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1 KISEP Original Article 생물정신의학 Vol. 14, No. 2, May 2007 안정상태뇌대사활성도에반영된정신분열병환자와정상인에서의감정이입과기분인식관련뇌영역 * 박일호 1)2) 전지원 1) 정영철 1)2) 석정호 3) 박해정 4) 이종두 4) 김재진 1)2)4) Empathy and Mood Awareness Reflected in the Resting-State Brain Metabolic Activity in the Patients with Schizophrenia and Normal Subjects * Il Ho Park, M.D., 1)2) Jiwon Chun, M.S., 1) Young Chul Jung, M.D., 1)2) Jeong Ho Seok, M.D., 3) Hae-Jeong Park, Ph.D., 4) Jong Doo Lee, M.D., Ph.D., 4) Jae-Jin Kim, M.D., Ph.D. 1)2)4) ABSTRACT bjectives:empathy O has been conceptualized as the ability of emotional resonance and perspective-taking. Emotional awareness has been proposed as the basis of empathy. In this study we examined the relationship between empathy and mood awareness and their neural correlates in resting-state activity in normal controls and patients with schizophrenia. Methods:Empathy and mood awareness scale scores were compared between 29 patients with schizophrenia and 21 normal controls by voxel-based t-tests and voxel-based correlation analyses of resting-state 18 F- FDG PET images. Results:Empathy and mood labeling scale scores were significantly decreased in schizophrenic patients. Mood monitoring was positively correlated with empathy score in normal controls, but not in schizophrenic patients. In normal controls, empathy was positively correlated with resting-state activities in the intraparietal sulcus and mood monitoring was positively correlated with the temporal pole, frontopolar cortex, inferior temporal gyrus, entorhinal cortex and the subgenual prefrontal cortex resting activities. The orbitofrontal cortex resting activity was positively correlated with mood monitoring-related subgenual prefrontal cortex activity in the normal controls. Patients with schizophrenia showed decreased orbitofrontal resting activity and loss of its correlations with mood monitoring-related regional activities. Conclusion:This study showed that alteration in the resting-state activity in schizophrenia may reflect dysfunc- * This study was supported by a grant of the Korea Health 21 R & D Project, Ministry of Health & Welfare, Republic of Korea (A040042). 1) 연세대학교의과대학의학행동과학연구소 Institute of Behavioral Science in Medicine, Yonsei University College of Medicine, Gwangju, Korea 2) 연세대학교의과대학정신과학교실 Department of Psychiatry, Yonsei University College of Medicine, Seoul, Korea 3) 한림대학교의과대학정신과학교실 Department of Psychiatry, Hallym University Sacred Heart Hospital, Anyang, Korea 4) 연세대학교의과대학진단방사선과학교실 Department of Diagnostic Radiology, Yonsei University College of Medicine, Seoul, Korea 교신저자 : 김재진, 경기도광주시탄벌동 전화 ) (031) , 전송 ) (031) , ) jaejkim@yonsei.ac.kr

