Characteristics of major depressive disorder according to family history of depression : A CRESCEND-K (Clinical Research Center for Depression in Korea) study / 한국역학회지

PURPOSE: People with a family history of mood disorder are more likely to have depression. This study compared the characteristics of non-psychotic major depression disorder according to family history of depression. METHOD: Subjects were total of 817 persons recruited for the CRESCEND-K multicenter trial. Characteristics of depression and suicide history of patients with and without a family history of depression were assessed. Family history was determined through self-report. RESULTS: Of 817 participants, 12.4% had a positive family history of depression. Those with family history of depression reported an earlier age at onset of MDD, and more psychiatric comorbidity. Severity of depression and anxiety were not different according to family history of depression. There were no difference in attempted suicide history, number of attempted suicide and age at onset of 1st attempted suicide according to such a family history. CONCLUSION: Patients with family history of depression reported earlier onset of MDD and more history of psychiatric comorbidity.

Effect of Amantadine on Weight Gain Induced by Olanzapine / 대한정신약물학회지

OBJECTIVE: Weight gain is a commonly encountered problem associated with atypical antipsychotics, especially olanzapine. To investigate the weight reducing effect of amantadine, we conducted an prospective open label study. METHODS: We started amantadine treatment in outpatients who had gained weight during olanzapine treatment (mean dose of 11.94 mg/day, mean weight gain of 6.33 kg). Data were collected at St. Mary's Hospital, College of Medicine, The Catholic University of Korea. The add-on treatment of amantadine was given at a mean dose of 161.9 mg/day with mean duration of administration for 110.2 day. Brief Psychiatric Rating Scale (BPRS), Extrapyramidal Symptom Scale were checked to evaluate the tolerability of amantadine. RESULTS: Before administration of amantadine, the mean dose of olanzapine was 11.94+/-4.58 mg and mean duration of administration was 123.1+/-174.6 days. Body weight and BMI during this period was significantly increased mean 6.33+/-4.45 kg (Z=-3.839, p<0.001), 4.94+/-0.75 (Z=-3.724, p<0.001) respectively. Amantadine was administered mean dose of 161.90+/-58.96 mg for mean 110.2+/-78.7 days. Body weight and BMI was decreased mean 0.96+/-3.44 kg, 0.71+/-2.7, respectively. There was no deterioration in psychiatric symptoms, as shown in BPRS score decrement and no adverse effects were reported. CONCLUSION: The present data suggests that amantadine does not significantly decrease weight gain experienced by some patients during olanzapine treatment and does not worse psychotic symptoms. Randomized placebo-controlled trial should be needed to confirm these findings.

Application of Vagus Nerve Stimulation in Neuropsychiatry / 신경정신의학

OBJECTIVES: Several novel and minimally invasive techniques to stimulate the brain have recently developed. Among these newer somatic interventions, vagus nerve stimulation(VNS) is regarded as a promising tool in the treatment of various neuropsychiatric disorders. This article reviews the history, methodology, and the future of VNS technique and its emerging research and therapeutic applications in the field of neuropsychiatry. METHODS: Wide ranged literature reviews and discussion with pioneering researchers were performed. RESULTS: VNS has been used in the treatment of refractory seizure disorder and depression. There are some reasons to hope that VNS might have other therapeutic applications in neuropsychiatric disorders, as well as advanced understanding about the pathophysiology of these disorders. CONCLUSION: Regardless of its clinical role as a new therapeutic technique, the capacity of VNS as a research tool to alter brain activity should lead to important advances in the understanding of brain-behavior relationships.

A Naturalistic Study of Risperidone Treatment in Affiliated University Hospitals: Focus on Clinical Characteristics / 신경정신의학

