Psychiatric morbidity in epilepsy: a case controlled study of adults receiving disability benefits

To access publisher full text version of this article. Please click on the hyperlink in Additional Links fieldOBJECTIVE: To compare the prevalence of non-organic psychiatric disorders among disabled patients of normal intelligence with epilepsy with the prevalence of similar psychiatric disorders among age and sex matched disabled patients with other somatic diseases. METHODS: A case-control study was carried out in Iceland among people receiving disability benefits using information available at the State Social Security Institute. There were 344 patients with epilepsy in Iceland 16 to 66 years of age (inclusive) receiving disability benefits in 1995. By excluding mentally retarded patients, autistic patients, and patients with organic psychoses, 241 index cases with epilepsy qualified for the study. For each case two age and sex matched controls were selected from all patients receiving disability benefits who had cardiovascular diseases, respiratory diseases, or arthropathies. The same exclusion criteria were applied to the controls as the index cases. In both patient groups psychiatric diagnoses were classified into one of the four following categories: (1) psychotic illness; (2) neurotic illness or personality disorders; (3) alcohol or drug dependence or misuse; and (4) other mental disorders. RESULTS: Psychiatric diagnosis was present among 35% (85/241) of the cases compared with 30% (143/482) of the controls (p=0.15). There was a difference in the distribution of the two groups into different psychiatric categories (p=0.02). This was mainly due to an excess of men in the index group with psychosis, particularly schizophrenia or paranoid states. CONCLUSION: The results suggest that there is not a difference in the prevalence of non-organic psychiatric disorders among disabled patients of normal intelligence with epilepsy compared with patients with other disabling somatic diseases. However, the data indicate that when psychopathology is present disabled patients with epilepsy are more likely to have psychotic illness than the other disabled patients

Support for involvement of the AHI1 locus in schizophrenia

To access publisher full text version of this article. Please click on the hyperlink in Additional Links fieldRecently, markers in the Abelson Helper Integration Site 1 (AHI1) region were shown to be associated with schizophrenia in a family sample of Israeli-Arabs. Here, we report a study evaluating the relevance of the AHI1 region to schizophrenia in an Icelandic sample. Seven markers shown to confer risk in the previous report were typed in 608 patients diagnosed with broad schizophrenia and 1,504 controls. Odds ratios for the overtransmitted alleles in the Israeli-Arab families ranged from 1.15 to 1.29 in the Icelandic sample. After Bonferroni correction for the seven markers tested, two markers were significantly associated with schizophrenia. Thus, our results are in general agreement with the previous report, with the strongest association signal observed in a region upstream of the AHI1 gene

Genome-wide study of association and interaction with maternal cytomegalovirus infection suggests new schizophrenia loci.

Genetic and environmental components as well as their interaction contribute to the risk of schizophrenia, making it highly relevant to include environmental factors in genetic studies of schizophrenia. This study comprises genome-wide association (GWA) and follow-up analyses of all individuals born in Denmark since 1981 and diagnosed with schizophrenia as well as controls from the same birth cohort. Furthermore, we present the first genome-wide interaction survey of single nucleotide polymorphisms (SNPs) and maternal cytomegalovirus (CMV) infection. The GWA analysis included 888 cases and 882 controls, and the follow-up investigation of the top GWA results was performed in independent Danish (1396 cases and 1803 controls) and German-Dutch (1169 cases, 3714 controls) samples. The SNPs most strongly associated in the single-marker analysis of the combined Danish samples were rs4757144 in ARNTL (P=3.78 × 10(-6)) and rs8057927 in CDH13 (P=1.39 × 10(-5)). Both genes have previously been linked to schizophrenia or other psychiatric disorders. The strongest associated SNP in the combined analysis, including Danish and German-Dutch samples, was rs12922317 in RUNDC2A (P=9.04 × 10(-7)). A region-based analysis summarizing independent signals in segments of 100 kb identified a new region-based genome-wide significant locus overlapping the gene ZEB1 (P=7.0 × 10(-7)). This signal was replicated in the follow-up analysis (P=2.3 × 10(-2)). Significant interaction with maternal CMV infection was found for rs7902091 (P(SNP × CMV)=7.3 × 10(-7)) in CTNNA3, a gene not previously implicated in schizophrenia, stressing the importance of including environmental factors in genetic studies

Lipocalin 2 expression is associated with aggressive features of endometrial cancer

