Ho Tiffany C, Connolly Colm G, Henje Blom Eva, LeWinn Kaja Z, Strigo Irina A, Paulus Martin P, Frank Guido, Max Jeffrey E, Wu Jing, Chan Melanie, Tapert Susan F, Simmons Alan N, Yang Tony T
Department of Psychiatry, Division of Child and Adolescent Psychiatry, University of California, San Francisco, San Francisco, California.
Department of Psychiatry, Division of Child and Adolescent Psychiatry, University of California, San Francisco, San Francisco, California.
Biol Psychiatry. 2015 Nov 1;78(9):635-46. doi: 10.1016/j.biopsych.2014.09.002. Epub 2014 Sep 16.
Functional magnetic resonance imaging research suggests that major depressive disorder (MDD) in both adults and adolescents is marked by aberrant connectivity of the default mode network (DMN) during resting state. However, emotional dysregulation is also a key feature of MDD. No studies to date have examined emotion-related DMN pathology in adolescent depression. Comprehensively understanding the dynamics of DMN connectivity across brain states in individuals with depression with short disease histories could provide insight into the etiology of MDD.
We collected functional magnetic resonance imaging data during an emotion identification task and during resting state from 26 medication-free adolescents (13-17 years old) with MDD and 37 well-matched healthy control subjects. We examined between-group differences in blood oxygenation level-dependent task responses and emotion-dependent and resting-state functional connectivity of the two primary nodes of the DMN: medial prefrontal cortex and posterior cingulate cortex (PCC). Additionally, we examined between-group differences in DMN functional connectivity and its relationship to depression severity and onset.
Relative to healthy control subjects, unmedicated adolescents with MDD demonstrated reduced medial prefrontal cortex and PCC emotion-related deactivation and greater medial prefrontal cortex and PCC emotion-dependent functional connectivity with precuneus, cingulate gyrus, and striatum/subcallosal cingulate gyrus. The PCC-subcallosal cingulate connectivity remained inflexibly elevated in the subjects with MDD versus healthy control subjects during resting state. Stronger PCC emotion-dependent functional connectivity was associated with greater depression severity and an earlier age of depression onset.
Adolescent depression is associated with inflexibly elevated DMN connections. Given more recent evidence of DMN maturation throughout adolescence, our findings suggest that early-onset depression adversely affects normal development of functional brain networks.
功能磁共振成像研究表明,成人和青少年的重度抑郁症(MDD)在静息状态下的默认模式网络(DMN)连接异常。然而,情绪调节障碍也是MDD的一个关键特征。迄今为止,尚无研究探讨青少年抑郁症中与情绪相关的DMN病理学。全面了解病程较短的抑郁症患者在不同脑状态下DMN连接的动态变化,有助于深入了解MDD的病因。
我们收集了26名未服用药物的青少年(13 - 17岁)MDD患者和37名匹配良好的健康对照者在情绪识别任务和静息状态下的功能磁共振成像数据。我们研究了两组在血氧水平依赖任务反应以及DMN两个主要节点(内侧前额叶皮质和后扣带回皮质,PCC)的情绪依赖和静息状态功能连接方面的差异。此外,我们还研究了两组在DMN功能连接方面的差异及其与抑郁严重程度和发病年龄的关系。
与健康对照者相比,未服用药物的青少年MDD患者内侧前额叶皮质和PCC与情绪相关的失活减少,内侧前额叶皮质和PCC与楔前叶、扣带回和纹状体/胼胝体下扣带回的情绪依赖性功能连接增强。在静息状态下,MDD患者与健康对照者相比,PCC - 胼胝体下扣带回连接持续升高。更强的PCC情绪依赖性功能连接与更高的抑郁严重程度和更早的抑郁发病年龄相关。
青少年抑郁症与DMN连接持续升高有关。鉴于最近有证据表明DMN在整个青春期成熟,我们的研究结果表明,早发性抑郁症会对功能性脑网络的正常发育产生不利影响。