The completion of the rough draft of the human genome is a remarkable achievement. It provides the overall structures of huge DNA molecules that constitute the genome and an outline of the information needed to create a human being. This paper reviewed new ideas, projects, and scientific advances made by the Human Genome Project. We also discussed the future of medicine and biomedical research in postgenomic era.

The genome sequencing project has generated and will continue to generate enormous amounts of sequence data including 5 eukaryotic and about 60 prokaryotic genomes. Given this ever-increasing amounts of sequence information, new strategies are necessary to efficiently pursue the next phase of the genome project-the elucidation of gene expression patterns and gene product function on a whole genome scale. In order to assign functional information to the genome sequence, DNA chip(or gene microarray) technology was developed to efficiently identify the differential expression pattern of independent biological samples. DNA chip provides a new tool for genome expression analysis that may revolutionize many aspects of biotechnology including new drug discovery and disease diagnostics.

The pharmacotherapy of schizophrenia exhibits wide inter-individual variabilities in clinical efficacy and adverse effects. Recently, human genetic diversity has been known as one of the essential factors to the variation in human drug response. This suggests that drug therapy should be tailored to the genetic characteristics of the individual. Pharmacogenetics is the field of investigation that attempts to elucidate genetic basis of an individual's responses to pharmacotherapy, considering drug effects divided into two categories as pharmacokinetics and pharmacodynamics. The emerging field of pharmacogenomics, which focuses on genetic determinants of drug response at the level of the entire human genome, is important for development and prescription of safer and more effective individually tailored drugs and will aid in understanding how genetics influence drug response. In schizophrenia, pharmacogenetic studies have shown the role of genetic variants of the cytochrome P450 enzymes such as CYP2D6, CYP2C19, and CYP2A1 in the metabolism of antipsychotic drugs. At the level of drug targets, variants of the dopamine $D_2$, $D_3$ and $D_4$, and 5-$HT_{2A}$ and 5-$HT_{2C}$ receptors have been examined. The pharmacogenetic studies in schizophrenia presently shows controversial findings which may be related to the multiple involvement of genes with relatively small effects and to the lack of standardized phenotypes. For further development in the pharmacogenomics of schizophrenia, there would be required the extensive outcome measures and definitions, and the powerful new tools of genomics, proteomics and so on.

As numbers of serotonin's function are so many, studies of serotonin are numerous nowadays. In the beginning, concentration of metabolites such as 5-HIAA was a key issue, but recent studies have been challenged for serotonin receptor genes and their relation to mood disoder. Serotonin transporter(5-HTT) gene is a strong candidate gene of mood disoder for following reason. Serotonin transporter is a key protein in the serotonin pathway as it regulate the concentration of serotonin in the synaptic clept and essential pathophysiology of depression is dysregulation of 5-HTT so that all antidepressants have effect of 5-HTT antagonist. The decrease of 5-HTT in the platelet and in brain of the depressive patients is much consistent results in the studies of the pathophysiology of mood disorder till now. By this, we will be able to develop simple and easy marker for diagnosis, type, and treatment monitoring of depression. Many psychiatrists have sought the independent genes in relation to depression or schizophrenia. Obviously, the hereditary vulnerability contributes to etiology of mood disorders, but it is difficult to discriminate the independent genes because of many environmental factors. Moreover, in the hereditarily complex diseases such as mood disorder, the only vulnerability of gene can not sufficiently explain the etiology. In the future, to exclude the role of the gene-environmental interaction, the methods such as gene transfer can be considered. In the opposite direction, by using the gene destruction method, the role of target genes can be examined. As yet the concept of the gene expression, neural plasticity, neurogenesis and etc, is the elementary stage. The development of this field will help to establish the treatment strategy of chronic and refractory mood disorders.

The pharmacotherapy of depression has reduced morbidity and improved outcome for many depressive patients. A wide range of classical and new antidepressants are available for their treatment. However, 30-40% of all patients do not respond sufficiently to the initial treatment and present adverse effects. Pharmacogenetics studies the genetic basis of an individual's ability to respond to pharmacotherapy. Recently, some reports on serotonin transporter gene polymorphisms and their influence on the response to antidepressive therapy provide an interesting diagnostic tool in assessing the chances of response to antidepressants. We also investigated the relationship between serotonin transprter polymorphisms(5-HTTLPR) and the long-term effect of the antidepressant treatment. 128 depressive patients were enrolled into 2nd year study. The therapeutic response of each subset was not different at 8th, 16th week, but the subset with homozygote(l/l) of long variant showed a better therapeutic response to antidepressant than the heterozygote(l/s) of long and short variant, which showed a better therapeutic response than the subset with homozygote (s/s) of short variant at 1st year and 2nd year after the antidepressant treatment. This result shows that the serotonin transporter polymorphisms may be related to the long-term effect of antidepressant treatment. The potential for pharmacogenomics, the use of genetic information to guide pharmacotherapy and improve outcome by providing individualized treatment decisions, has gained increasing attention. pharmacogenomics will contribute to individualize drug choice by using genotype to predict positive clinical outcomes, adverse reactions, and levels of drug metabolism. Personalized medicine, the use of marker-assisted diagnosis and targeted therapies derived from an individual molecular profile, will impact the antidepressant therapy and this approach will replace the traditional trial-and-error practice of medicine.

