한국인 조현병 환자에서의 지연성 운동이상증과 TNF (Tumor Necrosis Factor)-α 유전자 다형성과의 연관성

소수정,강승걸,윤호경,박영민,이헌정,김린 대한조현병학회 2013 대한조현병학회지 Vol.16 No.1

Objectives : There are emerging evidences suggest that the development of tardive dyskinesia (TD) is related to the oxidative stress, excitotoxicity, and immune activation. The purpose of this study is to investigate whether single-nucleotide polymorphisms (SNPs) of tumor necrosis factor (TNF)-α genes are associated with the susceptibility of TD and schizophrenia. Methods : We investigated two hundred and eighty Korean schizophrenic patients. The schizophrenic participants consisted of patients with (n=105) and without (n=175) TD who were matched for antipsychotic drug exposure and other relevant variables. The TNF-α gene -308G/A SNPs were analyzed by polymerase chain reaction (PCR)-based methods. Results : The frequencies of genotype (χ2=0.33, p=0.848) of the TNF-α gene -308 G/A SNP did not differ significantly between schizophrenic patients with and without TD. The difference of allele frequencies (χ2=0.28, p=0.594) of the TNF-α gene between the schizophrenic patients with and without TD were not significant. Conclusion : These results suggest that the TNF-α gene -308 G/A SNPs are not associated with TD and schizophrenia in a Korean population. Further association studies of TD with other candidate genes for cytokines would help us understand the pathophysiological mechanisms of TD. 지연성 운동이상증은 항정신병 약물을 장기간 복용하는 조현병 환자에서 발생하는 비가역적인 부작용으로, 여러 새로운항정신병 약물이 개발된 현재에도 가장 심각한 부작용으로 여겨지고 있다. 따라서 조현병 환자 중 지연성 운동이상증의 발생에 감수성을 가지는 환자를 예측할 수 있다면 그 예방과 치료에 많은 도움이 될 것이다. 이러한 배경하에 본 연구는 한국인조현병 환자를 대상으로 TNF-α 유전자의 유전자 다형성과 지연성 운동이상증의 연관성을 알아보기 위해 시행되었으나, 지연성 운동이상증의 발생에 있어 TNF-α 유전자 다형성이 유전적 감수성의 원인이 됨을 밝히지는 못 하였다. 그러나 현재까지 지연성 운동이상증과 TNF-α 유전자 다형성 간의 연관성에 대한 연구가 극히 부족한 실정에서, 본 연구는 TNF-α 뿐 아니라 나아가 시토카인과 지연성 운동이상증의 발생에 대한 향후의 연구들에 있어 일말의 단서를 제공한다고 할 수 있겠다. 추후 보다 다양한 임상적 변인을 포함하여 TNF-α 유전자 다형성과 지연성 운동이상증의 관련성에 대한 연구가 이루어져야 할 것이다. 또한 지연성 운동이상증과 시토카인에 대한다른 후보유전자와의 연관 연구가 지연성 운동이상증의 병태생리학적 기전을 이해하는 데 도움을 줄 것으로 생각된다.

