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Anxiety sensitivity (AS) is implicated in the development and maintenance of several psychopathological conditions. Non-clinical individuals with high autistic traits may develop anxiety disorders and depressive symptoms. Here, we investigated the relationships of autistic traits with AS dimensions and depression, considering sex. We referred to the two-factor model of the autism spectrum quotient to distinguish social and non-social autistic traits and assessed 345 university students on AS and depression scales. Results showed that only social autistic traits predicted general AS and anxiety-related concerns regarding social and cognitive domains. The present results emphasize the need of assessing multiple domains of anxiety in individuals on the autistic spectrum, differentiating social and non-social traits.

In two studies, we used the Gottschaldt’s Hidden Figure Test (GHFT) for assessing figure disembedding ability in children aged 7–11. Study 1 demonstrated in a large sample of typically developing children that GHFT accuracy and time scores differed across age groups, without sex and socioeconomic differences. Thus, we provided normative data only taking into account children’s age. In Study 2, GHFT normative values were used to assess children with autism, who were also compared with a closely age-matched group of typical controls. Children with autism achieved time scores at or above the 50th centile and significantly differed from the controls for time score. The GHFT seems a valuable tool for defining the cognitive profile of children with autism.

Nicotinic signaling regulates top-down circuit maturation and restores attention deficits in mouse model of fragile X syndrome., Cognitive function depends on frontal cortex development; however, the mechanisms driving this process are poorly understood. Here, we identify that dynamic regulation of the nicotinic cholinergic system is a key driver of attentional circuit maturation associated with top-down frontal neurons projecting to visual cortex. The top-down neurons receive robust cholinergic inputs, but their nicotinic tone decreases following adolescence by increasing expression of a nicotinic brake, Lynx1. Lynx1 shifts a balance between local and long-range inputs onto top-down frontal neurons following adolescence and promotes the establishment of attentional behavior in adulthood. This key maturational process is disrupted in a mouse model of fragile X syndrome but was rescued by a suppression of nicotinic tone through the introduction of Lynx1 in top-down projections. Nicotinic signaling may serve as a target to rebalance local/long-range balance and treat cognitive deficits in neurodevelopmental disorders.

Childhood critical periods of experience-dependent plasticity are essential for the development of environmentally appropriate behavior and cognition. Disruption of critical periods can alter development of normal function and confer risk for neurodevelopmental disorders. While genes and their expression relevant to neurodevelopment are associated with schizophrenia, the molecular relationship between schizophrenia and critical periods has not been assessed systematically. Here, we apply a transcriptome-based bioinformatics approach to assess whether genes associated with the human critical period for visual cortex plasticity, a well-studied model of cortical critical periods, are aberrantly expressed in schizophrenia and bipolar disorder. Across two dozen datasets encompassing 522 cases and 374 controls, we find that the majority show aberrations in expression of genes associated with the critical period. We observed both hyper- and hypo-critical period plasticity phenotypes at the transcriptome level, which partially mapped to drug candidates that reverse the disorder signatures in silico. Our findings indicate plasticity aberrations in schizophrenia and their treatment may need to be considered in the context of subpopulations with elevated and others reduced plasticity. Future work should leverage ongoing consortia RNA-sequencing efforts to tease out the sources of plasticity-related transcriptional aberrations seen in schizophrenia, including true biological heterogeneity, interaction between normal development/aging and the disorder, and medication history. Our study also urges innovation towards direct assessment of visual cortex plasticity in humans with schizophrenia to precisely deconstruct the role of plasticity in this disorder.