OBJECTIVE: This retrospective naturalistic study was designed to compare the clinical characteristics including psychopathology of two groups of patients, long-term maintenance group and short-term drop-out group, who were taking risperidone. METHOD: Datas were collected for 210 schizophrenic patients with complete medical records among 580 patients who were enrolled with risperidone administration from January 1996 to December 1996 in 8 affiliated hospital of the Catholic University. The short-term drop-out patients group were assigned to whom treatment period was less than 6 month, and the long-term maintained patients group, treatment period was more than 2 years. We assessed demographics, psychopathology, and other variables related with medication based on past medical records. RESULTS: Among subjects of 210, short-term drop-out patients group were 67(31.9%) and long-term maintained patients group were 143(68.1%). Demographics and psychopathology were not significantly different between two groups. The starting and maximal dosage of risperidone was not significantly different between two groups but the maintenance dosage of risperidone was lower in long-term medicated patients group than short-term drop-out patients group(t=3.698, p<0.05). Additionally, the result of this study showed differences in experiences of past antipsychotic use as following. The number of no previous use of antipsychotic was 39(58.2%), the number of high potency antipsychotic use was 27(40.3%), and the number of low potency antipsychotic use was 1(1.5%) in short-term drop-out group. The number of no previous use of antipsychotic was 58(40.6%), the number of high potency antipsychotic use was 77(53.8%), the number of low potency antipsychotic use was 8(5.6%) in long-term maintained group(X 2=6.559, df=2, p<0.05). CONCLUSION: According to these results, administration of low therapeutic dosage should be recommended for long-term maintenance as if possible. Multi-center based retrospective naturalistic study like this would be useful for getting informations about efficacy and some other aspects of antipsychotic administration in practical field.

Comparison of Risperidone Prescription Trend for Psychiatric Inpatients between University Hospital of Korea and USA / 대한정신약물학회지

OBJECTIVE: Recently, the domestic use of risperidone and the studies of risperidone administration in naturalistic setting have been increased. This retrospective naturalistic study was designed to evaluate the prescription trend and related variables in risperidone administered-psychiatric inpatients at a university hospital, and to compare with those of a university hospital in USA, simultaneously. METHODS: Data of 42 psychiatric inpatients with first administration of risperidone at St. Mary's Hospital from Oct 1999 to Mar 2000 and 61 of McLean Hospital, Harvard Medical School, USA from Mar 1998 to Jun 1998, were collected, respectively. Data on patient's age, sex, number of past admission, diagnosis distribution, duration of hospitalization, multiple antipsychotic therapy, combined psychotropics, initial, maximal, and discharge dosage of risperidone were analyzed and compared. RESULTS: In forty-two patients of St. Mary's hospital, 17 were male and 25 were female, among sixty-one patients of McLean hospital, 23 were male and 38 were female. The mean age and number of past admission were significantly higher at St. Mary's hospital than McLean hospital. In terms of diagnosis, risperidone was most widely prescribed to psychotic disorder, nextly to mood disorder and other psychiatric disorder at St. Mary's hospital, but in order of mood disorder, other psychiatric disorder, and psychotic disorder at McLean hospital, these diagnostic distribution was significantly different. The mean initial dose, maximal dose, and discharge dose of risperidone were significantly higher at St. Mary's hospital than McLean hospital. In aspects of psychotropic combination, these were significantly different, anxiolytic was most highly used at St. Mary's hospital but antidepressant at McLean hospital, additionally, the two hospital have tendency to take a polypharmacy. CONCLUSION: Prescription trend of risperidone in psychiatric inpatient between two hospital was different, St. Mary's hospital prescribed risperidone by diagnosis but McLean hospital did by symptomatic management. In furture, further systematic study should be conducted to refine these differences including various clinical variables.

Transcranial Magnetic Stimulation in Neuropsychiatry / 신경정신의학

OBJECTIVES: Transcranial magnetic stimulation(TMS) is a new, noninvasive procedure of a localized pulsed magnetic field to the surface of the head to cause a depolarization of neurons in the brain cortex underneath. The magnetic field(Magnetic) is generated by passing current pulses by conducting coil, held close to the scalp so that the field is passing the skull(Transcranial) and is focused in the cortex(Stimulation). Here we provide a summarized review of the methodology of TMS and its application to research and therapeutics in the field of neuropsychiatry. METHODS: We described the history, procedures, basic researches, clinical applications, safety issues, mode of action, and future of TMS using literature review and interview with experts. RESULTS: The earlier clinical uses of TMS had been restricted to the field of neurology where it was used to examine the central and peripheral nervous conduction. However this technology has been widely used to map various brain functions such as visual information processing, language, memory, emotion, and movement. The ability to excite local areas of brain cortex has raised the possibility of the use of TMS as a novel therapeutic tool for various psychiatric disorders. CONCLUSION: TMS is a relatively new and noninvasive method to investigate regional brain activity and to treat several psychiatric diseases. Further work is necessary to firmly establish the efficacy and safety of this promising tool.

