Young C B, Chen T, Nusslock R, Keller J, Schatzberg A F, Menon V
Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, USA.
Department of Psychology, Northwestern University, Evanston, IL, USA.
Transl Psychiatry. 2016 May 17;6(5):e810. doi: 10.1038/tp.2016.80.
Anhedonia, the reduced ability to experience pleasure in response to otherwise rewarding stimuli, is a core symptom of major depressive disorder (MDD). Although the posterior ventromedial prefrontal cortex (pVMPFC) and its functional connections have been consistently implicated in MDD, their roles in anhedonia remain poorly understood. Furthermore, it is unknown whether anhedonia is primarily associated with intrinsic 'resting-state' pVMPFC functional connectivity or an inability to modulate connectivity in a context-specific manner. To address these gaps, a pVMPFC region of interest was first identified using activation likelihood estimation meta-analysis. pVMPFC connectivity was then examined in relation to anhedonia and general distress symptoms of depression, using both resting-state and task-based functional magnetic resonance imaging involving pleasant music, in current MDD and healthy control groups. In MDD, pVMPFC connectivity was negatively correlated with anhedonia but not general distress during music listening in key reward- and emotion-processing regions, including nucleus accumbens, ventral tegmental area/substantia nigra, orbitofrontal cortex and insula, as well as fronto-temporal regions involved in tracking complex sound sequences, including middle temporal gyrus and inferior frontal gyrus. No such dissociations were observed in the healthy controls, and resting-state pVMPFC connectivity did not dissociate anhedonia from general distress in either group. Our findings demonstrate that anhedonia in MDD is associated with context-specific deficits in pVMPFC connectivity with the mesolimbic reward system when encountering pleasurable stimuli, rather than a static deficit in intrinsic resting-state connectivity. Critically, identification of functional circuits associated with anhedonia better characterizes MDD heterogeneity and may help track of one of its core symptoms.
快感缺失是指对通常具有奖赏性的刺激产生愉悦体验的能力下降，是重度抑郁症（MDD）的核心症状。尽管腹内侧前额叶皮质后部（pVMPFC）及其功能连接一直被认为与MDD有关，但其在快感缺失中的作用仍知之甚少。此外，尚不清楚快感缺失主要是与内在的“静息态”pVMPFC功能连接有关，还是与无法以特定情境方式调节连接有关。为了填补这些空白，首先使用激活可能性估计元分析确定了一个感兴趣的pVMPFC区域。然后，在当前的MDD组和健康对照组中，使用静息态和基于任务的功能磁共振成像（涉及愉悦音乐），研究了pVMPFC连接与快感缺失及抑郁症的一般痛苦症状之间的关系。在MDD组中，在听音乐期间，pVMPFC与包括伏隔核、腹侧被盖区/黑质、眶额皮质和脑岛在内的关键奖赏和情感处理区域，以及参与追踪复杂声音序列的额颞区域（包括颞中回和额下回）的连接与快感缺失呈负相关，但与一般痛苦无关。在健康对照组中未观察到这种分离，并且静息态pVMPFC连接在两组中均未将快感缺失与一般痛苦区分开来。我们的研究结果表明，MDD中的快感缺失与遇到愉悦刺激时pVMPFC与中脑边缘奖赏系统连接的特定情境缺陷有关，而不是内在静息态连接的静态缺陷。至关重要的是，识别与快感缺失相关的功能回路可以更好地表征MDD的异质性，并可能有助于追踪其核心症状之一。
