The development of molecular biology has brought many changes in psychiatry. Molecular biology makes us possible to know the cause of mental disorders that provide the way to prevent the disorders, and to develop various accurate diagnostic and treatment methods for mental disorders. The author discusses the concept, cause, and treatment of mental disorders in the aspect of molecular biology. Importing the methods of molecular biology into psychiatry, we can anticipate to get a number of the goals of psychiatric genetics, including identification of specific susceptibility genes, clarification of the pathophysiological processes whereby these genes lead to symptoms, establishment of epigenetic factors that interact with these genes to produce disease, validation of nosological boundaries that more closely reflect the actions of these genes, and development of effective preventive and therapeutic interventions based on genetic counseling, gene therapy, and modification of permissive or protective environmental influences. In addition to their capacity to accelerate the discovery of new molecules participating in the nervous system's response to disease or to self-administered drugs, molecular biological strategies can also be used to determine how critical a particular gene product may be in mediating a cellular event with behavioral importance. Molecular biology probably enables us discover the environmental factors of mental disorders and allow rational drug design and gene therapies for mental disorders, by isolation of gene products that facilitate a basic understanding of the pathogenesis of these disorders. A specific genetic linkage may suggest a novel class of drugs that has not yet been tried. With respect to gene therapy, the hypothetical method would use a gene delivery system, most likely a modified virus, to insert a functional copy of a mutant gene into those brain cells that require the gene for normal function.

The development of inexpensive high throughput methods to identify individual DNA sequences is important to the future growth of medical genetics. This has become increasingly apparent as psychiatric geneticists focus more attention on the molecular basis of complex multifactorial diseases at which most of psychiatric disease is estimated. Furthermore, candidate gene approaches used in identifying disease associated genes necessitate screening large sequence blocks for changes tracking with the disease state. Even after such genes are isolated, large scale mutational analysis will often be needed for risk assessment studies to define the likely medical consequences of carrying a mutated gene. This review provide basic knowledge of up-to-date technology, cDNA microarray which enables above mentioned various research themes.

Even the pharmacotherapy is more effective than placebo for the treatment of depression, the outcome of pharmacoltherapy remains unsatisfactory for many patients. Apart from side effects, there are two major limitations of antidepressant therapy. One is the delayed onset of improvement and another is partial response. In order to address these clinical dilemmas, many psychiatrists more commonly employ add-on therapy. In past, the practice of using multiple drugs to enhance treatment response was called polypharamcy, and was disparaged as poor clinical practice. However, with improved understanding of how drugs affects the central nervous system and increased communication in journals and on computer networks about the relative merits of specific combinations, the scientific basis for the combining drugs is being defined. Indeed, the use of multiple medications as a stratege to enhance response has become both acceptable and widespread now a days. It is now referred to more positively as add-on therapy, co-medication, combination therapy, or drug augmentation. Thus, as the methods of practical strategies for treatment of depression, switching classes antidepressant drugs, combination therapy, augmentation strategies and brief treatment algorithm will be presented with items of considerations. However, when combination of drugs being tried, knowledges about the action of mechanism, pharamcokinetics, and pharmacodynamics are essential to cope with the possible adversive reactions and to get the appropriate responses for the treatment of depressive symptoms.

P450 CYP2D6 enzyme(=debrisoquine hydroxylase) is known to metabolize many neuroleptics and some genetic polymorphisms in the CYP2D6 gene were reported to be associated with tardive dyskinesia(TD). We investigeted the association of two genetic polymorphisms in the CYP2D6 gene, $CYP2D6^*4$ and $CYP2D6^*10$, with TD in Korean schizophrenic subjects. Subjects consisted of 71 Korean schizophrenics and TD was evaluated using the Abnormal Involuntary Movement Scale (AIMS). There were no statistically significant differences in the demographic variables of age, male to female percentage and the current antipsychotic(CPZ equivalent) dose between the group with TD and the group without TD. But the duration of antipsychotic drug exposure was significantly higher in the group without TD(p=0.000, by independent t-test). The mean AIMS score in the group with TD was $11.2{\pm}6.6$(S.D.). Genotypings for the presence of $CYP2D6^*4$ and $CYP2D6^*10$ were done using PCR amplifications and endonuclease digestions. There were no statistically significant genotypic and alleleic associations between TD and $CYP2D6^*4$(by chisquare tests), and between TD and $CYP2D6^*10$(by chi-square tests). These results indicate that the $CYP2D6^*4$ and $CYP2D6^*10$ polymorphisms have no significant roles in the causation of TD.