Functional Magnetic Resonance Imaging during Motor Activation in Patients with Schizophrenia / 신경정신의학

OBJECTIVES: Recently, functional magnetic resonance imaging(fMRI) has been an important tool for mapping in various functional brain disorders. And it is known that soft neurologic signs are frequently found in schizophrenia. The purpose of this study was to investigate the pattern of cerebral activation to motor tasks examining soft neurologic signs in patients with schizophrenia, non-schizophrenic psychoses, and control subjects, using functional MRI. METHODS: Nine patients with schizophrenia, and six patients with non-schizophrenic psychoses, and six healthy control subjects were examined. A paradigm, in a resting condition followed by an activation state(finger-to-thumb opposition task and fistring task by right hand) was used for blood oxygen level dependent f-MRI. Activated voxels in both motor cortices and supplementary motor cortex were recorded and the lateralization index of cortical response was measured. RESULTS: Patients with schizophrenia showed typical increased activation in right motor cortex and reversed lateralization by finger-to-thumb opposition task compared with non-schizophrenic psychoses and contol subjects. CONCLUSION: The present study provides evidence for specific reversed lateralizaiton in fMRI brain activation by motor task in patients with schizophrenia. FMRI will be used as a powerful tool for elucidating the pathophysiology of schizophrenia.

A Naturalistic Study of Atypical Antipsychotic Use in Inpatients with Bipolar I Disorder / 신경정신의학

OBJECTIVES: This study was conducted to evaluate the prescription patterns, overall efficacy, and safety of atypical antipsychotics for inpatients with bipolar I disorder. METHODS: Inpatients with bipolar I disorder, who had received adjunctive treatment with olanzapine or risperidone, beyond 1 month, along with mood stabilizers were selected for a retrospective study. The charts of those patients(N=56) were reviewed for the details of efficacy, safety, and other pharmacological variables of the two drugs. RESULTS: Olanzapine and risperidone showed equivalent efficacy by the evaluation in accordance with clinical global impression scale (CGI) and global assessment of functioning scale(GAF) score. Different side effect profiles were noted between two drugs. CONCLUSION: These limited results suggested that the efficacy and safety of risperidone and olanzapine were similar for the treatment of inpatients with bipolar I disorder. Prospective controlled study for efficacy and safety of risperidone and olanzapine in the treatment of bipolar I disorder should be conducted in future.

Restriction Fragment Length Polymorphism of Tumor Necrosis Factorbeta Gene in Schizophrenia / 신경정신의학

OBJECTIVE: Schizophrenia is known to have high genetic influences. Recently, the main focus of etiologic study in schizophrenia has been concentrated on molecular genetic approach including polymorphism analysis. This study was designed to investigate the relationship between schizophrenia and immunologic influences by analyzing polymorphism of TNFB that is involved in interaction between immunologic system and CNS. METHOD: 146 schizophrenic patients diagnosed by DSM-IV criteria were included and data of 206 normal population from the Catholic Hemopoietic Stem Cell Information Bank(Seoul, Korea) were used as a control group in this study. DNA was extracted from whole blood, thereafter amplified by polymerase chain reaction, and digested by NcoI. We obtained and assessd RFLP of two alleles, TNFB1 which has a NcoI restriction site generating 555bp and 185bp fragments, and TNFB2 which lacks the NcoI restriction site. All data were analyzed by K 2 test. RESULTS: There were no significant differences in frequency of TNFB1/1, TNFB1/2, and TNFB2/2 between the schizophrenic patient and the control group. Alleric frequencies of TNFB1 and TNFB2 were significantly different between schizophrenic patient and control group. CONCLULSION: We found the possible association between alleles of TNFB and schizophrenia in this study. To clarify the influences of TNFB on schizophrenia, further systematic studies should be conducted.

