Learned helplessness reveals a population at risk for depressive-like behaviour after myocardial infarction in mice

Area of Science:

• Cardiology
• Psychiatry
• Animal Models

Background:

• Myocardial infarction (MI) and heart failure (HF) are known risk factors for depression.
• The mechanistic link between HF and depression is not fully understood, partly due to challenges in modeling this psychosomatic comorbidity in vivo.
• Existing models struggle to capture the complex interplay between cardiac events and mental health outcomes.

Purpose of the Study:

• To investigate the sequence of events linking HF to different aspects of depression.
• To explore the potential for in vivo modeling of psychosomatic comorbidity after cardiac events.
• To identify potential early markers for depression following HF.

Main Methods:

• Male C57BL6 mice underwent MI and subsequent behavioral and echocardiographic assessments.
• Standard tests for depression-like behavior (sucrose preference, tail suspension, Porsolt swim test) and learned helplessness (LH) were employed.
• Cardiac gene expression, specifically nr4a1, was analyzed in relation to behavioral outcomes.

Main Results:

• MI did not significantly alter motility, exploration, or anxiety-like behavior in mice.
• Standard depression tests did not reveal increased depressive-like behavior post-MI.
• A subtle predisposition to LH was observed after HF, with a distinct subpopulation showing increased risk and elevated cardiac nr4a1 expression.

Conclusions:

• The learned helplessness (LH) paradigm identified a subtle predisposition to depressive-like behavior after MI, suggesting a 'multiple-hits' hypothesis for comorbid depression.
• Traditional tests for anhedonia and despair were insufficient to detect behavioral changes, highlighting the sensitivity of the LH model.
• LH symptoms may serve as a marker for subclinical depression post-MI, warranting further investigation into its impact and the underlying cardio-psychogenic signaling.