Neuro-transcriptomic signatures for mood disorder morbidity and suicide mortality

Mbemba Jabbi¹, Dhivya Arasappan², Simon B Eickhoff³, Stephen M Strakowski⁴, Charles B Nemeroff⁵, Hans A Hofmann⁶

Affiliations

¹ Department of Psychiatry, Dell Medical School, University of Texas at Austin, United States; The Mulva Clinic for Neurosciences, Dell Medical School, University of Texas at Austin, United States; Institute of Neuroscience, University of Texas at Austin, United States; Department of Psychology, University of Texas at Austin, United States. Electronic address: mbemba.jabbi@austin.utexas.edu.
² Center for Biomedical Research Support, University of Texas at Austin, United States.
³ Institute of Systems Neuroscience, Heinrich Heine University Düsseldorf, Germany; Institute of Neuroscience and Medicine (INM-7), Research Centre Jülich, Germany.
⁴ Department of Psychiatry, Dell Medical School, University of Texas at Austin, United States; The Mulva Clinic for Neurosciences, Dell Medical School, University of Texas at Austin, United States.
⁵ Department of Psychiatry, Dell Medical School, University of Texas at Austin, United States; The Mulva Clinic for Neurosciences, Dell Medical School, University of Texas at Austin, United States; Institute of Early Life Adversity Research, United States.
⁶ Institute of Neuroscience, University of Texas at Austin, United States; Department of Integrative Biology, The University of Texas at Austin, United States.

PMID: 32485434
DOI: 10.1016/j.jpsychires.2020.05.013

Meta-Analysis

Neuro-transcriptomic signatures for mood disorder morbidity and suicide mortality

Mbemba Jabbi et al. J Psychiatr Res. 2020 Aug.

. 2020 Aug:127:62-74.

doi: 10.1016/j.jpsychires.2020.05.013. Epub 2020 May 18.

Authors

Mbemba Jabbi¹, Dhivya Arasappan², Simon B Eickhoff³, Stephen M Strakowski⁴, Charles B Nemeroff⁵, Hans A Hofmann⁶

Affiliations

¹ Department of Psychiatry, Dell Medical School, University of Texas at Austin, United States; The Mulva Clinic for Neurosciences, Dell Medical School, University of Texas at Austin, United States; Institute of Neuroscience, University of Texas at Austin, United States; Department of Psychology, University of Texas at Austin, United States. Electronic address: mbemba.jabbi@austin.utexas.edu.
² Center for Biomedical Research Support, University of Texas at Austin, United States.
³ Institute of Systems Neuroscience, Heinrich Heine University Düsseldorf, Germany; Institute of Neuroscience and Medicine (INM-7), Research Centre Jülich, Germany.
⁴ Department of Psychiatry, Dell Medical School, University of Texas at Austin, United States; The Mulva Clinic for Neurosciences, Dell Medical School, University of Texas at Austin, United States.
⁵ Department of Psychiatry, Dell Medical School, University of Texas at Austin, United States; The Mulva Clinic for Neurosciences, Dell Medical School, University of Texas at Austin, United States; Institute of Early Life Adversity Research, United States.
⁶ Institute of Neuroscience, University of Texas at Austin, United States; Department of Integrative Biology, The University of Texas at Austin, United States.

PMID: 32485434
DOI: 10.1016/j.jpsychires.2020.05.013

Abstract

Suicidal behaviors are strongly linked with mood disorders, but the specific neurobiological and functional gene-expression correlates for this linkage remain elusive. We performed neuroimaging-guided RNA-sequencing in two studies to test the hypothesis that imaging-localized gray matter volume (GMV) loss in mood disorders, harbors gene-expression changes associated with disease morbidity and related suicide mortality in an independent postmortem cohort. To do so, first, we conducted study 1 using an anatomical likelihood estimation (ALE) MRI meta-analysis including a total of 47 voxel-based morphometry (VBM) publications (i.e. 26 control versus (vs) major depressive disorder (MDD) studies, and 21 control vs bipolar disorder (BD) studies) in 2387 (living) participants. Study 1 meta-analysis identified a selective anterior insula cortex (AIC) GMV loss in mood disorders. We then used this results to guide study 2 postmortem tissue dissection and RNA-Sequencing of 100 independent donor brain samples with a life-time history of MDD (N = 30), BD (N = 37) and control (N = 33). In study 2, exploratory factor-analysis identified a higher-order factor representing number of Axis-1 diagnoses (e.g. substance use disorders/psychosis/anxiety, etc.), referred to here as morbidity and suicide-completion referred to as mortality. Comparisons of case-vs-control, and factor-analysis defined higher-order-factor contrast variables revealed that the imaging-identified AIC GMV loss sub-region harbors differential gene-expression changes in high morbidity-&-mortality versus low morbidity-&-mortality cohorts in immune, inflammasome, and neurodevelopmental pathways. Weighted gene co-expression network analysis further identified co-activated gene modules for psychiatric morbidity and mortality outcomes. These results provide evidence that AIC anatomical signature for mood disorders are possible correlates for gene-expression abnormalities in mood morbidity and suicide mortality.

Keywords: Anterior insula; Bipolar disorder; Gene expression; Major depression; Mood disorders; Suicide.

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Conflict of interest statement

Declaration of competing interest Mbemba Jabbi, none. Dhivya Arasappan, none. Simon Eickhoff none. Hans Hofmann, none. Stephen Strakowski: chairs DSMBs for Sunovion as a Consultant, and has research grants with Janssen pharmaceuticals and Alkermes. Charles Nemeroff: 1) Consulting (last three years) for Xhale, Takeda, Taisho Pharmaceutical Inc., Bracket (Clintara), Fortress Biotech, Sunovion Pharmaceuticals Inc., Sumitomo Dainippon Pharma, Janssen Research & Development LLC, Magstim, Inc., Navitor Pharmaceuticals, Inc., TC MSO, Inc., Intra-Cellular Therapies, Inc; 2) Stockholder for Xhale, Celgene, Seattle Genetics, Abbvie, OPKO Health, Inc., Antares, BI Gen Holdings, Inc., Corcept Therapeutics Pharmaceuticals Company, TC MSO, Inc., Trends in Pharma Development, LLC; 3) Scientific Advisory Board member for American Foundation for Suicide Prevention (AFSP), Brain and Behavior Research Foundation (BBRF), Xhale, Anxiety Disorders Association of America (ADAA), Skyland Trail, Bracket (Clintara), Laureate Institute for Brain Research (LIBR), Inc; 4) Board of Directors member for AFSP, Gratitude America, ADAA; 5) Income sources or equity of $10,000 or more from American Psychiatric Publishing, Xhale, Bracket (Clintara), CME Outfitters, Takeda, Intra-Cellular Therapies, Inc., Magstim, EMA Wellness; 6) Patents: Method and devices for transdermal delivery of lithium (US 6,375,990B1); Method of assessing antidepressant drug therapy via transport inhibition of monoamine neurotransmitters by ex vivo assay (US 7,148,027B2); Compounds, Compositions, Methods of Synthesis, and Methods of Treatment (CRF Receptor Binding Ligand) (US 8,551, 996 B2).

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Neuro-transcriptomic signatures for mood disorder morbidity and suicide mortality

Affiliations

Neuro-transcriptomic signatures for mood disorder morbidity and suicide mortality

Authors

Affiliations

Abstract

Conflict of interest statement

Publication types

MeSH terms

LinkOut - more resources

Full Text Sources

Medical