title: The heartbreak of depression: 'Psycho-cardiac' coupling in myocardial infarction.
abstract: Ample evidence identifies strong links between major depressive disorder (MDD) and both risk of ischemic or coronary heart disease (CHD) and resultant morbidity and mortality. The molecular mechanistic bases of these linkages are poorly defined. Systemic factors linked to MDD, including vascular dysfunction, atherosclerosis, obesity and diabetes, together with associated behavioral changes, all elevate CHD risk. Nonetheless, experimental evidence indicates the myocardium is also directly modified in depression, independently of these factors, impairing infarct tolerance and cardioprotection. It may be that MDD effectively breaks the heart's intrinsic defense mechanisms. Four extrinsic processes are implicated in this psycho-cardiac coupling, presenting potential targets for therapeutic intervention if causally involved: sympathetic over-activity vs. vagal under-activity, together with hypothalamic-pituitary-adrenal (HPA) axis and immuno-inflammatory dysfunctions. However, direct evidence of their involvement remains limited, and whether targeting these upstream mediators is effective (or practical) in limiting the cardiac consequences of MDD is unknown. Detailing myocardial phenotype in MDD can also inform approaches to cardioprotection, yet cardiac molecular changes are similarly ill defined. Studies support myocardial sensitization to ischemic insult in models of MDD, including worsened oxidative and nitrosative damage, apoptosis (with altered Bcl-2 family expression) and infarction. Moreover, depression may de-sensitize hearts to protective conditioning stimuli. The mechanistic underpinnings of these changes await delineation. Such information not only advances our fundamental understanding of psychological determinants of health, but also better informs management of the cardiac consequences of MDD and implementing cardioprotection in this cohort.
authors.affiliation: School of Medical Science, Griffith University, Southport, QLD 4217, Australia; Menzies Health Institute QLD, Griffith University, Southport, QLD 4217, Australia. Electronic address: j.headrick@griffith.edu.au.
authors.forename: John P
authors.initials: JP
authors.lastname: Headrick
authors.affiliation: School of Medical Science, Griffith University, Southport, QLD 4217, Australia; Menzies Health Institute QLD, Griffith University, Southport, QLD 4217, Australia.
authors.forename: Jason N
authors.initials: JN
authors.lastname: Peart
authors.affiliation: School of Medical Science, Griffith University, Southport, QLD 4217, Australia.
authors.forename: Boris P
authors.initials: BP
authors.lastname: Budiono
authors.affiliation: School of Applied Psychology, Griffith University, Southport, QLD 4217, Australia; Menzies Health Institute QLD, Griffith University, Southport, QLD 4217, Australia.
authors.forename: David H K
authors.initials: DHK
authors.lastname: Shum
authors.affiliation: School of Applied Psychology, Griffith University, Southport, QLD 4217, Australia; Menzies Health Institute QLD, Griffith University, Southport, QLD 4217, Australia.
authors.forename: David L
authors.initials: DL
authors.lastname: Neumann
authors.affiliation: School of Applied Psychology, Griffith University, Southport, QLD 4217, Australia; Menzies Health Institute QLD, Griffith University, Southport, QLD 4217, Australia.
authors.forename: Nicolas J C
authors.initials: NJC
authors.lastname: Stapelberg
mesh_terms: D017209:Apoptosis / Q000235:genetics; D050197:Atherosclerosis / Q000150:complications / Q000503:physiopathology* / Q000523:psychology; D003865:Major Depressive Disorder / Q000150:complications / Q000503:physiopathology* / Q000523:psychology; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism / Q000473:pathology; D009203:Myocardial Infarction / Q000150:complications / Q000235:genetics / Q000503:physiopathology* / Q000523:psychology; D009206:Myocardium / Q000473:pathology*; D012307:Risk Factors
keywords: Cardioprotection; Chronic stress; Ischemic heart disease; Major depressive disorder; Myocardial infarction