In the post-genomic era, the mechanisms controlling activation of genes are thought to be more important. Gene-environment interactions are crucial in both development and treatment of psychiatric disorders as they are complex genetic disorders. Epigenetics is defined as a change of gene expression that occurs without a change of DNA sequence and can be heritable by certain mechanisms. Epigenetic changes play essential roles in control of gene activation. DNA methylation, chromatin remodeling and RNAi act as key mechanisms for epigenetic modifications of genes. Here, we review the basic mechanisms of epigenetics and discuss their potential involvement of human diseases, including psychiatric disorders.

Objectives : The neural substrate of fear is thought to be highly conserved among species including human. The purpose of this review was to address the neural substrates of fear based on recent findings obtained from animal and human studies. Methods : Recent studies on brain regions related to fear, particularly fear conditioning in rodents and humans, were extensively reviewed. Results : This paper suggests high consistency in anatomical structure and physiological mechanisms for fear perception, response, learning and modulation in animals and humans. Conclusions : Fear is manifested and modulated by well conserved neural circuits among species interconnected with the amygdala, such as the hippocampus and the ventromedial prefrontal cortex. Further research is required to incorporate findings from animal studies into a better understanding of neural circuitry of fear in human in a translational approach.

Depression is common in patients with end-stage renal disease(ESRD) and has a negative effect on the quality of life, functional ability, and mortality of the patients, with a prevalence rate as high as 20-25%. Especially, the increasing tendency of mortality in ESRD patients is associated with recent or current depression, and the suicide rate is also increased by depression in patients with ESRD. Therefore, accurate detection and appropriate treatment of depression is very important in ESRD patients. Also, a deferential diagnosis is needed concerning uremic symptoms and depression in ESRD patients. However, there has been little data so far particularly in terms of randomized clinical trials. This review focused on the recent knowledge of depression in ESRD, and could encourage clinical study and trials in this field.

본 논문에서는 우울증과 관상동맥 질환의 연관성에 대해 병태생리학적 기전을 중심으로 고찰하였다. 현재까지 선행 연구들을 통해 제시된 주요 병태생리학적 기전으로는 우울증에서의 증가된 혈액 응고 경향, HPA 축 기능 및 ANS 조절 이상, 상승된 염증 반응 상태 등과 더불어 관상동맥 질환과 우울증이 공통된 유전적 위험 인자를 공유하고 있을 가능성 등이 있다. 혈액 응고와 관련되어서는 혈소판의 활성 및 반응성 증가, 혈관 내피 기능 이상, 혈액 응고 인자의 증가 등이 구체적인 병리 기전으로 제시 되었으며, HPA 축 및 ANS 기능 이상과 관련되어서는 혈장내 카테콜라민의 증가와 이와 연관된 심박수 증가 및 심박 변이성의 감소, 기타 혈역학적 스트레스의 증가 등으로 인한 부정맥 및 죽상경화증의 촉진이 주요한 기전으로 제시되었다. 또한 CRP 등과 같은 염증 표지자 연구를 통해 우울증에서의 증가된 염증 반응이 죽상경화증이나 혈전 형성과 관계 되어있을 가능성 역시 제시되었다. 하지만 역으로 관상동맥 질환과 우울증의 동반 이환율이 높다는 사실은 잘 알려져 있음에도 불구하고 관상동맥 질환에서의 어떤 병태생리적 변화가 우울증의 발병 및 경과와 관련되어 있는지에 대해서는 체계적인 연구가 매우 적은 것이 사실이다. 이 이외에도 우울증과 관상동맥 질환 외의 제3의 요인 즉, 유전적 위험 인자가 두 질환에 선행함을 제시하여 우울증과 관상동맥 질환이 공통된 유전적 취약성을 공유하고 있을 가능성을 제기한 연구들도 있다. 그 밖에도 우울증과 대사 증후군과의 연관성에 기반한 연구나 ${\Omega}$-3 지방산, homocystein 수준에 주목한 일부 연구들이 존재하며, 관상동맥 질환을 가진 환자는 뇌혈관에도 죽상경화증이 있을 가능성이 높고 이로 인해 뇌의 특정 부위에 혈류장애가 있을 가능성이 높아서 이것이 혈관성 우울증을 야기할 가능성이 있다는 보고를 한 연구들도 있다. 우울증이 관상동맥 질환의 발생 및 경과에 부정적인 영향을 끼친다는 많은 연구 결과들은 우울증과 관상동맥 질환의 원인적 연관성에 대한 연구를 지속적으로 촉진시키고 있다. 하지만 우울증이라는 대상 질환 자체의 이질성과 관상동맥 질환을 가지고 있는 환자들은 대부분 항응고제 등의 약물을 투여하고 있다는 사실 등이 병태생리 규명 연구에 어려움을 주고 있는 것이 사실이다. 우울증과 관상동맥 질환의 병태생리적 연관성에 대한 지속적이고 다각적인 연구는 향후 관상동맥 질환 환자에서의 우울증의 중요성을 치료자에게 인식시키는 계기가 될 수 있으며 더 나아가 관상동맥 질환의 치료 예후의 개선으로 이어질 수 있는 통로를 제공할 것이다.