조현병에 대한 유전학연구의 최신현황

정희정,이병대,박제민,이영민,문은수 대한조현병학회 2013 대한조현병학회지 Vol.16 No.1

이러한 유전(gene), 환경(environment), 나이(age), 성(sex)이라는 변수인자(variable)가 어떻게 조현병을 포함한 다양한 정신의학적 표현형을 이룰것이냐 하는 문제는 결국에는 물리적 과학의 언어일수 있는 수학적 규명의 영역으로 갈수도 있을것이다. 이러한 방정식(equation)을 푸는 과정은 신의 영역에 도전하는 인간의 노력에 비유될수도 있을것이다. 그밖에도 에너지학-에너지 유전체학(Energyomics-energe-nomics), 미토콘드리아 연구의 전사적 접근(Translational Ap-proaches to Mitochondrial Research), 흔한 질환의 미토콘드리아적 원인(A mitochondrial etiology of common diseases), 면역유전학 및 정신내분비학(Immunogenetics : Psychoneu-roendocrinology), 진화유전학(Evolutionary Genetics), 통계유전학(Statistical Genetics), 생명통계학/생명정보학(Biosta-tistics/Bioinformatics), 약물유전체학(Pharmacogenomics), 유전자에 대한 소유권문제(Owning the Genome) 등의 많은 이슈들이 제기된다. 유전적 위험도에 대한 예측(Genetic risk prediction) 및 유전적 성과를 바탕으로 한 새로운 치료법의 개발(Development of novel therapeutics)은 개인형 맞춤 진단과 치료의 이른 전망(Prospects for personalized interventions and therapeu-tics)도 낳게한다. Schizophrenia is a devastating mental illness that can lead to deterioration in the social and occupational functioning of affected individuals with a major cost to society. A wide range of studies suggest a genetic component to the inheritance of schizophrenia. The molecular genetic studies on schizophrenia have been actively performed since late 1980s. In linkage studies, no loci were replicated across studies and there were no loci surpassing genome-wide significance. Candidate gene association studies showed generally inconsistent results and there were no enrichment of smaller P-values. In the GWAS era, the community has coalesced into large international consortia. The largest schizophrenia GWAS to date is 50,000 samples and efforts are ongoing to accumulate 50,000 cases and 50,000 controls as part of ‘PGC2’ collaboration. With the limitation of GWAS results, several alternatives are being explored. In genotyping, the concepts of allelic spectrum including from common polygenic to rare penetrant variation are emerging. Phenotypes include all phenomena beyond DNA. The developments in transcriptomic & proteomic approach and intensive research on endophenotype will bring crucial insights into the nature of schizophrenia in the future. But there still remains our task about research on many factors including environment that influence gene expression (epigenetics), age, and gender.

조현병 환자에서의 Mismatch Negativity와 기능 상태의 연관성 연구

김민아,김성년,이민희,이수지,권준수 대한조현병학회 2013 대한조현병학회지 Vol.16 No.2

Objectives : It has been constantly reported that mismatch negativity (MMN) is impaired in patients with schizophrenia. However, the mechanism which relates impaired MMN and schizophrenia is not clear yet. The aim of this study is to investigate the association between MMN and clinical variables including functional status in patients with schizophrenia. Methods : The present study assessed MMN using passive auditory oddball task in 26 patients with schizophrenia and 48 healthy controls. Repeated measures Analysis of Variance with age as a covariate was carried out for comparing peak amplitude and latency of MMN at 8 central line electrodes (FPz, Fz, FCz, Cz, CPz, Pz, POz, Oz) across groups. Pearson’s correlation was performed to reveal the relationship between MMN and clinical variables including neurocognitive test results and the Global Assessment of Functioning score. Results : MMN amplitude was significantly reduced in patients with schizophrenia compared with healthy controls. Pearson’s correlation showed that subsets of short form of Korean Wechsler Adult Intelligence Scale scores and GAF scores were associated with MMN amplitude in patients with schizophrenia. Conclusion : These findings suggest that MMN amplitude is associated with current functional status including cognitive function in patients with schizophrenia. 본 연구는 MMN과 조현병 환자의 기능 상태를 포함한 임상 지표들 사이의 연관성을 밝히고자 하였다. 26명의 조현병 환자와 48명의 정상 대조군에서 수동적 oddball task를 수행하는 동안 뇌파를 측정하여 MMN을 평가하였고, MMN 진폭의 집단간 차이와 함께 신경인지기능검사를 포함한 임상 평가 결과, GAF 점수와의 상관관계를 분석하였다. 그 결과 정상 대조군에 비하여 조현병 환자군에서 Fz, FCz, Cz, CPz, Pz, POz의 뇌파 측정 부위에서 MMN의 진폭이 유의하게 감소하였음을 발견하였다. 피어슨 상관분석 결과 조현병 환자군에서단축형 한국판 성인 지능 검사의 소검사들과 MMN 진폭이 통계적으로 유의한 상관 관계를 보였다. 또한, MMN 진폭은 Fz, Cz, CPz에서 GAF 점수와 관련이 있었다. 본 연구는 조현병환자들에서 MMN 진폭의 감소가 인지 기능 및 심리사회적 기능의 손상과 관련이 있음을 밝힘으로써, MMN이 환자들의 기능 상태를 평가하고 치료 반응 및 예후에 대한 정보를 얻는 데중요한 역할을 할 수 있음을 제시하였다.

