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Methods: Participants were 4,964 youths (ages 5-17 years) from seven international sites, presenting with a wide range of symptom severity (healthy, non-selected, high-risk, or clinically-anxious youth). Participants were assessed using the child-reported Screen for Child Anxiety Related Emotional Disorders, a standard measure with strong psychometric properties for dimensionally assessing symptom severity along domains that follow pediatric anxiety DSM diagnostic categories: generalized anxiety disorder (GAD), separation anxiety disorder (SEP), social anxiety disorder (SOC), and panic disorder (PAN); additionally, school avoidance symptoms (SCH). We then applied computational network analytic tools to quantify the anxiety symptom network structure by estimating the magnitude of unique associations (edges) among symptom domains (nodes) using regularized partial correlations. Differences between networks were tested using permutation tests of network invariance.
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Methods: 3T fMRI data were acquired for three tasks in 36 TD children (mean age=13, range 8-18, 20 males) and 19 children with WS (mean age=13, range 8-18, 5 males). For each trial of the first (Task 1), an aversive scene was presented as a target image at the top of the screen with two possible choices on the bottom, one of which was identical to the target; participants pressed a button to select the matching picture. For each trial of the second (Task 2), two images were shown sequentially, first an image was shown on the left side of the screen, and it disappeared before a second image appeared on the right; participants judged whether the second image was the same as the first and made a button press response. For the third task (Task 3), images of tools were presented one at a time; participants pressed a button when an image was the same as the preceding one. For each task, scrambled images presented in the same way and requiring the same button press served as a sensorimotor control.
Background: It has been suggested that early intervention can improve developmental outcomes of Autism Spectrum disorder (ASD). Delay in the identification of ASD impedes early access to interventions and causes negative developmental outcomes. However, identifying children with ASD is difficult, especially in girls. We need biomarker considering gender differences. Recently, a lot of studies have identified unique gaze fixation patterns in individuals with ASD using eye-tracking systems. Such gaze fixation patterns in individuals with ASD are considered to be associated with social attention. Recently Gaze fixation patterns have attracted attention as the indicator of sociality. The purpose of this study is to clarify the gender difference of gaze fixation patterns in 5-year-old children and analyze these results statistically along with other existing tools, after then to examine the utility for early diagnosis of ASD.
Background: Drug discovery, development and translation for central nervous system disorders pose many unique challenges. Neuropsychiatric disorders have been difficult to treat due to the complexity of the disorders and lack of knowledge that we have of the fundamental biology and pathophysiological underpinnings. We aim to better model neuropsychiatric disorders utilizing human genetic sequencing studies and human induced pluripotent stem cells (hiPSCs). Whole exome and genome sequencing studies have identified disease-causing rare risk variants in patients with high effect size. By introducing the risk variants into hiPSCs using CRISPR/CAS9 genome editing tools and differentiating the cells into neurons, we can study how the variant and gene may be contributing to neuropsychiatric disorders in a human system. We chose to investigate variants in the voltage-gated sodium channel SCN2A (Nav1.2) because it harbors the highest number of risk variants identified in patients with autism, intellectual disorder, and schizophrenia. Variants identified in these patients are predicted to be loss of function. We selected the risk variant V1282F because it has been identified in two unrelated individuals with schizophrenia and is a coding variant. We hypothesize V1282F neurons will have attenuated sodium currents and are interested in uncovering the secondary effects this variant.
Methods: CRISPR/CAS9 genome editing tools were used to introduce disorder-associated risk variants into hiPSCs to create risk and protective variant isogenic human cell lines. hiPSCs were differentiated into neurons and matured for two months. Na currents were measured by whole-cell patch clamp.
Methods: Since 2012, we have been gathering high-quality transcriptomics studies from both public and internal sources, applying consistent preprocessing, QC, normalization and statistical inference procedures to all studies of the same technology platforms, then integrating them into the Janssen BodyMap database. We have implemented various tools to comprehensively profile targets in individual tissues and cells at baselines, changes in diseases, responses to treatments in human animal models. To understand the effect of disease-linked mutations at the cellular level, Cripsr-Cas9 gene editing was performed to introduce the desired base pair change to produce isogenic cell line containing either the protective or risk alleles.