Background Worldwide, over 14% of individuals hospitalized for psychiatric reasons have readmissions to hospitals within 30 days after discharge. Predicting patients at risk and leveraging accelerated interventions can reduce the rates of early readmission, a negative clinical outcome (i.e., a treatment failure) that affects the quality of life of patient. To implement individualized interventions, it is necessary to predict those individuals at highest risk for 30-day readmission. In this study, our aim was to conduct a data-driven investigation to find the pharmacological factors influencing 30-day all-cause, intra- and interdepartmental readmissions after an index psychiatric admission, using the compendium of prescription data (prescriptome) from electronic medical records (EMR). Methods The data scientists in the project received a deidentified database from the Mount Sinai Data Warehouse, which was used to perform all analyses. Data was stored in a secured MySQL database, normalized and indexed using a unique hexadecimal identifier associated with the data for psychiatric illness visits. We used Bayesian logistic regression models to evaluate the association of prescription data with 30-day readmission risk. We constructed individual models and compiled results after adjusting for covariates, including drug exposure, age, and gender. We also performed digital comorbidity survey using EMR data combined with the estimation of shared genetic architecture using genomic annotations to disease phenotypes. Results Using an automated, data-driven approach, we identified prescription medications, side effects (primary side effects), and drug-drug interaction-induced side effects (secondary side effects) associated with readmission risk in a cohort of 1275 patients using prescriptome analytics. In our study, we identified 28 drugs associated with risk for readmission among psychiatric patients. Based on prescription data, Pravastatin had the highest risk of readmission (OR = 13.10; 95% CI (2.82, 60.8)). We also identified enrichment of primary side effects (n = 4006) and secondary side effects (n = 36) induced by prescription drugs in the subset of readmitted patients (n = 89) compared to the non-readmitted subgroup (n = 1186). Digital comorbidity analyses and shared genetic analyses further reveals that cardiovascular disease and psychiatric conditions are comorbid and share functional gene modules (cardiomyopathy and anxiety disorder: shared genes (n = 37; P = 1.06815E-06)). Conclusions Large scale prescriptome data is now available from EMRs and accessible for analytics that could improve healthcare outcomes. Such analyses could also drive hypothesis and data-driven research. In this study, we explored the utility of prescriptome data to identify factors driving readmission in a psychiatric cohort. Converging digital health data from EMRs and systems biology investigations reveal a subset of patient populations that have significant comorbidities with cardiovascular diseases are more likely to be readmitted. Further, the genetic architecture of psychiatric illness also suggests overlap with cardiovascular diseases. In summary, assessment of medications, side effects, and drug-drug interactions in a clinical setting as well as genomic information using a data mining approach could help to find factors that could help to lower readmission rates in patients with mental illness.

High and increasing prevalence of neurodevelopmental disorders place enormous personal and economic burdens on society. Given the growing realization that the roots of neurodevelopmental disorders often lie in early childhood, there is an urgent need to identify childhood risk factors. Neurodevelopment is marked by periods of heightened experience-dependent neuroplasticity wherein neural circuitry is optimized by the environment. If these critical periods are disrupted, development of normal brain function can be permanently altered, leading to neurodevelopmental disorders. Here, we aim to systematically identify human variants in neuroplasticity-related genes that confer risk for neurodevelopmental disorders. Historically, this knowledge has been limited by a lack of techniques to identify genes related to neurodevelopmental plasticity in a high-throughput manner and a lack of methods to systematically identify mutations in these genes that confer risk for neurodevelopmental disorders. Using an integrative genomics approach, we determined loss-of-function (LOF) variants in putative plasticity genes, identified from transcriptional profiles of brain from mice with elevated plasticity, that were associated with neurodevelopmental disorders. From five shared differentially expressed genes found in two mouse models of juvenile-like elevated plasticity (juvenile wild-type or adult Lynx1-/- relative to adult wild-type) that were also genotyped in the Mount Sinai BioMe Biobank we identified multiple associations between LOF genes and increased risk for neurodevelopmental disorders across 10,510 patients linked to the Mount Sinai Electronic Medical Records (EMR), including epilepsy and schizophrenia. This work demonstrates a novel approach to identify neurodevelopmental risk genes and points toward a promising avenue to discover new drug targets to address the unmet therapeutic needs of neurodevelopmental disease.