A Case of Mirtazapine Induced Restless Legs Syndrome / 대한정신약물학회지

A 56 year-old female patient with major depressive disorder, single episode with unremarkable findings on past medical and psychiatric history visited due to various depressive symptoms. Mirtazapine of 15 mg/day at evening was administered for the control of her depressive symptoms along with alprazolam of 0.5 mg/day at morning and evening for the control of anxiety. On fifth hospitalized day, she complained of creeping and crawling sensation on both legs which was aggravated at night after about one hour of mirtazapine intake and improved with movement. She also had a difficulty in falling a sleep as well as onset of discomfort on both legs. We rendered her discomfort as restless legs syndrome (RLS) due to mirtazapine disposition. Therefore, we maintained mirtazapine of 15 mg/day at evening and added clonazepam of 1 mg/day at morning and evening for the control of RLS. After 7 days observation, the patient complained of aggravated natures of RLS and wanted to stop the drug. Though the effectiveness of mirtazapine for control of depressive symptoms, the drug was switched to paroxetine of 20 mg/day at 16th hospitalized day and 4 days later the RLS was completely terminated.

The Frequencies of HLA Alleles in Bipolar Disorder / 신경정신의학

OBJECTIVES: To evaluate the potential of HLA as a candidate gene for the genetic marker of bipolar disorder, we carried out the association study between allelic frequency of HLA and bipolar disorder. METHODS: HLA class I and class II allelic frequencies were assessed in 87 Korean bipolar disorder patients and were compared with the data from 206 normal controls. HLA class I typing was performed with microlymphocytotoxicity method and HLA class II(DQB1 and DRB1) genotyping with reverse dot hybridization. The allelic frequencies were analyzed using x2 test with two-tailed Fisher's exact test. RESULTS: Bipolar disorder patients showed increased allelic frequencies of HLA-A29 and B54 and decreased allelic frequencies of HLA-B51 and DRB1*02 compared to normal controls. CONCLUSION: These results suggest the possibility of association between HLA gene and bipolar disorder. To clarify the genetic influences of HLA on bipolar disorder, further systematic studies should be conducted.

Restriction Fragment Length Polymorphism of Interleukin-10 Gene in Schizophrenia / 신경정신의학

OBJECTIVE: Recently, molecular genetic methods have been progressed, this study was to investigate the relationship between schizophrenia and immunologic aspects by analyzing polymorphism of IL-10 gene, which is involved in interaction of immunologic system and CNS. METHOD: 141 schizophrenic patients diagnosed by DSM-IV were included and data of 146 normal controls obtained from the Catholic Hemopoietic Stem Cell Information Bank of Korea were used in this study. DNA was extracted from whole blood, thereafter amplified by polymerase chain reaction, and digested by Mae III After that procedure, we obtained and assessed RFLP of two alleles, IL-10T and IL-10C. All data were analyzed by x2 test with two-tailed Fisher's exact test. RESULTS: 1) There were no significant differences genotype frequencies of IL-10*T/T, IL-10*T/C, and IL-10*C/C in between schizophrenic patients group and control group. 2) There were no significant differences gene frequencies of IL-10*T and IL-10*C in between schizophrenic patients group and control group. CONCLUSION: We did not verified the frequency differences of IL-10*T/*IL-10*C gene between schizophrenic patients and normal controls, respectively. We do suggest that further systematic studies including various clinical variables should be conducted.

Gene Polymorphism of Tumor Necrosis Factor Beta in Major Depressive Disorder / 신경정신의학

