Abstract:

Amino acids play key roles in the function of the central nervous system, and their alterations are implicated in psychiatric disorders. In the search for a biomarker for major depressive disorder (MDD), we used high-performance liquid chromatography to measure amino acids and related molecules in the cerebrospinal fluid (CSF) of 52 patients with MDD (42 depressed and 10 remitted; DSM-IV) and 54 matched controls. Significant differences were found in four amino acid concentrations between the depressed patients and controls. After Bonferroni correction, only ethanolamine (EA) levels remained significantly reduced in depressed patients (nominal P = 0.0000011). A substantial proportion of the depressed patients (40.5%) showed abnormally low CSF EA levels (<12.1 μM) (P = 0.000033; OR = 11.6, 95% CI: 3.1-43.2). When patients with low EA and those with high EA levels were compared, the former had higher scores for overall depression severity (P = 0.0033) and 'Somatic Anxiety' symptoms (P = 0.00026). In unmedicated subjects, CSF EA levels showed a significant positive correlation with levels of homovanillic acid (P = 0.0030) and 5-hydroxyindoleacetic acid (P = 0.019). To our knowledge, this is the first study showing that patients with MDD have significantly lower CSF EA concentrations compared with control subjects. CSF EA could be a state-dependent biomarker for a subtype of MDD.

日本語要旨:

大うつ病性障害の診断や類型化に用いられる生化学的マーカーは今のところなく、いまだに問診によって行われている。我々はうつ病のバイオマーカーを探索するために、脳脊髄液中のアミノ酸およびその関連分子に着目して解析した。その結果、エタノールアミンの濃度はうつ病患者群で有意な減少を示し、約40%のうつ病患者が健常者群の下位５パーセンタイル値を基準とした値よりも低値を示した。患者群においてエタノールアミン低値群は髙値群と比べて重症度が高かった。また、エタノールアミン濃度はドパミン代謝物質であるホモバニリン酸やセロトニンの代謝物質である５-ヒドロキシインドール酢酸と有意な正の相関を示した。これらはうつ病の類型化マーカーあるいは状態依存的マーカーとなりうる可能性が示唆された。