Visual Abstract, Throughout childhood and adolescence, periods of heightened neuroplasticity are critical for the development of healthy brain function and behavior. Given the high prevalence of neurodevelopmental disorders, such as autism, identifying disruptors of developmental plasticity represents an essential step for developing strategies for prevention and intervention. Applying a novel computational approach that systematically assessed connections between 436 transcriptional signatures of disease and multiple signatures of neuroplasticity, we identified inflammation as a common pathological process central to a diverse set of diseases predicted to dysregulate plasticity signatures. We tested the hypothesis that inflammation disrupts developmental cortical plasticity in vivo using the mouse ocular dominance model of experience-dependent plasticity in primary visual cortex. We found that the administration of systemic lipopolysaccharide suppressed plasticity during juvenile critical period with accompanying transcriptional changes in a particular set of molecular regulators within primary visual cortex. These findings suggest that inflammation may have unrecognized adverse consequences on the postnatal developmental trajectory and indicate that treating inflammation may reduce the burden of neurodevelopmental disorders.

Background: Low adherence to treatment in Multiple Sclerosis (MS) has been shown to lead to poor health outcomes. Various strategies to improve adherence have been suggested including educative programs, injection devices and dedicated nurse assistance. Objective: To assess the impact of elements of the patient support program on adherence; to explore disease factors affecting adherence; and to determine whether these factors influence the choices of supportive elements. Methods: A prospective, observational cohort study was conducted. MS patients were eligible if they had switched to Interferon beta-1b (IFNB-1b) between 1 and 3 months prior to inclusion. Data were collected at months 6, 12, 18 and 24 after inclusion. Adherence was defined as completion of both study protocol and medication at 24 months. Patients underwent evaluations of disability, quality of life, depression, and coping styles. Results: A total of 1077 patients from 15 countries were included, of which 61.8% were adherent to IFNB-1b after 24-months. Depression, quality of life and autoinjector devices were baseline predictors of adherence at 24-months. Coping styles did not show to have substantial impact on adherence. Lower quality of life increased the probability of choosing supportive elements. Conclusion: The study showed that the usage of autoinjector devices chosen during the study was the strongest predictor of drug adherence of all the supportive elements tested in this study. (C) 2011 Elsevier B.V. All rights reserved.

BACKGROUND: The aim of the Betaferon Efficacy Yielding Outcomes of a New Dose (BEYOND) trial was to compare the efficacy, safety, and tolerability of 250 microg or 500 microg interferon beta-1b with glatiramer acetate for treating relapsing-remitting multiple sclerosis. METHODS: Between November, 2003, and June, 2005, 2447 patients with relapsing-remitting multiple sclerosis were screened and 2244 patients were enrolled in this prospective, multicentre, randomised trial. Patients were randomly assigned 2:2:1 by block randomisation with regional stratification to receive one of two doses of interferon beta-1b (250 microg or 500 microg) subcutaneously every other day or 20 mg glatiramer acetate subcutaneously every day. The primary outcome was relapse risk, defined as new or recurrent neurological symptoms separated by at least 30 days from the preceding event and that lasted at least 24 h. Secondary outcomes were progression on the expanded disability status scale (EDSS) and change in T1-hypointense lesion volume. Clinical outcomes were assessed quarterly for 2.0-3.5 years; MRI was done at screening and annually thereafter. Analysis was by per protocol. This study is registered, number NCT00099502. FINDINGS: We found no differences in relapse risk, EDSS progression, T1-hypointense lesion volume, or normalised brain volume among treatment groups. Flu-like symptoms were more common in patients treated with interferon beta-1b (p

BACKGROUND: The effect of carotid endarterectomy in lowering the risk of stroke ipsilateral to severe atherosclerotic carotid-artery stenosis is offset by complications during or soon after surgery. We compared surgery under general anaesthesia with that under local anaesthesia because prediction and avoidance of perioperative strokes might be easier under local anaesthesia than under general anaesthesia. METHODS: We undertook a parallel group, multicentre, randomised controlled trial of 3526 patients with symptomatic or asymptomatic carotid stenosis from 95 centres in 24 countries. Participants were randomly assigned to surgery under general (n=1753) or local (n=1773) anaesthesia between June, 1999 and October, 2007. The primary outcome was the proportion of patients with stroke (including retinal infarction), myocardial infarction, or death between randomisation and 30 days after surgery. Analysis was by intention to treat. The trial is registered with Current Control Trials number ISRCTN00525237. FINDINGS: A primary outcome occurred in 84 (4.8%) patients assigned to surgery under general anaesthesia and 80 (4.5%) of those assigned to surgery under local anaesthesia; three events per 1000 treated were prevented with local anaesthesia (95% CI -11 to 17; risk ratio [RR] 0.94 [95% CI 0.70 to 1.27]). The two groups did not significantly differ for quality of life, length of hospital stay, or the primary outcome in the prespecified subgroups of age, contralateral carotid occlusion, and baseline surgical risk. INTERPRETATION: We have not shown a definite difference in outcomes between general and local anaesthesia for carotid surgery. The anaesthetist and surgeon, in consultation with the patient, should decide which anaesthetic technique to use on an individual basis. FUNDING: The Health Foundation (UK) and European Society of Vascular Surgery.

