Attentional bias in individuals with depression and adverse childhood experiences: influence of the noradrenergic system?

Rationale: Major depressive disorder (MDD) is a severe mental disorder with affective, cognitive, and somatic symptoms. Mood congruent cognitive biases, including a negative attentional bias, are important for development, maintenance, and recurrence of depressive symptoms. MDD is associated with maladaptive changes in the biological stress systems such as dysregulations of central noradrenergic alpha2-receptors in the locus coeruleus-noradrenergic system, which can affect cognitive processes including attention. Patients with adverse childhood experiences (ACE), representing severe stress experiences in early life, might be particularly affected. Objectives: With an experimental design, we aimed to gain further knowledge about the role of noradrenergic activity for attentional bias in MDD patients with and without ACE. Methods: We tested the effect of increased noradrenergic activity induced by the alpha2-receptor blocker yohimbine on attentional bias in a placebo-controlled repeated measures design. Four groups were included as follows: MDD patients with and without ACE, and healthy participants with and without ACE (total N = 128, all without antidepressant medication). Results: A significant effect of MDD on attentional bias scores of sad face pictures (p = .037) indicated a facilitated attentional processing of sad face pictures in MDD patients (compared to non-MDD individuals). However, we found no such effect of ACE. For attentional bias of happy face pictures, we found no significant effects of MDD and ACE. Even though a higher increase of blood pressure and salivary alpha-amylase following yohimbine compared to placebo indicated successful noradrenergic stimulation, we found no significant effects of yohimbine on attentional bias of happy or sad face pictures. Conclusions: Our results are consistent with the hypothesis of a negative attentional bias in MDD patients. However, as we found no effect of ACE or yohimbine, further research is needed to understand the mechanisms by which ACE increases the risk of MDD and to understand the biological basis of the MDD-related negative attentional bias

Risk of acute appendicitis in and around pregnancy: a population-based cohort study from England

Objective: To determine the absolute and relative risk of acute appendicitis during the antepartum and postpartum periods compared with the time outside pregnancy among women of childbearing age. Background: Acute appendicitis is the most common nonobstetric surgical emergency during pregnancy. Estimates of the incidence of acute appendicitis in pregnancy remain imprecise and inconsistent. Methods: All potential fertile women aged 15 to 44 years registered within Clinical Practice Research Datalink with linkages to the Hospital Episodes Statistics between 1997 and 2012 were identified. Absolute rates of acute appendicitis were calculated during the antepartum and postpartum periods and were compared with the time outside pregnancy in terms of incidence rate ratio (IRR) using a Poisson regression model. Results: Among 1,624,804 women, there were 362,219 pregnancies resulting in live or stillbirths. Compared with the time outside pregnancy, the rate of acute appendicitis was 35% lower during the antepartum period [IRR, 0.65; 95% confidence interval (CI), 0.55–0.76], with the lowest rate reported during the third trimester (IRR, 0.47; 95% CI, 0.35–0.64) for all ages; no increased risk of acute appendicitis was observed in the postpartum period compared with the time outside pregnancy among women aged 15 to 34 years but an 84% increased risk for women older than 35 years (IRR, 1.84; 95% CI, 1.18–2.86). The highest and lowest rates of negative appendectomy were encountered in the second and the third trimesters, respectively. Conclusions: Pregnant women are less likely to be diagnosed with acute appendicitis than nonpregnant women, with the lowest risk reported during the third trimester

Systemic neutrophil-to-lymphocyte ratio in colorectal cancer: the relationship to patient survival, tumour biology and local lymphocytic response to tumour

Background: Colorectal cancer (CRC) is a major cause of mortality and morbidity. The impact of inflammatory biomarkers (C-reactive protein etc.) on CRC is increasingly studied including systemic neutrophil-to-lymphocyte ratio (NLR) as they seem to predict outcome. Methods: All patients who underwent curative resection for CRC from 2000 to 2004 at Leeds Teaching Hospitals NHS Trust had pre-operative NLR calculated. Demographic, histopathological and survival data were collected. Tissue microarrays were created and stained to determine the mismatch repair (MMR) protein status of each tumour. Local lymphocytic response to the tumour was assessed and graded. Results: About 358 patients were eligible. Of these 88 had an NLR greater than or equal to5, which predicted lower overall survival and greater disease recurrence. A high NLR is associated with higher pT- and pN-stage and a greater incidence of extramural venous invasion. MMR protein status was not associated with NLR. A pronounced lymphocytic reaction at the invasive margin (IM) indicated a better prognosis and was associated with a lower NLR. Conclusion: Neutrophil-to-lymphocyte ratio predicts disease-free and overall survival and is associated with a more aggressive tumour phenotype. The lymphocytic response to tumour at the IM is associated with NLR however dMMR is not. Neutrophil-to-lymphocyte ratio is a cheap, easy-to-access test that predicts outcome in CRC