2 tional empathy and distorted characteristic of emotional awareness. However, the resting-state activity may not reflect the relationship between emotional awareness and empathy. KEY WORDS:Empathy Emotional awareness Schizophrenia Resting-state Orbitofrontal cortex PET. 서론 정신분열병증상에대한성공적인약물치료에도불구하고환자들에게남아있는사회기능장애는이들이삶의질을회복하는완전한치유에이르는데걸림돌이된다. 최근에는사회기능에있어서대인관계시상대방을이해하고상대방의반응과행동을예측할수있는능력의중요성이부각되면서사회인지 (social cognition) 에대한연구들이활발하게이루어지고있다. 사회인지에있어서다른사람의의도나믿음을상상할수있는능력인마음의추론 (theory of mind) 와함께, 다른사람의기분을함께나누는감정이입 (empathy) 능력이중요하다고볼수있으며, 최근마음의추론과정서인식에대한연구결과들에서정신분열병환자에서감정이입능력이저하되어있음이시사되었다. 이들연구들은정신분열병환자가타인의심리상태 (mental state) 를잘인식하지못하고타인의의도를잘파악하지못하며, 긍정적인감정보다는부정적인감정이얼굴표정에나타날때잘인식하지못한다고보고하고있다. 1) 또한마음의추론장애를보이는대표적인질환인자폐증과정신분열병을비교한연구에서도정신분열병환자가자폐증환자와같이타인의믿음, 인식 (percept) 에대한상대방의관점을이해하지못할뿐아니라더불어감정에대한감정이입적관점획득 (empathic perspective-taking) 에장애를보인다고보고한바있다. 2) 감정이입은다른사람의감정을지각하고이해하며이를바탕으로적절하게반응할수있는능력을일컫는데, 최근에는이를신경과학적으로이해하기위한개념화가이루어지기도하였다. 감정이입은좁은의미또는기본기능측면에서는감정적전이 (emotional contagion) 라하여자동적, 무의식적으로상대방의얼굴표정, 음조, 자세, 움직임을흉내내고동조하는현상으로보며, 3) 보다넓은의미또는통합되고성숙된기능측면에서는감정적전이와함께상대방의관점에서바라보고이해할수있는능력 (perspective-taking) 과함께상황에따라서감정이입 반응을조절하여적절하게반응, 행동할수있는능력으로보기도한다. 4) 이에따른관련뇌영역으로관점획득 (Perspective-taking) 의경우, ToM 의신경학적관련부위로보고되고있는내측전전두엽피질 (medial prefrontal cortex), 후상측두고랑 (posterior superior temporal sulcus), 측두극 (temporal pole) 이관여할것으로보고되고있다. 감정적전이는상대방의감정상태를바라보거나상상할때관찰자에게서상대방의감정상태에대한표상및그에상응하는자율신경또는신체적반응이함께활성화된다고보고되고있다. 3) 이와관련된부위들로서, 뇌섬엽 (anterior insula cortex), 전대상회 (anterior cingulate), 하전두이랑판개부 (pars opercularis), 안와전두피질 (orbitofrontal cortex), 편도체 (amygdala), 2 차신체감각피질 (secondary somatosensory cortex) 와거울신경세포 (mirror neuron) 과연관된전운동피질 (premotor cortex) 과두정엽 (parietal cortex) 영역이있다. 3)4) 감정적전이와관련된위영역들은내부신체상태에대한정서적인식과연관되어활성화된다고보고된부위들이기도하다. 5) Damasio 6) 는그의 somatic marker hypothesis 에서감정은신체상태에대한뇌의표상의변화에서나타난다고주장한바있다. 또한자기의식 (selfawareness) 기능과자신또는타인의심리상태에대한귀인 (mental state attribution) 기능이공유하는신경인지처리과정이있다고보고되기도하였고 7) ToM 관련신경부위들도계통발생적으로기존에존재하던기능으로부터새로운기능이진화되어나타난것이라는관점 8) 을종합해보면, 감정이입능력은자신의내부적인감정상태를인식하는신경체계에근간을두고있다고유추해볼수있다. 정신분열병환자에서는자신의기분을인식하는데있어서도장애를보인다고하는데, 정신분열병환자에서대개부정적인감정수준이증가되어있다고하며 9) 정신분열병에서의감정표현불능증 (alexithymia) 에대한연구에서는정신분열병환자가정서적각성 (emotional arousal) 은증가되어있으나감정을말로표현하거나식별하는능력이저하되어있다고보고한바있다. 10)

3 대부분감정이입, 정서인식에대한뇌영상연구들은타인에게통증자극이가해지는장면을관찰하게하거나감정을유발시키는사진을보여주는등자극을통한뇌활성화상태 (state) 를보는연구들 4)11) 로, 감정이입과정서인식의소질 (trait) 에대하여보고된뇌영상연구는없었다. 자가보고식설문조사는조사대상의소질및주관적경험을반영하므로이를반영하는뇌기능이자극이나과제를이용한상태활성도에만국한되어반영된다고보기는어렵다. 뇌기능의기본상태 (default mode of brain function) 가설은과제독립적으로비활성화되거나목표지향적활동시활성도가감쇄되는뇌영역들의발견을통해안정상태에서의뇌활성상태에조직적인뇌기능이존재한다고보며선행 fmri 연구들에서는안정상태뇌활성도에내재적인기능적연결성 (intrinsic functional connectivity) 이있다고보고하기도하였다 ) 이러한안정상태뇌기능은과제와관계없는심상이나사고, 의식상태, 자기관련정신활동, 내관적사고등주관적경험과관련이있을것이라보고되고있다. 15)16) 이는안정상태의뇌활성도에주관적경험과관련된소질이반영될수있음을시사한다. 본연구는정상대조군과정신분열병환자군에서주관적경험으로서의정서인식능력과감정이입능력을자가보고식설문지를통해평가비교하고안정상태에서의 18 F- FDG PET 스캔을통해정서인식과감정이입의관련뇌활성화영역을조사하고이들간의연관성을알아보고자하였다. 또한환자에서의안정상태뇌기능저하가주관적정서인식과감정이입에미치는영향을알아보고자하였다. 