TY - JOUR
T1 - Structural brain networks in remitted psychotic depression
AU - Neufeld, Nicholas H.
AU - Kaczkurkin, Antonia N.
AU - Sotiras, Aristeidis
AU - Mulsant, Benoit H.
AU - Dickie, Erin W.
AU - Flint, Alastair J.
AU - Meyers, Barnett S.
AU - Alexopoulos, George S.
AU - Rothschild, Anthony J.
AU - Whyte, Ellen M.
AU - Mah, Linda
AU - Nierenberg, Jay
AU - Hoptman, Matthew J.
AU - Davatzikos, Christos
AU - Satterthwaite, Theodore D.
AU - Voineskos, Aristotle N.
N1 - Funding Information:
Grant support for this study was provided by the National Institute of Mental Health (NIMH) under the following grant numbers: BSM (U01MH062518), AJR (U01MH062624), EMW (U01MH062565), AJF (U01MH062446), and ANV (R01MH099167). Eli Lilly provided olanzapine and matching placebo pills and Pfizer provided sertraline; neither company provided funding for the study, participated in data analysis, or participated in the preparation of this manuscript. In addition to support for this study, NHN reported grants from the Canadian Institutes of Health Research (CIHR), University of Toronto, and Physicians' Services Incorporated Foundation. ANK reported grants from the NIMH and the Brain and Behavior Research Foundation (BBRF). AS reported no conflict of interest. BHM reported grants from Brain Canada, Centre for Addiction and Mental Health (CAMH) Foundation, CIHR, and NIMH; nonfinancial support from Pfizer, Eli Lilly, Capital Solution Design LLC, HAPPYneuron, and General Electric. EWD reported grants from the NIMH and BBRF. AJF reported grants from NIMH, National Institutes of Health (NIH), Patient-Centered Outcomes Research Institute, CIHR, Brain Canada, Ontario Brain Institute, and Alzheimer's Association; nonfinancial support from Pfizer and Eli Lilly. BSM reported grants from the NIMH; nonfinancial support from Pfizer and Eli Lilly. GSA reported grants from the NIMH under grant number P50MH113838; nonfinancial support from Pfizer and Eli Lilly; personal fees from Takeda, Lundbeck, Otsuka, Allergan, Astra Zeneca, and Sunovion. AJR reported grants from the NIMH, the Irving S. and Betty Brudnick Endowed Chair in Psychiatry, Allergan, Janssen, and Takeda; nonfinancial support from Pfizer and Eli Lilly; personal fees from Alkermes, GlaxoSmithKline, Sage Therapeutics, Sanofi-Aventis, UMass Medical School, the American Psychiatric Press, and UpToDate. EMW reported grants from the NIMH, NIH, and Health Resources and Services Administration; nonfinancial support from Pfizer and Eli Lilly. LM reported grants from the Alzheimer's Society of Canada, Brain Canada, Centre for Aging and Brain Health Innovation, and Ontario Ministry of Health and Long-Term Care; nonfinancial support from Brainsway Ltd. JN reported nonfinancial support from Alkermes. MJH reported grants from the American Foundation for Suicide Prevention and University of Toronto/NIMH; salary from the New York State Office of Mental Health; consulting fees from Kessler Research Foundation. CD reported grant support under grant numbers R01MH112070 and RF1AG054409. TDS reported grant support under grant numbers R01MH120482, R01MH107703, R01MH112847, and R01MH113550. ANV reported grants from the NIMH, CIHR, Canadian Foundation for Innovation, CAMH Foundation, BBRF, and the University of Toronto.
Publisher Copyright:
© 2020, The Author(s), under exclusive licence to American College of Neuropsychopharmacology.
PY - 2020/6/1
Y1 - 2020/6/1
N2 - Major depressive disorder with psychotic features (psychotic depression) is a severe disorder. Compared with other psychotic disorders such as schizophrenia, relatively few studies on the neurobiology of psychotic depression have been pursued. Neuroimaging studies investigating psychotic depression have provided evidence for distributed structural brain abnormalities implicating the insular cortex and limbic system. We examined structural brain networks in participants (N = 245) using magnetic resonance imaging. This sample included healthy controls (n = 159) and the largest cross-sectional sample of patients with remitted psychotic depression (n = 86) collected to date. All patients participated in the Study of Pharmacotherapy of Psychotic Depression II randomized controlled trial. We used a novel, whole-brain, data-driven parcellation technique—non-negative matrix factorization—and applied it to cortical thickness data to derive structural covariance networks. We compared patients with remitted psychotic depression to healthy controls and found that patients had significantly thinner cortex in five structural covariance networks (insular-limbic, occipito-temporal, temporal, parahippocampal-limbic, and inferior fronto-temporal), confirming our hypothesis that affected brain networks would incorporate cortico-limbic regions. We also found that cross-sectional depression and severity scores at the time of scanning were associated with the insular-limbic network. Furthermore, the insular-limbic network predicted future severity scores that were collected at the time of recurrence of psychotic depression or sustained remission. Overall, decreased cortical thickness was found in five structural brain networks in patients with remitted psychotic depression and brain-behavior relationships were observed, particularly between the insular-limbic network and illness severity.
AB - Major depressive disorder with psychotic features (psychotic depression) is a severe disorder. Compared with other psychotic disorders such as schizophrenia, relatively few studies on the neurobiology of psychotic depression have been pursued. Neuroimaging studies investigating psychotic depression have provided evidence for distributed structural brain abnormalities implicating the insular cortex and limbic system. We examined structural brain networks in participants (N = 245) using magnetic resonance imaging. This sample included healthy controls (n = 159) and the largest cross-sectional sample of patients with remitted psychotic depression (n = 86) collected to date. All patients participated in the Study of Pharmacotherapy of Psychotic Depression II randomized controlled trial. We used a novel, whole-brain, data-driven parcellation technique—non-negative matrix factorization—and applied it to cortical thickness data to derive structural covariance networks. We compared patients with remitted psychotic depression to healthy controls and found that patients had significantly thinner cortex in five structural covariance networks (insular-limbic, occipito-temporal, temporal, parahippocampal-limbic, and inferior fronto-temporal), confirming our hypothesis that affected brain networks would incorporate cortico-limbic regions. We also found that cross-sectional depression and severity scores at the time of scanning were associated with the insular-limbic network. Furthermore, the insular-limbic network predicted future severity scores that were collected at the time of recurrence of psychotic depression or sustained remission. Overall, decreased cortical thickness was found in five structural brain networks in patients with remitted psychotic depression and brain-behavior relationships were observed, particularly between the insular-limbic network and illness severity.
UR - http://www.scopus.com/inward/record.url?scp=85081611872&partnerID=8YFLogxK
U2 - 10.1038/s41386-020-0646-7
DO - 10.1038/s41386-020-0646-7
M3 - Article
C2 - 32109935
AN - SCOPUS:85081611872
SN - 0893-133X
VL - 45
SP - 1223
EP - 1231
JO - Neuropsychopharmacology
JF - Neuropsychopharmacology
IS - 7
ER -