Background: Increased expression of lipocalin 2 (LCN2) has been observed in several cancers. The aim of the present study was to investigate LCN2 in endometrial cancer in relation to clinico-pathologic phenotype, angiogenesis, markers of epithelial-mesenchymal transition (EMT), and patient survival. Methods: Immunohistochemical staining was performed using a human LCN2 antibody on a population-based series of endometrial cancer patients collected in Hordaland County (Norway) during 1981-1990 (n = 256). Patients were followed from the time of primary surgery until death or last follow-up in 2007. The median follow-up time for survivors was 17 years. Gene expression data from a prospectively collected endometrial cancer series (n = 76) and a publicly available endometrial cancer series (n = 111) was used for gene correlation studies. Results: Expression of LCN2 protein, found in 49% of the cases, was associated with non-endometrioid histologic type (p = 0.001), nuclear grade 3 (p = 0.001), >50% solid tumor growth (p = 0.001), ER and PR negativity (p = 0.028 and 0.006), and positive EZH2 expression (p < 0.001). LCN2 expression was significantly associated with expression of VEGF-A (p = 0.021), although not with other angiogenesis markers examined (vascular proliferation index, glomeruloid microvascular proliferation, VEGF-C, VEGF-D or bFGF2 expression). Further, LCN2 was not associated with several EMT-related markers (E-cadherin, N-cadherin, P-cadherin, β-catenin), nor with vascular invasion (tumor cells invading lymphatic or blood vessels). Notably, LCN2 was significantly associated with distant tumor recurrences, as well as with the S100A family of metastasis related genes. Patients with tumors showing no LCN2 expression had the best outcome with 81% 5-year survival, compared to 73% for intermediate and 38% for the small subgroup with strong LCN2 staining (p = 0.007). In multivariate analysis, LCN2 expression was an independent prognostic factor in addition to histologic grade and FIGO stage. Conclusion: Increased LCN2 expression is associated with aggressive features and poor prognosis in endometrial cancer

Evidence for He I 10830 \AA~ absorption during the transit of a warm Neptune around the M-dwarf GJ 3470 with the Habitable-zone Planet Finder

Understanding the dynamics and kinematics of out-flowing atmospheres of hot and warm exoplanets is crucial to understanding the origins and evolutionary history of the exoplanets near the evaporation desert. Recently, ground based measurements of the meta-stable Helium atom's resonant absorption at 10830 \AA~has become a powerful probe of the base environment which is driving the outflow of exoplanet atmospheres. We report evidence for the He I 10830 \AA~in absorption (equivalent width $\sim$ $0.012 \pm 0.002$ \AA) in the exosphere of a warm Neptune orbiting the M-dwarf GJ 3470, during three transits using the Habitable Zone Planet Finder (HPF) near infrared spectrograph. This marks the first reported evidence for He I 10830 \AA\, atmospheric absorption for a planet orbiting an M-dwarf. Our detected absorption is broad and its blueshifted wing extends to -36 km/sec, the largest reported in the literature to date. We modelled the state of Helium atoms in the exosphere of GJ3470b based on assumptions on the UV and X-ray flux of GJ 3470, and found our measurement of flux-weighted column density of meta-stable state Helium $(N_{He^2_3S} = 2.4 \times 10^{10} \mathrm{cm^{-2}})$, derived from our transit observations, to be consistent with model, within its uncertainties. The methodology developed here will be useful to study and constrain the atmospheric outflow models of other exoplanets like GJ 3470b which are near the edge of the evaporation desert.Comment: Accepted in Ap

Association studies of up to 1.2 million individuals yield new insights into the genetic etiology of tobacco and alcohol use.

Tobacco and alcohol use are leading causes of mortality that influence risk for many complex diseases and disorders1. They are heritable2,3 and etiologically related4,5 behaviors that have been resistant to gene discovery efforts6-11. In sample sizes up to 1.2 million individuals, we discovered 566 genetic variants in 406 loci associated with multiple stages of tobacco use (initiation, cessation, and heaviness) as well as alcohol use, with 150 loci evidencing pleiotropic association. Smoking phenotypes were positively genetically correlated with many health conditions, whereas alcohol use was negatively correlated with these conditions, such that increased genetic risk for alcohol use is associated with lower disease risk. We report evidence for the involvement of many systems in tobacco and alcohol use, including genes involved in nicotinic, dopaminergic, and glutamatergic neurotransmission. The results provide a solid starting point to evaluate the effects of these loci in model organisms and more precise substance use measures

