Thalamic and prefrontal GABA concentrations but not GABAA receptor densities are altered in high-functioning adults with autism spectrum disorder.

The gamma aminobutyric acid (GABA) neurotransmission system has been implicated in autism spectrum disorder (ASD). Molecular neuroimaging studies incorporating simultaneous acquisitions of GABA concentrations and GABAA receptor densities can identify objective molecular markers in ASD. We measured both total GABAA receptor densities by using [18F]flumazenil positron emission tomography ([18F]FMZ-PET) and GABA concentrations by using proton magnetic resonance spectroscopy (1H-MRS) in 28 adults with ASD and 29 age-matched typically developing (TD) individuals. Focusing on the bilateral thalami and the left dorsolateral prefrontal cortex (DLPFC) as our regions of interest, we found no differences in GABAA receptor densities between ASD and TD groups. However, 1H-MRS measurements revealed significantly higher GABA/Water (GABA normalized by water signal) in the left DLPFC of individuals with ASD than that of TD controls. Furthermore, a significant gender effect was observed in the thalami, with higher GABA/Water in males than in females. Hypothesizing that thalamic GABA correlates with ASD symptom severity in gender-specific ways, we stratified by diagnosis and investigated the interaction between gender and thalamic GABA/Water in predicting Autism-Spectrum Quotient (AQ) and Ritvo Autism Asperger's Diagnostic Scale-Revised (RAADS-R) total scores. We found that gender is a significant effect modifier of thalamic GABA/Water's relationship with AQ and RAADS-R scores for individuals with ASD, but not for TD controls. When we separated the ASD participants by gender, a negative correlation between thalamic GABA/Water and AQ was observed in male ASD participants. Remarkably, in female ASD participants, a positive correlation between thalamic GABA/Water and AQ was found.

Self-Reported Speeding Among New York City Adult Drivers, 2015-2016.

Motor vehicle crashes are a leading cause of injury related deaths. Urban areas accommodate multiple road users and pedestrians account for a larger share of traffic fatalities. Speed reduction has been one component of New York City's multidisciplinary approach to reduce traffic fatalities-Vision Zero. Data from the New York City (NYC) Community Health Survey 2015-2016 were used to document population-based estimates of self-reported speeding (defined as driving ten miles per hour or more over the posted speed limit in the past 30 days) among NYC adult drivers collected soon after the adoption of Vision Zero in 2014. Self-reported speeding is common, with nearly two-thirds (63%) of adult drivers indicating they ever sped and 13% often speeding. In adjusted multivariable models, often speeding was more common among younger drivers vs. older drivers (adjusted prevalence ratio: 2.77; 95%CI 1.93-3.98), males vs. females (adjusted prevalence ratio: 1.59; 95%CI 1.35-1.87), wealthier drivers vs. poorer drivers (adjusted prevalence ratio: 1.37; 95%CI 1.10-1.70) and those reporting worse perceived social cohesion vs. better perceived social cohesion (adjusted prevalence ratio 1.51; 95%CI 1.09-2.10). Population-based health surveys facilitate exploration of a range of potential influences on health behaviors.

Pilot study of patron sound level exposure in loud restaurants, bars, and clubs in New York city.

Visiting restaurants, bars, clubs, and lounges is a regular part of urban cultural life for residents and tourists alike; however, anecdotal reports and diner surveys suggest that sound levels are excessive and diners dislike them. High sound levels in these venues can contribute to both patron and employee overexposure, and young people may be particularly at risk. To supplement the paucity of literature and data on noise in urban venues, patron noise exposure was measured inside a sample of loud New York City restaurants, bars, clubs, and lounges. Sound level measurements were obtained in 59 venues. Field staff conducted one 20-162 minute visit per venue on a Thursday, Friday, or Saturday evening. The equivalent continuous sound pressure level on the A-scale (LAeq) was calculated for each visit. Median and mean LAeq among all venues sampled were both 92 decibels (dBA). Clubs and lounges had a higher mean LAeq than restaurants and bars (97 vs. 91 dBA, p < 0.05). A greater number of patrons was associated with a higher LAeq. Higher LAeq values were observed during later hours of the evening (9 PM and later). For 80% (N = 47) of the venues, the LAeq was above 85 dBA. In 49% (N = 29) of the venues, the visit exceeded the maximum allowable daily noise dose based on National Institute of Occupational Safety and Health (NIOSH) Recommended Exposure Limit (REL) of 85 dBA 8-hr Time-Weighted Average (TWA). Venues should assess indoor sound levels including employee exposure and aim to maintain sound levels that are within NIOSH guidelines.

Attitudes toward neuroscience education in psychiatry: a national multi-stakeholder survey.

OBJECTIVE: The objective of this study is to assess the attitudes of chairs of psychiatry departments, psychiatrists, and psychiatry trainees toward neuroscience education in residency programs and beyond in order to inform future neuroscience education approaches. METHOD: This multi-stakeholder survey captured data on demographics, self-assessments of neuroscience knowledge, attitudes toward neuroscience education, preferences in learning modalities, and interests in specific neuroscience topics. In 2012, the authors distributed the surveys: by paper to 133 US psychiatry department chairs and electronically through the American Psychiatric Association to 3,563 of its members (1,000 psychiatrists and 2,563 trainees). RESULTS: The response rates for the chair, psychiatrist, and trainee surveys were 53, 9, and 18 %, respectively. A large majority of respondents agreed with the need for more neuroscience education in general and with respect to their own training. Most respondents believed that neuroscience will help destigmatize mental illness and begin producing new treatments or personalized medicines in 5-10 years. Only a small proportion of trainees and psychiatrists, however, reported a strong knowledge base in neuroscience. Respondents also reported broad enthusiasm for transdiagnostic topics in neuroscience (such as emotion regulation and attention/cognition) and description at the level of neural circuits. CONCLUSIONS: This study demonstrates the opportunity and enthusiasm for teaching more neuroscience in psychiatry among a broad range of stakeholder groups. A high level of interest was also found for transdiagnostic topics and approaches. We suggest that a transdiagnostic framework may be an effective way to deliver neuroscience education to the psychiatric community and illustrate this through a case example, drawing the similarity between this neuroscience approach and problem-based formulations familiar to clinicians.

