Natural killer cell reduction and uteroplacental vasculopathy

Uterine natural killer cells are important for uteroplacental development and pregnancy maintenance. Their role in pregnancy disorders, such as preeclampsia, is unknown. We reduced the number of natural killer cells by administering rabbit anti-asialo GM1 antiserum in an established rat preeclamptic model (female human angiotensinogen×male human renin) and evaluated the effects at the end of pregnancy (day 21), compared with preeclamptic control rats receiving normal rabbit serum. In 100% of the antiserum-treated, preeclamptic rats (7/7), we observed highly degenerated vessel cross sections in the mesometrial triangle at the end of pregnancy. This maternal uterine vasculopathy was characterized by a total absence of nucleated/living cells in the vessel wall and perivascularly and prominent presence of fibrosis. Furthermore, there were no endovascular trophoblast cells within the vessel lumen. In the control, normal rabbit serum-treated, preeclamptic rats, only 20% (1/5) of the animals displayed such vasculopathy. We confirmed the results in healthy pregnant wild-type rats: after anti-asialo GM1 treatment, 67% of maternal rats displayed vasculopathy at the end of pregnancy compared with 0% in rabbit serum-treated control rats. This vasculopathy was associated with a significantly lower fetal weight in wild-type rats and deterioration of fetal brain/liver weight ratio in preeclamptic rats. Anti-asialo GM1 application had no influence on maternal hypertension and albuminuria during pregnancy. Our results show a new role of natural killer cells during hypertensive pregnancy in maintaining vascular integrity. In normotensive pregnancy, this integrity seems important for fetal growth

A cross-sectional testing of The Iowa Personality Disorder Screen in a psychiatric outpatient setting

<p>Abstract</p> <p>Background</p> <p>Patients suspected of personality disorders (PDs) by general practitioners are frequently referred to psychiatric outpatient clinics (POCs). In that setting an effective screening instrument for PDs would be helpful due to resource constraints. This study evaluates the properties of The Iowa Personality Disorder Screen (IPDS) as a screening instrument for PDs at a POC.</p> <p>Methods</p> <p>In a cross-sectional design 145 patients filled in the IPDS and were examined with the SCID-II interview as reference. Various case-findings properties were tested, interference of socio-demographic and other psychopathology were investigated by logistic regression and relationships of the IPDS and the concept of PDs were studied by a latent variable path analysis.</p> <p>Results</p> <p>We found that socio-demographic and psychopathological factors hardly disturbed the IPDS as screening instrument. With a cut-off ≥4 the 11 items IPDS version had sensitivity 0.77 and specificity 0.71. A brief 5 items version showed sensitivity 0.82 and specificity 0.74 with cut-off ≥ 2. With exception for one item, the IPDS variables loaded adequately on their respective first order variables, and the five first order variables loaded in general adequately on their second order variable.</p> <p>Conclusion</p> <p>Our results support the IPDS as a useful screening instrument for PDs present or absent in the POC setting.</p

What we learn about bipolar disorder from large-scale neuroimaging:Findings and future directions from the ENIGMA Bipolar Disorder Working Group

MRI-derived brain measures offer a link between genes, the environment and behavior and have been widely studied in bipolar disorder (BD). However, many neuroimaging studies of BD have been underpowered, leading to varied results and uncertainty regarding effects. The Enhancing Neuro Imaging Genetics through Meta-Analysis (ENIGMA) Bipolar Disorder Working Group was formed in 2012 to empower discoveries, generate consensus findings and inform future hypothesis-driven studies of BD. Through this effort, over 150 researchers from 20 countries and 55 institutions pool data and resources to produce the largest neuroimaging studies of BD ever conducted. The ENIGMA Bipolar Disorder Working Group applies standardized processing and analysis techniques to empower large-scale meta- and mega-analyses of multimodal brain MRI and improve the replicability of studies relating brain variation to clinical and genetic data. Initial BD Working Group studies reveal widespread patterns of lower cortical thickness, subcortical volume and disrupted white matter integrity associated with BD. Findings also include mapping brain alterations of common medications like lithium, symptom patterns and clinical risk profiles and have provided further insights into the pathophysiological mechanisms of BD. Here we discuss key findings from the BD working group, its ongoing projects and future directions for large-scale, collaborative studies of mental illness