Objective : Major depression is known to have immunologic dysfunctions, the recent studies revealed that cytokines including IL-6 and IL-$1{\beta}$ were increased in patients with major depression. Since molecular genetic methods have been progressed, this study was to investigate the relationship between major depression and immunologic aspects by analyzing polymorphism of IL-10 gene. Method : 92 patients with major depression 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 ${\chi}^2$ test. Results : 1) There were no significant difference in genotype frequencies of $IL-10^*T/T$, $IL-10^*T/C$, and $IL-10^*C/C$ between major depression patients group and control group. 2) There were no significant difference in allelic frequencies of $IL-10^*T$ and $IL-10^*C$ between major depression patients group and control group. Conclusion : We did not verified the differences in frequencies of $IL-10^*T/^*IL-10^*C$ gene between the major depression patients group and control group, respectively. But the results of this study do not declare that the IL-10 gene has no association with major depression. We do suggest that further systematic studies including various clinical variables should be conducted.

정신분열병과 DRD4 다형성이 연관이 없다는 보고들이 있어왔다. 그러나 지금까지의 결과로부터 정신분열병과 DRD4가 연관이 없다고 결론 내리는 것은 성급한 것일 수도 있다. 정신분열병의 유전적 취약성은 여러 유전자좌(locus)들이 같이 상호작용(interaction) 또는 공작용(coaction)에 의한 것일 가능성이 크다. 저자들은 DRD4 유전자의 exon III 48-염기쌍 다형성 [D4E3]과 exon I 12-염기쌍 다형성[D4E1]의 조합과 정신분열병의 연관성에 관하여 연구하였다. 207명의 친척이 아닌 한국인 정신분열병 환자와 191명의 정상 대조군이 연구에 참여했다. DRD4 유전자형을 중합효소연쇄반응을 통하여 확인하였으며, 정신분열병 환자군과 정상 대조군의 유전자형과 대립유전자의 빈도간의 차이를 연구하였다. 두 군간에 다형성에 있어 통계적 유의한 차이는 보이지 않았으며, 모든 유전자형의 빈도는 Hardy-Weinberg equilibrium에서 예상되는 분포와 유의한 차이가 없었다. 정신분열병 환자군과 정상 대조군에서 DRD4 유전자의 다형성을 조합하여, D4E1과 D4E3 다형성의 조합의 분포에 있어 비교하였을 때, $A1A2^*2/4$의 분포에 있어 두 군간에 유의한 차이가 있었다(p<0.01). 이러한 소견은 D4E1과 D4E3 다형성의 조합중 하나인 $A1A2^*2/4$이 정신분열병의 취약성에 있어 방어적인 역할을 할 가능성을 시사하는 것이다.

Background : Dopamine receptors are strong candidates for involvement in schizophrenia and are target of a wide variety of antipsychotics. Dopamine $D_5$ receptor(DRD5) gene polymorphisms may be associated with various treatment response. The purpose of our study was define to what significance can be held as a predictor of treatment response in this polymorphism. Method : The total number of 116 Korean chronic schizophrenic patients was assessed after 48 weeks treatment. The Positive and Negative Syndrome Scale(PANSS) was rated for the clinical response to various antipsychotics. With the use of polymerase chain reaction amplification, we assessed this dopamine $D_5$ receptor polymorphism in schizophrenic patients who had been treated with antipsychotics, and related genotype with treatment response, to test the hypothesis that DRD5 polymorphism may lead to varying response to antipsychotics. Result : DRD5 polymorphism was not associated with treatment response to a variety of antipsychotics in chronic schizophrenic patients. Conclusion : Genetic variation of $D_5$ receptors do not predict treatment response to antispychotics.

