Depressive-like behavior, its sensitization, social buffering, and altered cytokine responses in rhesus macaques moved from outdoor social groups to indoor housing

ABSTRACT

Psychosocial stressors appear to promote the onset of depressive illness through activation and sensitization of inflammatory mechanisms. Here, adult male rhesus monkeys brought from large outdoor social groups to indoor housing for 8 days reliably exhibited a hunched, depressive-like posture. When rehoused indoors a second 8 days about 2 weeks later, monkeys housed alone, but not those with an affiliative partner, showed sensitization of the depressive-like hunched posture. Housing indoors also affected circulating pro-inflammatory cytokines: IL-1β showed increased responsiveness to immune challenge, and IL-1β and TNF-α showed reduced suppression by dexamethasone. Sensitivity of the anti-inflammatory cytokine IL-10 to immune challenge exhibited a relative increase from the first to the second round of indoor housing in animals housed in pairs, and a relative decrease in animals housed alone. Cytokine levels during indoor housing were positively correlated with duration of depressive-like behavior. Plasma cortisol levels increased but did not differentiate housing conditions or rounds. Results demonstrate a rapid induction and sensitization of depressive-like behavior to indoor individual housing, social buffering of sensitization, and associated inflammatory responses. This paradigm may provide a practical nonhuman primate model for examining inflammatory-mediated consequences of psychosocial stressors on depression and possible social buffering of these effects.

KEYWORDS:

• Depression
• depressive response
• social stress
• isolation
• inflammation
• glucocorticoid resistance
• immune challenge
• social buffering
• nonhuman primate model
• rhesus macaque

Acknowledgments

The authors would like to thank Laura Calonder, Nancy Gee, and JoAnn Yee for technical assistance, Brenda McCowan for consultation, Primate Services at the CNPRC, particularly Paul-Michael Sosa, for animal handling, care, and coordination, and W. Tang Watanasriyakul for assistance constructing figures.

Disclosure statement

No potential conflict of interest was reported by the authors.

Notes

¹ A complication of the scoring system is that animals in the With Partner condition sometimes sat side by side in a manner that meets the definition for the hunched posture. In this case, it may be that animals were simply huddling with the partner and so exhibiting positive affiliative behavior. Although our primary analysis was of the more conservative measure (all instances of the hunched posture included), we also calculated the time that this posture was exhibited by animals in the With Partner condition in the absence of additional measures of positive social interaction (i.e., contact and grooming initiated and received). For this “nonsocial hunched posture” measure, differences between groups were magnified and significant during the first as well as the second 8 weeks of testing. In the outdoor field cages, all of the limited instances of the hunched posture observed occurred in the context of social behavior.

Additional information

Funding

The work was funded by grant MH099361 to MBH.