Objectives : We investigated the association of Val108/158Met polymorphism on catechol-O-methyl transferase(COMT) gene with smooth pursuit eye movement(SPEM) abnormality in Korean schizophrenia patients. Methods : We measured SPEM in 217 Korean schizophrenia patients(male 116, female 101) and divided them into two groups, one was a good SPEM function group and the other was a poor SPEM function group. Then we analyzed Val108/158Met polymorphism on COMT gene. We compared the differences of genotype and allele distributions of the polymorphism on COMT gene between the two groups. Results : The natural logarithm value of signal/noise ratio(Ln S/N ratio) of the good SPEM function group was $4.39{\pm}0.33$(mean${\pm}$s.d.) and that of poor SPEM function group was $3.17{\pm}0.71$. There were no statistically significant differences of age and male/female ratio between the two groups. There were no significant differences of genotype or allele distributions of the Val108/158Met polymorphism on COMT gene between the two schizophrenic groups. Conclusions : The results suggest that Val108/158Met polymorphism on COMT gene is not related to SPEM function abnormality in schizophrenia.

Objectives : The purpose of this study is to investigate whether the ability of facial affect perception is associated with schizotypal personality traits in healthy normal controls. Methods : 241 normal subjects were recruited in this study. The age range of all subjects was from 19 to 63 years. The schizotypal personality questionnaire(SPQ) and facial affect identification test(FAIT), which were developed and standardized in Korea, were applied. Subjects from high 1 standard deviation(H group, N=40) and low 1 standard deviation(L group, N=26) on SPQ score were compared. Results : We found that the H group showed significantly reduced ability on the correctness of sadness and neutral compared with the L group. But, no significant association between SPQ and intensity or reaction point was observed in all subjects. Conclusion : This study suggests the individuals with high schizotypal personality trait have impairments on the facial affect identification. Also, these findings may provide the reasonable explanation of social cognition deficit of schizotypal personality disorder.

Objectives : Some reports have suggested that 5-HT5A polymorphism allelic association was associated with depression, however, there has been no report about relationship between the 5-HT5A gene and antidepressant response. We conducted the association study of the 5-HT5A receptor gene polymorphisms (-19G/C,12A/T) and response to citalopram in Korean patients with major depressive disorder(MDD). Methods : A total of 106 patients with major depressive disorder were included in this study. The patient's symptoms were measured by 21-item Hamilton Depression Rating Scale(HAMD) at baseline, week 1, week 2, week 4 and week 8 during citalopram treatment. A Responder to citalopram was defined by 50% reduction of total HAMD scores. To analyze genetic polymorphisms, a polymerase chain reaction based method was used. Results : At week 8, responders were 62, non-responders were 44. No significant differences of genotypes or allelic association in 19G/C and 12A/T polymorphisms were observed between responsive and non-responsive patients. Conclusion : These results do not support the hypothesis that this polymorphism of the HT5A receptor gene is involved in the therapeutic response to citalopram.

Objectives : The evaluation of disability after trauma in psychiatry is relatively subjective compared with other departments. A consensus among evaluators could improve reliability of evaluations. We compared disability rate of common psychiatric disorders without definite brain injury depending on their diagnosis from experienced evaluators in Korea. Methods : A written questionnaire was mailed to each evaluator and the reply was analyzed. The questions included disability rate ranges of postconcussional syndrome, PTSD and depression. Other questions related with admission for evaluation, expected duration of treatment, life expectancy and need of supporting person were also asked. Results : Range of disability rate were from $8.6{\pm}4.5%$ to $26.6{\pm}12.8%$ in postconcussional syndrome, from $10.4{\pm}6.8%$ to $36.4{\pm}13.8%$ in PTSD and from $10.0{\pm}4.6%$ to $30.6{\pm}10.3%$ in depressive disorder. There were lots of diversity in expected duration of treatment with psychiatric disability. Decline of life expectancy and need of supporting person were considered at least 50% of disability. Conclusion : There is much diversity in evaluation of psychiatric disabilities with disability rate and expected duration of treatments even among experienced evaluators. A common consensus among experts may increase reliability of psychiatric evaluations after trauma.