Effect of D2R, NMDAR and CB1R genetic variants associated with cannabis use and childhood trauma in first-episode psychosis in a Brazilian population [abstract only]

Introduction Gene-environment interactions increase psychosis risk (Gayer-Anderson et al. Soc Psychiatry Psychiatr Epidemiol 2020; 55(5):645-657). However, identifying the genetic variants involved and how they interact with environmental risk factors underlying psychosis remains challenging. Objectives To investigate whether there are gene-environment interactions in the relationships of childhood trauma, lifetime cannabis use, and single nucleotide variants (SNVs) of dopamine D2 receptor (D2R: DRD2), N-methyl-d-aspartate receptor (NMDAR: GRIN1, GRIN2A and GRIN2B) and cannabinoid receptor type 1 (CB1R: CNR1) with psychosis. Methods In a population-based case-control study nested in an incident study (STREAM, Brazil) (Del-Ben et al. Br J of Psychiatry 2019; 215(6):726-729), part of the EU-GEI consortium (Gayer-Anderson et al. Soc Psychiatry Psychiatr Epidemiol 2020; 55(5):645-657), 143 first-episode psychosis patients and 286 community-based controls of both sexes aged between 16 and 64 years were included over a period of 3 years. Twenty-three SNVs of D2R (rs1799978, rs7131056, rs6275), NMDAR (GRIN1: rs4880213, rs11146020; GRIN2A: rs1420040, rs11866328; GRIN2B: rs890, rs2098469, rs7298664), and CB1R genes (CNR1: rs806380, rs806379, rs1049353, rs6454674, rs1535255, rs2023239, rs12720071, rs6928499, rs806374, rs7766029, rs806378, rs10485170, rs9450898), were genotyped from peripheral blood DNA using a custom Illumina HumanCoreExome-24 BeadChip. Environmental adversities were evaluated using the Cannabis Experience Questionnaire (Di Forti et al. The Lancet Psychiatry 2009; 6(5):427–436) and the Childhood Trauma Questionnaire (Grassi-Oliveira et al. Rev Saude Publica 2006; 40(2):249-55). Associations between SNVs and environmental risk factors were performed using the nonparametric multifactor dimensionality reduction software (version 3.0.2). Results Single locus analysis showed no association among the 23 SNVs with psychosis; however, gene-environment analysis was significant for the polymorphic loci rs12720071 and rs7766029 in CNR1. The best association models were the two-factor representing by the combination of CNR1 rs12720071 with lifetime cannabis use (p<0.001), and CNR1 rs12720071 with childhood trauma (p<0.05), both suggesting an increased risk of psychosis. Additionally, when considering the interaction of both environmental factors in the same model, we found CNR1 rs7766029 to be associated with psychosis (p<0.001). Conclusions Our study supports the hypothesis of gene-environment interactions for psychosis involving the T allele carriers of CNR1 SNVs (rs12720071 and rs7766029), childhood trauma and lifetime cannabis use in psychosis

Totally laparoscopic, multi-stage, restorative proctocolectomy for inflammatory bowel diseases. A prospective study on safety, efficacy and long-term results

Background: Laparoscopic ileo-pouch-anal anastomosis (IPAA) has been reported as having low morbidity and several advantages. Aims: To evaluate safety, efficacy and long-term results of laparoscopic IPAA, performed in elective or emergency settings, in consecutive unselected IBD patients. Methods: All the patients received totally laparoscopic 2-stage (proctocolectomy and IPAA \u2013 stoma closure) or 3-stage (colectomy \u2013 proctectomy and IPAA \u2013 stoma closure) procedure according to their presentation. Results: From July 2007 to July 2016, 160 patients entered the study. 50.6% underwent a 3-stage procedure and 49.4% a 2-stage procedure. Mortality and morbidity were 0.6% and 24.6%. Conversion rate was 3.75%. 8.7% septic complications were associated with steroids and Infliximab treatment (p = 0.0001). 3-stage patients were younger (p = 0.0001), with shorter disease duration (p = 0.0001), minor ASA scores of 2 and 3 (p = 0.0007), lower inflammatory index and better nutritional status (p = 0.003 and 0.0001), fewer Clavien-Dindo's grade II complications (p = .0001), reduced rates of readmission and reoperation at 90 days (p = 0.03), and shorter hospitalization (p = .0001), but with similar pouch and IPAA leakage, compared to 2-stage patients. 8 years pouch failure and definitive ileostomy were 5.1% and 3.7%. Conclusion: A totally laparoscopic approach is safe and feasible, with very low mortality and morbidity rates and very low conversion rate, even in multi-stage procedures and high-risk patients