주제찾기 수행을 통해 평가한 조현병 환자에서의 추상적 사고 능력의 저하

오주영,전지원,김재진 대한조현병학회 2013 대한조현병학회지 Vol.16 No.1

Objectives : Patients with schizophrenia often have a concrete thinking or an impairment in abstract thinking, but there has been a limitation in quantitatively measuring this cognitive function. The aim of the current study was to investigate a deficit in abstract thinking in patients with schizophrenia using the theme identification task. Methods : Twenty subjects with schizophrenia and 20 healthy volunteers participated in the behavioral study for theme identification. The visual stimuli were composed of a series of pictures, which contained positive or negative emotional situations. Three words, indicating a main theme of the picture, a theme-related item and a theme-unrelated item, respectively, were presented in the bottom of the pictures, and participants had to select a theme. Results : The patient group selected theme words at significantly lower rate in both emotional conditions than the control group (positive, p=0.002 ; negative, p=0.001). Especially, in the negative condition, the patient group more selected theme-unrelated items than the control group (p=0.001). The rates of theme identification were inversely correlated with scores of the Social Anhedonia Scale (positive, r=-0.440, p=0.007 ; negative, r=-0.366, p=0.028). Conclusion : Patients with schizophrenia exhibited an impairment in abstract thinking, and it was remarkable in the negative condition. The ability to think abstractly was associated with the severity of social anhedonia. The impairment of abstract thinking may become one of the reasons for poor social functioning in socially anhedonic patients. 본 연구는 상기 제시된 제한점에도 불구하고 몇 가지 중요한 사실을 제시하고 있다. 첫째, 조현병 환자들의 추상적 사고 능력은 일상적인 상황을 나타내는 사진에서의 주제찾기 수행을 통해 평가하였을 때에도 정상인에 비해서 저하되어 있다. 둘째, 조현병 환자에서의 추상적 사고 능력의 저하는 다른 인지적 과제 수행 시와 비슷하게 부정적 정서가 동반되었을 때 두드러진다. 셋째, 조현병의 핵심 병리 중 하나인 사회적 무쾌감증이 심할수록 추상적 사고 능력의 저하가 두드러진다. 이러한 연구 결과는 결론적으로, 추상적 사고 능력에 대한 올바른 평가 및 이해를 위해서는 동반된 정서에 대한 고려가 필요하다는 것을 의미하고, 사회적 무쾌감 증상이 있는 환자의 저하된 사회적 기능의 원인 중 하나로 추상적 사고 능력을 고려해 볼 수 있다는 사실을 제시한다. 물론, 본 결과는 앞서 제시된 여러 가지 제한점을 극복하고, 다른 연구들을 통하여 추후 검증되어야 할 것이다.

