Contagion of depression: a double-edged sword

Abstract

Depression is a significant mental health issue with extensive economic implications, and recent studies suggest it may be transmitted between individuals. However, the mechanisms of this contagion remain unclear, and the social buffering effect has been understudied. This research employs three rodent models, including stress crossover, cohabitation-induced, and non-contact induced depression contagion models, to explore these mechanisms. Here, we report that that naive mice cohabiting with depressed mice showed increased corticosterone levels and depressive behaviors, unlike those with stressed mice, who did not exhibit these changes and even mitigated desperation in stressed mice. Non-contact cohabitation did not produce significant behavioral differences, but exposure to bedding from depressed mice reduced sucrose preference in naive mice. This study introduces reliable models of depression contagion, suggesting it operates independently of stress transmission. The interplay between depression contagion and social buffering may vary in different contexts. These findings provide new insights into the mechanisms of depression contagion and potential strategies for preventing depressive disorders.

Fig. 1. Schematic diagram illustrating the experimental findings.

Created in BioRender. BioRender.com/s47q887.

Fig. 2. Stressed mice could not trigger stress transmission to healthy mice after cohabitation.

Four groups were cohoused or intervened for five weeks according to the experimental plan. Behavioral and corticosterone tests were conducted after the scheduled time (A). The sucrose preference percentage of CUMS and DM was significantly reduced by chronic stress (B), while the immobility time of CUMS in the tail suspension test (C) and serum CORT levels (D) of CUMS and DM was increased. However, no significant difference was observed between CON and OB mice (B–D). (Group DM represented demonstrator mice who underwent the chronic unpredictable mild stress procedure, while Group OB consisted of naive mice cohabiting with DM mice. *p < 0.05, **p < 0.01, ***p < 0.001, n_(DM) = 16, n_(Other) = 8) (Created in BioRender. BioRender.com/g71g470).

Fig. 3. Depressed mice contribute to depressive behaviors in naive mice after cohabitation.

Two groups of naive mice were cohoused with two groups of demonstrators for five weeks, respectively. Behavioral and corticosterone tests were conducted after the scheduled time (A). After 5-week CUMS, the sucrose preference percentage of DP was lower than that of CON (B), and the immobility time in the tail suspension test of DP was also higher (C). Following a 5-week cohabitation, depressive behaviors persisted and stress levels increased in the DP mice (D–F). Naive mice cohabiting with DP mice showed similar behavioral and physiological changes (G–I). (Group BC represented naive mice cohabiting with CON mice, while group BD represented naive mice cohabiting with DP mice. *p < 0.05, **p < 0.01, ***p < 0.001, n_(DP&CON) = 20, n_(BC&BD) = 10) (Created in BioRender. BioRender.com/k05d903).

Fig. 4. Non-contact cohabitation failed to induce depression contagion between depressed and naïve mice.

Two groups of naive mice were cohoused with two groups of demonstrators for five weeks, with a transparent acrylic board separating them. Behavioral and corticosterone tests were conducted after the scheduled time (A). Before cohabitation, the sucrose preference percentage of DP decreased significantly (B), while TST immobility time increased (C). However, no significant difference was observed between CON and DP mice in TST immobility time and serum corticosterone after 5-week cohabitation (E, F). Sucrose preference percentage remained lower in DP than in CON (D). Moreover, no difference was found between VD and VC in behavior tests and serum corticosterone level (G–I). (Group VC represented naive mice lived in the same cages with healthy mice, while Group VD represents naive mice cohoused with depressed mice. *p < 0.05, **p < 0.01, ***p < 0.001, n_(DP&CON) = 16, n_(VD&VC) = 8) (Created in BioRender. BioRender.com/p75t345).

Fig. 5. The transplantation of the bedding mediated depression contagion without stress transmission.

The two groups of naive mice received bedding from depressed mice and healthy mice, respectively. Behavioral and corticosterone tests were conducted after the scheduled time (A). After a duration of 5 weeks, the sucrose preference percentage in ND was found to be lower compared to that in NC (B), but no differences were found in the tail suspension test (C) and serum corticosterone levels (D). (Group NC consisted of naive mice housed in bedding from healthy mice, while Group ND comprised those housed in bedding from depressed mice. *p < 0.05, **p < 0.01, ***p < 0.001, n = 8) (Created in BioRender. BioRender.com/a24n235).