Recent basic and clinical studies demonstrate a major role for neural plasticity in the etiology and treatment of depression and stress-related illness. The neural plasticity is reflected both in the birth of new cell in the adult brain(neurogenesis) and the death of genetically healthy cells(apoptosis) in the response to the individual's interaction with the environment. The neural plasticity includes adaptations of intracellular signal transduction pathway and gene expression, as well as alterations in neuronal morphology and cell survival. At the cellular level, repeated stress causes shortening and debranching of dendrite in the CA3 region of hippocampus and suppress neurogenesis of dentate gyrus granule neurons. At the molecular level, both form of structural remodeling appear to be mediated by glucocorticoid hormone working in concert with glutamate and N-methyl-D-aspartate(NMDA) receptor, along with transmitters such as serotonin and GABA-benzodiazepine system. In addition, the decreased expression and reduced level of brain-derived neurotrophic factor(BDNF) could contribute the atrophy and decreased function of stress-vulnerable hippocampal neurons. It is also suggested that atrophy and death of neurons in the hippocampus, as well as prefrontal cortex and possibly other regions, could contribute to the pathophysiology of depression. Antidepressant treatment could oppose these adverse cellular effects, which may be regarded as a loss of neural plasticity, by blocking or reversing the atrophy of hippocampal neurons and by increasing cell survival and function via up-regulation of cyclic adenosine monophosphate response element-binding proteins(CREB) and BDNF. In this article, the molecular and cellular mechanisms that underlie stress, depression, and action of antidepressant are precisely discussed.

우울증으로 고통받는 많은 환자들에서 보이는 다양항 양상과 다양한 경과를 자주 접하면서 분류를 어떻게 하여야 임상적으로 유용한가 의문을 가지게 된다. 이에 저자들은 우울증의 아형 평가의 필요성과 평가도구들을 문헌을 통하여 고찰하였다. 원래부터 이들이 이질적인 집단으로 구성되어 있는지, 하나의 유전적 소인이 있어 개인에 따라서 병의 진행 시기에 따라서 여러 우울증의 spectrum으로 표현되는 것인지 문제가 제기되어 왔지만, 현재로서는 분명히 알 수 없다. 저자들은 먼저 "우울증 스펙트럼" "양극성 우울과 단극성 우울이 공통의 하나의 유전적 인자를 가지는가" "양극성 스펙트럼 장애"등 강한 주장들이 있어 문헌 고찰을 통해서 알아보았다. 그리고, 최근 생물학적인 연구로부터 나온 세로토닌 관련 우울증 가설을 알아보았다. 이 우울증 가설(SeCA depression)은 조기 모성 분리 혹은 모성 박탈 같은 유년시절의 부정적 경험, 불안, 공격성, co-rtisol 증가, cortisol flattening, DST 양성, 스트레스 사건, CRF 상승, 5HIAA저하 등을 연결하여 우울증의 역동을 쉽게 설명하였고 생물-심리-사회적 접근을 가능하게끔 하는 우울증의 모델이다. 둘째로 고전적인 생물학적 지표 즉 DST, TRH 자극 검사, 및 뇨 MHPG 검사 결과에 따르는 우울증 아형을 구분하고 특징을 살펴보았고 이들의 역사적이고 임상적인 의미를 알아보았다. 그밖에 APOE epsilon 4 allele, 기질-성격이론(Temperament Character Inventory : TCI) 심박동 변이도(heart rate variability : HRV) 같은 요인들을 비롯하여 잘 알려진 증상이나 진단으로 분류된 아형들을 조사하여 임상적인 의미를 찾아보았다.

