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Functional and structural brain alterations in anorexia nervosa: a multimodal meta-analysis of neuroimaging studies1Medical Imaging Center, First Affiliated Hospital of Jinan University, Guangzhou, China, 2Department of Radiology, Six Affiliated Hospital of Sun Yat-sen University, Guangzhou, China, 3Department of Applied Psychology, Guangdong University of Foreign Studies, Guangzhou, China
Synopsis
Anorexia nervosa (AN) is a complex psychiatric disorder with poorly understood etiology. A whole-brain meta-analysis on resting-state functional imaging and VBM studies that measured differences in the intrinsic functional activity and gray matter volume (GMV) between AN patients and healthy controls. Overall, patients with AN displayed decreased resting-state functional activity in the bilateral ACC and MCC and increased in the right parahippocampal gyrus. In VBM studies, with AN patients displayed decreased GMV in the bilateral MCC , and left inferior parietal lobe. This multimodal meta-analysis identified functional activity and GMV reductions in the anterior and median cingulate in patients with AN.
Introduction
Anorexia nervosa (AN) is a severe psychiatric disorder that is mainly found in adolescent girls and young women (female-male ratio of 10:1) [1, 2]. The nutritional compromise associated with AN affects most major organ systems and may cause a variety of disturbances [3-6]. Over the past decade, numerous studies of resting-state functional imaging [7-10] and voxel-based morphometry (VBM) [11-15] have provided strong evidence of abnormal brain intrinsic functional activity and structure in AN [16]. However, the conclusions have been inconsistent [10, 17-20].Thus, we attempted to conduct a comprehensive meta-analysis to identify true-positive findings and common abnormalities in the literature.Methods and materials
A comprehensive and systematic literature search of the following databases: Web of Science, Embase, PubMed, Sinomed, China National Knowledge Infrastructure, and WanFang databases for resting-state functional imaging and VBM studies published between January 1990 and July 2020, was conducted. We used a 10-point checklist to assess individual study quality for meta-analyses. A whole-brain meta-analysis of resting-state functional activity differences (293 AN; 246 controls) and the structural substrates of altered cerebral volume (645 AN; 633 controls) between patients and healthy controls (HCs) was conducted using the SDM software package (version 6.12 for Windows) in a standard process (www.sdmproject.com) [21,22]. To test the repeatability of the results, and inspect the heterogeneity and publication bias, we performed a jackknife sensitivity analysis, funnel plots and Egger’s tests (P < 0.05) [23]. Meta-regression analyses were carried out to explore the associations between the analytic results and clinical variables as well. In addition, to localize brain regions with both resting-state functional activity and GMV abnormalities in AN, between-group contrasts of multimodal brain imaging were summarized in a meta-analytic map [24]Results
Overall, patients with AN displayed decreased resting-state functional activity in the bilateral anterior cingulate cortex and bilateral median cingulate cortex, and increased resting-state functional activity in the right parahippocampal gyrus. In VBM studies, patients with AN displayed decreased GMV in the bilateral median cingulate cortex (extending to the bilateral anterior and posterior cingulate cortex), and left inferior parietal lobe. The whole-brain jackknife sensitivity analysis revealed that in patients with AN, the resting-state functional activity decrease in the bilateral anterior cingulate cortex and bilateral median cingulate cortex, and increase in the right parahippocampal gyrus were highly repetitive, because these findings were preserved in at least 85% of the combinations; the most robust data were acquired for decreases in GMV in the bilateral median cingulate cortex (extending to the bilateral anterior and posterior cingulate cortex) and left inferior parietal lobe, replicable in all 30 datasets. The funnel plot does not show asymmetries, and the Egger's tests show no publication bias in these areas as well. BMI and illness duration were not associated with AN-related resting-state functional activity or GMV changes. We were unable to assess the relationship to AN symptom severity because this was reported using a variety of incompatible measures (n≤10). In addition, a conjunction analysis further found that the anterior cingulate cortex and median cingulate cortex were altered in AN in both resting-state functional and VBM studies. Specifically, AN patients showed concurrent hypoactivity and decreased GMV in these regions.Conclusion
This multimodal meta-analysis identified functional activity and gray matter reductions in the anterior and median cingulate in patients with AN, which contributes to being further understanding the physiopathology of AN.Acknowledgements
The study was supported by grants from the National Natural Science Foundation of China (81671670 and 81971597); Project in Basic Research and Applied Basic Research in General Colleges and Universities of Guangdong, China (018KZDXM009); Planned Science and Technology Project of Guangzhou, China (201905010003). The funding organizations played no further role in study design, data collection, analysis and interpretation and paper writing.References
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