Due to the high population prevalence of major depression and the strong emphasis on pharmacotherapy for this disorder, antidepressants are among the most frequently prescribed pharmacological agents. But the clinicians are still unable to predict accurately the response of their depressed patients to medication. This article reviews the biological predictors of treatment response including monoamine, neuroendocrine, pharmacogenetic, and psychophysiologic markers. The biological predictors of response, despite some interesting leads that may in the long term be of considerable importance, are not yet sufficiently established to be of routine clinical usefulness. Many of the predictive factors explored in this article are examples of mediators and moderators that affect outcomes. Each one alone may not provide definitive answers for predicting response to treatment, but each must be taken into account at the outset of treatment. It is clear that treatments must be individualized for each patient. It would be necessary to develop the algorithm in order to predict the responsiveness of antidepressant treatment with integration of the results from the previous studies.

Background:Serotonin transporter gene-linked polymorphism region(5-HTTLPR) and catechol-O-methyltransferase( COMT) genes are thought to be important factors in some personality traits and the etiology of anxiety disorder. The goal of this study was to determine the role of these genes in personality traits. Method:The participants included 116 healthy adults with no history of psychiatric disorders and other physical illness for the last 6 months. All participants were tested by Temperament and Character Inventory(TCI). The 5-HTTLPR, COMT val158met gene polymorphisms were analyzed with PCR(Polymerase Chain Reaction). Differences on TCI dimensions and sub-scales among groups were examined with t-test and ANOVA. Result:There were possible relationships of the 5-HTTLPR with self-transcendence(P=0.050) and COMT val158met polymorphism with cooperativeness(P=0.053). Conclusion:We found associations between 5-HTTLPR, COMT polymorphisms and the some TCI character dimensions. Further studies of polymorphisms of other genes and their interactions may clarify the complex relationship between personality and genes.

Objective:There have been a kind of transmethylation theory that high homocysteine serum concentration affects schizophrenia by neurotoxic mechanism and clinical reports that some schizophrenic patients with high homocysteine were improved by high folate ingestion. This study was done to confirm previous research results and find the clinical characteristics of schizophrenia showing high serum homocysteine and low folate. Method:We compared the serum levels of homocysteine, folate and vitamin B12 level between 234 schizophrenic patients(male 99, female 135) group and 234 normal controls(male 99, female 135) group. The subjects of two groups were age and sex matched. The evaluated clinical characteristics items were sex, age, onset of disease, hereditary loading, disease course, hallucination and subtype of schizophrenia. Results:1) Homocysteine level of the schizophrenia group was significantly higher than the normal control group and folate level of the schizophrenia group was significantly lower than the normal control group. Homocysteine level was more negatively correlated with folate level in the schizophrenia group than the normal control group. 2) The percentage of high homocysteine(above 12.46umol/L;90 percentile of normal control) was 33.8% of schizophrenia patients and 51.5% of male schizophrenia. The percentage of low folate(below 3.8nM/L;bottom tertile of normal control) was 66.2% of schizophrenia. 3) In low folate group and not-low folate group, schizophrenia showed significantly higher homocysteine level than normal control. Especially, low folate schizophrenia group showed significantly higher homocysteine level than low folate normal control group. Conclusions:Some schizophrenia patients with high serum homocysteine may be genetic defector and having low folate serum level. In that case, folate ingestion could be a good management for clinical improvement.

Objectives:Abnormalities in neurotrophic factors that regulate neuronal development and synaptic plasticity are often implicated as some causes of schizophrenia. In previous studies, researchers reported that brain and serum BDNF levels underwent similar changes during maturation and aging processes in rats. They also found a positive correlation between serum and cortical BDNF levels. In this study, we investigated whether the serum levels of BDNF in Korean schizophrenic patients would be different from those of healthy controls. Methods:Using an ELISA kit, serum BDNF levels were assessed in schizophrenic group(N=49) and control group(N=50). Results:Serum BDNF levels in the schizophrenic group($36.29{\pm}19.78$ng/ml) were significantly higher than those in control group($22.4{\pm}14.4$ng/ml). The BDNF levels did not correlate with duration of treatment, age or daily dose of antipsychotics in patients with schizophrenia. Conclusions:This result suggests that schizophrenia is characterized by high serum BDNF levels and supports the hypothesis of neurotrophic factor involvement in psychotic disorder. Serum BDNF level is likely to be one of the possible biological markers for schizophrenia.