지역사회에 거주하는 조현병 환자와 보호자들의 장기지속형 주사제 항정신병약물에 대한 선호도 조사

이융,이남영,윤탁,최용성,정인원 대한조현병학회 2013 대한조현병학회지 Vol.16 No.1

Objective : The prescription rates of long-acting injectable (LAI) antipsychotics are very low around 1% in Korea. This study was aimed to explore the preference of LAIs in patients with schizophrenia, who are currently living in community, and their caregivers. Methods : The patients, diagnosed with schizophrenia by DSM-IV TR and were registered in the 31 mental health centers of Gyeonggi province and their caregivers were inquired the knowledge of the LAIs. The questionnaires contained information such as demographic characteristics, history of psychiatric treatment, and so on. Results : About 5,318 were registered in 31 community mental health centers of Gyeonggi province in February 2012. The questionnaires of 614 patients and 365 caregivers were gathered from 20 community mental health centers. The mean ages (±SD) of patients and caregivers were 41.9 (±10.2) and 62.2 (±13.4) years old, respectively. 272 patients (44.6%) had experienced the discontinuation of medications without doctor’s consent. 217 patients (35.9%) and 97 caregivers (27.1%) knew about the LAIs. The preference rates for LAIs were 35.2% and 46.8% for the patients and caregivers, respectively. Conclusion : There is still huge discrepancy between the preference and the real prescriptions of LAIs in community-dwelling patients and their caregivers, much higher than in those of hospital settings. This study suggests that both patients and caregivers registered in the community mental health centers have a strong commitment to live in the community. The obstacles against the benefits of LAIs need to be resolved. 본 조사연구 결과에 의하면 지역사회의 환자 및 보호자들은 약물치료의 중요성을 잘 알고 있었으며 장기지속형 주사제에 대한 선호도는 의료기관을 대상으로 조사한 결과에서 보다 높게 나타났다. 장기지속형 주사제를 선호하는 환자들은 투여 간격이 1개월이라는 점과 치료효과에 대한 기대가 높았으며, 부작용에 대해서도 우려하고 있었다. 장기지속형 주사제를 거절하는 환자들은 주사 자체를 싫어하였으며 경구용 약물의 치료효과로 만족하고 있었으며 장기지속형 주사제의 높은 가격과 장기 지속 효과에 대한 염려를 하고 있었다. 장기지속형 주사제를 선호하는 보호자들도 1개월 간격의 투여방법을 선호하였으며 장기지속형 주사제의 부작용과 낮은 임상적 효과를 우려하고 있었다. 장기지속형 주사제를 선호하지 않는 보호자들은 경구용 약물에 만족하고 있었다. 특히 보호자들 중에서 그들의 환자가 입원 또는 약물 중단의 경험이 많은 경우에 장기지속형 주사제의 선호도가 높아서 보호자들이 환자들의 지속적인 약물 복용의 관리에 대한 부담감이 높다는 것을 의미하며 전체적으로 환자 및 보호자들 모두에서 환자의 지역사회 거주에 대한 의지가 높았다는 것을 확인할 수 있었다.

정신병의 수용전념치료

나의현 대한조현병학회 2022 대한조현병학회지 Vol.25 No.1

There has been increasing interest in the psychosocial treatment of psychosis based on Acceptance and Commitment Therapy (ACT), which has the primary aim of helping people more effectively engage in their lives guided by their values. The approach includes various techniques to change one’s relationship to private experiences, such as hallucination and delusion, rather than rectifying the contents of these experiences. Using the six core processes of the ACT model (hexaflex) tailored to the characteristics of people with psychosis may help alleviate their distress from the symptoms and shape pragmatic value-consistent behaviors. This review introduces the ACT model of psychosis and illustrates the specific ways of applying ACT to people with psychotic experiences.

조현병 환자의 금연 약물 치료

김성진,정도운,김유나 대한조현병학회 2018 대한조현병학회지 Vol.21 No.1

Schizophrenia is a major chronic mental illness with various symptoms that is often accompanied by substance use disorders. Patients with schizophrenia have a higher smoking rate than the general population and a lower smoking cessation success rate. Further, their motivation for smoking cessation is often low. Individuals with schizophrenia that are past or present cigarette smokers are more difficult to treat in terms of psychotic symptoms, are more likely to have physical illnesses, and have higher mortality rates. A variety of treatments, both pharmacological and non-pharmacological, are used to aid smoking cessation in patients with schizophrenia. Among these, bupropion, varenicline, and nicotine replacement therapy can be safely used in patients with schizophrenia, and several studies have demonstrated their effects. Cigarette smoking is an important health problem. The study of smoking cessation in individuals with schizophrenia may help improve their ability to function and their quality of life through active evaluation and treatment.