연구대상및방법 1. 연구대상지역사회에서모집한 21 명의정상성인과세브란스정신건강병원에내원한 29명의정신분열병환자를대상으로하였다. 정신분열병의진단및배제기준에대한선별은한국판구조화임상면담도구 (Structured Clinical interview for DSM-Ⅳ) 17) 를이용한구조적면담을통해이루어졌다. 과거력상정상대조군에서주요정신질환이있는경우, 정신분열병환자군에서정신분열병을제외한기타주요정신질환이있는경우배제하였고두군모두뇌외상병력, 알코올을포함한약물남용병력이있는경우, 혹 은기타내과적, 신경과적이상소견이있는경우배제하였다. 손잡이설문지 (Annett s Handedness Questionnaire) 18) 를이용하여정상대조군 21명과환자군 29명전원이오른손잡이임을확인하였다. 두군은성별, 연령, 교육년수에대하여짝짓기 (matching) 하였다 ( 표 1). 모든환자들은 risperidone, olanzapine, clozapine, quetiapine, aripiprazole, amisulpiride, chlorpromazine, haloperidol 의항정신병약물들을한가지또는세가지까지혼합처방받았다. 본연구는세브란스정신건강병원의임상시험심의위원회 (Institutional Review Board) 의승인을받았으며, 모든참여자에게서면동의서를받았다. 2. PET 영상촬영영상자료는 4.8mm full width at half maximum (FWHM) 의공간분해능을가진 GE ADVANCE PET scanner(ge, Milwaukee, Wisconsin, USA) 를이용하여얻었다. 15.2cm 의 longitudinal field에서 4.25mm 간격의단면으로영상자료를얻었다. 피검자들에게 18 F-FDG 를 185 MBq(5mCi) 정맥주사하고약간어두운방에서눈을감고 40분동안기다리도록하였다. 감쇠 (attenuation) 보정을위해서 8분간 Ge-68 투과스캔 (transmission scan) 을시행하였고방출스캔 (emission scan) 은귀마개나눈가리개없이 3차원모드로 15분간시행하였다. 모든피검자들은촬영시간동안눈은감되잠은들지않는안정상태를유지하도록지시받았다. 3. 자가보고식정서척도 PET 영상촬영후모든피검자들은감정이입과기분인식을측정하는자가보고식설문지를작성하고 Positive and Negative Symptom Scale(PANSS) 19) 평가를위한면담을시행받았다. 감정이입척도 는타인의감정상태를느끼고이해하며이를통해타인을도와주고싶은마음이생기는지여부를 예 / 아니오 로대답하는 17개의항목으로구성된척도로감정이입능력을측정하며, 이수정과이훈구 20) 가 Trait Meta-Mood Scale 의타당화연구중개발하였던척도이다. 기분인식척도 (Mood Awareness Scale) 21) 는자신의감정에대하여지속적으로주목하고감정의경험을지칭하는처리과정을측정한다고한다. 이척도는각각 5개항목으로구성된기분감시 (mood monitoring) 와기분식별 (mood labeling) 차원 (dimension) 으로구성되어있고각항목은 6점 Likert scale 로채점된다. 본연구에서는한국어번역판 20) 을사용하였다

4 4. 인구학적특성및척도의통계분석정상대조군과정신분열병환자군간에인구학적특성, 감정이입척도점수, 기분인식척도총점및기분인식척도의차원점수비교는독립표본 t 검증 (independent samples t-test) 과 chi-square 검증을시행하였다. 또한두군에서감정이입척도점수와기분인식척도총점및기분인식척도의두차원점수들의연관성, 정신분열병환자군에서항정신병약물용량 (chlorpromazine dose equivalent) 과감정이입척도및기분인식척도점수와의연관성을알아보기위해상관분석을시행하였다. 통계분석의유의수준은 p<0.05 로규정하였고통계분석에는 SPSS version 11.5 가사용되었다. 5. PET 영상자료의처리및통계분석스캐너를통해획득한영상자료는 transaxial 8.5mm Hanning filter 와 8.5mm axial Ramp filer를이용하여노이즈를제거한후, 역투사방법 (back-projection) 을이용하여횡단면 matrix, mm pixel size 로재구성하였다. 재구성된영상자료는 Statistical Parametric Mapping 2(SPM2, University College of London, UK) 로공간적전처리 (spatial pre-processing) 를시행하고통계분석하였다. 재구성된모든영상자료들은피험자간해부학적변이성 (inter-subject anatomical variability) 를제거하기위해 affine transformation과추가적으로 nonlinear registration을이용하여. 표준 PET templete 에공간정규화하였다. 정규화된영상자료들은 14mm FWHM 의 Gaussian kernel 로평편화 (smoothing) 를하여신호대잡음비 (signal-tonoise ratio) 를향상시켰고미세한해부학적구조들의차이를조정하였다. 교란요소로작용할수있는뇌전체대사변동을제거하기위해 SPM2상전체대복셀 (voxel) 의비율을비교치로이용하는 proportional scaling 을이용하였다. 정신분열병환자군에서정상대조군보다감소되거나증가된뇌피질대사활성도영역들을찾아보기위해복셀단위 T- 검증을시행하였다. 해석의편의를위해복셀별 t-값은표준가우시안분포 (Gaussian distribution) 에서 Z-값으로변환한값을사용하였다. 복셀에대한미수정 (uncorrected) p값이 미만이고클러스터 (cluster) 의크기가 20개를초과하는서로인접한복셀들로구성될때통계학적으로유의미하다고보았다. T-검증결과에서정 상대조군과정신분열병환자군간대사활성도차이를보이는뇌영역들에대하여각군에서의영역별보정평균대사활성도 (adjusted mean regional metabolic activity) 를계산하였다. 