I will try to serve as the basis for the development of a clinical therapeutic guideline of antipsychotic drugs. Knowing that many patients fail standard treatment recommendations, either because of insufficient efficacy or intolerance to adverse effects, led us to emphasize the importance of the guideline. The clinicians continually assimilate new information about recent advances, including : novel agents targeted to impact specific components of various neurotransmitter systems ; combination strategies ; alternative uses of existing agents ; and specialized requirements of a growing number of identified diagnostic subtypes. The cost to benefit ratio must always be considered when developing a therapeutic guideline.

Several different classes of antidepressants(ADs) with newer drugs becoming available have been used for the phamacological management of a broad spectrum of mental disorders, among which depressive disorder is most commonly indicated. Successful clinical use of ADs requires a complete understanding of the psychopharmacological properties of ADs and on accurate knowledge of patients, characteristics based on clinical experience and theoretical framework. This paper aims at providing some practical information on the clinical use of ADs to assist clinicians in treating patients with major depression. The author describes (1) different classes of ADs and their presumed mechanisms of action, (2) clinical characteristics of ADs focusing on side-effect profiles, (3) some issues arising during the treatment course such as : a) pretreatment tasks, b) choice of ADs, c) therapeutic drug dose and monitoring of drug concentration, d) three stages of treatment and e) strategies in refractory depression and (4) ADs in special patient groups.

Anxiety and anxiety disorders are one of the most common and most serious psychiatric problems. Anti-anxiety drugs are one of the most effective treatment method for these problems. Benzodiazepines have various side-effects and the risk of overuse and abuse. Therefore, physicians should prescribe benzodiazepines carefully. However, they should not be discouraged from prescribing benzodiazepines when they have a knowledge of the pharmacological characteristics of these drugs and there is a clear indication for their use. Generally speaking, problems of benzodiazepine use such as dependence withdrawal symptoms, and cognitive impairment are more likely to occur with high dose, long-term use(more than 4 months), in geriatric patients and patients with a history of alcohol or other sustance abuse. But long-term or high-dose use can be jusified for patients with panic disorder of agoraphobia, and medically-ill patients with persistent anxiety that cannot be otherwise treated. In summary, there cannot be a general prescribing formulation for benzodiazepine use. Physician should always make their decision based on the individual patient's risk/benefit factors.

The introduction of lithium salts for the treatment of mood disorder by Code in 1949 was a major therapeutic breakthrough. Yet it is far from the universal therpeutic agent in the treatment of mood disorders. Indeed, some acutely manic patients do not respond adeqately to lithium and some individuals experience breakthrough affective episodes during lithium maintenance. In the last decode, it has become c1ear that a significant number of patients with more highly recurrent disorders may require alternative or enhanced forms of prophylactic treatment. For these reasons, a variety of other drugs hove been employed for the treatment and prophylaxis of mood disorders. Efforts to develop new pharmacologic strategies for mood disorder hove included a diverse array of medications, ranging from potent benzodiazepines to novel neuroleptics and from anticonvulsants to calcium channel blockers. The anticonvulsants appear particularly useful in cases of dysphoric mania and rapid cycling state, subforms of bipolar disorder that respond quite poorly to conventional treatments. Among all of these new pharmacologic strategy, carbamazepine and sodium valproate have received the broadest clinical applications as maintenance therapies. The data documenting the short-term antimanic effectiveness of the calcium channel blocker verapamil and benzodiazepins such as clonazepam and lorazepam appear also promising. A number of other theoretically interesting, as well as clinically relevant therapies, which are not presently employed routinly, hove also been studied, including 2 blocker clonidine, atypical antipsychotic clozapine, cholinomimetics, 5-HT enhancers, thyroid and magnesium preparations. Now prophylaxis in mood disorder remains a considerable therapeutic challenge. Controlled testing of the prophylactic efficacy of compounds such as carbamazepine, valproic acid, and the calcium channel blockers represent important next step in the clinical trials for mood disorder.

Advances in molecular biology have renewed hope for the discovery of disease relevant gene. The basic strategy is gene mapping and likely to have on important role in psychiatric research and practice. Recent linkage studies of chromosomal loci to psychiatric diseases shed light on the potential for new genetics in psychiatric science. This article reviews molecular application to psychiatrymethodological issues in genetic linkage, study of gene expression by analysis of mRNA, and current linkage studies in psychiatric diseases.