The effect of pituitrin on the pregnant uterus in the latter part of gestation is well known. In recent years the response of the uterus in its different physiologic phases to pituitrin and its oxytocic principle—pitocin has been studied experimentally and clinically. As a result of this more recent work, the reaction of the uterus in early pregnancy to posterior lobe extracts and especially to pitocin is now described as a means of diagnosing pregnancy and of differentiating the pregnant uterus from other abdominal or pelvic tumors. Since many of the experimental and clinical observations are not in entire agreement, it seemed worth while to undertake some studies of our own to test the merits of this method as a test for pregnancy in the human. In this paper we shall describe, for the most part, the response of the uterus in early pregnancy to the intravenous injection of pitocin and also reference will be made to the use of the method as a means of differential diagnosis.

An evaluation was carried out of the effect of domperidone on gastro-intestinal symptoms in patients with irritable bowel syndrome. Ninety-eight patients were included; 32 in an open pilot study and 66 in a double-blind placebo-controlled study. Domperidone was taken at a dosage of 10 mg tablets 4-times daily. At the end of the 4-week treatment, symptoms had disappeared or were at least markedly improved in about 80% of the domperidone-treated patients. Significant superiority of domperidone to the placebo was observed for the symptom clusters 'post-prandial flatulence', 'abdominal pain' and 'abnormal bowel habit'. No side-effects were reported.

In this study, an IgM monoclonal antibody (MAb600D11) directed against human small cell lung cancer (NCI-H69) was radiolabeled with iodine-131, and the biodistribution and image quality of the radiolabeled antibody was evaluated. Radiolabeling was achieved in a solid-phase system consisting of 1,3,4,6-tetrachloro-3a,6a-diphenylglycoluril. Labeling efficiencies and protein purification were accomplished using gel exclusion chromatography while radioimmunoreactivity was determined using a solid-phase radioimmunoassay procedure. The biodistribution of I-131-labeled MAbs was determined in Sprague-Dawley rats up to 7 days after injection. Highest organ concentrations were observed in liver (3.91 +/- 0.47 (SD) and 0.17 +/- 0.04 (SD) mean percent injected dose at 1-7 days after injections) and in thyroid (5.33 +/- 0.71 (SD) and 5.32 +/- 2.01 (SD) mean percent injected dose at 1-7 days after injection). Nude mice, bearing either a small cell lung tumor (NCI-H69) or a nonspecific tumor (adenocarcinoma), were injected with 400-800 microCi of I-131 labeled monoclonal antibody. Optimum tumor visualization was observed 2-4 days after injection with tumor concentrations as high as 10.4% of the initial injected dose. The results demonstrated that radioimmunoimaging of human small cell lung carcinoma was feasible with the tumor-specific IgM I-131-labeled MAb.

A laboratory procedure for the diagnosis of pregnancy has been a subject of interest to obstetricians for many years. The early work in this field, which seemed most promising at first, has been shown to have little or no practical value. Since then, advances in physiology and endocrinology have added much to our knowledge of the function of the ductless glands and of their physiologic changes during pregnancy. It is on this fundamental work that the pregnancy tests of Aschheim and Zondek, of Brouha and of Friedman depend. In this study these three reactions, as well as the empiric reactions of Bercovitz and of Manoilov, have been performed, so far as possible, on each individual in a series of pregnant and nonpregnant patients. It is our purpose to ascertain their relative values as diagnostic procedures in gynecologic as well as obstetric cases. A large amount of experimental work has been