Whenever a clinician manages the patients with depression, he may meet various problems that make it difficult to treat them. Even though he has good skills and knowledge about depression, some barriers will be appear during his practice. In general, the difficulties in treating depression are treatment-resistance, adverse effects of antidepressants, pregnancy in female patients, comorbid medical conditions, poor compliance, drug-drug interactions, and so on, which are related with pharmacological treatments. Here, only the two of them, the treatment-resistant depression and difficult problems concerned with pregnancy, were discussed. Some level of treatment resistance is the norm rather than the exception. As the treatment failure stems from inadequate treatment, it is important that the clinician should prescribe medications with sufficient doseage and adequate duration. And to overcome the treatment resistant depression the polypharmacy is necessary, in that case, the side effects and toxicities should be explored and managed immediately. So the clinician have to learn more about the pharmacokinetic and pharmacodynamic mechanisms of each drugs used in treatment of depression. When the risk of the fetus by the exposure is higher than the risk of untreated maternal psychiatric disorder, psychotropic medications should be used during pregnancy. Women who are maintained on psychotropics and become pregnant, as well as women with the new onset of psychiatric symptoms during pregnancy, should be carefully reassessed. However, data concerning the potential risk of long-term behavioral changes following prenatal exposure to psychotropics is rare, so further longitudinal follow-up studies are needed.

It is known that the personality is the crucial factor in the treatment outcome of depression. The authors tried to identify the results of such studies and various components which determine the treatment outcome of depression. Nearly 60 papers published between the year 1990 and 2000 about the treatment of depression and personality were reviewed. Among them about 30 papers were selected to compare the research methods, results and discussions. The arguments and critics of the papers were discussed. In the many debates, the authors admitted the fact that premorbid personality trait influences the treatment outcome of depression negatively regardless of treatment method. Subtyping of depression is feasible along the presence of good or bad predictors of treatment outcome for depression. Differentiation of depression and personality seems to have no problem, however test of personality state before the development of psychiatric disorder such as depression is not amenable. For example, cluster A personality trait is often misunderstood as depression in clinical setting. In some cases cognitive behavioral therapy is effective in the treatment of depression accompanying personality disorder. The authors insist that the analysis of personality in the dimensional aspect rather than in the categorical aspect gives more information in the research of personality influencing the treatment outcome of depression. In addition, the reason why we understand the relationship between depression and personality were discussed.

현재 국내 신경정신의학계가 당면하고 있는 학문과 진료 영역의 문제점들과 그 원인들을 살펴보고 정신과 의사들의 학문적인 성숙과 진료 영역의 확대를 위한 해결 방안을 모색해 보았다. 진료 영역이 축소된 이유로 의료계 내부에서는 최근에 이루어진 신경과학의 눈부신 발전, 신경정신과에서 신경과와 정신과로의 분리, 의료 제도의 변화, 정신과 의사들의 안이한 대처, 정신의학 교육의 왜곡 등을 생각할 수 있다. 의료계 외부의 조건들로는 정신의학과 정신과에 대한 사회적 편견, 의료에 대한 외부의 규제를 들 수 있다. 정신의학의 영역을 확대하기 위해서는 의과대학생 교육, 전공의 수련 과정, 전문의 연수 교육, 정신의학 교과서의 편찬 등을 통한 정신의학 교육의 개편 강화, 신경정신의학의 정체성 재확립, 그리고 신경과학과 신경학 교육의 강화 등을 적극적으로 추진해야 할 것이다. 아울러 정신과 의사들의 활동 분야를 확대하고 행동과학을 임상 진료 과목으로 개발하며 정신의학과 유관한 제 3 의 전문 진료 과목을 창출하고 정신과 의사의 기본적인 술기에 일차 진료 의사의 역할을 추가하는 방안들도 고려해 볼 필요가 있다.

Alzheimer's disease(AD) is associated with a characteristic neuropathology. The major hallmarks of AD are senile plaques (SPs) and neurofibrillary tangles(NFTs). ${\beta}$-amyloid protein($A{\beta}$) is derived from the proteolysis of amyloid precursor protein(APP) and then converted to SPs. Mature SPs produce cytotoxicity through direct toxic effects and activation of microglia and complement. NFTs are composed of paired helical filaments(PHFs) including abnormally phosphorylated form of the microtubule-associated protein(MAP) tau and increased tau level in cerebrospinal fluid may be observed in most AD. The aggregation of $A{\beta}$ and tau formation are thought to be a final common pathway of AD. Acetylcholine, dopamine, serotonin, GABA and their receptors are associated with AD. Especially, decreased nicotinic acetylcholine receptors(nAChRs) in AD are reported. Genetic lesions associated with AD are mutations in the structural genes for the APP located on chromosome 21, presenilin(PSN)1 located on chromosome 14 and PSN2 located on chromosome 1. Also, trisomy 21, Apo-E gene located on chromosome 19, PMF locus, low density lipoprotein receptor-related protein and ${\alpha}$-macroglobulin increase risk of AD. In this article, we will review about the neurobiology of AD and some newly developed research areas.