그리고이들영역별보정평균대사활성도와정신분열병환자군에서의증상심각도와의연관성을알아보기위해 PANSS 의양성및음성증상점수와의상관분석을시행하였다. 이때정상대조군에서는피어슨상관계수 (Pearson correlation coefficient) 를, 정신분열병환자군에서는항정신병약물의용량을보정한편상관계수 (Partial correlation coefficient) 를구하였으며통계학적유의수준은 p<0.05 로규정하였다. 정상대조군과정신분열병환자군에서뇌영역별대사활성도와감정이입척도점수, 기분인식척도총점및차원별점수와의관계를알아보기위해 복셀단위상관분석 (voxel-based correlation analysis) 을시행하였다. 통계적으로유의미한영역은복셀의미수정 p값이 미만, 클러스터가서로인접한 20개를초과하는복셀들로구성될때로규정하였다. 복셀단위상관분석결과에서도각군에서감정이입및기분인식차원별점수와상관관계를보인뇌영역별활성도들에대하여영역별보정평균대사활성도를계산하였다. 정신분열병환자군에서정상대조군에비해안정상태뇌활성도가감소또는증가됨으로인해감정이입, 기분감시, 기분식별관련안정상태뇌활성영역들에영향을미치는지알아보기위해환자군과대조군간활성도차이를보인영역들중대뇌변연계와관련이있는영역의보정평균대사활성도와복셀단위상관분석을통해구한감정이입, 기분감시, 기분식별점수관련영역들의보정평균대사활성도와의상관분석을시행하였다. 이때의통계적유의미수준은 p<0.05 로규정하였다. 결과 1. 정상대조군과정신분열병환자군간척도점수들의차이및척도점수들간상관관계정신분열병환자군이정상대조군보다감정이입척도점수가유의미하게낮았고 (t=3.84, p<0.01) 기분인식척도의기분감시차원점수는차이가없었으나 (t=1.76, p= 0.09) 기분식별차원에서유의미하게낮았다 (t=2.20, p< 0.05)( 표 1). 감정이입척도점수와기분감시차원점수는정상대조군에서만유의미한양의상관관계를보였고정

5 Sex Table 1. Demographic and clinical characteristics Normal controls (n=21) Patients with schizophrenia (n=29) Mean SD Mean SD Male Female Age Years of education Duration of illness Dosage of antipsychotics (chlorpromazine DEq) Duration of medication PANSS Positive Negative General Total Empathy scale MAS Total Mood monitoring Mood labeling* SD:standard deviation, DEq:dose equivalent, PANSS:Positive and Negative Symptom Scale, MAS:Mood Awareness Scale, *:p<0.05 in independent-samples T-test, :p<0.01 in independent-samples T-test Х 2 /t p Table 2. Pearson correlation coefficients between the empathy scale and the mood awareness scale(mas) scores Normal controls Empathy scale Patients with schizophrenia MAS-total 0.41* MAS-mood monitoring 0.44* MAS-mood labeling 0.16* *:p<0.05 신분열병환자군에서는유의미한상관관계를보이지않았다 ( 표 2). 정신분열병환자군에서 PANSS 의양성증상, 음성증상, 일반정신병리척도점수, 총점중 PANSS 의총점만기분감시차원점수와유의미한양의상관관계를보였고 (r= 0.37, p<0.05) 그외양성증상, 일반정신병리척도점수와는경향성수준 (p<0.1) 의양의상관관계를보였다 ( 각각 r=0.35, p=0.06, r=0.32, p=0.09). 감정이입과기분인식척도의점수들과항정신병약물의투여용량 (chlorpromazine dose equivalent), 약물투여기 간, 유병기간과는유의미한상관관계를보여주지않았다. 2. 정상대조군과정신분열병환자군간안정상태뇌대사활성도의차이 ( 표 3) 정신분열병환자군은정상대조군에비해광범위한안정상태뇌대사활성도의차이를보였다. 환자군에서정상대조군에비해대사활성도가감소된영역은등쪽내측전전두피질 (dorsomedial prefrontal cortex), 안와전두피질 (orbitofrontal cortex), 상전두고랑 (superior frontal sulcus), 전운동피질 (premotor cortex), 판개부 (pars opercularis) 를포함하는전두엽부위로국한되었고, 환자군에서의뇌대사활성도의증가는주로기저핵 (basal ganglia) 과소뇌 (cerebellum) 을포함하는뇌후방의여러부위들에서관찰되었다. 본래규정하였던유의수준으로는기저핵과소뇌에서의클러스터들이너무크고서로겹쳐져서각클러스터의보정평균대사활성도를구할수없었다. 따라서기저핵과소뇌에대해서만유의수준을미수정 p< 와 20개를초과하는인접한복셀들로조정하여두영역의보정평균대사활성도를구하였다