The author examined the relationship of two markers, D5S39(p105-153Ra), D5S76(p105-599Ha) of chromosome 5 and $D_2$, $D_3$ receptor genes in a Korean schizophrenic pedigree using polymerase chain reaction(PCR). The results were as follows : 1) On D5S39 locus, 5 different alleles(224/226 bp : 4 cases, 218/226 bp : 3 cases, 222/226 bp : 3 cases, 218/230 bp : 1 case, 222/224 bp : 1 case) were produced. 2) On D5S76 locus, 5 different alleles(102/112 bp : 4 cases, 94/112 bp : 3 cases, 108/112 bp 3 cases, 94/94 bp : 1 case, 102/108 bp 1 case) were produced. 3) On $D_2$ receptor gene, 3 different alleles($A_1A_2$ : 8 cases, $A_1A_1$ : 2 cases, $A_2A_2$ : cases) were produced. 4) On $D_3$ receptor gene, 2 different alleles(1/2 : 7 cases, 1/1 : 5 cases) were produced. The author had not find any specific alleles on all four loci in all pedigree nor any specific alleles in the schizophrenic patients. Though the author has not found absolute relationship between the four loci and the onset of schizophrenia, there still remains the possibilities if the more detailed and elaborated pedigree studies are done.

For the purpose of evaluating the human leukocyte antigen(HLA) disease-association with bipolar disorder, HLA class I and class II allelic frequencies were assessed in 37 bipolar patients and were compared to the data from normal population. HLA class 1 typing was performed with microlymphocytotoxicity method while class II(DRB1) genotyping with reverse dot blot hybridization and sandwich method. Statistical analysis consisted of relative risk, Haldane's modified relative risk, Fisher's exact test and Bonferoni's corrected P. The results were as follows : 1) Bipolar patients showed increased allelic frequency of HLA A3 which has statistical significance. 2) Allelic frequencies of HLA B7, B14 and B54 were higher, while those of B51 and B55 were lower in bipolar patients, but they were not statistically significant. 3) Both of increased frequencies of DR2 in bipolar patients and DR15 in normal controls had statistical significance. The results of the present study suggested that some of HLA allelic types might be associated with bipolar disorder. To clarify the genetic influence of HLA to bipolar disorder, we should do consecutive study of bipolar disorder with new information about HLA system including alleles.

Many evidences are compatible with the correlation between the inhibition of [$^3H$] imipramine([$^3H$]IMI) and [$^3H$]paroxetine([$^3H$]PAT) binding to the 5-hydroxytryptamine(5-HT) transporter complex and the 5-HT uptake of 5-HT neurons and platelets, and most antidepressants have been shown to inhibit the [$^3H$]IMI and [$^3H$]PAT binding and the neuronal 5-HT uptake. However, several paradoxical research findings led to doubt about the pharmacological significance of the [$^3H$]IMI and [$^3H$]PAT binding sites. This study was carried to clarify the correlation between the [$^3H$]IMI and [$^3H$]PAT binding parameters and the tissue 5-HT content or/and [$^3H$]5-HT uptake in the rabbit platelet, which contains 40 times ad much 5-HT as that of human platelet and shows the 10 fold higher $B_{max}$ of the 5-HT transporter binding to a 5-HT uptake inhibitor. The rabbits were treated for 28 days with amitriptyline(4mg/kg/day : AP), fluoxetine(0.5mg/kg/day : FO), and sertraline(0.5mg/kg/day : SA) via an Alzet osmotic pump implanted for constant infusion. The [$^3H$]IMI binding $B_{max}$ and $K_d$ of the rabbit platelets were $6.4{\pm}1.2$pmol/mg protein and $10.9{\pm}2.1$nM and those in the [$^3H$]PAT binding were $8.6{\pm}1.1$pmol/mg protein and $1.6{\pm}0.3$nM, respectively. AP slightly increased $B_{max}$ of [$^3H$]IMI binding and both [$^3H$]IMI binding and [$^3H$]PAT binding $K_d$, and i contrast, it slightly decreased $B_{max}$ of [$^3H$]PAT binding. FO Slightly increased $K_d$ of both and [$^3H$]IMI and [$^3H$]PAT binding and slightly decreased $B_{max}$ of [$^3H$]IMI and [$^3H$]PAT binding. SA produced the significant increase of [$^3H$]PAT binding $B_{max}$ and the slight increase of both [$^3H$]IMI and [$^3H$]PAT binding $K_d$ and in contrast, it slightly decreased $B_{max}$ and of [$^3H$]IMI binding. And, the $V_{max}$ and $K_m$ of platelet [$^3H$]5-HT uptake were $24.2{\pm}2.4$pmol/$10^8$ platelets/min and $3.3{\pm}0.3$nM, respectively. The $V_{max}$ was little affected by AP, FO, or SA, but the [$^3H$]5-HT uptake $K_m$ value was moderately increased by FO. However, the platelet 5-HT content was moderately decreased by all of the 5-HT uptake inhibitors used in this study. These results seem to be consistent with the allosterical and competitive interaction of 5-HT uptake inhibiting antidepressants with each other as well as 5-HT in the 5-HT transporter binding, and provide no support for the view that the potencies of 5-HT uptake inhibitors to inhibit the [$^3H$]IMI or [$^3H$]PAT binding with 5-HT transporter complex correlate with their antidepressant potencies.

