Neuroscience and Aphasia Research Unit, School of Psychological Sciences, The University of Manchester and Manchester Academic Health Sciences Centre, Manchester, England.
Cognitive and Behavioral Neuroscience Unit, D'Or Institute for Research and Education, Rio de Janeiro, Brazil.
JAMA Psychiatry. 2015 Nov;72(11):1119-26. doi: 10.1001/jamapsychiatry.2015.1813.
Patients with remitted major depressive disorder (MDD) were previously found to display abnormal functional magnetic resonance imaging connectivity (fMRI) between the right superior anterior temporal lobe (RSATL) and the subgenual cingulate cortex and adjacent septal region (SCSR) when experiencing self-blaming emotions relative to emotions related to blaming others (eg, "indignation or anger toward others"). This finding provided the first neural signature of biases toward overgeneralized self-blaming emotions (eg, "feeling guilty for everything"), known to have a key role in cognitive vulnerability to MDD. It is unknown whether this neural signature predicts risk of recurrence, a crucial step in establishing its potential as a prognostic biomarker, which is urgently needed for stratification into pathophysiologically more homogeneous subgroups and for novel treatments.
To use fMRI in remitted MDD at baseline to test the hypothesis that RSATL-SCSR connectivity for self-blaming relative to other-blaming emotions predicts subsequent recurrence of depressive episodes.
DESIGN, SETTING, AND PARTICIPANTS: A prospective cohort study from June 16, 2011, to October 10, 2014, in a clinical research facility completed by 75 psychotropic medication-free patients with remitted MDD and no relevant comorbidity. In total, 31 remained in stable remission, and 25 developed a recurring episode over the 14 months of clinical follow-up and were included in the primary analysis. Thirty-nine control participants with no personal or family history of MDD were recruited for further comparison.
Between-group difference (recurring vs stable MDD) in RSATL connectivity, with an a priori SCSR region of interest for self-blaming vs other-blaming emotions.
We corroborated our hypothesis that during the experience of self-blaming vs other-blaming emotions, RSATL-SCSR connectivity predicted risk of subsequent recurrence. The recurring MDD group showed higher connectivity than the stable MDD group (familywise error-corrected P < .05 over the a priori SCSR region of interest) and the control group. In addition, the recurring MDD group also exhibited RSATL hyperconnectivity with the right ventral putamen and claustrum and the temporoparietal junction. Together, these regions predicted recurrence with 75% accuracy.
To our knowledge, this study is the first to provide a robust demonstration of an fMRI signature of recurrence risk in remitted MDD. Additional studies are needed for its further optimization and validation as a prognostic biomarker.
先前的研究发现，在经历自我责备情绪（例如“对自己感到内疚”）而不是责备他人的情绪（例如“对他人感到愤怒或愤慨”）时，缓解期的重度抑郁症（MDD）患者右侧上前颞叶（RSATL）与扣带前皮质下和相邻的隔区（SCSR）之间的功能磁共振成像连接（fMRI）出现异常。这一发现为过度泛化的自我责备情绪（例如“对所有事情都感到内疚”）的偏见提供了第一个神经特征，而这种偏见被认为是认知易感性 MDD 的关键因素。尚不清楚这种神经特征是否可以预测复发的风险，这是建立其作为预后生物标志物的关键步骤，迫切需要将其分层为病理生理学上更为同质的亚组，并为新的治疗方法提供依据。
在缓解期 MDD 患者的基线时使用 fMRI 来检验假设，即相对于其他责备情绪，自我责备情绪的 RSATL-SCSR 连接可预测随后抑郁发作的复发。
设计、环境和参与者：这是一项从 2011 年 6 月 16 日至 2014 年 10 月 10 日在临床研究机构进行的前瞻性队列研究，共纳入了 75 名接受抗精神病药物治疗且无相关共病的缓解期 MDD 患者。总共有 31 名患者处于稳定缓解期，25 名患者在 14 个月的临床随访中复发，并被纳入主要分析。招募了 39 名没有 MDD 个人或家族病史的对照参与者以进行进一步比较。
RSATL 连接的组间差异（复发与稳定 MDD），采用自我责备与其他责备情绪的预先设定 SCSR 感兴趣区域。
我们验证了我们的假设，即相对于其他责备情绪，RSATL-SCSR 连接在自我责备情绪体验时，可预测随后的复发风险。复发 MDD 组的连接性高于稳定 MDD 组（经过总体错误校正后，预先设定的 SCSR 感兴趣区域 P<0.05），也高于对照组。此外，复发 MDD 组还表现出 RSATL 与右侧腹侧苍白球和屏状核以及颞顶联合区的过度连接。这些区域共同以 75%的准确率预测复发。
据我们所知，这项研究首次提供了缓解期 MDD 复发风险的 fMRI 特征的稳健证据。需要进一步的研究来优化和验证其作为预后生物标志物的作用。
