Department of Psychiatry, University of Wisconsin-Madison, Madison, Wisconsin.
Department of Psychiatry, University of Wisconsin-Madison, Madison, Wisconsin.
Biol Psychiatry Cogn Neurosci Neuroimaging. 2018 Mar;3(3):274-284. doi: 10.1016/j.bpsc.2017.11.005. Epub 2017 Nov 22.
Cortisol has potent effects on learning and neuroplasticity, but little is known about its effects on negative memory biases in depression. Animal models show that aversive caregiving alters effects of glucocorticoids (primarily corticosterone in rodents and cortisol in primates) on learning and neuroplasticity into adulthood.
We investigated whether history of childhood emotional abuse (EA) moderated effects of cortisol administration (CORT) versus placebo on emotional memory formation in depression. Participants included 75 unmedicated women with varying levels of depression severity and/or EA history. In a double-blind crossover investigation, we used functional magnetic resonance imaging to measure effects of CORT (vs. placebo) on neural function during emotional memory formation.
CORT eliminated the well-known relationship between depression severity and negative memory bias, a finding explained by EA severity. For women with a history of severe EA, CORT reduced depression-related negative memory bias and normalized recall for pleasant stimuli. EA severity also moderated CORT effects on neural function: in women with history of severe EA, CORT increased activation in the supplementary motor area during viewing of unpleasant relative to pleasant pictures. Additionally, supplementary motor area activation predicted reduced negative bias for pictures encoded during CORT.
These results suggest that increasing cortisol signaling may be neurocognitively beneficial in depressed women with a history of maltreatment. The findings corroborate prior research suggesting that presence or absence of adverse caregiving is etiologically important in depression. These findings suggest potential neurocognitive mechanisms of therapeutics targeting cortisol signaling, which show promise in treating affective disorders.
皮质醇对学习和神经可塑性具有强大的影响,但对其在抑郁症中对负性记忆偏差的影响知之甚少。动物模型表明,令人痛苦的养育方式会改变糖皮质激素(主要是啮齿动物中的皮质酮和灵长类动物中的皮质醇)对成年后学习和神经可塑性的影响。
我们研究了童年期情感虐待(EA)史是否调节了皮质醇(CORT)与安慰剂对抑郁症患者情绪记忆形成的影响。参与者包括 75 名未接受药物治疗的女性,其抑郁严重程度和/或 EA 史各不相同。在一项双盲交叉研究中,我们使用功能磁共振成像来测量 CORT(与安慰剂相比)对情绪记忆形成过程中神经功能的影响。
CORT 消除了抑郁严重程度与负性记忆偏差之间的已知关系,这一发现可以用 EA 严重程度来解释。对于有严重 EA 史的女性,CORT 减少了与抑郁相关的负性记忆偏差,并使愉快刺激的回忆正常化。EA 严重程度也调节了 CORT 对神经功能的影响:在有严重 EA 史的女性中,CORT 增加了观看不愉快图片相对于愉快图片时辅助运动区的激活。此外,辅助运动区的激活预测了 CORT 期间编码的图片的负性偏差减少。
这些结果表明,增加皮质醇信号可能对有虐待史的抑郁女性的神经认知有益。这些发现与先前的研究结果一致,即不良养育方式的存在与否在抑郁症中具有重要的病因学意义。这些发现表明,针对皮质醇信号的治疗具有潜在的神经认知机制,这为治疗情感障碍提供了希望。