The etiology and pathophysiology of schizophrenia remain unknown. It has been postulated that infectious-autoimmune process may play a role in the pathogenesis of symptoms in some schizophrenic patients. Findings of altered interleukin(IL) regulation have been regarded as additional proof that schzophrenia has an infectious-autoimmune background. In the present study, we measured mitogen-stimulated production of and serum level of IL-$1{\beta}$, IL-2, IL-6 using ELISA in 16 neuroleptic-free schizophrenic patients and in 16 age, sex matched healthy controls. The results were as follows : 1) There was a significant decrease of IL-2 production in schizophrenic patients than in normal controls(respectively $1.90{\pm}0.13ng/m{\ell}$, $2.79{\pm}0.14ng/m{\ell}$, p<0.001). But there was no significant difference of IL-$1{\beta}$ production and IL-6 production between schizophrenic patients and normal controls. 2) There was a significant increase of serum level of IL-2 in schizophrenic pateitns than in normal controls(respectively $184.8{\pm}12.8pg/m{\ell}$, $104.2{\pm}34.2pg/m{\ell}$, p<0.01). Serum level of IL-$1{\beta}$ was partially detected in both groups and serum level of IL-6 was not detected in both groups. 3) There was no significant differences of IL-$1{\beta}$, -2, -6 production & serum level of IL-2 according to male vs female, paranoid type vs undifferentiated type, drug-naive group vs drug-free group in schizophrenic patients. 4) There was significant correlation between IL-$1{\beta}$ and IL-6 production(r=0.86, p<0.001). No correlation between IL-$1{\beta}$, -2, -6 production, serum level of IL-2 and age, duration of illness, and BPRS score was found. It has been suggested that the low lymphocyte production of IL-2 in the patients with autoimmune disease occurs because the T cells are activated and lymphocyte-derived IL-2 has been released into the serum. The authors suggest that decreased IL-2 production in our schizophrenic patients is due to increased IL-2 serum level in those patients. Thus our finding of low IL-2 production and high serum level of IL-2 in our schizophrenic patients is compatible with the possibility that our patients have an autoimmune process. Further study on relationship between IL alteration and other immunological abnormalities(the presence of serum autoantibody and of anti-brain antibody, $CD4^+$, $CD8^+$ cell index, etc) in schizophrenic patients will be warranted.

연구배경: 정신분열증 환자에서 보이는 인지기능의 장애와 음성증상과의 관계는 아직 정확히 밝혀져 있지 않다. 음성증상을 효과적으로 호전시키는 것으로 알려진 clozapine을 만성 정신분열증 환자들에게 9개월 간 투여하여 인지기능이 호전될 수 있는지 조사하고 임상증상의 호전 정도와 인지기능의 호전정도 사이의 상관 관계를 평가하였다. 방 법: 만성정신분열증 환자(16명)를 대상으로 Wisconsin Card Sorting Test, Digit Span Test 및 Judgment of Line Orientation Test 등의 심리검사를 clozapine 투약 전과 9개월 후 각각 실시하였다. 또한 BPRS를 사용하여 투약전과 9개월 간의 투약 이후의 정신병리를 평가하였으며 이를 신경심리검사 결과와 비교하였다. 결 과: Clozapine은 만성정신분열증 환자의 양성 및 음성 증상을 모두 유의하게 호전시켰다. 신경심리검사 결과 집중력, 단기 기억력, 시각-지각력에는 유의한 호전이 있었으며 집행능력에서도 통계적으로 의의있지는 않으나 호전되는 경향을 보였다(p=0.066). 환자들의 임상증상과 신경심리검사 결과 사이에는 아무런 상관관계도 발견할 수 없었다. 결 론: 만성정신분열증 환자들에서 clozapine 장기 투여를 통해 임상증상은 물론 집중력 및 단기기억력 등 일부 인지기능의 호전을 기대할 수 있으며 특히 보다 정교한 정보처리와 관련되는 집행능력 역시 9개월 이상 장기 치료를 통해서 호전될 수 있음을 시사하였다. 또한 정신분열증 환자에서 나타나는 인지기능의 장애는 임상증상에 의한 2차적 현상이 아니라 하나의 독립된 병리임을 추측할 수 있다. 향후 보다 객관적인 결론을 위하여 타 항정신병약물과의 비교 연구가 지속적으로 필요하다고 본다.