Objectives:Recently, polymorphisms of several serotonin genes have been suggested to be associated with suicide, but the results are still unclear. We examined whether the T102C polymorphisms of the serotonin 2A receptor gene and the G861C polymorphisms of the serotonin 1B receptor gene were associated with suicidal behavior using drug intoxication. Methods:The subjects were 52 patients who visited emergency room with suicidal behaviors. Fifty controls were selected from healthy volunteers matched for sex and age to the suicide subjects. The polymorphisms were analyzed with TaqMan$^{(R)}$ assay using primers based on previous studies. Results:The T102C polymorphism of the serotonin 2A receptor gene showed no significant difference between the suicidal attempters and controls in both genotype and allele frequency analyses(p=0.179 and p=0.422, respectively). There was no statistically significant difference between the suicidal attempters and the controls in the G861C polymorphism of the serotonin 1B receptor gene and any significant effect of the genotype distributions or the allele frequencies was not observed(p=0.092 and p=0.987, respectively). Conclusion:These findings suggest that the T102C polymorphism in serotonin 2A receptor gene and the G861C polymorphism in serotonin 1B receptor gene are not related to the susceptibility to suicide attempts using drugs. To clarify the genetic influences of the serotonergic system on suicidal behavior, the polymorphisms of other candidate genes in the serotonergic system should be studied with larger numbers of subjects.

Objects:It has been reported that the incidence of tardive dyskinesia(TD), the remarkable abnormal involuntary movement, was higher in the schizophrenics with high blood sugar levels and that TD had been improved by small amount of insulin-injection for 90 days. And also it was generally known that the blood lipids were higher in the schizophrenics with tardive dyskinesia. Thus, we tried to replicate the correlations of abnormal involuntary movements with blood sugar levels and blood lipids in chronic schizophrenics treated with antipsychotics. Methods:Thirty-eight male schizophrenic inpatients who were stable in clinical state with medications, were included. The patients who had been already diagnosed as diabetes mellitus(DM), organic brain disorder, substance- related disorder, physical illness were excluded and also we excluded female patients to remove the hormonal effect on TD. Eleven patients who ranked higher(above five) in the Abnormal Involuntary Movement Scale(AIMS) were assigned into 2 groups, a dibenese group and a placebo group. Diabinese or placebos were administrated for 3 weeks with antipsychotics and AIMS was rechecked. Results:There were no correlations between the total AIMS scores and blood sugar and lipids levels in all subjects. The means of total and subscale scores(objective, face, and extremity) of AIMS did not reveal statistical significances between diabinese and placebo groups. However(total, jaw, face, upper arm, and objective feeling), were statistically higher in the diabinese group than those in the placebo group. And correlations of total cholesterol(TC) with fast blood sugar(FBS), weight with body mass index(BMI) and waist, total glycerol (TG) with BMI were statistically significant. Conclusion:In this study, there were statistical significances in the changes in ratings of AIMS scores between the diabinese group and the placebo group. Application of oral hypoglycemic agent might be a way of improving abnormal involuntary movements in schizophrenics with abnormal involuntary movements or TD. Althogugh it was not certain that there were correlations of abnormal involuntary movement with blood sugar and lipids, correlations of TC/TG with AIMS, of FBS with AIMS cautiously suggest that the regular check of $HbA_1C$, waist, and weight are recommended for schizophrenics.

