One of the most widely recognized neurophysiologic endophenotypes for schizophrenia is deficient gating or inhibition of the P50 component of the auditory event-related potential(ERP). A deficit in P50 sensory gating refers to a dysfunction in the mechanism responsible for modulating the brain's sensitivity of filtering out irrelevant or background stimuli, perhaps as a result of dysfunction in inhibitory neural circuits. In this paper, we review the neuronal and genetic aspects as well as medication effects on P50 in schizophrenia.

Objectives : Cognitive therapy is the most extensively researched psychological treatment for nonpsychotic unipolar outpatient depressive disorders. This review focused on the utility of this approach in severe or chronic depressive disorders, in relapse prevention and also on the potential benefits of combining cognitive therapy with medication. Methods : The author reviewed original studies and quantitative analyses on the effects of cognitive therapy, predictors of response, and neuroimaging studies of cognitive therapy in major depressive disorder. The sources used for the literature search were data bases : PubMed, EMBASE, CDSR on the internet, references in papers or books. Results : This review suggests that cognitive therapy is as effective as antidepressant medication in severe depressive disorders. And cognitive therapy can be an effective alternative to antidepressant medication. Patients benefited significantly more from combined cognitive therapy and antidepressant treatment than from either treatment alone. Most importantly, the addition of cognitive therapy to usual treatment appears to protect against future relapse in individuals known to be at high risk of repeated episodes of depression. In addition, subjects who received cognitive therapy showed significantly greater improvements in chronic depression than receiving antidepressant medication. Pooled data suggests that there is a significant relationship between the therapist's level of training or experience, the type of therapy used and patient outcome. Recent functional imaging studies examining brain changes following cognitive therapy report a variety of regional effects, but there is no consistent pattern across the few published studies. Conclusion : Cognitive therapy has proved beneficial in treating depressive patients. Despite empirical data supporting its efficacy, there are still problems in gaining access to cognitive therapy in clinical practice.

Objective : The relationship between the total daily dose of clozapine given and the plasma concentrations of clozapine and its metabolites(N-desmethylclozapine and clozapine N-oxide) and the effect of Glu158Lys (wild-type : Glu, 'H' ; variant : Lys, 'h') and Glu308Gly(wild-type : Glu, 'D' ; variant : Lys, 'd') variation in FMO3 gene on plasma concentrations of clozapine and its metabolites was studied in schizophrenic patients. Methods : Trough plasma concentrations of clozapine and its metabolites were measured in 34 schizophrenic patients receiving clozapine. The genetic variation of 'h' and 'd' in FMO3 were analyzed in 21 among 34 patients. Results : A linear relationship between the total daily dose of clozapine given(mg/kg body weight per day) and the plasma concentrations(nM) of clozapine was revealed by regression analysis(p<0.001) in the 23 patients receiving a constant daily dose of clozapine for 8 days. The plasma molar concentration ratios of clozapine N-oxide/clozapine in 8 subjects with 'hh' or 'Hh' alleles were not different from those in 6 subjects with 'HH' alleles and the plasma molar concentration ratios in 6 subjects with 'dd' or 'Dd' alleles were not different from those in 8 subjects with 'DD' alleles. Conclusion : The effect of Glu158Lys and Glu308Gly variation in FMO3 gene on clozapine metabolism could not be shown.

Objective : Since some studies have shown that the brain-derived neurotrophic factor(BDNF) has an important role in the pathophysiology of depression, this study investigated the relationship between BDNF genetic polymorphism and the long-term outcome of the antidepressant treatment. Method : One hundred and eight patients with major depressive disorder were evaluated for the long-term outcome(up to 3 years) of antidepressant treatment. The severity and improvement of depression were assessed with the Clinical Global Impression(CGI) Scale. The genotypes of BDNF 196A/G polymorphism in the patients were determined using Restriction Fragment Length Polymorphism(RFLP). Result : The genotypes of 128 patients were investigated and 95 patients of those have been evaluated for 3 years. No significant differences were noted comparing three-genotype groups for CGI scales at baseline, 4 weeks, 8 weeks, 1 year, 2 years and 3 years. Conclusion : This result shows that BDNF polymorphism investigated in this study was not associated with the long-term outcome of the antidepressant treatment. However, further studies with another BDNF polymorphism should be needed.