Influence of postpartum onset on the course of mood disorders

BACKGROUND: To ascertain the impact of postpartum onset (PPO) on the subsequent time course of mood disorders. METHODS: This retrospective study compared per year rates of excited (manic or mixed) and depressive episodes between fifty-five women with bipolar (N = 22) or major depressive (N = 33) disorders with first episode occurring postpartum (within four weeks after childbirth according to DSM-IV definition) and 218 non-postpartum onset (NPPO) controls. Such patients had a traceable illness course consisting of one or more episodes alternating with complete symptom remission and no additional diagnoses of axis I disorders, mental retardation or brain organic diseases. A number of variables reported to influence the course of mood disorders were controlled for as possible confounding factors RESULTS: Bipolar women with postpartum onset disorder had fewer excited episodes (p = 0.005) and fewer episodes of both polarities (p = 0.005) compared to non-postpartum onset subjects. No differences emerged in the rates of depressive episodes. All patients who met criteria for rapid cycling bipolar disorder (7 out of 123) were in the NPPO group. Among major depressives, PPO patients experienced fewer episodes (p = 0.016). With respect to clinical and treatment features, PPO-MDD subjects had less personality disorder comorbidity (p = 0.023) and were less likely to be on maintenance treatment compared to NPPO comparison subjects (p = 0.002) CONCLUSION: Such preliminary findings suggest that PPO mood disorders may be characterized by a less recurrent time course. Future research in this field should elucidate the role of comorbid personality disorders and treatment. Moreover it should clarify whether PPO disorders are also associated with a more positive outcome in terms of social functioning and quality of life

Genotypes and haplotypes in the insulin-like growth factors, their receptors and binding proteins in relation to plasma metabolic levels and mammographic density

<p>Abstract</p> <p>Background</p> <p>Increased mammographic density is one of the strongest independent risk factors for breast cancer. It is believed that one third of breast cancers are derived from breasts with more than 50% density. Mammographic density is affected by age, BMI, parity, and genetic predisposition. It is also greatly influenced by hormonal and growth factor changes in a woman's life cycle, spanning from puberty through adult to menopause. Genetic variations in genes coding for hormones and growth factors involved in development of the breast are therefore of great interest. The associations between genetic polymorphisms in genes from the IGF pathway on mammographic density and circulating levels of IGF1, its binding protein IGFBP3, and their ratio in postmenopausal women are reported here.</p> <p>Methods</p> <p>Samples from 964 postmenopausal Norwegian women aged 55-71 years were collected as a part of the Tromsø Mammography and Breast Cancer Study. All samples were genotyped for 25 SNPs in IGF1, IGF2, IGF1R, IGF2R, IGFALS and IGFBP3 using Taqman (ABI). The main statistical analyses were conducted with the PROC HAPLOTYPE procedure within SAS/GENETICS™ (SAS 9.1.3).</p> <p>Results</p> <p>The haplotype analysis revealed six haploblocks within the studied genes. Of those, four had significant associations with circulating levels of IGF1 or IGFBP3 and/or mammographic density. One haplotype variant in the IGF1 gene was found to be associated with mammographic density. Within the IGF2 gene one haplotype variant was associated with levels of both IGF1 and IGFBP3. Two haplotype variants in the IGF2R were associated with the level of IGF1. Both variants of the IGFBP3 haplotype were associated with the IGFBP3 level and indicate regulation in cis.</p> <p>Conclusion</p> <p>Polymorphisms within the IGF1 gene and related genes were associated with plasma levels of IGF1, IGFBP3 and mammographic density in this study of postmenopausal women.</p

Can Seismic Observations of Bed Conditions on Ice Streams Help Constrain Parameters in Ice Flow Models?

