불안 관련 장애의 신경생물학적 이해
Neurobiological Basis of Anxiety Related Disorders
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불안과 두려움은 스트레스나 위협에 대한 정상적인 반응이다. ‘불안(anxiety)’은 내적이며 모호하고 알지 못하는 위협에 대한 반응이고, ‘두려움(fear)’은 외적이며 분명하고 알 수 있는 위협에 대한 반응이다. ‘걱정(worry)’은 예상되는 잠재적인 위협에 대한 부정적인 생각, 이미지, 감정 등을 말한다. 이러한 감정-행동의 세트는 시각, 청각, 후각, 체감각의 외 수용성 자극이나, 내장, 내분비, 자율신경계를 통한 내 수용성 감각에 대한 반응으로 일어난다고 알려져 있다.1)불안은 스트레스와 위협에 대한 예상(anticipation), 해석(in-terpretation), 기억(memory)을 통한 인지적 과정(cognitive process)에 의해 나타난다.2) 또한, 감정적 과정으로도 일어나는데, 이는 크게 세 가지 단계로 나누어진다. 첫 번째는 ‘평가(evaluation)’ 단계로 이전의 조건화(conditioning) 과정과 행동 강화(behavior reinforcement) 경험을 통한 자극의 유사성을 평가하여 감정을 느끼게 되는 것이고,3)4) 두 번째는 감정적인 반응을 행동, 내분비계, 자율 신경계로 나타내는 ‘표현(expres-sion)’ 단계이며, 마지막 세 번째 단계는 반응과 함께 나타나는 주관적인 느낌인 ‘경험(experience)’을 말한다.1)이러한 불안과 관련된 신경 해부학적 연구는 오래 전에 시작되어 현재까지 다양한 결과가 보고되었다. Walter Cannon (1927)은 스트레스 관련 연구의 개척자로, ‘싸움 또는 도주 반응(fight or flight response)’에 대해 처음으로 언급하였다. 그는 고양이에서 일부 대뇌 피질을 제거할 경우 두려움의 반응이 유발된다는 사실을 보고하였고, 해부학적으로 중뇌(mid-brain) 위쪽의 시상하부(hypothalamus), 대상회(cingulate), 시상(thalamus) 등의 구조물이 불안과 관련된 뇌 부위임을 제시하였다.5)6) 이후, Papez(1937)는 광견병 동물을 연구하여 공격성(aggression)이 해마(hippocampus)의 손상과 관련되어 있으며, 해마를 중심으로 한 뇌의 각 영역 및 이들 사이의 백질 연결성이 자율 신경계 반응과 연관되어 불안에서 중요한 역할을 담당하는 뇌 신경 회로(neural circuit)를 구성할 것이라고 제시하였다.7)8) 그 즈음, Kluver와 Bucy가 원숭이의 측두엽(temporal lobe)을 제거했을 때, 감정 표현이 무뎌지며 과거 경험상 공포의 대상에게도 두려움을 나타내지 않게 되는 ‘정신맹(psychic blindness)’의 개념을 설명하였고,9) 이후 Maclean(1949)은 ‘변연계 뇌(limbic brain)’를 명명하고, 편도체(amygdala)와전전두엽 피질(prefrontal cortex) 부위를 포함한 뇌 부위가 어떻게 감정을 조절하고 매개하는지에 대한 통합적인 모델을 제시하였다.10)최근에는 불안반응이 어떻게 유발되는지에 대해, 이러한 신경 해부학적 구조물뿐만 아니라 신경전달물질 및 신경화학적관점에 이르기까지 광범위한 연구가 진행되어 왔다. 본 종설에서는 불안장애의 생물학적 치료와 연구에 기본이 되는 신경생물학적 관점 전반에 대해 논의하고자 한다.
Abstract
Anxiety disorders are characterized by dysregulation of neuroendocrine, neurotransmitter and neuroanatomical functions. Substantial advances in research method offered new insights into the neurobiologic mechanisms in anxiety disorders. Advances in molecular biology have enabled illumination of hormone and neurotransmitters that have important roles in anxiety. The neuroanatomic circuits related to anxiety are also being elucidated by improvements in neuroimaging technology such as structural and functional magnetic resonance imaging. This article reviews the research data in relation to the neurobiology underlying fear and pathologic anxiety and discusses their implications for development of biological treatments for anxiety disorders.
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