6 Table 3. The brain regions with significant difference in the resting-state metabolic activity between the normal controls and the patients with schizophrenia and their corresponding adjusted mean metabolic activities and the correlations between the adjusted mean regional metabolic activities in the patient group and the PANSS scores Region Zmax MNI coordinates x y z Voxels Adjusted mean Adjusted mean metabolic activity metabolic activity in control in schizophrenia PCC with PANSS P PCC with PANSS N Decreased in patients with schizophrenia Dorsomedial 3.94* prefrontal cortex (BA8/9) 3.75* )01095* 91.7± ± Superior frontal 4.02* * 89.6± ± sulcus(ba8) Premotor cortex 3.71* * 72.8± ± (BA6) Pars opercularis (BA44) Left 4.05* * 81.8± ± Right 3.43* * 88.8± ± Orbitofrontal 3.33* * 59.1± ± cortex(ba11) Increased in patients with schizophrenia Lentiform 6.16* nucleus* 5.85* )12872* 68.9± ± Cerebellum* Vermis 4.37* Hemisphere 3.85* )07435* 72.0± ± Intraparietal sulcus 3.76* * 71.8± ± (BA5) Inferior temporal 3.42* * 67.1± ± gyrus(ba20) Parietal operculum Right(BA43) 3.73* * 72.4± ± Left(BA43) 3.45* * 68.7± ± Central sulcus 3.33* * 69.0± ± The threshold of significance was defined as an uncorrected p<0.001 with contiguous voxels >20. *:Adjusted threshold of significance to an uncorrected p< with contiguous voxels >20 due to excessive cluster sizes causing difficulty obtaining adjusted mean metabolic activity, :p<0.05, :p<0.01. PANSS:Positive and Negative Symptom Scale, PANSS P:PANSS positive symptom score, PANSS N:negative symptom score, PCC:Partial correlation coefficient controlling for chlorpromazine dose equivalent T 검증에서얻은영역들의보정평균대사활성도와 PANSS 양성및음성증상척도를항정신병약물의용량을보정하여편상관분석을시행하였을때, 등쪽내측전전두피질과전운동피질 (premotor cortex) 의뇌대사활성도가양성증상척도점수와유의미한역상관관계를보였고, 소뇌의뇌대사활성도는양성및음성증상척도점수모두와유의미한상관관계를보였다. 3. 정상대조군과정신분열병환자군내안정상태뇌대사활성도와기분감시차원, 기분식별차원, 감정이입척도점수와의상관관계 ( 표 4, 그림 1, 2) 감정이입척도점수와뇌대사활성도가유의미한양의 상관관계를보이는영역으로정상대조군에서는두정내고랑 (intraparietal sulcus) 이정신분열병환자군에서는미상핵머리 (head of caudate nucleus) 가관찰되었다. 기분감시차원점수와유의미한양의상관관계를보이는뇌영역대사활성도로는정상대조군에서는측두극 (temporal pole), 전두극피질 (frontopolar cortex), 하측두이랑 (inferior temporal gyrus), 내후각뇌피질 (entorhinal cortex), 슬하전전두피질 (subgenual prefrontal cortex) 이, 정신분열병환자군에서는상전두고랑 (superior frontal sulcus) 만이관찰되었다. 정상대조군에서만기분식별차원점수와유의미한상관관계를보이는뇌영역대사활

7 Table 4. The regional resting-state brain metabolic activities showing correlation with the empathy scale scores and the dimension scores of the mood awareness scale in the normal controls and the patients with schizophrenia Regions Empathy scale Positive correlation Intraparietal sulcus (BA40) Normal controls Z MNI coordinates x y z Vox AMA (SD) Regions Empathy scale Positive correlation Head of caudate (2.0) nucleus Negative correlation Negative correlation None None MAS-mood monitoring MAS-mood monitoring Temporal pole Superior frontal (BA38) 61.4 Sulcus(BA8) )328 (3.7) Frontopolar cortex (BA10) (2.3) Inferior temporal gyrus(ba37) (3.0) Entorhinal cortex (BA28) (3.7) Subgenual prefrontal cortex(ba25) (3.0) None None MAS-mood labeling MAS-mood labeling Positive correlation Positive correlation