장기 재원 조현병 환자에서 재입원 혹은 탈원에 따른 사회적 및 임상적 특징 차이

김민선,박선영,최진숙 대한조현병학회 2020 대한조현병학회지 Vol.23 No.1

Objectives: Dehospitalization of long-term inpatients with schizophrenia can be difficult because of complex factors such as chronic symptoms and low family and social support. The aim of this study was to identify factors related to dehospitalization and readmission of long-term inpatients with schizophrenia. Methods: This retrospective study reviewed the medical records of patients discharged from a psychiatric hospital in Yongin, South Korea, from February 1, 2016, to July 31, 2017. Patients who were hospitalized for over 3 months were divided into two groups: readmission (n=47) and dehospitalization (n=55). Differences in sociodemographic and clinical factors were analyzed between the two groups. Results: Regarding sociodemographic characteristics, female sex, familylessness, discharge to nursing homes, and discharge after symptom improvement were more prevalent in the dehospitalization group, whereas male sex, having a sibling as next of kin, and discharge because of other problems were more prevalent in the readmission group. Among clinical characteristics, hospital stay was longer in the readmission group. Conclusion: In this study, patients without a family showed a tendency to not be readmitted when they were discharged to nursing homes after symptom improvement. Expansion of social welfare support may encourage dehospitalization of long-term inpatients with schizophrenia. .

유럽인 자료로 산출된 조현병 다유전자 위험도 점수의 한국인 조현병 환자를 대상으로 한 적용

이진영,이동빈,조은영,백지현,홍경수 대한조현병학회 2020 대한조현병학회지 Vol.23 No.2

OBJECTIVES This study aimed to explore whether common genetic variants that confer the risk of schizophrenia have similar effects between Korean and European ancestries using the polygenic risk score (PRS) analysis. METHODS Study subjects included 713 Korean patients with schizophrenia and 497 healthy controls. The Korea Biobank array was used for genotyping. Summary statistics of the most recent genome-wide association study (GWAS) of the European population were used as baseline data to calculate PRS. Logistic regression was conducted to determine the association between calculated PRS of European patients with schizophrenia and clinical diagnosis of schizophrenia in the Korean population. RESULTS Schizophrenia PRS was significantly higher in patients with schizophrenia than in healthy controls. The PRS at the pvalue threshold of 0.5 best explained the variance of schizophrenia (R2=0.028, p=4.4×10-6). The association was significant after adjusting for age and sex (odds ratio=1.34, 95% confidence interval=1.19-1.51, p=1.1×10−6). The pattern of the association remained similar across different p-value thresholds (0.01-1). CONCLUSION Schizophrenia PRS calculated using the European GWAS data showed a significant association with the clinical diagnosis of schizophrenia in the Korean population. Results suggest overlapping genetic risk variants between the two populations.

조현병 관련 주요 일간지 기사에 대한 텍스트 마이닝 분석

남희정,유승형 대한조현병학회 2020 대한조현병학회지 Vol.23 No.2

OBJECTIVES In this study, we conducted an exploratory analysis of the current media trends on schizophrenia using text-mining methods. METHODS First, web-crawling techniques extracted text data from 575 news articles in10 major newspapers between 2018 and 2019, which were selected by searching “schizophrenia” in the Naver News. We had developed document-term matrix (DTM) and/or term-document matrix (TDM) through pre-processing techniques. Through the use of DTM and TDM, frequency analysis, cooccurrence network analysis, and topic model analysis were conducted. RESULTS Frequency analysis showed that keywords such as “police,” “mental illness,” “admission,” “patient,” “crime,” “apartment,” “lethal weapon,” “treatment,” “Jinju,” and “residents” were frequently mentioned in news articles on schizophrenia. Within the article text, many of these keywords were highly correlated with the term “schizophrenia” and were also interconnected with each other in the co-occurrence network. The latent Dirichlet allocation model presented 10 topics comprising a combination of keywords: “police-Jinju,” “hospital-admission,” “research-finding,” “care-center,” “schizophrenia-symptom,” “society-issue,” “family-mind,” “woman-school,” and “disabled-facilities.” CONCLUSION The results of the present study highlight that in recent years, the media has been reporting violence in patients with schizophrenia, thereby raising an important issue of hospitalization and community management of patients with schizophrenia.