정신분열증 환자에서 연성 신경학적 증상이 많이 나타나는 것은 많은 연구에서 확인된 바 있으나 이것이 항정신병 약물 복용 등에 의하여 발생하는 부수적인 현상일 가능성이 배제되지 않고 있다. 본 연구는 항정신병 약물 복용군과 비복용군간의 연성 신경학적 증상 발현의 차이를 알아보고자 시도되었다. 항정신병 약물을 전혀 복용하지 않은 28명과 현재 항정신병 약물로 치료 중에 있는 31명의 정신분열증 환자에서 연성 신경학적 증상을 구조화된 평가척도인 한국어판 신경학적 평가척도로 조사하였고 약물용량과 투여기간 및 부작용과의 관계도 알아보았다. 항정신병 약물 비복용군의 신경학적 평가척도의 총점은 $27.14{\pm}5.66$점으로 복용군의 $19.58{\pm}6.55$점보다 유의하게 높았다 (t=-4.76, P<0.001). 하위 기능영역 중에서도 운동조정(t=-5.52, P<0.001), 복합운동활동 순서화(t=-2.20, P<0.05), 기타 항목(t=-5.14, P<0.001)등의 점수는 비복용군에서 높았다. 감각통합 영역은 약물 복용군과 비복용군 사이에 유의한 차이가 없었다. 약물 용량, 연령, 성별 등을 통제한 후의 조사에서는 총점(F=11.13, P=0.00), 운동조정(F=28.46, P=0.00), 기타 항목(F=10.79, P=0.00)등은 약물 비복용군에서 높았으나 복합운동활동 순서화는 이들 공변량의 영향을 받아 약물 복용군과 비복용군사이에 유의한 차이가 없었다. 약물 복용군에서 현재의 항정신병 약물 복용량은 신경학적 평가척도 점수 중 운동 조정 영역과만 유의한 상관성을 보였으며 약물 복용기간, 부작용 등은 연성 신경학적 증상과 상관성이 없었다. 위와 같은 결과로 항정신병 약물은 정신분열증의 신경학적 증상 발현에 상대적인 영향만을 준다고 할 수 있었으며 연성 신경학적 증상이 정신분열증의 주요한 형질 표지자의 하나가 될 가능성이 있다고 하겠다. 또한 향후 보다 통제된 집단에서의 추적연구가 필요할 것으로 생각되었다.

항정신병약물 perphenazine 20mg/day, chlorpromazine 100mg/day. trifluoperazine 15mg/day 등을 투여중인 정신분열증 42세 여자 환자에서 심실성 빈맥의 하나인 torsade de pointes이 나타난 사례를 보고한다. 본 환자는 항정신병약물을 복용하여 오던 중 여러차례 실신과 호흡곤란을 경험하였으며, 심전도상에 QT 간격의 연장과 함께 다양한 모양의 QRS 파를 동반한 심실성 빈맥의 소견이 있어 torsade de pointes을 의심할 수 있었다. 심혈관계에 영향이 적은 항정신병약물인 haloperidol로 바꾼 후 부정맥의 소견이 없다가 퇴원 후 haloperidol을 증량하는 과정에 흉부 불편감, 실신의 증상과 함께 QT 간격의 연장이 다시 발생하여 torsade de pointes이 나타난 원인이 항정신병약물 때문이라는 것을 확인할 수 있었다. 항정신병약물을 사용중인 환자에서 발생하는 급사의 원인으로 심실성 빈맥이 가장 흔하게 제기되고 있다. 따라서 항정신병약물을 처방하는 임상의들은 이에 대한 충분한 지식과 주위가 필요할 것으로 생각된다.