This study was carried out to investigate the direct neurotoxicity of alcohol on CNS and the effects of piracetam or vitamins on ultrastructural changes of the rat cerebellar and hippocampal neurons during long-term alcohol treatment. To evaluate the results, quantitative analysis were done for light and electronic microscopic findings. On the light microscopy, red degeneration of pyramidal cells and Purkinje cells was found more apparently in the alcohol only treated group than in the control group. On the electron microscopy, increased lipofuscin pigments were found in cerebellum and hippocampus. In quantitative analysis, vitamins significantly reduced red degeneration in both hippocampus and cerebellum. However, piracetam significantly reduced red degeneration in cerebellum but not in hippocampus. Lipofuscin pigments in Purkinje cells and pyramidal cells were significantly reduced in the alcohol with piracetam treated group than the alcohol only treated group. However, vitamins had no significant reducing effect of lipofuscin pigments in Purkinje cells and pyramidal cells. According to the results, it is concluded that vitamins deficiency might cause red degeneration of pyramidal cell after long-term alcohol treatment, but increment of lipofuscin pigments in pyramidal and Purkinje cell may be caused by alcohol itself or its metabolite rather than vitamins deficiency. Piracetam seems to improve cognitive function impairment caused by alcohol consumption.

연구목적 : 환청이 자기감시체계의 이상이라고 주장하는 일부 학자들은 청각적 언어상상과 관련된 뇌 활성화 소견을 이용하여 환청의 병리기전을 밝히고자 하였다. 그런데 대부분의 환청의 내용은 부정적 감정을 동반하는 내용이다. 이런 점에서 저자들은 부정적 감정이 청각적 언어상상에 의해 유발된 대뇌 피질 활성에 어떤 식으로 영향을 미치는지 알아보고, 이를 통해 부정적 감정이 환청발생에 미칠 수 있는 영향을 이해해 보고자 하였다. 방법 : 정상인과 정신분열병 환자를 대상으로 부정적 내용의 청각적 언어상상 과제와 부정적 내용의 청각적 언어상상 과제를 수행토록 하였다. 이 두 가지 과제를 수행하면서 정량화뇌파검사를 시행하였고, 이때의 대뇌피질 활성의 차이를 paired t-test를 이용하여 분석하였다. 그리고 이러한 차이가 정신분열병 환자와 정상인에서 각기 어떤 식으로 달리 나타나는가 비교하였다. 결과 : 정상인의 경우 중립적 감정일 때에 비해 부정적 감정의 청각적 언어상상시, 좌측 측두엽 부위(TCP1)에서 beta주파수대의 뇌파 진폭이 증가하였고, 대뇌 우반구의 몇몇 부위(FP2, F4, C4, CP2, P4)에서 theta주파수대의 뇌파 진폭이 감소하였다. 그러나 정신분열병 환자의 경우, 두 가지 과제를 수행하는 동안 모든 주파수대에서 뇌파 진폭의 차이가 관찰되지 않았다. 결론 : 본 연구 결과는 좌측 측두엽의 더 많은 활성이 요구되는 부정적 내용의 청각적 언어상상을 하게 될 때, 정신분열병 환자에서는 적절한 활성화가 이루어지지 못하는 것을 지지하는 소견으로 생각된다. 그리고 이에 따른 자기감시체계의 활성의 저하가 환청과 밀접하게 관련될 수 있는 것으로 시사된다.

Objective : The present study was designed to compare Global Field Power Measurement and conventional method in P300 determination. Method : The subjects were composed of patients(N=20) with schizophrenia by DSM-IV and normal controls(N=20). The auditory event related potential P300 was measured by "oddball paradigm". P300 components were determined by Global Field Power Measurement and conventional method at 5 electrodes(Fz, Cz, Pz, $T_3$, $T_4$). Results : P300 amplitudes of patients were smaller than those of controls across all electrodes and in both methods, but there was no differential power in P300 determination between two methods. Asymmetry of auditory event-related potential P300 was not shown between patients with schizophrenia and normal controls. Conclusion : It is implicated that it depends on clinical situations and research purposes what method of P300 determination will be more appropriate for patients with schizophernia.

