetine treated groups showed significant differences from the control group at 3 week training-testing interval. 4) The paroxetine and the choline treated groups showed significant differences from the control group 4 week training-testing interval. In summary, paroxetine had on effect on long term memory processing from 1st week to 4th week. Also, fluoxetine(or 3rd week) and choline(at 4th week) had effect on long term memory processing. Sertraline, clomipramine were ineffective on memory processing during 4 weeks observation. Possible explanations why paroxetine had early effect on memory processing than the other selective serotonin reuptake inhibitors are rapid bioavailability, which is the characteristics of pharmacokinetics of paroxetine. In clinical situation, author carefully suggest that SSRI would be beneficial to improve the memory function caused by depressive neurochemical changes.

Psychiatric Characteristics of the Patients with Myofascial Pain Syndrome / 신경정신의학

We investigated the possible association between depression, anxiety, severity of recent stress in patients with myofascial paul, with chronic myofacial pain syndrome. On the initial visit, 30 subjects completed the following psychometiic battery Beck Depression Inventory, Spielberger State-Trait Anxiety Inventory and Global Assessment of Recent Stress. As compared with the neurosis control group and the healthy control group, the results were as follows: 1) The myofascial paul group showed higher scores than the healthy controls but lower than the neurosis controls, in the Spielberger State-Trait Anxiety Inventory. 2) The myofascial pain group showed higher scores than the healthy controls but lower than the neurosis controls, in the total score of Beck Depression Inventory. 3) The myofascial pain group showed higher scores than the healthy controls but lower than the neurosis controls, in the score of Global Assessment of Recent Stress. 4) In the factor analysis of Beck Depression Inventory, the myofascial pain group showed significantly higher scores than the healthy controls but lower than the neurosis control in the somatic symptom subscale. However, there were no significant differences among the myofascial pain group and other control groups in the other subscales. These findings suggest that the myofacial pain group is more anxious and depressed and more preoccupied with their somatic symptoms due to their myofacial pain and more stressed in recent periods. The authors propose that the psychiatric management is helpful in intervening with the progression of myofacial pain.

A Study of Self-Engulfment in Schizophrenic Patients / 신경정신의학

OBJECTIVE: This study was conducted to identify demographic variables and illness related variables which may affect the severity of self-engulfment in the patients with schizophrenia. We also studied the relationship between self-engulfment and insight, and the relationship between self-engulfment and self-esteem. METHODS: Data on demographic variables and illness related variables for the subjects were gathered from hospital records and clinical interviews by the psychiatrists. Degree of insight far the subjects was assessed through clinical interviews by the psychiatrists. Degree of self-engulfment and self-esteem for the subject was assessed from the self-engulfment scale and the self-esteem state respectively. A total of 111 patients with schizophrenia were selected for statistical analysis. RESULTS: 1) The females exhibited significantly higher socres than the males on the self-engulfment scale . 2) There was no illness related variable, which exhibited a significant difference among subgroups on the self-engulfment scale. 3) There was no significant correlation between the self-engulfment stores and the insight scores . 4) There was a significantly inverse correlation between the self-engulfment scores and the self esteem scores. CONCLUSION: The results of this preliminary study suggest that self-engulfment may develop despite lack of insight, and that there was inverse relationship between self-engulfment and self-esteem in the patients with schizophrenia. It also suggests that females are more subject to self-engulfment than males. So, authors suggest that it is valuable to do further studies of self-engulfment in the patients with schizophrenia.

The Effect of Meditation on Problem Solving Ability and Self-Perception / 신경정신의학

This study was conducted to evaluate the effectiveness of meditation on problem solving and self-perception in psychiatric outpatients. Meditation group which had taken the medication and participated in 20 meditation session, and comparison group which had only taken the medication were given Social Problem Solving Inventory(SFSI) and Self-Perception Inventory(SPSI) at pretest and posttest period. The results were as follows: when compared pretest score and posttest score, scores of problem solving cognition subscale and problem solving emotion subscale were increased at a statistically significant level in meditation group. However, scores of comparison group were not changed. In comparison group, scores of problem solving behavior subscale and decision making subscale were decreased at a statistically significant level, and attitudes of self-perception were changed negatively whereas scores of meditation group were not. The results of present study suggested that meditation might have positive effects on perspectives of approaching the problem, and have buffering effects on decreasing of problem solving behavior, decreasing of decision making and negative change of self- perception.