본 연구는 비전형적 항정신병약물이 체중과 혈당에 미치는 영향을 알아보고 그에 관계되는 여러 변인들의 관련성을 알아보고자 하였으며 이를 위해 비전형적 항정신병약물인 risperidone과 clozapine을 쓰는 환자 각각 20명, 대조군으로 전형적 항정신병약물인 haloperidol을 쓰는 환자 20명을 대상으로 입원 후 4주, 8주, 12주째 체중과 공복 시 혈당을 입원 초기 체중 및 혈당과 비교하였으며 각 약물군 간의 차이를 조사하여 다음과 같은 결과를 얻었다. 첫째, 연구 대상 환자의 초기 특성 상 clozapine군이 haloperidol과 risperidone군에 비하여 입원 시 체중이 높은 상태였는데 이는 clozapine을 복용하는 환자들이 이전에 haloperidol과 risperidone을 포함한 여러 가지 항정신병약물을 복용했던 경험이 있고 이로 인해 이미 어느 정도의 체중 증가가 있었던 것으로 생각해볼 수 있다. 둘째, 체중 변화는 risperidone과 clozapine군 모두 haloperidol을 쓴 군과 유의한 차이가 없었다. 셋째, 혈당 변화도 비전형적 항정신병약물인 risperidone과 clozapine군이 haloperidol군에 비해 의미 있는 차이가 없었다. 넷째, 몇 가지 변수들이 체중과 혈당의 변화에 연관성을 가지고 있었으나 그 정도는 크지 않았고 그 인과관계를 증명할 수는 없었다. 위의 결과들에서 볼 때 유병 기간이 길고 이전에 여러가지 항정신병약물을 복용한 경험이 있는 환자, 약물 복용에 따른 증상의 호전 정도가 두드러지지 않는 만성적인 정신분열병 환자들에서는 비전형적 항정신병약물이 전형적 항정신병약물에 비해 체중 변화와 혈당의 수치를 변화시키는 경향이 크지 않다는 점을 알 수 있었다.

Objectives:Genetic variations of the tryptophan hydroxylase(TPH) gene and the serotonin transporter linked polymorphic region(5-HTTLPR) polymorphism have been associated with its functional capacity. The authors investigated whether the allelic constitution of the TPH gene and 5-HTTLPR are associated in Korean panic patients. Methods:244 Korean patients with panic disorder and 227 normal healthy controls were tested for a genetic polymorphism of TPH A218C and 5-HTTLPR polymorphism. To assess the severity of panic disorder during the last one month, anticipatory anxiety, panic difficulty, panic distress, agoraphobic difficulty and agoraphobic distress were measured with visual analogue scale(VAS) score, STAI-S & T, BDI, SCL-90-R, ASI-R, CGI, PDSS, and HAMD. Results:There was no significant difference in genotype and allele frequencies of TPH A218C and 5-HTTLPR polymorphism between panic patients and controls. Although we observed some differences in genotype and allele frequencies of TPH A218C polymorphism among male subjects, these differences disappeared after Bonferroni correction. And there were no significant differences in clinical variables. Conclusion:Our results suggested that there are no association between the genetic polymorphism of TPH gene and 5-HTTLPR with panic disorder.

Objective:Attention deficit hyperactivity disorder(ADHD) is the most common childhood psychiatric disorder, affecting 3-5% of school-aged children. Although the biological basis of ADHD is unknown, family studies provide strong evidence that ADHD has a genetic basis. Recent genetic studies have suggested associations between ADHD and serotonin 1B(5HT1B) receptor gene G861C polymorphism. The aim of this study is to test for the association between ADHD and 5HT1B receptor gene G861C polymorphism in Korean population. Method:We processed DNA extraction and genotyping. 106 Korean children with ADHD and their parents were analyzed using the transmission disequilibrium test(TDT) and haplotype-based haplotype relative risk (HHRR). And the ADHD children were compared with 212 age and gender matched normal controls. Results:There was no statistical difference of distributions between ADHD cases and controls. We did not observe any preferential transmission of alleles of 5HT1B receptor gene G861C polymorphism in ADHD. Conclusions:Though there is the possibility of failing to detect small genetic effects, our results show no evidence of an association between ADHD and 5HT1B receptor gene G861C polymorphism in the Korean population and indicate that it is unlikely that the 5HT1B receptor is implicated in the susceptibility to ADHD.

