IReach Lab, Unit of Clinical and Health Psychology, Department of Psychology, University of Fribourg, Fribourg, Switzerland; Section on Neurobiology of Fear and Anxiety, National Institute of Mental Health, Bethesda, Maryland, USA.
IReach Lab, Unit of Clinical and Health Psychology, Department of Psychology, University of Fribourg, Fribourg, Switzerland.
Neuroimage Clin. 2020;26:102193. doi: 10.1016/j.nicl.2020.102193. Epub 2020 Jan 22.
Anhedonia, a core symptom of Major Depressive Disorder (MDD), manifests as a lack or loss of motivation as reflected by decreased reward responsiveness, at both behavioral and neural (i.e., striatum) levels. Exposure to stressful life events is another important risk factor for MDD. However, the mechanisms linking reward-deficit and stress to MDD remain poorly understood. Here, we explore whether the effects of stress exposure on reward processing might differentiate between Healthy Vulnerable adults (HVul, i.e., positive familial MDD) from Healthy Controls (HCon). Furthermore, the well-described reduction in cognitive resources in MDD might facilitate the stress-induced decrease in reward responsiveness in HVul individuals. Accordingly, this study includes a manipulation of cognitive resources to address the latter possibility.
16 HVul (12 females) and 16 gender- and age-matched HCon completed an fMRI study, during which they performed a working memory reward task. Three factors were manipulated: reward (reward, no-reward), cognitive resources (working memory at low and high load), and stress level (no-shock, unpredictable threat-of-shock). Only the reward anticipation phase was analyzed. Imaging analyses focused on striatal function.
Compared to HCon, HVul showed lower activation in the caudate nucleus across all conditions. The HVul group also exhibited lower stress-related activation in the nucleus accumbens, but only in the low working memory (WM) load condition. Moreover, while stress potentiated putamen reactivity to reward cues in HVul when the task was more demanding (high WM load), stress blunted putamen reactivity in both groups when no reward was at stake.
Findings suggest that HVul might be at increased risk of developing anhedonic symptoms due to weaker encoding of reward value, higher difficulty to engage in goal-oriented behaviors and increased sensitivity to negative feedback, particularly in stressful contexts. These findings open new avenues for a better understanding of the mechanisms underlying how the complex interaction between the systems of stress and reward responsiveness contribute to the vulnerability to MDD, and how cognitive resources might modulate this interaction.
快感缺失是重性抑郁障碍（MDD）的核心症状之一，表现为行为和神经水平（即纹状体）上的奖励反应性降低，反映出动机缺失或丧失。暴露于应激性生活事件是 MDD 的另一个重要危险因素。然而，将奖励缺陷和应激与 MDD 联系起来的机制仍知之甚少。在这里，我们探讨应激暴露对奖励处理的影响是否可以区分健康易损成年人（HVul，即 MDD 阳性家族史）和健康对照（HCon）。此外，MDD 中认知资源的明显减少可能会促进 HVul 个体在应激下奖励反应性的降低。因此，这项研究包括对认知资源的操纵，以解决后者的可能性。
16 名 HVul（12 名女性）和 16 名性别和年龄匹配的 HCon 完成了 fMRI 研究，在此期间他们执行了一项工作记忆奖励任务。操纵了三个因素：奖励（奖励，无奖励）、认知资源（低和高工作记忆负载）和应激水平（无冲击，不可预测的冲击威胁）。仅分析奖励预期阶段。成像分析侧重于纹状体功能。
与 HCon 相比，HVul 在所有条件下的尾状核激活均较低。HVul 组在伏隔核中也表现出较低的应激相关激活，但仅在低工作记忆（WM）负载条件下。此外，虽然应激增强了 HVul 中纹状体对奖励线索的反应性，但当任务要求更高（高 WM 负载）时，应激削弱了两组纹状体对奖励线索的反应性，而无奖励时则没有。
研究结果表明，由于奖励价值的编码较弱、更难以进行目标导向行为以及对负面反馈的敏感性增加，HVul 可能面临更大的发展快感缺失症状的风险，尤其是在应激环境中。这些发现为更好地理解应激和奖励反应性系统之间的复杂相互作用如何导致对 MDD 的易感性以及认知资源如何调节这种相互作用的机制提供了新的途径。
