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Garrett, L. ; Trümbach, D. ; Spielmann, N. ; Wurst, W. ; Fuchs, H. ; Gailus-Durner, V. ; Hrabě de Angelis, M. ; Hölter, S.M.

A rationale for considering heart/brain axis control in neuropsychiatric disease.

Mamm. Genome 34, 331-350 (2022)
Verlagsversion Forschungsdaten DOI PMC
Open Access Gold (Paid Option)
Creative Commons Lizenzvertrag
Neuropsychiatric diseases (NPD) represent a significant global disease burden necessitating innovative approaches to pathogenic understanding, biomarker identification and therapeutic strategy. Emerging evidence implicates heart/brain axis malfunction in NPD etiology, particularly via the autonomic nervous system (ANS) and brain central autonomic network (CAN) interaction. This heart/brain inter-relationship harbors potentially novel NPD diagnosis and treatment avenues. Nevertheless, the lack of multidisciplinary clinical approaches as well as a limited appreciation of molecular underpinnings has stymied progress. Large-scale preclinical multi-systemic functional data can therefore provide supplementary insight into CAN and ANS interaction. We here present an overview of the heart/brain axis in NPD and establish a unique rationale for utilizing a preclinical cardiovascular disease risk gene set to glean insights into heart/brain axis control in NPD. With a top-down approach focusing on genes influencing electrocardiogram ANS function, we combined hierarchical clustering of corresponding regional CAN expression data and functional enrichment analysis to reveal known and novel molecular insights into CAN and NPD. Through 'support vector machine' inquiries for classification and literature validation, we further pinpointed the top 32 genes highly expressed in CAN brain structures altering both heart rate/heart rate variability (HRV) and behavior. Our observations underscore the potential of HRV/hyperactivity behavior as endophenotypes for multimodal disease biomarker identification to index aberrant executive brain functioning with relevance for NPD. This work heralds the potential of large-scale preclinical functional genetic data for understanding CAN/ANS control and introduces a stepwise design leveraging preclinical data to unearth novel heart/brain axis control genes in NPD.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Review
Korrespondenzautor
Schlagwörter Heart-rate-variability; Autism Spectrum Disorder; De-novo Mutations; Risk-factors; Cardiovascular-system; Myocardial-infarction; Posttraumatic-stress; Insular Cortex; Association; Depression
ISSN (print) / ISBN 0938-8990
e-ISSN 1432-1777
Zeitschrift Mammalian Genome
Quellenangaben Band: 34, Heft: 2, Seiten: 331-350 Artikelnummer: , Supplement: ,
Verlag Springer
Verlagsort One New York Plaza, Suite 4600, New York, Ny, United States
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Developmental Genetics (IDG)
Institute of Experimental Genetics (IEG)
Institute of Metabolism and Cell Death (MCD)
Förderungen Bundesministerium für Bildung und Forschung
MHdA
German Center for Diabetes Research
DZD