On 2016 May 27, Carmine Pariante commented:

We are grateful to Dr. Carroll for his comment, which has allowed us to clarify this point. Dr. Carroll is right that we use 'specific' as indicating the outcome of statistical analyses. However, we refer to pathways and genes 'specifically' regulated in depressed patients (or, indeed, in the group that does not develop depression) because these genes/pathways are only regulated in the depressed (or in the non-depressed) group. In this sense, we are using 'specific' to differentiate these genes/pathways from the many genes/pathways that are regulated equally in both groups. We also agree that there are limitations in using IFN-alpha as a model of ordinary major depressive disorder, although we are confident that our findings are relevant to at least the subgroup of depressed patients with high levels of peripheral inflammation. We hope that this reply is helpful.

On 2016 May 08, Bernard Carroll commented:

Several issues arise with this report. 1. Authors claimed that "specific signatures" of gene expression changes distinguished depressed versus non-depressed patients. After reading the full paper plus the Supplemental material it is clear that specificity was not established. No data were presented on conditional probabilities or on diagnostic confidence or prognostic confidence. 2. Multiple, misleading, references to specificity in the article actually just denote statistically significant differences in gene expression between the 2 groups of patients. 3.No group-wise differences in cytokine concentrations were found. 4. Validity of IFN-alpha induced depression as a model of ordinary major depressive disorder has not been established.

On 2016 May 08, Bernard Carroll commented:

Several issues arise with this report. 1. Authors claimed that "specific signatures" of gene expression changes distinguished depressed versus non-depressed patients. After reading the full paper plus the Supplemental material it is clear that specificity was not established. No data were presented on conditional probabilities or on diagnostic confidence or prognostic confidence. 2. Multiple, misleading, references to specificity in the article actually just denote statistically significant differences in gene expression between the 2 groups of patients. 3.No group-wise differences in cytokine concentrations were found. 4. Validity of IFN-alpha induced depression as a model of ordinary major depressive disorder has not been established.