The routine interictal electroencephalogram(EEG) continues to play an important role in the diagnosis and treatment of epilepsy. The clinical investigation of brain disease in the last decade has been marked by dramatic advances in functional imaging, magnetic resonance scanning and digitized EEG. Epilepsy is a disorder of electrical hyperirritability of cerebral cortex and the interictal EEG remains the most convenient means available to demonstrate cortical hyperirritability. The sensitivity and specificity of the EEG in the diagnosis of epilepsy have been disputed. In this review, the type of EEG findings in epilepsy are reviewed and the sensitivity and specificity of interictal epileptiform discharge are discussed. And also the role of EEG in various clinical situations are summarized.

Objective : Dopamine transporter is member of family of Na/Cl dependent neurotransmitter transporter, 12 transmembrane domain, that has high substrate specificity, affinity. It is related with dopamine reuptake in presynaptic vesicle. DAT has a VNTR in its 3'-untranslated region(UTR). 3'-UTR VNTR polymorphism is related with modification of dopamine transmission. The association between with VNTR polymorphism and neuropsychiatric disorders such as alcohol dependence, and low activity ALDH has been studied, but their relationship is unclear. We study about association of 3'-UTR VNTR of DAT gene and G2319A and alcohol dependence. Method : Group of Korean subjects were studied with alcohol dependence(n=49 male) compared to mentally healthy controls(n=53 male). The peripheral blood sample was acquired, and Polymerase Chain Reaction(PCR) amplification, MspI procedure was done. Result : There was a significant difference between alcohol dependence group and normal control(genotype frequency p<0.05, allele frequency p<0.05) Allele A frequency and genotype(GG, GA) frequency was a significant difference between alcohol dependence group and normal control(p<0.05). Conclusion : Our study showed that genetic polymorphism of DAT1 G2319A had relation with alcohol dependence.

The dopamine D4 receptor gene has a hypervariable segment in the coding region characterized by a varying number of 48bp repeats in exon III of the gene. Varying the numbers of repeated segments may change the length, structure, and function of the receptor, which makes this gene a possible candidate for variations in dopamine-related behaviors, such as alcoholism and drug abuse. We evaluated the dopamine D4 receptor genotype in male alcoholics and normal controls. All alcoholics and controls were unrelated and from the Korean population. Genotype and allele frequencies in 67 alcoholics were compared to 67 controls who were free of alcohol abuse, substance abuse, and major mental illness. No association was found between the dopamine D4 receptor allele and alcoholism. This result indicate that there is no association of the dopamine D4 receptor with alcoholism in Korean. Further systemized investigation to determine the role of dopamine D4 receptor gene in alcoholism with a larger sample size will be required.

Backgrounds : Gamma band oscillatory activity is considered to be related to cognitive functions and illustrates that the concept of event-related oscillations bridges the gap between single neurons and neural assemblies. An event-related gamma oscillation is the time-locked responses of specific frequency, and can be identified by computing the amplitude frequency characteristics of the averaged event-related potentials(ERPs) after stimulation. Objectives : We purposed to present experimental paradigm to investigate ${\gamma}$-band oscillation activities from the recording of ERPs by using auditory oddball paradigm and investigate the difference of ${\gamma}$-band activity between schizophrenia and normal controls. Methods : The ERPs resulting from auditory stimuli with oddball paradigm in a group of schizophrenics(n=11), and also a group of age-, sex-, and handedness matched normal controls, were recorded by 128 channel EEG. The ${\gamma}$-band oscillatory activities were calculated by using time-frequency wavelet decomposition of the signal between 20 and 80Hz. The ${\gamma}$-band oscillatory activities of both groups were compared by t-test. Results : The ${\gamma}$-band oscillatory of the leads Fz, Cz, and Pz of both groups were represented well in the time-frequency maps. Significant increases of the ${\gamma}$-band activity in normal controls compared with schizophrenics were observed around 160 msec, 350 msec, and 800 msec after stimulation. Conclusions : Our results suggested that the increment in ${\gamma}$-band oscillatory activity during cognitive operations and decreased ${\gamma}$-band activity in schizophrenics may be associated with the cognitive dysfunctions and the pathophysiology of the schizophrenia.