We investigate correlations between seismically derived estimates of basal acoustic impedance and basal slipperiness values obtained from a surface-to-bed inversion using a Stokes ice flow model. Using high-resolution measurements along several seismic profiles on Pine Island Glacier (PIG), we find no significant correlation at kilometer scale between acoustic impedance and either retrieved basal slipperiness or basal drag. However, there is a stronger correlation when comparing average values along the individual profiles. We hypothesize that the correlation appears at the length scales over which basal variations are important to large-scale ice sheet flow. Although the seismic technique is sensitive to the material properties of the bed, at present there is no clear way of incorporating high-resolution seismic measurements of bed properties on ice streams into ice flow models. We conclude that more theoretical work needs to be done before constraints on mechanical conditions at the ice-bed interface from acoustic impedance measurements can be of direct use to ice sheet models

Breast cancer risk genes: association analysis in more than 113,000 women

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Neuroanatomical Pattern of Mitochondrial Complex I Pathology Varies between Schizophrenia, Bipolar Disorder and Major Depression

BACKGROUND:Mitochondrial dysfunction was reported in schizophrenia, bipolar disorderand major depression. The present study investigated whether mitochondrial complex I abnormalities show disease-specific characteristics. METHODOLOGY/PRINCIPAL FINDINGS:mRNA and protein levels of complex I subunits NDUFV1, NDUFV2 and NADUFS1, were assessed in striatal and lateral cerebellar hemisphere postmortem specimens and analyzed together with our previous data from prefrontal and parieto-occipital cortices specimens of patients with schizophrenia, bipolar disorder, major depression and healthy subjects. A disease-specific anatomical pattern in complex I subunits alterations was found. Schizophrenia-specific reductions were observed in the prefrontal cortex and in the striatum. The depressed group showed consistent reductions in all three subunits in the cerebellum. The bipolar group, however, showed increased expression in the parieto-occipital cortex, similar to those observed in schizophrenia, and reductions in the cerebellum, yet less consistent than the depressed group. CONCLUSIONS/SIGNIFICANCE:These results suggest that the neuroanatomical pattern of complex I pathology parallels the diversity and similarities in clinical symptoms of these mental disorders

What we learn about bipolar disorder from large-scale neuroimaging: Findings and future directions from theENIGMABipolar Disorder Working Group

MRI‐derived brain measures offer a link between genes, the environment and behavior and have been widely studied in bipolar disorder (BD). However, many neuroimaging studies of BD have been underpowered, leading to varied results and uncertainty regarding effects. The Enhancing Neuro Imaging Genetics through Meta‐Analysis (ENIGMA) Bipolar Disorder Working Group was formed in 2012 to empower discoveries, generate consensus findings and inform future hypothesis‐driven studies of BD. Through this effort, over 150 researchers from 20 countries and 55 institutions pool data and resources to produce the largest neuroimaging studies of BD ever conducted. The ENIGMA Bipolar Disorder Working Group applies standardized processing and analysis techniques to empower large‐scale meta‐ and mega‐analyses of multimodal brain MRI and improve the replicability of studies relating brain variation to clinical and genetic data. Initial BD Working Group studies reveal widespread patterns of lower cortical thickness, subcortical volume and disrupted white matter integrity associated with BD. Findings also include mapping brain alterations of common medications like lithium, symptom patterns and clinical risk profiles and have provided further insights into the pathophysiological mechanisms of BD. Here we discuss key findings from the BD working group, its ongoing projects and future directions for large‐scale, collaborative studies of mental illness

Cortical thickness across the lifespan: Data from 17,075 healthy individuals aged 3–90 years

Delineating the association of age and cortical thickness in healthy individuals is critical given the association of cortical thickness with cognition and behavior. Previous research has shown that robust estimates of the association between age and brain morphometry require large-scale studies. In response, we used cross-sectional data from 17,075 individuals aged 3–90 years from the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Consortium to infer age-related changes in cortical thickness. We used fractional polynomial (FP) regression to quantify the association between age and cortical thickness, and we computed normalized growth centiles using the parametric Lambda, Mu, and Sigma method. Interindividual variability was estimated using meta-analysis and one-way analysis of variance. For most regions, their highest cortical thickness value was observed in childhood. Age and cortical thickness showed a negative association; the slope was steeper up to the third decade of life and more gradual thereafter; notable exceptions to this general pattern were entorhinal, temporopolar, and anterior cingulate cortices. Interindividual variability was largest in temporal and frontal regions across the lifespan. Age and its FP combinations explained up to 59% variance in cortical thickness. These results may form the basis of further investigation on normative deviation in cortical thickness and its significance for behavioral and cognitive outcomes