BACKGROUND Research in adolescents and adults has suggested that altered neural processing of reward following early life adversity is a highly promising depressive intermediate phenotype. However, very little is known about how stress response, neural processing of reward, and depression are related in very young children. The present study examined the concurrent associations between cortisol response following a stressor, functional brain activity to reward, and depression severity in children 4 to 6 years old. METHODS Medication-naïve children 4 to 6 years old (N = 52) participated in a study using functional magnetic resonance imaging to assess neural reactivity to reward, including gain, loss, and neutral outcomes. Parent-reported child depression severity and child cortisol response following stress were also measured. RESULTS Greater caudate and medial prefrontal cortex reactivity to gain outcomes and increased amygdala reactivity to salient (i.e., both gain and loss) outcomes were observed. Higher total cortisol output following a stressor was associated with increased depression severity and reduced amygdala reactivity to salient outcomes. Amygdala reactivity was also inversely associated with depression severity and was found to mediate the relationship between cortisol output and depression severity. CONCLUSIONS Results suggest that altered neural processing of reward is already related to increased cortisol output and depression severity in preschoolers. These results also demonstrate an important role for amygdala function as a mediator of this relationship at a very early age. Our results further underscore early childhood as an important developmental period for understanding the neurobiological correlates of early stress and increased risk for depression.

中文翻译：

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杏仁核奖赏反应介导学龄前压力反应与抑郁严重程度之间的关联

背景 青少年和成人的研究表明，早期生活逆境后奖励的神经处理改变是一种非常有希望的抑郁中间表型。然而，对于非常年幼的儿童的压力反应、奖励的神经处理和抑郁之间的关系知之甚少。本研究调查了 4 至 6 岁儿童压力源后皮质醇反应、功能性大脑奖励活动和抑郁严重程度之间的同时关联。方法 4 至 6 岁（N = 52）未接受药物治疗的儿童参与了一项研究，该研究使用功能磁共振成像来评估对奖励的神经反应，包括获得、损失和中性结果。还测量了父母报告的儿童抑郁严重程度和儿童压力后的皮质醇反应。结果 观察到尾状和内侧前额叶皮层对获得结果的反应性更强，杏仁核对显着（即获得和损失）结果的反应性增加。压力源后较高的总皮质醇输出与抑郁症的严重程度增加和杏仁核对显着结果的反应性降低有关。杏仁核反应性也与抑郁症的严重程度呈负相关，并被发现调节皮质醇输出与抑郁症严重程度之间的关系。结论 结果表明，改变奖励的神经处理已经与学龄前儿童皮质醇输出增加和抑郁严重程度有关。这些结果还表明，杏仁核在很小的时候就作为这种关系的中介发挥了重要作用。