Thai Michelle, Başgöze Zeynep, Klimes-Dougan Bonnie, Mueller Bryon A, Fiecas Mark, Lim Kelvin O, Albott C Sophia, Cullen Kathryn R
Psychology Department, College of Liberal Arts, University of Minnesota, Twin Cities, MN, United States.
Department of Psychiatry and Behavioral Sciences, School of Medicine, University of Minnesota, Twin Cities, MN, United States.
Front Psychiatry. 2020 Aug 18;11:820. doi: 10.3389/fpsyt.2020.00820. eCollection 2020.
Treatment-resistant depression (TRD) is a serious problem in adolescents. Development and optimization of novel interventions for these youth will require a deeper knowledge of the neurobiology of depression. A well-established phenomenon of depression is an attention bias toward negativity and away from positivity that is evidenced behaviorally and neurally, but it is unclear how symptom reduction is related to changes to this bias. Neurobiological research using a treatment probe has promise to help discover the neural changes that accompany symptom improvement. Ketamine has utility for such research because of its known rapid and strong antidepressant effects in the context of TRD. Our previous study of six open-label ketamine infusions in 11 adolescents with TRD showed variable response, ranging from full remission, partial response, non-response, or clinical worsening. In this study, we examined the performance of these participants on Word Face Stroop (WFS) fMRI task where they indicated the valence of affective words superimposed onto either congruent or incongruent emotional faces before and after the ketamine infusions. Participants also completed a clinical assessment (including measurement of depression symptomology and anhedonia/pleasure) before and after the ketamine infusions. Following ketamine treatment, better WFS performance correlated with self-reported decreased depressive symptoms and increased pleasure. Analyses of corticolimbic, corticostriatal and default mode (DMN) networks showed that across networks, decreased activation during all conditions (congruent negative, congruent positive, incongruent negative, and incongruent positive) correlated with decreases in depressive symptoms and with increases in pleasure. These findings suggest that in adolescents with TRD, clinical improvement may require an attenuation of the negativity bias and re-tuning of these three critical neural networks to attenuate DMN and limbic regions activation and allow more efficient recruitment of the reward network. Lower activation across conditions may facilitate shifting across different salient emotional stimuli rather than getting trapped in downward negative spirals.
难治性抑郁症（TRD）在青少年中是一个严重问题。针对这些青少年开发和优化新型干预措施需要对抑郁症的神经生物学有更深入的了解。抑郁症一个公认的现象是对消极信息的注意偏向以及对积极信息的注意偏离，这在行为和神经层面都有证据，但尚不清楚症状减轻与这种偏向的变化有何关联。使用治疗探针的神经生物学研究有望帮助发现伴随症状改善的神经变化。氯胺酮适用于此类研究，因为它在TRD背景下具有快速且强效的抗抑郁作用。我们之前对11名患有TRD的青少年进行的六项氯胺酮开放标签输注研究显示，反应各不相同，从完全缓解、部分反应、无反应到临床恶化。在本研究中，我们检查了这些参与者在单词面部斯特鲁普（WFS）功能磁共振成像任务中的表现，他们在氯胺酮输注前后指出叠加在一致或不一致情绪面孔上的情感词的效价。参与者在氯胺酮输注前后还完成了临床评估（包括抑郁症状学测量和快感缺失/愉悦感测量）。氯胺酮治疗后，更好的WFS表现与自我报告的抑郁症状减轻和愉悦感增加相关。对皮质边缘、皮质纹状体和默认模式（DMN）网络的分析表明，在所有网络中，所有条件（一致负性、一致正性、不一致负性和不一致正性）下激活的降低与抑郁症状的减轻以及愉悦感的增加相关。这些发现表明，在患有TRD的青少年中，临床改善可能需要减弱消极偏向，并重新调整这三个关键神经网络，以减弱DMN和边缘区域的激活，并允许更有效地激活奖赏网络。不同条件下较低的激活可能有助于在不同的显著情绪刺激之间转换，而不是陷入向下的消极螺旋。