Persistent starspot signals on M dwarfs: multi-wavelength Doppler observations with the Habitable-zone Planet Finder and Keck/HIRES

Young, rapidly-rotating M dwarfs exhibit prominent starspots, which create quasiperiodic signals in their photometric and Doppler spectroscopic measurements. The periodic Doppler signals can mimic radial velocity (RV) changes expected from orbiting exoplanets. Exoplanets can be distinguished from activity-induced false positives by the chromaticity and long-term incoherence of starspot signals, but these qualities are poorly constrained for fully-convective M stars. Coherent photometric starspot signals on M dwarfs may persist for hundreds of rotations, and the wavelength dependence of starspot RV signals may not be consistent between stars due to differences in their magnetic fields and active regions. We obtained precise multi-wavelength RVs of four rapidly-rotating M dwarfs (AD Leo, G 227-22, GJ 1245B, GJ 3959) using the near-infrared (NIR) Habitable-zone Planet Finder, and the optical Keck/HIRES spectrometer. Our RVs are complemented by photometry from Kepler, TESS, and the Las Cumbres Observatory (LCO) network of telescopes. We found that all four stars exhibit large spot-induced Doppler signals at their rotation periods, and investigated the longevity and optical-to-NIR chromaticity for these signals. The phase curves remain coherent much longer than is typical for Sunlike stars. Their chromaticity varies, and one star (GJ 3959) exhibits optical and NIR RV modulation consistent in both phase and amplitude. In general, though, we find that the NIR amplitudes are lower than their optical counterparts. We conclude that starspot modulation for rapidly-rotating M stars frequently remains coherent for hundreds of stellar rotations, and gives rise to Doppler signals that, due to this coherence, may be mistaken for exoplanets.Comment: Accepted for publication in the Astrophysical Journa

Genome-wide analyses for personality traits identify six genomic loci and show correlations with psychiatric disorders

Personality is influenced by genetic and environmental factors1 and associated with mental health. However, the underlying genetic determinants are largely unknown. We identified six genetic loci, including five novel loci2,3, significantly associated with personality traits in a meta-analysis of genome-wide association studies (N = 123,132–260,861). Of these genomewide significant loci, extraversion was associated with variants in WSCD2 and near PCDH15, and neuroticism with variants on chromosome 8p23.1 and in L3MBTL2. We performed a principal component analysis to extract major dimensions underlying genetic variations among five personality traits and six psychiatric disorders (N = 5,422–18,759). The first genetic dimension separated personality traits and psychiatric disorders, except that neuroticism and openness to experience were clustered with the disorders. High genetic correlations were found between extraversion and attention-deficit– hyperactivity disorder (ADHD) and between openness and schizophrenia and bipolar disorder. The second genetic dimension was closely aligned with extraversion–introversion and grouped neuroticism with internalizing psychopathology (e.g., depression or anxiety)

Integrated Genomic Analysis of the 8q24 Amplification in Endometrial Cancers Identifies ATAD2 as Essential to MYC-Dependent Cancers

Chromosome 8q24 is the most commonly amplified region across multiple cancer types, and the typical length of the amplification suggests that it may target additional genes to MYC. To explore the roles of the genes most frequently included in 8q24 amplifications, we analyzed the relation between copy number alterations and gene expression in three sets of endometrial cancers (N = 252); and in glioblastoma, ovarian, and breast cancers profiled by TCGA. Among the genes neighbouring MYC, expression of the bromodomain-containing gene ATAD2 was the most associated with amplification. Bromodomain-containing genes have been implicated as mediators of MYC transcriptional function, and indeed ATAD2 expression was more closely associated with expression of genes known to be upregulated by MYC than was MYC itself. Amplifications of 8q24, expression of genes downstream from MYC, and overexpression of ATAD2 predicted poor outcome and increased from primary to metastatic lesions. Knockdown of ATAD2 and MYC in seven endometrial and 21 breast cancer cell lines demonstrated that cell lines that were dependent on MYC also depended upon ATAD2. These same cell lines were also the most sensitive to the histone deacetylase (HDAC) inhibitor Trichostatin-A, consistent with prior studies identifying bromodomain-containing proteins as targets of inhibition by HDAC inhibitors. Our data indicate high ATAD2 expression is a marker of aggressive endometrial cancers, and suggest specific inhibitors of ATAD2 may have therapeutic utility in these and other MYC-dependent cancers