The current understanding of the neurobiology of anxiety is generally based on experimental animal model, empirical effective psychopharmacological agents, chemical and naturalistic challenge paradigms, and psychoendocinological assessment. This article focuses on reviewing neuroanantomical, neuroendocinological and neurofunctional research of anxiety disorder. In the decade ahead, we anticipate that extension of current research and the new integrated approach promise novel insight into mechanism of anxiety.

Objectives : To investigate the effects of (-)-3-PPP(0.5, 2, and 10mg/kg, s.c.) and haloperidol(0.1, 0.5, and 2mg/kg, s.c.) on the extracellular dopamine concentrations, and the effect of pretreatment with (-)-3-PPP(2mg/kg) on the haloperidol(2mg/kg)-induced extracellular dopamine concentrations in the nucleus accumbens(NAS) of free moving rats. Methods : Dopamine levels in dialysate were determined with high pressure liquid chromatography(HPLC) with electrochemical detection(ECD). Results : (1)(-)-3-PPP had dual actions depending on the doses: at 2mg/kg, it decreased and at 10mg/kg, increased extracellular dopamine concentrations ; (2) haloperidol at all doses increased dopamine levels with higher dose having a greater increase; and (3) pretreatment of (-)-3-PPP reduced the increase in dopamine levels elicited by acute treatment with haloperidol. Conclusions : These findings suggest that pretreatment of (-)-3-PPP in low dose could accelerate the onset of therapeutic effect of haloperidol by diminishing the haloperidol-induced dopamine release in the limbic system.

This study was designed to examine the effects of two antidepressant drugs on the expression of c-fos mRNA in cultured embryonic rat hippocampal neurons. The drugs used were imipramine and amitriptyline. On the fourth day of culture, hippocampal neurons were treated with variable concentrations of each drug. Competitive RT-PCR(Reverse Transcriptase-PCR) analysis was used to quantify the c-fos mRNA expression induced by each drug. Experimental results showed that acute and direct treatment with imipramine and amitriptyline with relatively low concentrations(imipramine ${\leq}10{\mu}M$, amitriptylne ${\leq}10{\mu}M$) had no inductive effect on the expression of c-fos mRNA in the rat hippocampal neurons. However, after treatment with relatively high concentrations(imipramine ${\geq}100{\mu}M$, amitriptyline ${\geq}100{\mu}M$) c-fos mRNA was not detected. These findings suggest the followings. Firstly, the action mechanisms of these drugs on the hippocampal neurons might not be mediated by c-fos but by other immediate-early genes(IEGs). Secondly, their actions may be mediated indirectly via other areas of the brain. Thirdly, the expression of c-fos might be inhibited by high concentrations of these drugs, or the high concentrations could induce cell death. Finally, though cell death remains to be confirmed, the inhibition of c-fos induction or cell death could play a role in the cognitive impairments known to be adverse effects of some antidepressants. This study is believed to be a first step toward understanding the mechanisms of learning and memory. Further studies are needed to investigate the expression of various IEGs and changes in the hippocampal neurons of rat resulting from chronic treatment with antidepressant drugs.

임파구 IMPase mRNA 양이 lithium 투여 전의 양극성 기분장애 환자와 정상대조군 사이에서 차이를 보이는지 알아보기 위하여 이 연구를 시행하였다. 또한 lithium 투여 전과 투여 4주후 측정한 환자군의 IMPase mRNA 양 사이에 변화가 있는지 알아보고, IMPase mRNA 양을 기준으로 환자의 정신병리와 임상경과를 예측할 수 있는지 알아보기 위하여 시행하였다. 최소 2주 이상 lithium을 투여하지 않은 상태의 16명(남자 6명, 여자 10명)의 양극성 기분장애 환자와 성별, 연령을 고려하여 선발한 정상 대조군의 임파구 IMPase mRNA 양을 RT-PCR을 이용하여 측정하였다. 환자군의 정신병리는 Young Mania Rating Scale과 Clinical Global Impression을 이용하여 입원 당일 및 4주 후에 각각 측정하였다. 결과는 다음과 같다. 환자군과 정상 대조군의 IMPase mRNA 양은 통계적으로 유의한 차이를 보이지 않았으며, lithium 투여 전과 투여 4주후 환자군의 IMPase mRNA 양의 변화도 통계적으로 유의하지 않았다. 그러나 lithium 투여 전에 측정한 환자군의 IMPase mRNA 양이 적을수록 4주 후의 정신병리가 심한 것으로 나타났다. 그리고 lithium 투여 전에 측정한 환자군의 IMPase mRNA양이 많을수록 4주 동안 뚜렷한 임상적 호전을 보였다. 이상의 결과를 종합하여 볼 때, 임파구 IMPase mRNA 양이 양극성 기분장애 환자를 정상 대조군과 구분해 줄 수 있는 생물학적 특성은 아니었다. 그러나 lithium 치료 전의 IMPase mRNA 양이 환자의 정신병리와 임상경과에 대한 예측인자로 이용될 가능성을 시사하고 있다.