Objective:The present study examined the association between basic neurocognitive functions and emotional recognition in chronic schizophrenia. Furthermore, to Investigate cognitive variable related to emotion recognition in Schizophrenia. Methods:Forty eight patients from the Yongin Psychiatric Rehabilitation Center were evaluated for neurocognitive function, and Emotional Recognition Test which has four subscales finding emotional clue, discriminating emotions, understanding emotional context and emotional capacity. Measures of neurocognitive functioning were selected based on hypothesized relationships to perception of emotion. These measures included:1) Letter Number Sequencing Test, a measure of working memory;2) Word Fluency and Block Design, a measure of executive function;3) Hopkins Verbal Learning Test-Korean version, a measure of verbal memory;4) Digit Span, a measure of immediate memory;5) Span of Apprehension Task, a measure of early visual processing, visual scanning;6) Continuous Performance Test, a measure of sustained attention functioning. Correlation analyses between specific neurocognitive measures and emotional recognition test were made. To examine the degree to which neurocognitive performance predicting emotional recognition, hierarchical regression analyses were also made. Results:Working memory, and verbal memory were closely related with emotional discrimination. Working memory, Span of Apprehension and Digit Span were closely related with contextual recognition. Among cognitive measures, Span of Apprehension, Working memory, Digit Span were most important variables in predicting emotional capacity. Conclusion:These results are relevant considering that emotional information processing depends, in part, on the abilities to scan the context and to use immediate working memory. These results indicated that mul- tifaceted cognitive training program added with Emotional Recognition Task(Cognitive Behavioral Rehabilitation Therapy added with Emotional Management Program) are promising.

Objective:Although polymorphism of dopamine transporter gene(DAT1) has been considered to be implicated in the pathogenesis of social phobia, previous investigations have been inconsistent and controversial. The authors investigated the relationship between DAT1 polymorphism and social phobia in Koreans. Methods:DAT1 and alleles of fifty subjects who met DSM-IV criterion of social phobia, and those of age- & sex- matched fifty normal controls in Korea were compared. Additionally, patients were grouped into generalized(33) and nongeneralized(17) types and DAT1 polymorphism was compared with that of age- & sex- matched controls. DAT1 with variable number of tandem repeats(VNTR) were determined by using polymerase chain reaction. To compare the distribution of the DAT1 polymorphism between different groups, Fisher's exact test was used. Results:There were no significant differences in either genotypic(p=0.451) or allelic(p=0.452) distributions between the social phobia patients and the controls. There also were no differences in genotypic distribution between subtypes of social phobia patients and the controls. Conclusion:We couldn't find any association between DAT1 polymorphism and social phobia. Further studies including larger number of samples and diverse clinical variables should be conducted to elucidate the present findings.

Over the last decade, EMDR(Eye Movement Desensitization and Reprocessing) has emerged as a promising new treatment for trauma and other anxiety-based disorders. However, neurobiological mechanism of EMDR has not been well understood. Authors report SPECT findings of two patients of PTSD before and after EMDR. Brain 99mTc-ECD-SPECT was performed before and after EMDR treatment. To evaluate the significance of changes in the regional cerebral perfusion, t-test was conducted on the resulting images using SPM99. In addition, clinical scales(CAPS, CGI, STAI) were employed to asses the changes in the clinical symptoms of the patients. After EMDR treatment, each showed significant improvement in clinical symptoms. The cerebral perfusion increased in bilateral dorsolateral prefrontal cortex, and decreased in the temporal association cortex. The differences in the cerebral perfusion between patients after treatment and normal controls decreased. These changes appeared mainly in the limbic area the and the prefrontal cortex. These results suggest that EMDR may show the therapeutic effect through 1) improvement in the emotional control by increased activity in the prefrontal cortex, 2) inhibited hyperstimuli on amygdala by deactivation of the association cortex, 3) inhibition on past trauma related memory, and 4) keeping the functional balance between the limbic area and the prefrontal cortex. This case report needs further replication from studies with larger sample.