168 Social Stress Can Break Your Heart

Abstract

Ischaemic heart disease (IHD) and Major Depressive Disorder (MDD) are two of the greatest health challenges of the 21st century. These disorders are also strongly linked, reciprocally promoting disease risks and worsening outcomes. At present, it is still largely unknown how MDD worsens the hearts response to ischaemia or infarction, or influences cardiac responses to protective therapy. We tested the impact of chronic social stress on the central nervous system (CNS), endocrine factors and the hearts response to simulated heart attack. Male C57Bl/6 male mice were subjected to 5 wks of social isolation, with twice daily episodes of ‘social defeat’ (return to group housing for 15 min) over the final 2 wks. Behaviour was tested pre- and post-experiment via open field and sucrose preference tests, and on sacrifice serum and CNS tissue was collected, while hearts were Langendorff perfused to assess ischaemic tolerance. Social stress was anxiogenic and induced anhedonia (reflecting a depressive phenotype) and significantly worsened myocardial tolerance to ischaemia-reperfusion (exaggerated diastolic contracture). These changes were associated with evidence of altered CNS GABA and dopamine signalling, and endocrine disruption (increased circulating leptin and ghrelin, reduced cardioprotective adiponectin). Interestingly, studies in female mice generally failed to produce these outcomes. Data reveal chronic social stress impairs mood and myocardial ischaemic tolerance, changes potentially linked to disturbed GABA, dopamine and adipokine signalling.