title: Pathogenesis of depression- and anxiety-like behavior in an animal model of hypertrophic cardiomyopathy.
abstract: Cardiovascular dysfunction is highly comorbid with mood disorders, such as anxiety and depression. However, the mechanisms linking cardiovascular dysfunction with the core behavioral features of mood disorder remain poorly understood. In this study, we used mice bearing a knock-in sarcomeric mutation, which is exhibited in human hypertrophic cardiomyopathy (HCM), to investigate the influence of HCM over the development of anxiety and depression. We employed behavioral, MRI, and biochemical techniques in young (3-4 mo) and aged adult (7-8 mo) female mice to examine the effects of HCM on the development of anxiety- and depression-like behaviors. We focused on females because in both humans and rodents, they experience a 2-fold increase in mood disorder prevalencevs.males. Our results showed that young and aged HCM mice displayed echocardiographic characteristics of the heart disease condition, yet only aged HCM females displayed anxiety- and depression-like behaviors. Electrocardiographic parameters of sympathetic nervous system activation were increased in aged HCM femalesvs.controls and correlated with mood disorder-related symptoms. In addition, when compared with controls, aged HCM females exhibited adrenal gland hypertrophy, reduced volume in mood-related brain regions, and reduced hippocampal signaling proteins, such as brain-derived neurotrophic factor and its downstream targetsvs.controls. In conclusion, prolonged systemic HCM stress can lead to development of mood disorders, possibly through inducing structural and functional brain changes, and thus, mood disorders in patients with heart disease should not be considered solely a psychologic or situational condition.-Dossat, A. M., Sanchez-Gonzalez, M. A., Koutnik, A. P., Leitner, S., Ruiz, E. L., Griffin, B., Rosenberg, J. T., Grant, S. C., Fincham, F. D., Pinto, J. R. Kabbaj, M. Pathogenesis of depression- and anxiety-like behavior in an animal model of hypertrophic cardiomyopathy.
authors.affiliation: Department of Biomedical Sciences, Florida State University, Tallahassee, Florida, USA.
authors.forename: Amanda M
authors.initials: AM
authors.lastname: Dossat
authors.affiliation: Division of Clinical and Translational Research, Larkin Community Hospital, South Miami, Florida, USA.
authors.forename: Marcos A
authors.initials: MA
authors.lastname: Sanchez-Gonzalez
authors.affiliation: Department of Biomedical Sciences, Florida State University, Tallahassee, Florida, USA.
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Koutnik
authors.affiliation: Department of Biomedical Sciences, Florida State University, Tallahassee, Florida, USA.
authors.forename: Stefano
authors.initials: S
authors.lastname: Leitner
authors.affiliation: Department of Biomedical Sciences, Florida State University, Tallahassee, Florida, USA.
authors.forename: Edda L
authors.initials: EL
authors.lastname: Ruiz
authors.affiliation: Department of Biomedical Sciences, Florida State University, Tallahassee, Florida, USA.
authors.forename: Brittany
authors.initials: B
authors.lastname: Griffin
authors.affiliation: The National High Magnetic Field Laboratory, Center for Interdisciplinary Magnetic Resonance, Florida State University, Tallahassee, Florida, USA; and.
authors.forename: Jens T
authors.initials: JT
authors.lastname: Rosenberg
authors.affiliation: The National High Magnetic Field Laboratory, Center for Interdisciplinary Magnetic Resonance, Florida State University, Tallahassee, Florida, USA; and.
authors.forename: Samuel C
authors.initials: SC
authors.lastname: Grant
authors.affiliation: Family Institute, Florida State University, Tallahassee, Florida, USA.
authors.forename: Francis D
authors.initials: FD
authors.lastname: Fincham
authors.affiliation: Department of Biomedical Sciences, Florida State University, Tallahassee, Florida, USA; jose.pinto@med.fsu.edu.
authors.forename: Jose R
authors.initials: JR
authors.lastname: Pinto
authors.affiliation: Department of Biomedical Sciences, Florida State University, Tallahassee, Florida, USA; mohamed.kabbaj@med.fsu.edu.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Kabbaj
mesh_terms: D000375:Aging; D000818:Animals; D001007:Anxiety / Q000235:genetics*; D002312:Cardiomyopathy, Hypertrophic / Q000150:complications* / Q000235:genetics; D003863:Depression / Q000235:genetics*; D004525:Efferent Pathways; D005260:Female; D055879:Gene Knock-In Techniques; D006801:Humans; D051379:Mice; D009154:Mutation; D012518:Sarcomeres / Q000235:genetics; D013564:Sympathetic Nervous System / Q000502:physiology; D014630:Vagus Nerve
keywords: adrenal gland; heart rate variability; mood disorder; sarcomeric protein; troponin