Objective : The authors experienced that cognitive behavioral therapy(CBT) could replace medication for controlling panic attacks and anticipatory anxiety symptoms. The objective of this study was finding out predicting factors of discontinuation of medication after CBT for patients with panic disorder. Method : A hundred forty-eight patients who met DSM-IV criteria for panic disorder with or without agoraphobia for at least 3 months had completed 12 weekly sessions of Panic Control Therapy(PCT ; Barlow et al). Eighty-one patients who could discontinue medication and sixty-seven patients who could not discontinue medication were measured with several scales as the pre- and post-treatment aassessment. The scales were Beck Depression Inventory(BDI), Clinical Global Impression(CGI), Spielberger State Anxiety Inventory(STAI-state), Anxiety Sensitivity Index(ASI), Body Sensation Questionnaire (BSQ), Panic Belief Questionnaire(PBQ), Agoraphobic Cognition Questionnaire(ACQ), Fear Questionnaire(FQ), Toronto Alexithymia Scale(TAS). Results : At the pre-treatment assessment, the scores of BDI, CGI, STAI-state, ACQ, BSQ were higher in the patients who could discontinue medication than in the patients who could not discontinue medication(t=-2.68, t=-4.88, t=-3.07, t=-3.68, t=-3.35, p<0.01). Conclusion : Patients with panic disorder who were less depressed, less anxious, less agoraphobic and who had less negative cognitions for the bodily sensation and who had higher scores in the therapist's assessment could discontinue their medications.

Objectives : Risperidone is a new antipsychotic drug developed to overcome the therapeutic limitation of conventional antipsychotics. It responses to negative as well as positive symptoms by blocking both dopaminergic and serotonergic receptors, causing no significant side effects such as agranulocytosis and seizure. It is, however, not known whether it induces any serious cardiovascular side effects as evoked by other conventional antipsychotic drugs. The aims of this study were to evaluate the effect of risperidone on cardiovascular function, and to discuss the factors affecting the cardiovascular function. Methods : For 42 patients(22 males and 20 females) diagnosed as schizophrenia, schizophreniform disorder or schizoaffective disorder according to the DSM-IV classification, the cardiovascular fuctions such as heart rate, systolic and diastolic blood pressure, PR interval, QRS interval and QT interval were successively checked before and after 2 weeks and 4 weeks risperidone administration. Furthermore, variables such as body weight, Brief Psychiatric Rating Scale(BPRS), Clinical Global Impression(CGI), Extrapyramidal Symptom Rating Scale(ESRS), Anticholinergic Rating Scale(ARS), serum cholesterol level, serum triglyceride level, serum high-density-lipoprotein level, serum WBC, serum Hb, serum platelet level, prothrombin time and partial thromboplastin time were also analyzed before and after 2 weeks and 4 weeks risperidone administration. Results : 1) Risperidone treatment resulted in a significantly decreased heart rate and increased QT interval after 4 weeks administration(p<0.005 respectively). 2) The scores of BPRS and CGI were significantly decreased after 2 weeks and 4 weeks risperidone administration as compared with baseline(p<0.001 respectively). The scores of ESRS and ASRS were significantly increased after 2 weeks and 4 weeks risperidone administration as compared with baseline(p<0.001 respectively). 3) There were positive correlations between heart rate after 4 weeks and total dose(P<0.05). Blood pressure was significantly(p<0.05) correlated with sex(higher in male) and significantly(p<0.05) positive correlated with body weight. QT interval was significantly(p<0.05) correlated with sex(longer in female) and smoking history(shorter in smokers). Conclusions : Risperidone could induce significant change in heart rate and Q-T interval. Therefore, the cardiovascular safety for risperidone should be reconsidered according to the duration and dosage increase.

Objectives : Risperidone and clozapine belong to a new generation of antipsychotics that are reportedly more effective and better tolerated than conventional neuroleptics. However, each of these agents costs far more per unit than conventional neuroleptics. The purpose of our retrospective study was to ascertain the total cost and effectiveness of treatment before and after administration of risperidone and clozapine in "revolving door" schizophrenia patients. Method : Data collected on revolving door schizophrenics for 2 years before clozapine and risperidone treatment and for at least 2 years after clozapine and risperidone treatment. Direct cost of inpatient and outpatient treatment was measured. Effectiveness was scaled as "years of mild disability gained". Result : Both risperidone and cloazpine result in higher costs and additional benefits to patients, for example, increased mild disability, reduced number of relapse, and reduced hospital length-of-stay. An ICER of risperidone was less than Rc and ICER of clozapine was greater than Rc. According to decision-analytic this model, risperidone had favorable cost-effectiveness ratios relative to clozapine. Conclusion : We have assumed that risperidone is more cost-effective than clozapine.