Background : Dopamine receptors have been regarded as a strong candidate involved in etiology of schizophrenia and a target for various antipsychotic drugs. The purpose of our study was to investigate whether dopamine $D_1$ receptor(DRD1) gene polymorphisms would predict the treatment response to antipsychotics in schizophrenia. Method : One hundred thirty-four schizophrenic patients, who met DSM-IV criteria for schizophrenia were entered into a 48 -week study. The psychopathology of the patients was assessed at baseline, 12th, 24th 48th weeks of treatment by PANSS. Responders were defined by a 20% of the reduction in total PANSS score at end point. The genomic DNA fragment corresponding to nucleotides of dopamine $D_1$ receptor gene was amplified by polymerase chain reaction(PCR). Result: Neither allelic frequencies nor genotypes for dopamine $D_1$ receptor differed significantly between responders and non-responders. Also, there was no difference of changes of PANSS scores among three genotype groups of the dopamine $D_1$ receptor. Conclusion : Allelic variation in the dopamine $D_1$ gene is not associated with individual differences in antipsychotic response.

An association study with Korean alcoholic patients(n=50) and normal controls(n=53) was performed to find the relationship between catechol-O-methyltransferase(COMT) gene polymorphism and alcoholism using polymerase chain reaction-restriction fragment length polymorphism. When we compared the allele and genotype frequencies of Nla III COMT gene polymorphism in alcoholism and normal controls, there was no significant difference between two groups. Our results do not support an association between the Nla III polymorphism of COMT gene and alcoholism.

Objectives : Schizophrenia manifests a variety of interindividual differences in therapeutic response to antipsychotics. This might be attributable to dopamine and serotonin receptors that a important target for various antipsychotics, and the $D_3$ receptor(DRD3) alleles they carry. The purpose of our study was to investigate whether the plasma levels of homovanillic acid(HVA) and 5-hydroxyindoleacetic acid(HIAA), and the polymorphism of DRD3 can be held as a predictor of treatment response in chronic schizophrenic patients. Methods : Therapeutic response for 116 korean schizophrenia patient treated during 48 weeks were assessed by PANSS used as the clinical symptom rating scales. The levels of concentration of HVA and 5-HIAA were examined by HPLC at baseline and at 48 weeks. We classified the polymorphism of DRD3 receptor using amplifying by polymerase chain reaction(PCR). Results : Neither concentrations of HVA and 5-HIAA nor genotype of dopamine 3 receptor were not significantly associated with the therapeutic response. But, the patients who has A1 alleles of DRD3 gene showed poor therapeutic responses. Conclusion : A1 allele of DRD3 gene is associated with poor prognosis of chronic schizophrenia.

