Correction to: Neuropsychopharmacology https://doi.org/10.1038/s41386-023-01771-5, published online 25 November 2023

In response to a Comment/Letter to the Editor submitted by Karadag et al., (2024), Figures 2B and 2C have been revised to show a “ND” or non-detectable indicator for experimental groups, where the data values fell below the range of the assay, rather than the sensitivity. The associated Figure 2 caption, the results section of the manuscript, and Supplemental Results Table 2 have been revised accordingly.

Because of the above comment in Karadag et al., (2024), the authors have removed the graphs showing correlations between the cytokine and corticosterone ELISA data. This resulted in the naming/alphabetization of the graphs changing on Figure 2. These revisions, based on Karadag’s recommendations, do not change the study findings or conclusions. The data validate that LPS induced an inflammatory response.

Figure 2 has also been corrected where the “###” significance indicators were inadvertently split across two lines, rather than appearing correctly on one line. This caused confusion in the scientific interpretation for Karadag et al. The figure caption has also been adjusted accordingly.

Figure 2 in the original article:

Fig. 2 Effect of metyrapone (MET) on maternal immune activation (MIA)-induced sickness behaviors and 3-hr post LPS physiological response measures in dams, placenta, and fetal brain. A Maternal sickness scores evaluated across a 6-hr period. Maternal sickness scores were elevated in Saline-LPS dams, and attenuated in MET-LPS dams, post MIA challenge. B Maternal plasma IL-17A concentrations were elevated by MIA. C Plasma IL-6 was elevated in MIA dams, which was modestly attenuated by MET. D MET protected against MIA induced elevations in maternal plasma corticosterone. E MET attenuated plasma corticosterone concentrations over a 6-hour period post G15 LPS challenge. F Maternal plasma corticosterone was positively correlated with maternal plasma IL-17A and maternal plasma IL-6 3-hours post MIA challenge across all dam groups. The far-right panel shows this significant correlation for Saline-LPS dams only. G Placental enzyme 11βHSD1 was increased in Saline-LPS males and females compared to the Saline-Saline groups 3-hours post MIA challenge. H Placental enzyme 11βHSD2 concentrations were reduced in Saline-LPS male and female placentas compared to the Saline-Saline groups 3-hours post MIA challenge. MET protected against decreased levels of 11βHSD2 in males only. Corticosterone was elevated in Saline-LPS male and female (I) placentas and (J) fetal brains compared to Saline-Saline groups, which was also attenuated by MET 3-hours post MIA challenge. K MIA was associated with increased IL-6R in male fetal brains, irrespective of MET treatment, and (L) fetal IL-6R in the brain was correlated with fetal brain corticosterone levels. Data are expressed as mean ± SEM. ***p < 0.001, **p < 0.01, *p < 0.05., Saline-Saline vs Saline-LPS; ###p < 0.001, ##p < 0.01, # p < 0.05, Saline-LPS vs MET-LPS; aaap < 0.001, aap < 0.01, a p < 0.05, Saline-Saline vs MET-Saline; bbbp < 0.001, bbp < 0.01, b p < 0.05, MET-LPS vs MET-Saline; ccp < 0.01, main effect of LPS/Saline. LPS – lipopolysaccharide.

Corrected Figure 2 in the updated article:

