TY - JOUR
T1 - Discovery and replication of cerebral blood flow differences in major depressive disorder
AU - Cooper Cortes, Crystal
AU - Chin Fatt, Cherise R.
AU - Liu, Peiying
AU - Grannemann, Bruce D
AU - Carmody, Thomas
AU - Almeida, Jorge R.C.
AU - Deckersbach, Thilo
AU - Fava, Maurizio
AU - Kurian, Benji T.
AU - Malchow, Ashley L.
AU - McGrath, Patrick J.
AU - McInnis, Melvin
AU - Oquendo, Maria A.
AU - Parsey, Ramin V.
AU - Bartlett, Elizabeth
AU - Weissman, Myrna
AU - Phillips, Mary L.
AU - Lu, Hanzhang
AU - Trivedi, Madhukar H.
N1 - Funding Information:
Acknowledgements The EMBARC study reported in this publication was supported by the National Institute of Mental Health of the National Institutes of Health under award numbers U01MH092221 (Trivedi MH PI) and U01MH092250 (Weissman MM PI). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. This work was supported by the EMBARC National Coordinating Center at UT Southwestern Medical Center and Data Center at Columbia University. Thomas S. Harris provided assistance with ASL data processing and analytic design. We thank Jennifer Fur-man, Ph.D. for her administrative assistance. The healthy control data, used to supplement analyses, were collected as part of the Dallas Lifespan Brain Study (http://fcon_1000.projects.nitrc.org/ indi/retro/dlbs.html), funded by R37 AG006265 (Study PI: Denise Park), R21 AG034318, and R01 MH084021 (ASL PI: Hanzhang Lu). Dr. Hanzhang Lu served as one of the EMBARC MR Physicists and the ASL consultant. Bruce Grannemann died on 9 January, 2019. We wish to dedicate this publication to him and the significant role he played in this work.
Publisher Copyright:
© 2019, The Author(s), under exclusive licence to Springer Nature Limited.
PY - 2020/7/1
Y1 - 2020/7/1
N2 - Major depressive disorder (MDD) is a serious, heterogeneous disorder accompanied by brain-related changes, many of which are still to be discovered or refined. Arterial spin labeling (ASL) is a neuroimaging technique used to measure cerebral blood flow (CBF; perfusion) to understand brain function and detect differences among groups. CBF differences have been detected in MDD, and may reveal biosignatures of disease-state. The current work aimed to discover and replicate differences in CBF between MDD participants and healthy controls (HC) as part of the EMBARC study. Participants underwent neuroimaging at baseline, prior to starting study medication, to investigate biosignatures in MDD. Relative CBF (rCBF) was calculated and compared between 106 MDD and 36 HC EMBARC participants (whole-brain Discovery); and 58 MDD EMBARC participants and 58 HC from the DLBS study (region-of-interest Replication). Both analyses revealed reduced rCBF in the right parahippocampus, thalamus, fusiform and middle temporal gyri, as well as the left and right insula, for those with MDD relative to HC. Both samples also revealed increased rCBF in MDD relative to HC in both the left and right inferior parietal lobule, including the supramarginal and angular gyri. Cingulate and prefrontal regions did not fully replicate. Lastly, significant associations were detected between rCBF in replicated regions and clinical measures of MDD chronicity. These results (1) provide reliable evidence for ASL in detecting differences in perfusion for multiple brain regions thought to be important in MDD, and (2) highlight the potential role of using perfusion as a biosignature of MDD.
AB - Major depressive disorder (MDD) is a serious, heterogeneous disorder accompanied by brain-related changes, many of which are still to be discovered or refined. Arterial spin labeling (ASL) is a neuroimaging technique used to measure cerebral blood flow (CBF; perfusion) to understand brain function and detect differences among groups. CBF differences have been detected in MDD, and may reveal biosignatures of disease-state. The current work aimed to discover and replicate differences in CBF between MDD participants and healthy controls (HC) as part of the EMBARC study. Participants underwent neuroimaging at baseline, prior to starting study medication, to investigate biosignatures in MDD. Relative CBF (rCBF) was calculated and compared between 106 MDD and 36 HC EMBARC participants (whole-brain Discovery); and 58 MDD EMBARC participants and 58 HC from the DLBS study (region-of-interest Replication). Both analyses revealed reduced rCBF in the right parahippocampus, thalamus, fusiform and middle temporal gyri, as well as the left and right insula, for those with MDD relative to HC. Both samples also revealed increased rCBF in MDD relative to HC in both the left and right inferior parietal lobule, including the supramarginal and angular gyri. Cingulate and prefrontal regions did not fully replicate. Lastly, significant associations were detected between rCBF in replicated regions and clinical measures of MDD chronicity. These results (1) provide reliable evidence for ASL in detecting differences in perfusion for multiple brain regions thought to be important in MDD, and (2) highlight the potential role of using perfusion as a biosignature of MDD.
UR - http://www.scopus.com/inward/record.url?scp=85070324067&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85070324067&partnerID=8YFLogxK
U2 - 10.1038/s41380-019-0464-7
DO - 10.1038/s41380-019-0464-7
M3 - Article
C2 - 31388104
AN - SCOPUS:85070324067
SN - 1359-4184
VL - 25
SP - 1500
EP - 1510
JO - Molecular psychiatry
JF - Molecular psychiatry
IS - 7
ER -