정신분열병 환자 16명(남자 12명, 여자4명), 양극성 장애 환자 15명(남자 7명, 여자 8명), 정상 대조군 16명(남자 8명, 여자 8명)을 대상으로 유발 전위검사 P300을 시행하여 얻은 결과는 다음과 같다. 1) 정신분열병 환자군의 Cz, Pz, T3에서의 P300 전위값은 정상 대조군에 비하여 유의하게 낮았다. 2) 정신분열병 환자군의 T3에서의 P300 전위값은 T4에 비하여 유의하게 낮았다. 3) 정신분열병 환자군의 T3에서의 P300 전위값은 양극성 장애 환자군에 비하여 유의하게 낮았다. 4) 정신분열병 환자군의 T3에서의 P300 잠복기는 T4에 비하여 유의하게 지연되어 있었다. 5) 정신분열병 환자군의 T3에서의 P300 잠복기는 양극성 장애 환자군에 비하여 유의하게 지연되어 있었다. 이상의 결과들을 종합해 보면 유발 전위검사 P300을 시행하여 얻은 검사 결과 정신분열병 환자군은 좌측 측두엽 기능 부전, 특히 좌측 상측두회의 기능 부전을 보였으나 양극성 장애 환자군은 정상 대조군과 마찬가지로 좌측 상측두회의 기능 부전을 보이지 않아 두 장애의 정신생리학적 발병 원인은 서로 차이가 있으며, 특히 정신분열병의 정신생리학적 발병 원인은 특히 좌측 상측두회의 기능 부전과 관련있음을 의미하는 것으로 생각된다.

This study was conducted to evaluate the effect of PTSD on memory function and hippocampal volume, and to identify major variables correlated to hippocampal volume and memory function. Thirty four Vietnam veterans were collected for this study, among whom eighteen were PTSD patients and sixteen were combat control subjects. The author used Impact of Event Scale(IES), Combat Exposure Scale(CES), Hamilton Depression Rating Scale(HDRS) and Beck Depression Inventory (BDI). Korea Memory Assessment Scale(K-MAS) was assessed for memory function. Magnetic resonance imaging(MRI) was used to measure hippocampal volume. There were significant differences between PTSD and Non-PTSD veterans in IES, HDRS and BDI. Significant difference was found in verbal memory and total memory of K-MAS between PTSD and Non-PTSD veterans. There was significant difference in hippocampal volume between PTSD and Non-PTSD veterans. Short term memory, verbal memory and total memory were positively correlated to hippocampal volume. Hippocampal volume was negatively correlated to IES, HDRS, and BDI. These results suggest that PTSD severity be associated with hippocampal atrophy and memory dysfunction. Reduced or smaller hippocampal volume may be preexisting risk factor for stress exposure or the development of PTSD on combat exposure.

In clinical setting, treatment-refractoriness, medication induced tardive dyskinesia and amenorrhea in chronic schizophrenia are frequently problematic. However, there are few guideline solving these problem available to clinicians. The goal of this study was collecting clinical data on clinical effectiveness and predictors of response of switching to olanzapine. We attempted to switch to olanzapine from risperidone and clozapine in chronic 31(risperidone 17, clozapine 14) schizophrenia and schizoaffective disorder patients suffering from sustained symptoms, weekly blood monitoring, medication induced tardive dyskinesia and amenorrhea. Previous antipsychotics dosage was gradually decreased for 2 or 3weeks, at the same time olanzapine dosage was gradually increased. At baseline, after 1 week, after 2 weeks and after 4 weeks we checked Brief Psychiatric Rating Scale, Clinical Global Impression Scale, Sympson-Angus Rating Scale, Barnes Akathisia Rating Scale and followed up after 12 months. Successful switch after 4 weeks was achieved in 25 patients(clozapine 9(64.2%), risperidone 16(94.1%)). Overall, mean BPRS and CGI scores increased significantly. Successful maintenance after 12 months was achieved in 17 patients(clozapine 5(35.7%), risperidone 12(70.5%)). Overall, mean BPRS and CGI scores increased significantly too. Switching to olanzapine from other atypical antipsychotics is recommendable in chronic schizophrenia with treatment refractoriness and drug induced side effect.

Objective : It has been thought that estrogen has neuroleptic like effect in women schizophrenic patients. This study aimed to investigate neuroleptic side-effects severity in women with schizophrenia and to investigate their putative association with variations in sex steroids over menstrual cycle. Based on the estrogen theory, The author hypothesized that parkinsonian side-effects would be exacerbated when estrogen levels were high. Method : 26 schizophrenic women were assessed using the ESRS(Extrapyramidal Symptom Rating Scale) and estrogen analysis. Tests were conducted twice, in the mid luteal and mid follicular phase. Result : It was hypothesized that high level of estrogen would lead to an exacerbation of parkinsonian side-effects but the results indicated that parkinsonian side effects decreased overall when estrogen levels were high. This effects were more marked for the group taking typical neuroleptics than those taking atypical neuroleptics. Conclusion : The results of this study suggest that estrogen and progesteron may reduce the severity of neuroleptic induced extrapyramidal side effects over menstrual cycle in women with schizophrenia. It was concluded that estrogen has different effects on dopamine dynamics in the mesolimbic and mesostriatal pathways according to estrogen, progesteron, catecol estrogen, prolactine.