Methods: This was a phase 1, randomised, double-blind, placebo-controlled study to evaluate the effects of 10 mg and 25 mg psilocybin as compared to placebo, in healthy participants, conducted at the Institute of Psychiatry, Psychology and Neuroscience, London, UK. The following assessment tools were administered: Tellegen Absorption Scale (TAS), NEO-Five Factor Inventory (NEO-FFI), Symptom Checklist-90 item (SCL-90), Positive and Negative Affect Schedule (PANAS), Pictorial Empathy Test (PET), Reading the Mind in the Eyes Test (RMET), Social Value Orientation (SVO), Toronto Empathy Questionnaire (TEQ), Scale of Social Responsibility (SSR), Spatial Working Memory (SWM), Rapid Visual Information Processing (RVP), Paired Associates Learning (PAL). Results from these instruments will be presented later. The study planned to recruit 90 participants, aged 18 plus, with no prior psilocybin experience within 1 year of enrolment. Participants were enrolled in the study for 12 weeks following study drug administration. They completed baseline assessments 1 day prior to study drug administration, including assessments of emotional processing and cognitive function. During this visit, they also took part in a 2-hour preparatory group session with the study psychiatrist, lead therapist and chaperones. On Day 0, participants stratified by sex and age (18-35 years old; > 35 years old) were randomised to the study drug (placebo, 10 mg psilocybin, or 25 mg psilocybin, administered orally, in a 1:1:1 ratio.). The sessions lasted approximately 6 hours and were supported by a trained chaperone and were supervised by the study psychiatrist and a lead therapist. The study drug could be administered simultaneously to up to 6 participants. All participants were assessed for safety and asked to complete the PANAS and 5D-Altered States of Consciousness questionnaire (5D-ASC). After the acute effects of study drug administration had subsided, participants returned home, coming back to the clinic the next morning for safety assessments and a discussion about the subjective experience during the session, conducted by study therapists.
Conclusions: The NEP-MDD-201 study did not apply a specific enrichment strategy. However, the inclusion of multidimensional assessments proved valuable because they provided insights across multiple symptom dimensions and because they enabled more robust treatment prediction models. In addition to practical lessons about deployment of these tools in multisite trials, we learned that no single analytical approach is sufficient to predict placebo vs. treatment responders. In fact, explainable models were only achievable through a combination of analytical approaches. Using only baseline data, the XAI analysis identified a group of patients who respond to BTRX246040. Generating an explainable (and testable) rule list creates an opportunity to conduct additional studies in which one can prospectively enrich for patients who are more likely to respond to NOP receptor antagonism. The overall profile of BTRX-246040, with its novel mechanism of action, encourages further clinical development. To best test the enrichment approach, we propose a study design similar to NEP-MDD-201 that applies a rule-based enrichment strategy.
Background: Excessive activity of midbrain dopamine projections is thought to be causal for psychotic experiences such as hallucinations. However, it remains open which neural circuits mediate the observed link between dopamine and hallucinations. Recent methodological developments in neurosciences have yielded powerful tools for the study of midbrain dopamine projections in rodents. To take advantage of these developments, it is crucial to find a reliable behavioural readout of hallucinations in rodents. Here, we built on recent work in human psychosis research relating hallucinations to quantifiable perceptual alterations that are eminently testable in rodents. We aimed at establishing a behavioural paradigm to measure perceptual alterations in rodents as a behavioural readout of hallucinations that would enable the circuit-level interrogation of the observed link between dopamine and hallucinations.
Analysis: "You won't find any advanced stats from Walker's on-field performance that suggest he should be drafted this high. But any analysis of his combine performance puts him as one of the best athletes on the edge of all time. That's a lot of developmental tools to work with."
Analysis: "Having added a game-changing offensive line piece with their first pick in this 2022 NFL Mock Draft, the Giants turn to the defensive side of the ball and do the same. Michigan's David Ojabo has all the pass-rush tools and athletic upside to be a monster in New York. While I believe his Michigan teammate is the better overall prospect, I prefer the schematic fit of Ojabo in the Giants defense."