Middle temporal gyrus(ba21) (4.2) None Inferior temporal gyrus(ba37) (4.1) Patients with schizophrenia Z MNI coordinates x y z Vox AMA (SD) ) (3.7) (3.0) Negative correlation Negative correlation None None The threshold of significance was defined as an uncorrected p<0.001 with contiguous voxels >20. Z:Zmax, Vox: voxels, AMA:adjusted mean activity, SD:standard deviation 성도가관찰되었는데, 중측두이랑 (middle temporal gyrus) 과하측두이랑 (inferior temporal gyrus) 의대사활성도가양의상관관계를보였다. 4. 정상대조군과정신분열병환자군간차이를보인변연계영역의안정상태대사활성도와기분감시, 기분식별, 감정이입관련뇌영역대사활성도간의상관관계 ( 표 5) 정상대조군과정신분열병환자군간뇌대사활성도차이를보인영역들중변연계와관련있는부위로는안와전두피질이있었다. 안와전두피질의안정상태활성도는정상대조군에서기분감시차원점수와활성도간상관관 계를보인뇌영역들중슬하전전두피질과만유의미한양의상관관계를보였다 (r=0.57, p<0.01). 정신분열병환자군에서는안와전전두피질의뇌활성도와유의미한상관관계를보이는기분감시차원, 감정이입관련뇌영역활성도는관찰되지않았다. 기분감시차원관련뇌영역활성도와감정이입관련뇌영역활성도는정상대조군과정신분열병환자군모두에서유의미한상관관계를보이지않았고, 기분식별차원관련뇌영역활성도와감정이입관련뇌영역활성도간상관분석은기분식별차원과감정이입척도점수와의상관관계를보이지않았기때문에시행하지않았다

8 Table 5. Pearson correlation coefficients between the adjusted mean metabolic activities of the orbitofrontal cortex, with difference between the normal controls and the patients with schizophrenia, and the mean metabolic activities of empathy and mood awareness related regions Normal controls Orbitofrontal cortex Empathy Intraparietal sulcus * MAS-mood monitoring Temporal pole * Frontopolar cortex * Inferior temporal gyrus * Entorhinal cortex -0.20*0 Subgenual prefrontal cortex -0.57*0 MAS-mood labeling Middle temporal gyrus -0.28*0 Inferior temporal gyrus -0.31*0 Patients with schizophrenia Empathy Head of caudate nucleus -0.23*0 MAS-mood monitoring Superior frontal sulcus -0.27*0 *:p<0.05 고찰 본연구에서는기존의연구결과들과일치되게정신분열병환자에서감정이입능력과자신의감정경험을지칭할수있는기분식별능력이유의미하게저하되어있음을보여주었다. 1)10) 한편, 정신분열병환자에서자신의감정상태에주목하는기분감시능력은유지되는것으로나타났는데, 이는정신분열병환자에서정서적각성상태가증가되어있다는보고와도상통한다고볼수있다. 10) 정상대조군에서는감정이입이기분인식의차원중기분감시와만양의상관관계를보여주었으나정신분열병환자군에서는감정이입이기분인식의어떤차원과도상관성을나타내지않았다. 즉, 정상인은자신의감정상태에대해감시하고의식할수있는능력이있으면타인에대하여감정이입이잘되는데반해, 정신분열병환자는자신의기분에대한감수성은유지되어있으면서도감정이입에어려움이있음을시사한다. 이는정신분열병환자들이자신의감정상태에몰입되어자폐적이되거나사회적으로위축되는현상을반영한결과라볼수있다. 본연구는정상대조군과약물을투여한정신분열병환자군간안정상태뇌대사활성도차이를보고한선행연구결과들과일치하는결과를보여주였다. 항정신병약물치료는기저핵의활성도를증가시키고피질영역들의활성도를감소시킨다고알려져있다. 22)23) 그러나본연 구결과에서와같은전두엽의활성도감소와소뇌의활성도증가는 drug-naive 정신분열병환자에서도나타난다고하며 24)25) 특히전두엽의활성도감소는약물에의한효과보다는정신분열병의병리소견으로서보고가더일관되어왔다. 26) 또한항정신병약물의사용이환자군과정상대조군간에뇌활성화차이에크게기여하지는못한다는메타분석결과가보고되기도하였다. 27) 투여된항정신병약물의용량을보정한편상관분석에서도감소된등쪽내측전전두피질과증가된소뇌의안정상태활성도가양성증상이나음성증상과상관관계를보였던점은약물효과가있음에도정신분열병의병리소견으로서의뇌활성화변화가충분히반영되고있음을시사한다고볼수있다. 또감정이입과기분인식에대한약물의영향을확인하기위해각척도의점수들과항정신병약물의투여용량과약물투여기간간상관분석을시행하였으나유의미한결과를보여주지않은점으로보아감정이입과기분인식에대한약물효과는크지않을것으로추정할수있다. 정서처리과정과연관된영역으로안와전두피질의안정상태활성도가정신분열병환자군에서저하되었다. 안와전두피질은신체내부와외부로부터의감각정보들이들어오는부위로내외부로부터의정보와감정의신체적반응을통합, 감시하는기능을가질것이라고보고있다. 15) 따라서정신분열병환자에서는안정상태에서자신과관련짓는정신활동및정서적온라인감시 (online monitoring) 에장애가있을것으로유추해볼수있다