Objectives : Disturbances of serotonergic system might be related to the possible mechanism of social phobia. This study was to investigate the association of serotonin transporter gene and social phobia. Methods : Sixty nine patients with social phobia(51 male(73.9%), mean age $35.17{\pm}11.89$ years) and seventy four normal controls(54 male(73.0%), mean age $33.46{\pm}9.63$ years) were tested for serotonin transporter gene-linked polymorphic region(5-HTTLPR) polymorphism. Additionally, patients were grouped into 46 generalized(GEN) and 23 nongeneralized(NGEN) subgroups and 5-HTTLPR polymorphism was compared with that of normal controls. The genotypes and allele frequencies of the 5-HTTLPR polymorphism between social phobia and the control group were compared. Genomic DNA was extracted from their blood and 5-HTTLPR polymorphisms were determined by using polymerase chain reaction. Results : Significant association was observed between the S(ss) genotype and social phobia, by functional classification(p=.010). In allele frequency analysis, a significant association was also observed between the short allele and social phobia(p=.030). A significant associations between S genotype and each subgroup were observed(GEN p=.045 ; NGEN p=.033), but there were no differences in allele frequency. And, no differences in genotype and allele distribution between two subgroups were found. Conclusion : The results in our Korean sample suggest that S genotype of 5-HTTLPR may be associated with social phobia and s allele may be an important genetic factor that activates social phobic symptoms. But, further studies including large number of samples are necessary to elucidate these present findings.

목 적: 유전적 요인에 다른 금단 증상의 차이를 파악하는 것은 알코올 의존의 유전적 요인을 파악하는데 도움이 될 수 있으며, 유전적 요인에 따라 개인별 금단 증상을 예측할 수 있다. 본 연구의 목적은 유전자군의 다형성에 따른 금단 증상의 심각도 및 증상의 종류를 파악하는 것이며 이에 따른 치료적 접근을 다양하게 하는 것이다. 방 법: 대상군으로는 19세 이상 65세 이하의 남자 입원 환자 108명을 대상으로 하였고, 유전자 분포 비교를 위하여 76명의 대조군을 두었다. 금단 증상의 평가는 마지막 알코올 섭취로부터 48시간이 지난 시점에서 Clinical Institute Withdrawal Assessment for Alcohol(이하 CIWA-Ar) 척도를 사용하여 평가하였다. 도파민 수송체, 도파민 수용체(DRD2), Catechol-O-Methyltransferase(COMT) 유전자형을 분석하였다. 결 과: 나이, 교육 기간, 유전자 형에서 알코올 의존 군과 대조군 사이의 유의한 차이는 없었다. DRD2 Taq I : 동형 유전자형에서 환청 항목의 점수가, 이형 유전자형에서 CIWA-Ar 총점의 점수가 높았다. 환청 항목의 비교 위험도가 1.34이었다. DAT1 : DAT-9 대립유전자를 가지지 않은 유전자형 집단에서 발한, 불안, CIWA-Ar 총점 항목에서 높은 점수를 보였다. COMT : 유전자 빈도를 보면 이형 유전자형이 동형 유전자형에 비해 CIWA-Ar 총점의 점수가 높았다. 결 론: DRD2, DAT1, COMT 유전자 다형성은 다양한 알코올 금단 증상과 관련이 있으며, 이는 각 유전자와 관련된 신경전달 물질과 연관되어 작용하는 것으로 생각된다. 또한 금단 증상의 심각도와도 밀접한 관련이 있는 것으로 생각되어 알코올 금단 증상을 보이는 환자의 치료에 중요한 역할을 할 것으로 생각된다.

Objectives : The purpose of this study was to investigate whether the cognitive functions would be correlated with psychotic symptoms and whether antipsychotic treatments would affect the cognitive functions after 8 weeks. Methods : The thirty-five schizophrenic patients were conducted in this study. The psychopathology was measured using PANSS. The memory function, executive function, and sustained attention were measured using Memory Assessment Scale(MAS), Wisconsin Card Sorting Test(WCST), and Vigilance(VIG) and Cognitrone(COG) in Vienna Test System. After 8 weeks of antipsychotic treatment, we retested the cognitive tests. Results : 1) The cognitive tests after the 8 week's treatment showed significant improvements in memory and executive function in the schizophrenic patients. On the other side, sustained attention did not show improvement. 2) The change of PANSS were correlated with perseverative response, perseverative error and total correct in WCST at baseline. WCST scores at baseline were correlated with negative symptoms, but not positive ones. Conclusion : These study suggests that 1) the impaired sustained attention could be a vulnerability marker in schizophrenia, 2) memory & executive function deficit could be reversible after treatment, and 3) medication might have a benefit in improving the cognitive functions in schizophrenia. Furthermore, the data supports that the better premorbid executive function was, the more favorable was the treatment response in schizophrenic patients. Finally, this study indicates that executive function might be an index of treatment improvement.