Objectives : Chronic alcohol consumption has been known to result in various neurocognitive deficits. Many neuropsychological studies revealed that the major disturbances occurred in the executive function, learning and short-term memory, visuospatial performance function, perceptuo-motor skills, and abstraction and problem solving abilities. This study was done to identify which cognitive areas might be mainly affected. Methods : The cognitive disturbance was evaluated using the Korean Version of the Mini Mental State Examination(MMSEK) and the 7 Minute Screen(7MS) in male inpatients with alcohol dependence(N=3 : as well as in age and education level matched healthy male controls(N=30). Four individual tests of the 7MS were consisted of the Benton Temporal Orientation Test, the Enhanced Cued Recall, the Clock Drawing and the Category Fluency. Results : 1) The average scores of four individual test of the 7MS for the alcoholics were $2.77{\pm}4.38$ for the Benton Temporal Orientation Test, $13.90{\pm}2.02$ for the Memory Test(the Cued Recall $6.77{\pm}1.94$, the Uncued Recall $7.10{\pm}2.45$), $5.84{\pm}1.86$ for the Clock Drawing, and $12.58{\pm}3.29$ for the Category Fluency. Except the Benton Temporal Orientation Test, there were statistically significant differences between test scores of alcoholics and those of controls(p<0.01). 2) The alcoholics who had MMSE-K score <24 were 9.68%. The average(${\pm}S.D.$) score of the MMSE-K for the patient group($27.23{\pm}2.62$) was significantly(p<0.001) lower than that of the healthy controls($29.20{\pm}1.24$). There were no statistically significant differences between four individual test scores of the 7MS of alcoholics with the MMSE-K score <24(N=3) and those of alcoholics with the MMSE-K score ${\geq}24$(N=28). 3) Four individual test scores of the 7MS seemed to have statistically significant association with such variables as MMSE-K, duration of alcohol drinking, blood magnesium concentration, liver function and thyroid function. Conclusion : Mild deficits of cognitive areas such as orientation, memory, visuospatial abilities and verbal fluency could be found in alcohol dependence.

Objective : The purpose of this study was to compare the plasma amitriptyline and nortriptyline level between before and after fluoxetine addition with patients who were currently taking amitriptyline. Method : From the inpatient and outpatient unit of Soon Chun Hyang University Hospital, Chunan, fourteen subjects who were taking amitriptyline 25mg more than 1 week at least were given fluoxetine 20mg. Before and 2 weeks after fluoxetine addition, the plasma level of amitriptyline and nortriptyline are analyzed simultaneously by High Performance Liquid Chromatography(HPLC). At the same times, HAM-D(Hamilton Rating Scale for Depression) score and the UKU(Uldvalg for Klinske Unders${\Phi}$ gelser) side effect scale were checked. Results : After fluoxetine addition to the patients who were taking amitriptyline, the plasma level of amitriptyline, nortriptyline and sum of amitriptyline and nortriptyline had risen. The mean plasma amitriptyline level increased from $168.9{\pm}89.4ng/ml$ to $183.0{\pm}102.0ng/ml$ after fluoxetine addition(p=0.011), but the change was not statistically significant. The mean plasma nortriptyline level increased significantly from $114.3{\pm}70.2ng/ml$ to $168.0{\pm}86.2ng/ml$ after fluoxetine addition(p=0.011). In addition, the mean plasma level of total amitriptyline and nortriptyline increased significantly from $283.1{\pm}125.3ng/ml$ to $350.9{\pm}78.4ng/ml$ after fluoxetine addition(p=0.016). After fluoxetine addition, no significant change was noted in the UKU side effect scale score. Conclusion : As consequence of comparison of plasma amitriptyline and nortriptyline level before and after fluoxetine addition, mean amitriptyline, nortriptyline and total plasma level was increased after fluoxetine addition. This suggests that coadministration of amitriptyline and fluoxetine may induce improvement of depressive symptom in depressive patients by way of increased plasma level of amitriptyline.

60세 남자 환자로 좌측 정중 전두엽과 양측 기저절 경색 후 발생한 과잉성욕 증상과 강박 증상을 주소로 내원하였다. 환자는 뇌졸중 후에 발생한 운동 기능 장애는 시간이 경과하면서 호전되어 발병 1개월 이내에 거의 정상화된 반면 과잉성욕 증상과 강박 증상은 호전되지 않았다. 환자에게 과잉성욕 증상과 강박 증상을 목표로 fluvoxamine과 perphenazine을 처방하였으며 치료 시작 후 2개월이 경과하면서 환자의 과잉성욕 증상과 강박 증상은 서서히 사라졌다. 이 증례는 기저절-시상전두엽 회로가 성적 행동과 강박 증상의 조절에 있어 중요한 역할을 하고 있음을 시사한다고 할 수 있다. 과잉성욕 증상은 임상에서 간과하기 쉽고 또한 일반적으로 성적 활동에 대한 변화는 환자들 스스로 보고하지 않는 경향이 많다. 따라서 뇌졸중 환자, 특히 정중 전두엽이나 기저절 병변을 동반한 환자들의 경우에는 비록 그 병변이 측두엽 침범이 없거나 Kluver-Bucy syndrome의 전형적인 증상을 보이지 않는다 할 지라도 성욕등 성적 활동에 대한 체계적인 조사가 필요할 것으로 생각된다. 또한 과잉성욕 증상과 강박 증상을 함께 가지고 있는 경우 선택적인 세로토닌 재흡수 억제제의 사용이 두 증상 모두를 효과적으로 치료하는 데에 도움이 될 수 있을 것이다.