Chemokine profile in women with moderate to severe anxiety and depression during pregnancy.

BACKGROUND: Cytokine levels have been extensively described in pregnant subjects under normal and pathological conditions, including mood-related disorders. Concerning chemokines, very few studies have reported their association with psychiatric disorders during pregnancy. Therefore, we explored the chemokine profile in women exhibiting anxiety and depression during late pregnancy in the present study. METHODS: One hundred twenty-six pregnant women in the 3rd trimester of pregnancy, displaying moderate to severe anxiety (ANX) alone and women exhibiting moderate to severe anxiety with comorbid depression (ANX + DEP), and 40 control pregnant women without affective disorders (CTRL) were evaluated through the Hamilton Anxiety Rating Scale (HARS) and the Hamilton Depression Rating Scale (HDRS). Serum chemokine levels of MCP-1 (CCL2), RANTES (CCL5), IP-10 (CXCL10), Eotaxin (CCL11), TARC (CCL17), MIP-1α (CCL3), MIP-1ß (CCL4), MIG (CXCL9), MIP-3α (CCL20), ENA-78 (CXCL5), GROα (CXCL1), I-TAC (CXCL11) and IL-8 (CXCL8)] were measured by immunoassay. Clinical, biochemical, and sociodemographic parameters were correlated with HARS and HDRS score values. RESULTS: Serum levels of most chemokines were significantly higher in the ANX and in the ANX + DEP groups, when compared to the CTRL group. Positive correlations were observed between MIP-1α/CCL3, MIP-1ß/CCL4, MCP-1/CCL2, MIP-3α/CCL20, RANTES/CCL5, Eotaxin/CCL11, and I-TAC/CXCL11 with high scores for anxiety (HARS) (p < 0.05) and for depression (HDRS) (p < 0.004). After controlling clinical measures for age + gwk + BMI, chemokines such as IL-8/CXCL8, MCP-1/CCL2 and MIP-1ß/CCL4 were found associated with high scores for anxiety (p < 0.05) in the ANX group. TARC/CCL17 and Eotaxin/CCL11 showed significant associations with high scores for depression (p < 0.04) whereas, MCP-1/CCL2 and MIP-1α/CCL3 were significantly associated with high scores for anxiety (p < 0.05) in the ANX + DEP group. Using a multivariate linear model, high serum levels of MIP-1ß/CCL4 and Eotaxin/CCL11 remained associated with depression (p < 0.01), while, IL-8/CXCL8, MIP-1ß/CCL4, MCP-1/CCL2, and MIP-1α/CCL3 were associated with anxiety (p < 0.05) in the symptomatic groups. CONCLUSIONS: Our data show that serum levels of distinct chemokines are increased in women exhibiting high levels of affective symptoms during late pregnancy. Our results suggest that increased levels of anxiety, depressive symptoms, and mood-related disorders may promote changes in specific functional chemokines associated with a chronic inflammatory process. If not controlled, it may lead to adverse obstetric and negative neonate outcomes, child development and neuropsychiatric alterations in the postnatal life. HIGHLIGHTS: Chemokine levels increase in affective disorders during pregnancy.

Cortisol and DHEA-S levels in pregnant women with severe anxiety.

BACKGROUND: A complex interaction between cortisol and dehydroepiandrosterone-sulphate (DHEA-S) is crucial in the stress system balance; several studies have reported increased cortisol levels during chronic stress and a weak counter-regulation by DHEA-S. During pregnancy, scarce information about this system is available, although cortisol and DHEA-S play an important role in the initiation and acceleration of labor. We conducted the present study in order to determine both cortisol and DHEA-S levels during the last trimester of pregnancy in patients exhibiting severe anxiety. METHODS: Pregnant women during the 3rd trimester of pregnancy were evaluated by using the self-reported version of the Hamilton Anxiety Rating Scale (HARS). According to the scores obtained from the psychometric scale, participants were divided into two groups: 1) patients exhibiting a cutoff score > 15 were considered with severe anxiety (ANX) (n = 101), and control pregnant subjects (CTRL) (n = 44) with a cutoff score < 5. Morning cortisol, DHEA-S and Cortisol/DHEA-S index were measured in all participants. Comparisons between groups were performed; additionally, correlations between clinical variables, biochemical data and HARS were calculated. RESULTS: Cortisol levels were significantly higher in the ANX group (p < 0.001), whereas those of DHEA-S were significantly lower in the same group (p < 0.01) when compared to healthy pregnant subjects. An increased cortisol/DHEA-S index was observed in the ANX group (p < 0.05). A significant association between cortisol and HARS scores (p = 0.03), was observed even after adjusting by gestational weeks (p = 0.004). CONCLUSIONS: Our data support that the cortisol/DHEA-S index is higher in pregnant women with high anxiety levels as compared with healthy pregnant women.

Cellular senescence in livers from children with end stage liver disease.

BACKGROUND: Senescent cells occur in adults with cirrhotic livers independent of the etiology. AIM: Investigate the presence rate of cellular senescence and expression of cell cycle check points in livers from children with end stage disease. METHODOLOGY/PRINCIPAL FINDINGS: Livers of five children aged three years or less undergoing liver transplantation due to tyrosinemia (n = 1), biliary atresia (n = 2), or fulminant hepatitis (n = 2) were analyzed for senescence associated beta-galactosidase (SA-betagal) activity and p16INK4a, p21cip1 and p53. All livers displayed positive cellular staining for SA-betagal in the canals of Hering and interlobular biliary ducts. In the presence of cirrhosis (3/5 cases) SA-betagal was found at the cholangioles and hepatocytes surrounding the regenerative nodules. Children with fulminant hepatic failure without cirrhosis had significant ductular transformation with intense SA-betagal activity. No SA-betagal activity was evident in the fibrous septa. Staining for p53 had a similar distribution to that observed for SA-betagal. Staining for p16(INK4a) and p21(cip1) was positive in the explanted liver of the patient with tyrosinemia, in the hepatocytes, the canals of Hering, cholangioles and interlobular bile ducts. In the livers with fulminant hepatitis, p21(cip1) staining occurred in the areas of ductular transformation and in the interlobular bile ducts. CONCLUSIONS/SIGNIFICANCE: Cellular senescence in livers of children with end stage disease is associated with damage rather than corresponding to an age dependent phenomenon. Further studies are needed to support the hypothesis that these senescence markers correlate with disease progression.