OBJECTIVE: Major depressive disorder is known to have high genetic predisposition and the main focus of recent genetic studies in major depressive disorder has been concentrated on association studies between genetic polymorphism and disease, since molecular genetic methods have been developed. This study was designed to investigate the relationship between major depressive disorder and immunogenetic influences by analyzing polymorphism of TNFB gene, which is involved in interaction of immune system and CNS. METHOD: 95 persons who had been diagnosed of major depressive disorder were assigned as patient group and, 202 data obtained from Catholic hemopoietic stem cell bank, College of medicine, the Catholic University of Korea, were used as normal controls in this study. DNA was extracted from whole blood, thereafter amplified by polymerase chain reaction, and digested by NcoI. After that procedure, we obtained and assessd restriction fragment length polymorphism of two alleles, TNFB*1 which has 555bp and 185bp fragments and carries the NcoI restriction site, and TNFB*2 of 740 bp fragment lacks the NcoI restriction site. All data were analyzed by x2 test with two-tailed Fisher's exact test. RESULTS: 1) The frequencies of TNFB*1/1, TNFB*1/2, and TNFB*2/2 were not statistically different between major depressive disorder patients and control group. 2) The frequencies of TNFB*2 and TNFB*1 were not statistically different between major depressive disorder patient group and normal control group. CONCLUSION: We did not verified the differences of frequency in TNFB*1/TNFB*2 gene between the major depressive disorder and normal controls, respectively. Consequently, there is no genetic relationship between major depressive disorder and gene polymorphism of TNFB. We do suggest that further systematic studies including various clinical variables should be conducted.

Changes in Serum Cortisol Levels and Clinical Symptoms after the Administration of Risperidone in Schizophrenic Patients / 신경정신의학

OBJECTIVE: This study was designed to identify the role of serotonin and cortisol in the pathophysiology of schizophrenia by measuring quantitative change of serum cortisol levels after risperidone(5HT2 antagonist) administration. METHOD: Subjects included 10 male and 7 female patients who met DSM-IV criteria for schizophrenia(n=17). Blood samples(4ml/sample) were taken at the baseline, 1st, 2nd, 3rd, 14th, 28th and 42nd days, twice, at 8:00 AM and at 10:00 AM in the morning after an overnight fast. The daily medication was administered after the first blood sampling at 8:00 AM. After baseline sampling, the same dose of risperidone was administered to each patient until the end of the 3rd day. The dose of risperidone was then decided by clinical evaluation. Serum cortisol concentrations were measured by standard double-antibody radioimmunoassay. RESULT: 1) Administration of risperidone significantly decreased serum cortisol levels(p<0.05). 2) There were significant reductions in positive symtom scores(21.7+/-3.8, vs 14.3+/-4.1) and negative symptom scores(20.5+/-5.2, vs 15.2+/-3.2), general symptom scores(44.3+/-5.4, vs 32.9+/-4.2) of PANSS after risperidone administration(p<0.05). 3) There were no significant differences in baseline serum cortisol levels and the reductions of serum cortisol levels after administration of risperidone between males and females. 4) There were no significant differences in baseline serum cortisol levels and the reductions of serum cortisol levels after administration of risperidone between positive symptom subgroup and negative symptom subgroup. CONCLUSION: These results suggest risperidone decreases serum cortisol levels in s chizophrenic patients and the reduction of cortisol by risperidone administration might be important factor in the treatment of schzophrenics, in contrast with typical antipsychotics.

Association Study of Alcohol Dependence with the Tyrosine Hydroxylase Gene Polymorphism / 신경정신의학

OBJECTIVES: To investigate the genetic relation of the tyrosine hydroxylase(TH) a ratelimiting enzyme in the synthesis of catecholamine, with alcohol dependence, we designed the association study between the microsatellite HUMTH01-VNTR polymorphic locus, located in the first intron of the TH gene, and the Korean alcoholic patients. METHOD: We typed 6 different alleles of the HUMTH01-VNTR locus using PCR and Automated sequencer in 58 alcoholic patients met with the criteria of DSM-IV and 64 normal controls. The frequencies of allele and genotype were compared between patients and normal controls and in patients group. To increase homogeneity of alcoholics group, we divided alcoholics group by clinical phenotypes such as family history, delrium tremens, alcohol withdrawl seizure. And then the allele frequencies were compared respectively. RESULTS: When we compared the frequencies of alleles and genotypes between alcoholics and normal controls, there were no significant differences between two groups. And there were no allelic associations of TH gene in the variable charisteristics(family history of alcohol dependence, presence of delrium tremens, and presence of alcohol withdrawl seizure) This result suggest that TH gene VNTR polymorphism is not associated with alcoholism in Koreans. CONCLUSION: The authors conclude that our data do not support an allelic association between the TH gene VNTR polymorphism and alcoholism. Further systemized studies will be necessary to determine whether the role of allele of TH is major effect gene or modifying effect gene in the pathogenesis of alcohol dependence.