Emotional Brain Institute, Nathan Kline Institute, Child Study Center, Child and Adolescent Psychiatry, New York University School of Medicine, Orangeburg, NY 10962, USA.
J Neurosci. 2012 May 30;32(22):7758-65. doi: 10.1523/JNEUROSCI.5843-11.2012.
Abuse during early life, especially from the caregiver, increases vulnerability to develop later-life psychopathologies such as depression. Although signs of depression are typically not expressed until later life, signs of dysfunctional social behavior have been found earlier. How infant abuse alters the trajectory of brain development to produce pathways to pathology is not completely understood. Here we address this question using two different but complementary rat models of early-life abuse from postnatal day 8 (P8) to P12: a naturalistic paradigm, where the mother is provided with insufficient bedding for nest building; and a more controlled paradigm, where infants undergo olfactory classical conditioning. Amygdala neural assessment (c-Fos), as well as social behavior and forced swim tests were performed at preweaning (P20) and adolescence (P45). Our results show that both models of early-life abuse induce deficits in social behavior, even during the preweaning period; however, depressive-like behaviors were observed only during adolescence. Adolescent depressive-like behavior corresponds with an increase in amygdala neural activity in response to forced swim test. A causal relationship between the amygdala and depressive-like behavior was suggested through amygdala temporary deactivation (muscimol infusions), which rescued the depressive-like behavior in the forced swim test. Our results indicate that social behavior deficits in infancy could serve as an early marker for later psychopathology. Moreover, the implication of the amygdala in the ontogeny of depressive-like behaviors in infant abused animals is an important step toward understanding the underlying mechanisms of later-life mental disease associated with early-life abuse.
早期生活中的虐待，特别是来自照顾者的虐待，会增加晚年出现精神病理学的易感性，如抑郁症。尽管抑郁的迹象通常要到晚年才会表现出来，但已经发现了早期出现的功能失调的社会行为迹象。婴儿期虐待如何改变大脑发育的轨迹，产生导致病理学的途径，目前还不完全清楚。在这里，我们使用两种不同但互补的大鼠早期生活虐待模型来解决这个问题：一种是自然主义范式，即母亲提供的筑巢垫料不足；另一种是更可控的范式，即婴儿经历嗅觉经典条件反射。在断奶前（P20）和青春期（P45）进行杏仁核神经评估（c-Fos）以及社会行为和强迫游泳测试。我们的结果表明，两种早期生活虐待模型都导致了社会行为的缺陷，甚至在断奶前就出现了；然而，只有在青春期才观察到类似抑郁的行为。青春期类似抑郁的行为与杏仁核对强迫游泳测试的反应性增加有关。杏仁核的暂时失活（muscimol 输注）表明，杏仁核与类似抑郁的行为之间存在因果关系，这挽救了强迫游泳测试中的类似抑郁的行为。我们的结果表明，婴儿期的社会行为缺陷可能是晚年精神病理学的早期标志物。此外，杏仁核在婴儿期受虐待动物中类似抑郁行为的发生中的作用是理解与早期生活虐待相关的晚年精神疾病的潜在机制的重要一步。