Gene and environmental risk factors: interplay between CNR1 genetic variants cannabis use, childhood trauma and psychosis [abstract only]

Background: Cannabis use and childhood trauma have been proposed as environmental risk factors for psychosis and its known that gene-environment (G×E) interactions increase the risk of psychosis [1]. In particular, a recent finding suggests a link between genetic variants in the cannabinoid receptor type 1 (CNR1) gene, which encodes CB1 receptors and is expressed widely in the central and peripheral systems, and cannabis playing a role in the multifactorial pathogenesis of psychosis [2]. However, how the genetic variants interact with lifetime cannabis use and other environmental risk factors, such as childhood trauma, underlying psychosis remains challenging. Objective: To investigate whether there are associations of gene and environmental factors with psychosis, as well as G×E interactions in the relationship between lifetime cannabis use, childhood trauma, and single nucleotide variants (SNVs) of CNR1 and psychosis in a Brazilian sample. Methods: In a population-based case-control study nested in an incident study (STREAM, Brazil) [3], part of the WP2 EU-GEI consortium, 143 first-episode psychosis patients (FEPp) and 286 community-based controls of both sexes, aged between 16 and 64 years, were included over a period of three years. Thirteen SNVs of CNR1 gene (rs806380, rs806379, rs1049353, rs6454674, rs1535255, rs2023239, rs12720071, rs6928499, rs806374, rs7766029, rs806378, rs10485170, rs9450898), were genotyped from peripheral blood DNA using a custom Illumina HumanCoreExome-24 BeadChip genotyping arrays (GWAS Cardiff chip). Environmental adversities were evaluated using the Cannabis Experience and the Childhood Trauma Questionnaires. Data were analysed using a binary logistic regression model (Adj OR, 95% CI), including a binary outcome (community-based controls and FEPp), adjusted by sex, age, skin colour, years of education and tobacco smoking. Genotype frequencies were analysed under the dominant model (homozygous ancestral x heterozygous + homozygous variant). The significance level was set at α≤0.05. Results: Lifetime cannabis use and childhood trauma increased the risk for psychosis (OR=3.7; 2.6-6.195% CI, p<0.001; OR=3.0; 1.9-4.7 95% CI, p<0.001, respectively). We also showed that the presence of CNR1 rs12720071-T-allele moderated the association between lifetime cannabis use and psychosis (OR=6.0; 2.0-17.5 95% CI; p=0.001). Moreover, the combination of CNR1 rs12720071-T-allele carriers with childhood trauma also suggests a change in the risk of psychosis (OR=3.6; 1.4-9.0 95% CI; p=0.006). No significant associations between the environmental factors and other SNVs were found. Conclusions: We demonstrated a significant interaction between CNR1 rs12720071 SNV and two important environmental risk factors in their association with psychosis. T allele carriers of CNR1 rs12720071 had a higher risk of psychosis when lifetime cannabis use or childhood trauma were present. Our results suggest a G×E interaction involving the CNR1 gene, trauma and cannabis in psychosis. We will explore the associations between genetic and epigenetic markers of the CNR1 gene with environmental factors in larger and longer follow-up cohorts to better understand the mechanisms of endocannabinoid system dysfunction in the etiology of psychosis

Effects of sleep deprivation on neural functioning: an integrative review

Sleep deprivation has a broad variety of effects on human performance and neural functioning that manifest themselves at different levels of description. On a macroscopic level, sleep deprivation mainly affects executive functions, especially in novel tasks. Macroscopic and mesoscopic effects of sleep deprivation on brain activity include reduced cortical responsiveness to incoming stimuli, reflecting reduced attention. On a microscopic level, sleep deprivation is associated with increased levels of adenosine, a neuromodulator that has a general inhibitory effect on neural activity. The inhibition of cholinergic nuclei appears particularly relevant, as the associated decrease in cortical acetylcholine seems to cause effects of sleep deprivation on macroscopic brain activity. In general, however, the relationships between the neural effects of sleep deprivation across observation scales are poorly understood and uncovering these relationships should be a primary target in future research

All-sky search for long-duration gravitational wave transients with initial LIGO

We present the results of a search for long-duration gravitational wave transients in two sets of data collected by the LIGO Hanford and LIGO Livingston detectors between November 5, 2005 and September 30, 2007, and July 7, 2009 and October 20, 2010, with a total observational time of 283.0 days and 132.9 days, respectively. The search targets gravitational wave transients of duration 10-500 s in a frequency band of 40-1000 Hz, with minimal assumptions about the signal waveform, polarization, source direction, or time of occurrence. All candidate triggers were consistent with the expected background; as a result we set 90% confidence upper limits on the rate of long-duration gravitational wave transients for different types of gravitational wave signals. For signals from black hole accretion disk instabilities, we set upper limits on the source rate density between 3.4×10-5 and 9.4×10-4 Mpc-3 yr-1 at 90% confidence. These are the first results from an all-sky search for unmodeled long-duration transient gravitational waves. © 2016 American Physical Society

