不安障害の分子遺伝学

Molecular genetics of anxiety disorders

　不安障害は，かつての診断概念では神経症の範疇に含まれており，患者の生来的な体質的要因に生育歴や個人的体験が加わって生じる，了解可能な症候として捉えられてきた。近年は，疫学的研究などにより，不安障害の発症に遺伝的素因が関与していることが確認され，病態の解明に向けた分子遺伝学的アプローチの報告が多く見られる。現在の方向性について述べた。不安障害全体に関しては，不安や恐怖の生じる機序として扁桃体の役割が重視され，GABA系や5-HT系に関わる遺伝的多型についての検討が盛んである。また，診断カテゴリー自体は表現型として位置づけるには無理が大きいことから，生物学的特性と直結する表現型を抽出する方向に進んでいる。すなわち，診断概念に含まれる諸症状を幾つかの次元に分け，それぞれのベクトルを量的形質として捉えて検討するmulti-dimensional-approachや，脳機能画像などをはじめとした，より生物学的な要素の大きいendophenotypesを見出そうとする努力である。それぞれの診断サブカテゴリーについても脳内メカニズムの解明が進みつつあり，それに伴って，不安障害全般に関連する要因に加えて，各サブカテゴリー特有の問題も検討される。例えばパニック障害では，NA作動性の神経系や，パニック発作を誘発するCCK等についての検討が報告されているし，強迫性障害では上述の次元の捉え方の検討が盛んで，これと画像所見，治療反応性，チック症状の有無や発症年齢などを組み合わせる方向での研究もみられる。

　Anxiety disorders were formerly included in the category of neurosis, and they have been interpreted as an understandable symptoms formed in the context of life histories and personal experiences added on the constitutional factor of the individuals. Recently, it is confirmed by etiological studies that hereditary factors are involved in the onset of these disorders, and there emerged many reports of approach with molecular genetics to elucidate the mechanism for the onset and progression of the diseases. We described here the current tendency in the directions of the researches about these conditions. About the whole category of the anxiety disorder, much attention is paid to the roles of the amygdala in the process in which the anxiety and fear are generated, and studies on genetic polymorphisms are actively proceeding about the GABA systems and 5-HT systems. In addition, as there are many difficulties to use the diagnostic categories as the phenotype in the genetic studies, advances are made to extract the phenotypes directly linking to biological conditions of the symptoms of patients and analogous tendency in the peoples within normal limits. Those are, the multi-dimensional-approach in which vectors of the symptoms observed in the patients included in a certain diagnostic category are divided into several dimensions and each of the dimension is analyzed as a quantity trait, and the effort to find the endophenotypes which are more strongly decided by biological factors. The latter includes the findings of the functional brain imaging. Elucidation of mechanism in a brain is advancing about each diagnostic sub-category, and problems specific for each sub-category are examined as well as factors related to the whole category of the anxiety disorder. For example, in relation to the panic disorder, studies about the NA Systems which is involved in the emergence of the panic attack and CCK which is known to provoke panic attacks are reported. As for obsessive-compulsive disorder, considerations about the establishment of the dimensions above-mentioned is vigorously reported and there are some studies towards the combination of the dimensions with brain imaging, efficacy of each treatment modality, presence of tic and age of onset and so on.