Figure 3. Path analysis and fit test for the general model (x2 = 1.21, df = 2, p = 0.751; CFI = 1.00; RMSEA,0.01, p = 0.792). Significant paths (*p,0.05; **p,0.01) are in black and non significant in gray. The squared multiple correlations (R2) of the endogenous variables are located in their right inferior corner in gray and italics. doi:10.1371/journal.pone.0008618.g003 measures on the behavioral outcome. According to the crite- ria established, this is a good-fitting model (x2 = 1.21, df = 2, p = 0.751; CFI = 1.00; RMSEA ,0.01, p = 0.792, see Table S3 for total and indirect effects). As frequently reported in the literature, in this model including all animals and experimental conditions, we confirm similar positive effects of fluoxetine treatment on levels of both Ki67-IR cells and BrdU-IR cells, as well as a negative effect of fluoxetine on immobility time in the FST. We also observed that BLA lesions reduced anxiety levels and immobility time in the FST, while increasing the expression of BrdU-IR cells specifically. Anxiety levels were negatively related to levels of Amygdala and Neurogenesis Ki67-IR cells, while the latter variable was in turn again negatively related to immobility time in the FST. Next, this general model was the basis to further assess whether the established relationships within the overall structure differed for each of the levels comprised in each of the three predicting variables (fluoxetine treatment, BLA lesion, anxiety levels). As a first step, three independent models were derived by excluding, in each case, one of the predicting variables. For each case, a good fitting model was obtained for at least one level (Figures 4–6), thus enabling multi-group stacked model analyses in order to directly compare both levels of the variable in question. Thus, specific path strength differences between the two levels of each variable could be statistically compared. Path analyses for the modulatory role of BLA lesions: To assess the potential modulation of BLA lesions over the neurogenic and behavioral actions of fluoxetine, a stacked, multi-sample analysis was used to compare Sham and BLA lesion groups (Figure 4). Importantly, stacked group analyses revealed an overall difference in the model fit between the sham and the BLA lesion groups (p,0.002, Table S4). This analysis also confirmed the existence of significant differences between Sham and BLA lesioned groups, as exhibited by the beta weights shown in Figure 4, specifically in three pathways: (i) the effect of fluoxetine treatment on BrdU-IR cells, reflecting the fact that in the BLA lesion condition, fluoxetine treatment was related to higher levels of BrdU-IR cells, a relationship that was absent in the sham lesion condition; (ii) the relation between anxiety and BrdU-IR cells: whereas anxiety predicted lower levels of BrdU-IR cells in the sham lesion condition, an opposite pattern was observed for BLA lesioned animals; (iii) the relationship between Ki67 levels and immobility in the FST, with this relationship been negative for BLA lesioned animals but inexistent in the sham group. In addition, it may be worth noting other pathways in which differences among the two groups approached significance. In all the following cases a relationship present in the BLA lesion group was notably weaker, if not absent, than in the intact BLA group: (i) a negative influence of fluoxetine in FST immobility; (ii) a positive relationship of BrdU on FST immobility; and (iii) a negative influence of anxiety in Ki67. Furthermore, as the beta weights show in Figure 4, specifically in the BLA lesion group, anxiety Figure 4. Path analysis for the models according to the lesion groups. A. Model fit was tested separately for the sham lesion group (x2 = 5.42, df = 2, p = 0.066; CFI = 0.48; RMSEA = 0.21, p = 0.083) and B. for the BLA lesion group (x2 = 0.52, df = 2, p = 0.771; CFI = 1.00; RMSEA,0.01, p = 0.783). Significant paths (p,0.05; **p,0.01) are in black and non significant in gray. The squared multiple correlations (R2) of the endogenous variables are located in their right inferior corner in gray and italics. doi:10.1371/journal.pone.0008618.g004 PLoS ONE | www.plosone.org 6 January 2010 | Volume 5 | Issue 1 | e8618