There had been few reports of arachnoid cyst accompanying psychiatric disturbance and no report treated with low-dose risperidone administration. We report a patient, developed first-transient psychotic episode considered to be provoked by an arachnoid cyst, responsive to risperidone, which was found in the middle cranial fossa as follows. A 57-year-old man was admitted by suddenly developed headache, auditory hallucination, delusion of persecution and, an arachnoid cyst in the anteromedial aspect of middle cranial fossa was found on MRI after admission. The psychotic episode was first to him and he was also negative to other clinical evaluation including endocrine abnormality, his psychotic symtom was suspected to be induced by arachnoid cyst and was well controlled to low-dose risperidone administration. He left hospital free from psychotic symptoms on 14 hospital days.

두부 외상을 받은 환자는 여러 가지 다양한 병태생리학적인 과정을 통해 뇌손상을 받으며 이로 인해 다양한 신경정신과적인 장애를 나타낸다. 두부외상을 받은 두 명의 환자에서 이에 대한 약물학적인 접근으로 amantadine을 사용하였고 증세의 호전을 경험하였다. 이에 대한 이론적인 근거로는 amantadine은 전연접(presynaptic)과 후연접(postsynaptic)에서 도파민 신경전달(dopamine neurotransmission)을 증진시켜 인지기능과 전두엽 기능장애에서 발생되는 특징적인 정신 행동학적인 증상을 호전시키고, NMDA 수용체 길항제(NMDA receptor antagonist)로 작용하여 흥분성 독성물질(excitotoxic substrate)에 의한 이차적인 신경손상을 차단하는 신경보호제(neuroprotective agent)로 작용한다. 이와 같이 amantadine은 급성과 만성 외상성 뇌손상 환자 모두에서 나타나는 인지, 기분과 행동장애의 치료에 효과적이고 안전하며 비싸지 않은 가격으로 사용될 수 있을 것으로 사료된다. 또한 이 영역에서 더욱 많은 대조군 연구가 필요하고, 나아가서 외상성 뇌손상 환자의 인지기능 호전을 위한 약물학적인 개입에 관한 연구가 필요할 것으로 사료된다.

The mirtazapine is a relatively new antidepressant that has noradrenergic and specific serotonin antagonist action(NaSSAs). This has been known as one of the most safest drugs because of its few side effects. Until now, there have been only one case report that mirtazapine causes a EPS side effect(restless leg syndrome). But the peculiar mechanism of this drug makes it impossible to explain the exact reasons why the mirtazapine could induce EPS symptoms. Authors observed three cases of mirtazapine induced akathisia. We could not explain the phenomenon the other way except akathisia. So here we presents the three case of mirtazapine induced akathisia and a few possible hypothesis of this phenomenon.

A 54-year old male patient who was suffering from bipolar I disorder for 19 years and was admitted to the National Bugok Mental Hospital due to a depressive episode, was referred to the Kosin University Gospel Hospital. On arrival at the emergency room, he had confused mentality with disorientation, memory impairment, hypomania, marked anxiety and hyperirritability. The change of neuromuscular activity such as ataxia, gait disturbance, tremor, shivering, myoclonus and epileptic seizures was also shown. In addition, the symptoms and signs of autonomic instability including diaphoresis, tachycardia, hypotension, fever and facial flushing were noticed. The above symptoms developed after the administration of sertraline successive to the discontinuation of fluoxetine without any washout period. The degree of severity seemed to be severe because he had epileptic seizures, fever and hypotension. He was recovered from the severe serotonin syndrome by the supportive symptomatic treatment with sodium valproate, clonazepam, lorazepam and cyproheptadine after cessation of the selective serotonin reuptake inhibitors during hospitalization. Therefore, this rare case of severe serotonin syndrome was reported and related literatures were also reviewed.