9 Empathy Empathy Mood monitoring Mood monitoring Fig. 1. Regions showing correlation between metabolic activities and the empathy scale scores and mood awareness scale-mood monitoring dimension scores in the normal controls. Empathy:intraparietal sulcus, mood monitoring. a:frontopolar cortex. b:subgenual prefrontal cortex and temporal pole. c:entorhinal cortex. d:inferior temporal gyrus. 본연구에서정상대조군은부분적으로감정이입관련뇌영역과상관관계를보였으나환자군에서는상관관계를보이지않았다. 정상대조군에서는두정엽내고랑의안정상태활성도가감정이입척도점수와상관관계를보였는데, 두정엽내고랑은감정적전이의한근거가된거울신경세포 (mirror neuron) 의활성에해당되는회로의한영역으로보고된바있고 4)28) 관찰된제스처, 활동의목표나순서와연관이있다고보고된바있다. 29)30) 또한공간적작업기억과외부정보에대한주의력과연관이있다고보고되기도하였다. 31) 하두정피질 (inferior parietal cortex) 은후대상피질과함께 뇌기능의기본상태 의기능적신경망을형성한다고보고된바있다. 14) 이신경망 Fig. 2. Regions showing correlation between metabolic activities and the empathy scale scores and mood awareness scale-mood monitoring dimension scores in the patients with schizophrenia. Empathy: head of caudate nucleus, mood monitoring: superior frontal sulcus. 은사회적자극에대한주의력과연관성을보이고안정시내부나외부환경의잠재적인변화에대응하기위한준비된정신활동기능을할것이라고제시된바있다. 13)15) 따라서두정내고랑의감정이입과연관된안정상태활성도의기능은타인의감정상태에대한주의력과민감성을유지하는데있고감정이입의초기반응으로서감정적전이의준비상태를반영한다고생각된다. 정신분열병환자군에서는감정이입이피질영역의활성도와는연관성을보이지않았고배쪽 (ventral) 미상핵머리의활성도와상관관계를보였다. 기저핵은쓸모없는운동을억제하는문지기 (gatekeeper) 로서의기능뿐아니라연상, 인지기능에있어서도영향을미친다고한다. 배쪽미상핵머리는안와및내측전전두피질로부터원

10 심성섬유를받고창백시상투사 (palidothalmic projection) 를통해다시안와와배쪽내측전전두피질 (ventromedial prefrontal cortex) 과연결성을이룸으로서정서처리과정과연관된신경망에속한다고볼수있다. 32) 이는정신분열병환자군에서피질구조의기능적장애또는피질구조와의연결성장애로인해감정이입능력이저하되고피질-피질하연결성의왜곡으로피질하구조의기능이감정이입에반영된것이라고생각된다. 정상대조군에서기분감시차원과연관성을보인안정상태뇌활성화영역들중슬하전전두피질과전두극피질은정서인식및감정적전이관련뇌영역들에대한선행연구결과들과부분적으로부합하였다. 정상대조군에서기분감시와연관성을보인뇌활성화영역들중슬하전전두피질과전두극피질은변연계의대표적인구조중하나인안와전두피질의하부영역들이다. 안와전두피질은외부감각정보뿐아니라내장계내부감각정보가입력되는부위로서 Damasio의체감표지이론 (somatic marker hypothesis) 에따르면, 내장계내수용성정보 (visceral interoceptive information) 가뇌섬엽 (insula) 을통해기본감정상태를반영하는신체적상태에대한정신적인상 (mental image) 을형성하면, 안와전두피질에서이를감정으로의식하게된다고한다. 33) 본연구에서는감정이유발되지않은안정상태에서의뇌활성도와상관관계를보았기때문에뇌섬엽 (insula) 보다는안와전두피질이기분인식과관련성을나타낸것으로보인다. 또한안와전두피질은보상가치에대한분별기능과연관성이있다고하는데 34) 본연구에서기분감시차원의문항들중과반수이상에서자신의기분상태를 평가 하는지여부를묻고있어안와전두피질과의연관성이더잘나타났을것으로생각된다. 뇌기능의기본상태 가설에서는배쪽내측전전두피질 (ventromedial prefrontal cortex) 이의식상태에서상황에따른감각적정보, 반응, 결과에대한온라인감시기능을담당하고있을것이라본다. 15) 따라서안정상태의의식상태에서안와전두피질의내부적정보및정서적정보에대한기저감지기능이기분감시의소질을반영한다고생각된다. 그외기분감시와상관관계를보인측두극과내후각뇌피질은자전적기억의회상과연관되어있다고보고된바있고 35) 특히측두극은일인칭시점, 자기자신의정신상태 (mental state) 에대한사고와연관된기능을가지고있을것으로추정하고있으며, 3)4) 하측두이랑의기능은얼 굴, 단어등의재인 (recognition) 과연관된다고알려져있다. 36) 기분인식척도의기분감시차원은개념적으로는자기의식 (self-consciousness) 과중첩되는부분이있어 21) 자전적기억과재인이정서에대한내관적감시에관여한다고볼수있다. 안와전두피질은다류처리영역 (polymodal processing area) 으로서측두극, 내후각뇌피질, 하측두이랑과도연결성을가지고있다고알려져있어, 37) 기분감시에중추적인기능을할것이라볼수있다. 정신분열병환자군에서는정서처리과정에관여하는영역들이기분감시와연관성을보이지않았으나, 기분감시차원점수는정상대조군과유의미한차이는없었다. 이는정신분열병환자에서자신의기분상태를감시하는기능은유지되고있으나안정상태뇌기능에는반영되지않는다는것을의미한다. 이전연구들에의하면정신분열병환자에서주관적정서경험은감소되어있지않으며정상인에비해오히려감정이유발되는상황에서의정서적반응성이더증가되어있다고한다. 