Narrowband Searches for Continuous and Long-duration Transient Gravitational Waves from Known Pulsars in the LIGO-Virgo Third Observing Run

Isolated neutron stars that are asymmetric with respect to their spin axis are possible sources of detectable continuous gravitational waves. This paper presents a fully coherent search for such signals from eighteen pulsars in data from LIGO and Virgo's third observing run (O3). For known pulsars, efficient and sensitive matched-filter searches can be carried out if one assumes the gravitational radiation is phase-locked to the electromagnetic emission. In the search presented here, we relax this assumption and allow both the frequency and the time derivative of the frequency of the gravitational waves to vary in a small range around those inferred from electromagnetic observations. We find no evidence for continuous gravitational waves, and set upper limits on the strain amplitude for each target. These limits are more constraining for seven of the targets than the spin-down limit defined by ascribing all rotational energy loss to gravitational radiation. In an additional search, we look in O3 data for long-duration (hours-months) transient gravitational waves in the aftermath of pulsar glitches for six targets with a total of nine glitches. We report two marginal outliers from this search, but find no clear evidence for such emission either. The resulting duration-dependent strain upper limits do not surpass indirect energy constraints for any of these targets. © 2022. The Author(s). Published by the American Astronomical Society

All-sky search for long-duration gravitational wave transients with initial LIGO

We present the results of a search for long-duration gravitational wave transients in two sets of data collected by the LIGO Hanford and LIGO Livingston detectors between November 5, 2005 and September 30, 2007, and July 7, 2009 and October 20, 2010, with a total observational time of 283.0 days and 132.9 days, respectively. The search targets gravitational wave transients of duration 10-500 s in a frequency band of 40-1000 Hz, with minimal assumptions about the signal waveform, polarization, source direction, or time of occurrence. All candidate triggers were consistent with the expected background; as a result we set 90% confidence upper limits on the rate of long-duration gravitational wave transients for different types of gravitational wave signals. For signals from black hole accretion disk instabilities, we set upper limits on the source rate density between 3.4×10-5 and 9.4×10-4 Mpc-3 yr-1 at 90% confidence. These are the first results from an all-sky search for unmodeled long-duration transient gravitational waves. © 2016 American Physical Society

Search for Gravitational Waves Associated with Gamma-Ray Bursts Detected by Fermi and Swift during the LIGO-Virgo Run O3b

We search for gravitational-wave signals associated with gamma-ray bursts (GRBs) detected by the Fermi and Swift satellites during the second half of the third observing run of Advanced LIGO and Advanced Virgo (2019 November 1 15:00 UTC-2020 March 27 17:00 UTC). We conduct two independent searches: A generic gravitational-wave transients search to analyze 86 GRBs and an analysis to target binary mergers with at least one neutron star as short GRB progenitors for 17 events. We find no significant evidence for gravitational-wave signals associated with any of these GRBs. A weighted binomial test of the combined results finds no evidence for subthreshold gravitational-wave signals associated with this GRB ensemble either. We use several source types and signal morphologies during the searches, resulting in lower bounds on the estimated distance to each GRB. Finally, we constrain the population of low-luminosity short GRBs using results from the first to the third observing runs of Advanced LIGO and Advanced Virgo. The resulting population is in accordance with the local binary neutron star merger rate. © 2022. The Author(s). Published by the American Astronomical Society

Search for gravitational waves from Scorpius X-1 in the second Advanced LIGO observing run with an improved hidden Markov model

We present results from a semicoherent search for continuous gravitational waves from the low-mass x-ray binary Scorpius X-1, using a hidden Markov model (HMM) to track spin wandering. This search improves on previous HMM-based searches of LIGO data by using an improved frequency domain matched filter, the J-statistic, and by analyzing data from Advanced LIGO's second observing run. In the frequency range searched, from 60 to 650 Hz, we find no evidence of gravitational radiation. At 194.6 Hz, the most sensitive search frequency, we report an upper limit on gravitational wave strain (at 95% confidence) of h095%=3.47×10-25 when marginalizing over source inclination angle. This is the most sensitive search for Scorpius X-1, to date, that is specifically designed to be robust in the presence of spin wandering. © 2019 American Physical Society