うつ病発症感受性と養育環境(シンポジウム:脳科学による心身症の解明,2008年,第49回日本心身医学会総会(札幌))  [in Japanese] Susceptibility to Depression and Maternal Care(Symposium/Psychosomatic Disorders as Revealed by Brain Science)  [in Japanese]

多くの疫学研究成果から,幼少期の不遇な養育環境は成長後のうつ病発症感受性を増大させることが報告されているが,その脳内メカニズムはほとんど未解明である.このため産褥期うつ病モデルラットとその仔ラットを用いて,幼少期の不遇な環境がおよぼす,うつ病発症感受性亢進のメカニズム解明を行った.うつ病感受性の評価は学習性無力(LH)試験を用い,産褥期うつ病モデルは産後3〜4日目にLH試験を行ってLHとなった産褥期ラットである.養育行動は出産後2〜14日目まで,ビデオ録画を撮り計測した.産褥期LHラットの養育行動は,non-LHラットと比較して減少していた.仔ラット成長後のLH試験の結果,産褥期LHラットに養育された仔ラットはLHになりやすかった.Glucocorticoid受容体(GR)mRNA発現の解析から,産褥期うつ病モデルの仔ラット海馬ではGR発現が減少していた.これらの結果は,早期の養育行動の減少が,成長後のうつ病発症を促進させる可能性を示唆している.

It is known that the early environment affects the mental development in offspring of rodents and humans. However, it has not been determined whether early postpartum depressive state enhances depressive state in offspring. Using the learned helplessness (LH) as an animal model of depression, we examined the influence of early postpartum LH on the stress reactivity of offspring. Dam rats were judged as LH or non-helpless (nLH) on postnatal day (PN) 2-3, and maternal behavior was recorded during PN2-14. On PN 45-46, offspring were subjected to the LH test. The hippocampal levels of glucocorticoid receptor (GR) mRNA were measured before and after the LH test in the offspring using real-time quantitative PCR. Active nursing in LH dams was significantly lower than that in nLH dams. Susceptibility to the LH test in the offspring of LH dams was significantly higher than that in the offspring of nLH dams, and was negatively correlated with active nursing in the LH dams. The levels of GR mRNA in the offspring of LH dams were significantly lower than those in the offspring of nLH dams before and after the LH test. These findings suggested that early postpartum LH decreased active nursing and increased depression-like behavior in the offspring with the decreased expression of GR mRNA in the hippocampus.