Figure 2. Effect of metyrapone (MET) on maternal immune activation (MIA)-induced sickness behaviors and 3-hr post LPS physiological response measures in dams, placenta, and fetal brain. A Maternal sickness scores evaluated across a 6-hr period. Maternal sickness scores were elevated in Saline-LPS dams, and attenuated in MET-LPS dams, post MIA challenge. Not surprisingly, maternal plasma B IL-17A and C IL-6 concentrations were always below the detection limit (ND) in Saline-Saline dams, whereas these cytokines were increased in Saline-LPS dams. D MET protected against MIA induced elevations in maternal plasma corticosterone. E MET attenuated plasma corticosterone concentrations over a 6-hour period post gestational day 15 LPS challenge. F Placental enzyme 11βHSD1 was increased in Saline-LPS males and females compared to the Saline-Saline groups 3-hours post MIA challenge. G Placental enzyme 11βHSD2 concentrations were reduced in Saline-LPS male and female placentas compared to the Saline-Saline groups 3-hours post MIA challenge. MET protected against decreased levels of 11βHSD2 in males only. Corticosterone was elevated in Saline-LPS male and female H placentas, and I fetal brains compared to Saline-Saline groups, but not in MET-LPS compared to Saline-LPS placentas 3-hours post challenge. J MIA was associated with increased IL-6R in male fetal brains, irrespective of MET treatment and K fetal IL-6R in the brain was correlated with fetal brain corticosterone levels. Data are expressed as mean ± SEM. ***p < 0.001, **p < 0.01, *p < 0.05., Saline-Saline vs Saline-LPS; ###p < 0.001, ##p < 0.01, #p < 0.05, Saline-LPS vs MET-LPS; aaap < 0.001, aap < 0.01, ap < 0.05, Saline-Saline vs MET-Saline; bbbp < 0.001, bbp < 0.01, bp < 0.05, MET-LPS vs MET-Saline; ccp < 0.01, main effect of LPS/Saline. LPS – lipopolysaccharide.

In the ‘Results’ section, the text excerpt

“Based on the skewness of the IL-17A data, a non-parametric analysis showed elevated cytokine levels following MIA (main effect LPS/ Saline): (X2 (1) = 8.669, p = 0.003; Fig. 2B). Surprisingly, MET partially protected against MIA-induced elevations in plasma IL-6 (G15 MET/Saline by G15 LPS/Saline interaction: F(1, 24) = 18.437, p = 0.001, np 2 = 0.434; Saline-Saline vs Saline-LPS: t(12) = − 6.518, p = 0.001; Saline-LPS vs MET-LPS: t(12) = 4.294, p = 0.001; Fig. 2C); this was only modest as they still had significantly higher concentrations of this cytokine than METSaline animals (p < 0.05; Fig. 2C). MET-Saline dams did not differ from SalineSaline on this measure (p > 0.05)”

was revised to read as follows:

“As expected, maternal IL-17A (Figure 2B) and IL-6 (Figure 2C) cytokine levels were not detectable in Saline-Saline dams, but they were detectably elevated in Saline-LPS mothers. Combined with the sickness behavior data, these results validate that an inflammatory response occurred following MIA challenge. In line with the sickness behavior data, maternal plasma IL-17A and IL-6 were not detectable in MET-LPS dams.”

Additionally, the following sentence was entirely removed: “Supplementary Results Statistical Table 2 outlines correlational results for several prenatal measures with a selection of data displayed in Fig. 2F” and the references to the different sections of “Figure 2” have been updated to reflect the changes in the figure.

In the ‘Discussion’ section, the following sentence “While MET inhibited maternal sickness behaviors and plasma IL-6 responses in our MIA dams, others have shown sustained elevations in IL-6 following treatment with this 11β-hydroxylase inhibitor” was revised to read as follows: “While MET inhibited maternal sickness behaviors, and plasma IL-6 responses were not detectable in METLPS dams, others have shown sustained elevations in IL-6 following treatment with this 11β-hydroxylase inhibitor”.

The authors have also added the following statement to clarify the confusion expressed in the Karadag et al., (2024) Comment/Letter to the Editor: “Notably, different manifestations of plasma cytokine expression (including suppression) are reported in rats based on sex and reproductive status in response to combined LPS and metyrapone treatment [55, 56].”

Finally, the Supplemental Results Table 2 has been revised to reflect the changes made in the main article.

Supplemental Results Table 2: ‘Statistical reporting table of maternal and offspring measures’ in the original article:

Supplemental Results Table 2. Statistical reporting table of maternal and offspring measures.

Table 1
Full size table

Corrected Supplemental Results Table 2: ‘Statistical reporting table of maternal and offspring measures’ in the updated article:

Supplemental Results Table 2. Statistical reporting table of maternal and offspring measures.

Table 2
Full size table

The original article has been corrected.