10) 따라서정신분열병에서는감정이유발되는상황에서의기분감시기능은유지되어있으나자극이주어지지않는안정상태에서의정서적온라인감시기능이떨어져있어내외의정서적신호에따른인식이늦어질수있음을추정해볼수있다. 본연구에서는상전두고랑의활성도가정신분열병환자의기분감시와연관성을보였는데, 상전두고랑은작업기억 (working memory) 의기능을담당하는등쪽외측전전두피질 (dorsolateral prefrontal cortex) 의한영역으로서는정보의감시및조작에관여한다고하며측두두정부와함께내적신호에따라주의를돌릴수있는능력 (endogenous orienting) 과연관되어있다고한다. 38)39) 이는정신분열병환자에서내적주의력이기분감시의주관적경험에주된영향을주고있음을시사한다. 정상대조군에서기분인식척도의차원중기분식별점수는중측두이랑및하측두이랑과양의상관관계를보였다. 중측두이랑은 뇌기능의기본상태 와관련된영역은아니나문자나그림과같은자극의종류와는독립적으로의미론적처리 (semantic processing) 시활성화되는부위로보고된바있고 40) 하측두이랑은얼굴, 사물, 시각적단어형태재인 (recognition) 과연관되어있다고알려져있다. 36) 따라서이들측두엽영역들은기분식별에있어서정서의언어적표현및재인을위한의미론적처리과정을반영하고있는것으로보인다. 정신분열병환자군에서주관적기분식별의저하는이들영역의안정상태활

11 성도와기분식별의연관성부재로반영되는기분식별관련신경망의왜곡과관련있을것으로생각한다. 본연구에서는정상인에서주관적으로보고된자신의기분상태를감시하는능력과타인에대하여감정이입할수있는능력이연관성이있음을보여주었다. 그러나이러한기분감시와감정이입의연관성은안정상태뇌활성화영역들에는반영되지않은한편, 기분감시관련영역들이감정이입관련영역들보다많았다. 이는안정상태뇌활성도가내부정서처리활동을더많이반영하기때문이라생각할수있다. 안정상태에서의내관적 -외관적신경망활성화의파동에대한보고에도불구하고 뇌기능의기본상태 에서최대활성도를보이는영역으로가장일관되게보고되는내측전전두엽과내측두정엽은자신과관련된정신활동과관련이있다고한다. 15)16) 본연구에서슬하전전두피질의활성도와기분감시와의연관성은이러한안정상태에서내관적정신활동의우세를반영한다고생각된다. 한편감정이입과연관성을보인두정내고랑이안정상태에서의외부정서자극에대한감정적전이의준비상태를반영한것으로볼때감정이입과정의일부분만반영이된것으로추정된다. 따라서기분감시와감정이입관련뇌영역간연관성은감정이입의모든내외관적과정이반영될수있는활성화실험에서찾아볼수있을것으로생각된다. 정상대조군에서의기분감시관련영역중슬하전전두피질의안정상태활성도는안와전두피질의활성도와연관성을보이는반면, 정신분열병환자군에서는안와전두피질의안정상태활성도가저하되어있으면서기분감시관련영역이정상대조군과달랐다. 이는정신분열병에서안와전두피질의안정상태기능저하로인해기분감시관련신경망의왜곡되었음을시사한다. 그리고기분감시관련신경망의왜곡이감정이입관련뇌신경망에도영향을미칠것이라추정해볼수있으나, 안정상태에서는감정이입관련뇌신경망이모두활성화되지않은상태로확인할수없었다. 본연구는첫번째주요제한점으로는항정신병약물의효과를보정하여통계분석하였음에도불구하고감정이입과정서인식에대한항정신병약물의효과를완전히배제할수없다는데있다. 그러나본연구의환자대상자군처럼장기간항정신병약물치료를받는정신분열병환자들이약물에의해정서적경험이영향을받는다면이는임상적으로관심을가져야할부분이라고볼수있다. 두 번째로는본연구에서사용된자기보고식측정도구들이정신분열병환자의감정이입과기분인식을얼마나타당성있게측정할수있었는지의문을제기할수있겠다. 따라서향후이들척도와함께정서유발자극을이용하여측정한뇌활성도를함께비교하는연구들이이루어져야할것이다. 또, 감정이입과정서인식의신경학적관련영역들의기능적상호관계는안정상태뇌대사활성에서만확인하였기때문에이들의네트워크상관련성여부에대한결론을내릴수없다. 본연구는정상대조군과정신분열병환자군에서안정상태에서의뇌대사활성도에주관적으로보고되는감정이입과기분인식의소질및기분인식과감정이입간의상호관계가반영되는지알아보았다. 연구결과, 정상안정상태뇌활성도에는슬하전전두피질을중심으로한기분감시의뇌신경망이잘반영되는데반해감정이입은기저신경망의일부만이반영되었다. 정신분열병환자에서는상대적으로감정이입, 기분식별, 기분감시관련신경망의안정상태활성도왜곡을보였는데, 이중기분감시관련신경망이안와전두피질의안정상태활성도의저하의영향을받았다. 향후약물을투여하지않은정신분열병환자에서감정이입과기분인식의소질과관련된활성화영역들에대한탐색과정서유발시뇌활성반응을통한감정이입과기분인식간상호관계를살피는연구가필요할것으로생각된다. 중심단어 : 감정이입 정서인식 정신분열병 안정상태 안와전두피질 PET. 참고문헌 1. Pinkham AE, Penn DL, Perkins DO, Lieberman J. Implications for the neural basis of social cognition for the study of schizophrenia. Am J Psychiatry 2003;160: Langdon R, Coltheart M, Ward PB. Empathetic perspective-taking is impaired in schizophrenia: evidence from a study of emotion attribution and theory of mind. Cognit Neuropsychiatry 2006;11: Singer T. The neuronal basis and ontogeny of empathy and mind reading: Review of literature and implications for future research. Neurosci Biobehav Rev 2006;30: Leiberg S, Anders S. The multiple facets of empathy: a survey of theory and evidence. Prog Brain Res 2006; 156:

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