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정신분열병 환자에서 항정신병 약물로 발생한 체중 증가의 유전적 원인： 연합 연구를 중심으로

Pharmacogenetics of Antipsychotic-Induced Weight Gain in Schizophrenic Patients : Based on Association Studies

정영조|박영민|이헌정
대한생물치료정신의학회 (Korean Society Of Biological Therapies In Psychiatry)|2007.12|생물치료정신의학 (Journal of the Korean Society of Biological Therapies in Psychiatry)|제13권 제2호|pp. 147-157

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항정신병 약물·체중 증가·유전자다형성·정신분열병·약물유전학.Antipsychotic-induced weight gain·Polymorphism·Schizophrenia pharmacogenetics·Neuroleptics.
주제분류정신과학

초록

항정신병 약물로 인한 체중 증가는 장기적인 건강 상태와 치료 순응도에 부정적인 영향을 많이 끼치게 된다. 2세대의 비전형 항정신병 약물이 개발되었으나 여전히 체중 증가에서 자유로울 수는 없었다. 항정신병 약물에 의한 체중 증가는 약물의 중단 혹은 순응도 감소의 가장 큰 이유가 되고 있다. 성인에서의 비만과 체중 증가는 고혈압, 2형 당뇨병, 관상동맥 질환, 뇌혈관 질환, 담낭 질환, 퇴행성 관절염, 수면 무호흡증, 호흡기 질환, 악성 종양 등의 건강에 심대한 손상을 주는 질환들과 관련이 되어 있다. 더구나 체중 증가는 자존감 저하, 사회적 기능 장애, 활동성 감소 등과 같은 심리적인 부분과 삶의 질에도 많은 영향을 주게 된다. 현재까지 많은 연구들이 진행되어왔다. 비록 연관 연구에서는 성과가 적었지만 연합 연구에서는 항정신병 약물에 의한 체중 증가와 관련된 후보 유전자들이 많이 발견되었다. 후보 유전자에는 5-hydroxytrptamin 2C(HTR2C), adr ener-gic α2a(ADR2α) receptor gene, leptin, guanine nu -cleotide binding protein(GNB3), synaptomal-associ -ated protein 25kDa(SNAP25) genes 등을 들 수 있다. 향후 연구는 더 많은 표본 수를 이용하여 더 긴 기간의 연구가 이루어져야 할 것이다. 나아가 밝혀지지 않은 새로운 유전자에 대한 연구와 유전자와 유전자간의 상호 작용 및 유전자와 환경간의 상호 작용에 대한 연구들이 이루어져야 할 것이다.

Abstract

Antipsychotic-induced weight gain is a major reason for discontinuation of and noncompliance with antipsychotics. Obesity and weight gain in adulthood have been associated with significant health complications, such as type II diabetes, coronary heart disease, stroke, gallbladder disease, osteoarthritis, sleep apnea, respiratory problems, and some types of cancer. Weight gain may also adversely affect self-esteem, social functioning, and physical activity. Futhermore, medication -induced weight gain has been associated with a lower quality of life, and is a leading barrier to continued compliance with psychiatric medications. An individual’s propensity to develop weight gain largely depends on genetic factor. Candidate gene studies have produced significant findings in the 5-hydroxytrptamin 2C(HTR2C), adrenergic α2a(ADR2α), receptor gene, as well as in the leptin, guanine nucleotide binding protein(GNB3) and synaptomal-associated protein 25kDa(SNAP25) genes in the association studies, although there have been short of positive results by the linkage studies. Future studies should employ larger samples. In addition, the possible involvement of as-yet-uncovered gene(s) that influence susceptibility to antipsychotic-induced weight gain should be evaluated, as well as the possibility of gene-gene and geneenvironment interactions.

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