Childhood maltreatment is associated with an automatic negative emotion processing bias in the amygdala

Major depression has been repeatedly associated with amygdala hyper‐responsiveness to negative (but not positive) facial expressions at early, automatic stages of emotion processing using subliminally presented stimuli. However, it is not clear whether this “limbic bias” is a correlate of depression or represents a vulnerability marker preceding the onset of the disease. Because childhood maltreatment is a potent risk factor for the development of major depression in later life, we explored whether childhood maltreatment is associated with amygdalar emotion processing bias in maltreated but healthy subjects. Amygdala responsiveness to subliminally presented sad and happy faces was measured by means of fMRI at 3 T in N = 150 healthy subjects carefully screened for psychiatric disorders. Childhood maltreatment was assessed by the 25‐item childhood trauma questionnaire (CTQ). A strong association of CTQ‐scores with amygdala responsiveness to sad, but not happy facial expressions emerged. This result was further qualified by an interaction of emotional valence and CTQ‐scores and was not confounded by trait anxiety, current depression level, age, gender, intelligence, education level, and more recent stressful life‐events. Childhood maltreatment is apparently associated with detectable changes in amygdala function during early stages of emotion processing which resemble findings described in major depression. Limbic hyper‐responsiveness to negative facial cues could be a consequence of the experience of maltreatment during childhood increasing the risk of depression in later life. Limitation: the present association of limbic bias and maltreatment was demonstrated in the absence of psychopathological abnormalities, thereby limiting strong conclusions. Hum Brain Mapp 34:2899–2909, 2013. © 2012 Wiley Periodicals, Inc.     

Opposing prognostic relevance of junction plakoglobin in distinct prostate cancer patient subsets

Both oncogenic and tumor suppressor functions have been described for junction plakoglobin (JUP), also known as γ‐catenin. To clarify the role of JUP in prostate cancer, JUP protein expression was immunohistochemically detected in a tissue microarray containing 11 267 individual prostatectomy specimens. Considering all patients, high JUP expression was associated with adverse tumor stage (P = 0.0002), high Gleason grade (P < 0.0001), and lymph node metastases (P = 0.011). These associations were driven mainly by the subset without TMPRSS2:ERG fusion, in which high JUP expression was an independent predictor of poor prognosis (multivariate analyses, P = 0.0054) and early biochemical recurrence (P = 0.0003). High JUP expression was further linked to strong androgen receptor expression (P < 0.0001), high cell proliferation, and PTEN and FOXP1 deletion (P < 0.0001). In the ERG‐negative subset, high JUP expression was additionally linked to MAP3K7 (P = 0.0007) and CHD1 deletion (P = 0.0021). Contrasting the overall prognostic effect of JUP, low JUP expression indicated poor prognosis in the fraction of CHD1‐deleted patients (P = 0.039). In this subset, the association of high JUP and high cell proliferation was specifically absent. In conclusion, the controversial biological roles of JUP are reflected by antagonistic prognostic effects in distinct prostate cancer patient subsets.     

Cell-Based Therapy for the Deficient Urinary Sphincter

When sterile culture techniques of mammalian cells first became state of the art, there was tremendous anticipation that such cells could be eventually applied for therapeutic purposes. The discovery of adult human stem or progenitor cells further motivated scientists to pursue research in cell-based therapies. Although evidence from animal studies suggests that application of cells yields measurable benefits, in urology and many other disciplines, progenitor-cell-based therapies are not yet routinely clinically available. Stress urinary incontinence (SUI) is a condition affecting a large number of patients. The etiology of SUI includes, but is not limited to, degeneration of the urinary sphincter muscle tissue and loss of innervation, as well as anatomical and biomechanical causes. Therefore, different regimens were developed to treat SUI. However, at present, a curative functional treatment is not at hand. A progenitor-cell-based therapy that can tackle the etiology of incontinence, rather than the consequences, is a promising strategy. Therefore, several research teams have intensified their efforts to develop such a therapy for incontinence. Here, we introduce candidate stem and progenitor cells suitable for SUI treatment, show how the functional homogeneity and state of maturity of differentiated cells crucial for proper tissue integration can be assessed electrophysiologically prior to their clinical application, and discuss the trophic potential of adult mesenchymal stromal (or stem) cells in regeneration of neuronal function.     

Soluble inflammation markers in nasal lavage from CF patients and healthy controls

BackgroundCF sinonasal and bronchial mucosa reveal identical ion channel defects. Nasal Lavage (NL) allows non-invasive repeated sampling of airway surface liquid. We compared inflammatory mediators in NL from CF-patients and healthy controls, and in CF in relation to sinonasal pathogen colonization.MethodsFrom 40 CF-patients (mean age 21.8 yrs, SD 11.8 yrs.) and 52 healthy controls (mean age 31.9 yrs., SD 13.7 yrs.) NL-fluid (10 ml/nostril) concentrations of MPO, IL-8, IL-17A, sICAM-1, IL-1β, IL-6, TNF-α, IL-10 and IL-5 were determined using cytometric bead arrays for flow cytometry.ResultsCF-patients showed significantly higher MPO-concentrations in NL-fluid and higher IL-8-levels (n.s.) than controls. MPO, IL-8, IL-17A, sICAM-1, IL-1β and IL-6 were significantly more often detectable in CF-patients than in controls. CF-patients with S. aureus colonization in both upper and lower airways had significantly elevated MPO and IL-8 levels in NL-fluid compared to S. aureus negatives.ConclusionNL-fluid differed substantially between CF-patients and healthy controls with most promising results for IL-8 and MPO, a primarily in CF-NL assessed mediator. Further studies are required to assess effects of sample collection and processing on concentrations of inflammatory markers and to evaluate potentials of NL analysis in research and clinical routine.     

Facilitative effects of VNS on the motor threshold: implications for its antidepressive mode of action?

In the present study, the effects of vagus nerve stimulation (VNS) on the resting motor threshold (rMT) of patients treated with repetitive transcranial magnetic stimulation were evaluated. Patients showed a significant decrease in the rMT during VNS-on stimulation. VNS was the only significant factor affecting rMT changes and did not appear to be a static variable. Further studies should focus on the effect of VNS on neural neurogenesis in depressive disorders, and the effects of other treatment options for major depressive disorder on the rMT should also be determined.