The integration of depressive behaviors and cardiac dysfunction during an operational measure of depression: investigating the role of negative social experiences in an animal model

Abstract

Objective: There is a bidirectional association between depression and cardiovascular disease. The neurobiological mechanisms underlying this association may involve an inability to cope with disrupted social bonds. This study investigated in an animal model the integration of depressive behaviors and cardiac dysfunction after a disrupted social bond and during an operational measure of depression, relative to the protective effects of intact social bonds.

Methods: Depressive behaviors in the forced swim test and continuous electrocardiographic parameters were measured in 14 adult, female socially monogamous prairie voles (rodents), after 4 weeks of social pairing or isolation.

Results: After social isolation, animals exhibited (all values are mean ± standard error of the mean; isolated versus paired, respectively) increased heart rate (416 ± 14 versus 370 ± 14 bpm, p < .05) and reduced heart rate variability (3.3 ± 0.2 versus 3.9 ± 0.2 ln(ms(2))). During the forced swim test, isolated animals exhibited greater helpless behavior (immobility = 106 ± 11 versus 63 ± 11 seconds, p < .05), increased heart rate (530 ± 22 versus 447 ± 15 bpm, p < .05), reduced heart rate variability (1.8 ± 0.4 versus 2.7 ± 0.2 ln(ms(2)), p < .05), and increased arrhythmias (arrhythmic burden score = 181 ± 46 versus 28 ± 12, p < .05).

Conclusions: The display of depressive behaviors during an operational measure of depression is coupled with increased heart rate, reduced heart rate variability, and increased arrhythmias, indicative of dysfunctional behavioral and physiological stress coping abilities as a function of social isolation. In contrast, social pairing with a sibling is behaviorally protective and cardioprotective. The present results can provide insight into a possible social mechanism underlying the association between depression and cardiovascular disease in humans.

Figure 1

Electrocardiographic examples of the most common arrhythmias observed and classified in the prairie vole. Classification criteria are defined in the methods. Arrows denote arrhythmic event. NSR = normal sinus rhythm; PVC = premature ventricular contraction.

Figure 2

Mean ± standard error of the mean heart rate in paired and isolated prairie voles at baseline (before isolation), after 4 weeks of isolation, and during the forced swim test (FST). * p < .05 between the paired and isolated groups.

Figure 3

Mean ± standard error of the mean heart rate variability, including amplitude of respiratory sinus arrhythmia (A) and standard deviation of normal-to-normal intervals (SDNN index; B) in paired and isolated prairie voles at baseline (before isolation), after 4 weeks of isolation, and during the forced swim test (FST). * p < .05 between the paired and isolated groups. ^ p < .07 between the paired and isolated groups.

Figure 3

Mean ± standard error of the mean heart rate variability, including amplitude of respiratory sinus arrhythmia (A) and standard deviation of normal-to-normal intervals (SDNN index; B) in paired and isolated prairie voles at baseline (before isolation), after 4 weeks of isolation, and during the forced swim test (FST). * p < .05 between the paired and isolated groups. ^ p < .07 between the paired and isolated groups.

Figure 4

Mean ± standard error of the mean arrhythmic burden during the forced swim test, including total arrhythmic burden (A), ventricular arrhythmic burden (B), and supraventricular arrhythmic burden (C) in paired and isolated prairie voles. * p < .05 versus the respective paired group.

Figure 4

Mean ± standard error of the mean arrhythmic burden during the forced swim test, including total arrhythmic burden (A), ventricular arrhythmic burden (B), and supraventricular arrhythmic burden (C) in paired and isolated prairie voles. * p < .05 versus the respective paired group.

Figure 4

Mean ± standard error of the mean arrhythmic burden during the forced swim test, including total arrhythmic burden (A), ventricular arrhythmic burden (B), and supraventricular arrhythmic burden (C) in paired and isolated prairie voles. * p < .05 versus the respective paired group.

Figure 5

Mean ± standard error of the mean immobility time during a 5-minute forced swim test in paired and isolated prairie voles. The remainder of the 300 seconds is composed of the active coping behaviors of swimming, struggling, and climbing (see text for further description). * p < .05 versus the respective paired group.