Psychiatric comorbidities in Asperger syndrome are related with polygenic overlap and differ from other Autism subtypes

There is great phenotypic heterogeneity within autism spectrum disorders (ASD), which has led to question their classification into a single diagnostic category. The study of the common genetic variation in ASD has suggested a greater contribution of other psychiatric conditions in Asperger syndrome (AS) than in the rest of the DSM-IV ASD subtypes (Non_AS). Here, using available genetic data from previously performed genome-wide association studies (GWAS), we aimed to study the genetic overlap between five of the most related disorders (schizophrenia (SCZ), major depression disorder (MDD), attention deficit hyperactivity disorder (ADHD), obsessive-compulsive disorders (OCD) and anxiety (ANX)), and AS, comparing it with the overlap in Non_AS subtypes. A Spanish cohort of autism trios (N = 371) was exome sequenced as part of the Autism Sequencing Consortium (ASC) and 241 trios were extensively characterized to be diagnosed with AS following DSM-IV and Gillberg's criteria (N = 39) or not (N = 202). Following exome imputation, polygenic risk scores (PRS) were calculated for ASD, SCZ, ADHD, MDD, ANX, and OCD (from available summary data from Psychiatric Genomic Consortium (PGC) repository) in the Spanish trios' cohort. By using polygenic transmission disequilibrium test (pTDT), we reported that risk for SCZ (Pscz = 0.008, corrected-PSCZ = 0.0409), ADHD (PADHD = 0.021, corrected-PADHD = 0.0301), and MDD (PMDD = 0.039, corrected-PMDD = 0.0501) is over-transmitted to children with AS but not to Non_AS. Indeed, agnostic clustering procedure with deviation values from pTDT tests suggested two differentiated clusters of subjects, one of which is significantly enriched in AS (P = 0.025). Subsequent analysis with S-Predixcan, a recently developed software to predict gene expression from genotype data, revealed a clear pattern of correlation between cortical gene expression in ADHD and AS (P < 0.001) and a similar strong correlation pattern between MDD and AS, but also extendable to another non-brain tissue such as lung (P < 0.001). Altogether, these results support the idea of AS being qualitatively distinct from Non_AS autism and consistently evidence the genetic overlap between AS and ADHD, MDD, or SCZ

Anti-tumour necrosis factor discontinuation in inflammatory bowel disease patients in remission: study protocol of a prospective, multicentre, randomized clinical trial

Background: Patients with inflammatory bowel disease who achieve remission with anti-tumour necrosis factor (anti-TNF) drugs may have treatment withdrawn due to safety concerns and cost considerations, but there is a lack of prospective, controlled data investigating this strategy. The primary study aim is to compare the rates of clinical remission at 1?year in patients who discontinue anti-TNF treatment versus those who continue treatment. Methods: This is an ongoing, prospective, double-blind, multicentre, randomized, placebo-controlled study in patients with Crohn?s disease or ulcerative colitis who have achieved clinical remission for ?6?months with an anti-TNF treatment and an immunosuppressant. Patients are being randomized 1:1 to discontinue anti-TNF therapy or continue therapy. Randomization stratifies patients by the type of inflammatory bowel disease and drug (infliximab versus adalimumab) at study inclusion. The primary endpoint of the study is sustained clinical remission at 1?year. Other endpoints include endoscopic and radiological activity, patient-reported outcomes (quality of life, work productivity), safety and predictive factors for relapse. The required sample size is 194 patients. In addition to the main analysis (discontinuation versus continuation), subanalyses will include stratification by type of inflammatory bowel disease, phenotype and previous treatment. Biological samples will be obtained to identify factors predictive of relapse after treatment withdrawal. Results: Enrolment began in 2016, and the study is expected to end in 2020. Conclusions: This study will contribute prospective, controlled data on outcomes and predictors of relapse in patients with inflammatory bowel disease after withdrawal of anti-TNF agents following achievement of clinical remission. Clinical trial reference number: EudraCT 2015-001410-1

Effect of replacing dietary corn with beet pulp on energy partitioning, substrate oxidation and methane production in lactating dairy goats

The objective of this experiment was to study the effect of substitution of corn by beet pulp on energy partitioning, substrate oxidation, nitrogen and carbon balance and milk performance in dairy goats during late lactation. Twelve multiparous lactating Murciano-Granadina goats were fed two diets. Six goats were fed a mixed ration with 310 g/kg DM of ground corn (diet CORN) and in the other diet the corn was substituted with 302 g/kg DM of beet pulp (diet BP) in a cross-over design. No significant differences between diets were observed for milk production (1.36 kg/day, on average) and differences were found for milk fat (5.39 and 4.21% for BP and CORN, respectively). The metabolisable energy intake was higher (P < 0.05) in the CORN diet than BP (1320 vs 1044 kJ/kg(0.75) BW, respectively). The difference in methane emissions between treatments was significant (P < 0.05) with values of 92 vs 61 kJ/kg(0.75) BW for BP and CORN, respectively, indicating that greater levels of starch in diet reduce methane production. Replacing corn with BP reduced significantly the energy body fat deposition (300 vs 44 kJ/kg(0.75) BW for CORN and BP diets, respectively). This reduction in energy retention for the BP diet did not compromise milk yield and milk energy output.This study was supported by INIA Project (ref. RTA2011-00107-C02-02).Ibáñez Sanchis, C.; López Luján, MDC.; Criscioni Ferreira, PF.; Fernández Martínez, CJ. (2015). Effect of replacing dietary corn with beet pulp on energy partitioning, substrate oxidation and methane production in lactating dairy goats. Animal Production Science. 55(1):56-63. https://doi.org/10.1071/AN13119S566355