Attitudes toward neuroscience education among psychiatry residents and fellows.

OBJECTIVE: The purpose of this study is to assess the attitudes of psychiatry trainees toward neuroscience education in psychiatry residency and subsequent training in order to inform neuroscience education approaches in the future. METHODS: This online survey was designed to capture demographic information, self-assessed neuroscience knowledge, attitudes toward neuroscience education, preferences in learning modalities, and interest in specific neuroscience topics. Volunteers were identified through the American Psychiatric Association, which invited 2,563 psychiatry trainees among their members. RESULTS: Four hundred thirty-six trainees completed the survey. Nearly all agreed that there is a need for more neuroscience education in psychiatry residency training (94%) and that neuroscience education could help destigmatize mental illness (91%). Nearly all (94%) expressed interest in attending a 3-day course on neuroscience. Many neuroscience topics and modes of learning were viewed favorably by participants. Residents in their first 2 years of training expressed attitudes similar to those of more advanced residents and fellows. Some differences were found based on the level of interest in a future academic role. CONCLUSIONS: This web-based study demonstrates that psychiatry residents see neuroscience education as important in their training and worthy of greater attention. Our results suggest potential opportunities for advancing neuroscience education.

A dual design thinking - universal design approach to catalyze neurodiversity advocacy through collaboration among high-schoolers.

Introduction: Neurodiversity describes the fact that humans all have different brains with unique qualities that contribute to society. Though understanding of neurodiversity is gaining traction among the general public, there remains considerable stigma and prejudice toward neurodiverse people. One way to combat these issues is to teach individuals about neurodiversity and encourage them to develop advocacy skills. Development of such knowledge is especially important for adolescents, as they have the capacity to make small (e.g., interpersonal interactions) and large (e.g., school-wide) impacts. Methods: Eighty-nine high schoolers participated in a two-week virtual summer camp in 2022; research consent/assent was obtained from 19 (11 neurodiverse/neurodivergent). Campers learned about neurodiversity, Universal Design for Learning (UDL), and Design Thinking (DT) through lectures from researchers and neurodivergent people, as well as group activities and discussions. Campers worked in small groups to design a neurodiversity advocacy project based on the principles of UDL and DT. Each group was facilitated by camp counselors-some of whom were neurodiverse-who were all committed to neurodiversity advocacy. Participants completed questionnaires about autism, ADHD, and dyslexia pre- and post-camp. Some also completed optional post-camp interviews. Results: Pre-camp stigma toward neurodiverse conditions was generally low. However, autism stigma was significantly higher than dyslexia stigma (Z = -2.24, p = 0.025). After camp, autism stigma decreased (Z = -2.98, p = 0.003;) and autism [t(13) = 3.17, p = 0.007] and ADHD [t(13) = 2.87, p = 0.013] knowledge improved. There were no significant changes in ADHD or dyslexia stigma or dyslexia knowledge. Participants reported enjoying collaborating with other campers and learning about UDL and DT. Thematic analysis of interviews generated four themes: Increased Understanding of Neurodiversity; Increasing Empathy and Becoming Less Judgmental; Creating a Neurodiverse Community; and More Awareness is Needed. Discussion: This pilot investigation suggests that a virtual summer camp can be effective in improving attitudes toward and knowledge of neurodiversity. Qualitative analysis indicated participants became more accepting after the camp, both in terms of being less judgmental toward neurodiverse people and more self-accepting among neurodivergent campers. Future research should investigate the long-term effects of such a program, particularly with diverse samples of students.

"Self-compassion changed my life": The self-compassion experiences of autistic and non-autistic adults and its relationship with mental health and psychological wellbeing.

Self-compassion is a gentle way of relating to oneself, linked to a host of mental health benefits in non-autistic people. Although many autistic individuals report high anxiety and depression symptoms, no research to-date has examined the self-compassion experiences of autistic individuals and determined if self-compassion is associated with psychopathology. Therefore, the purpose of the current study was to address this research gap. The participants (153 autistic and 93 non-autistic adults) completed on online survey and 11 autistic participants were also interviewed. Autistic participants reported significantly lower self-compassion than non-autistic adults, and in both groups, those with higher self-compassion reported higher psychological wellbeing and lower depression symptoms. Demographic predictors of self-compassion were identified. These findings have both clinical and research implications.

Conceptualizing neurodevelopmental disorders through a mechanistic understanding of fragile X syndrome and Williams syndrome.

PURPOSE OF REVIEW: The overarching goal of this review is to compare and contrast the cognitive-behavioral features of fragile X syndrome (FraX) and Williams syndrome and to review the putative neural and molecular underpinnings of these features. Information is presented in a framework that provides guiding principles for conceptualizing gene-brain-behavior associations in neurodevelopmental disorders. RECENT FINDINGS: Abnormalities, in particular cognitive-behavioral domains with similarities in underlying neurodevelopmental correlates, occur in both FraX and Williams syndrome including aberrant frontostriatal pathways leading to executive function deficits, and magnocellular/dorsal visual stream, superior parietal lobe, inferior parietal lobe, and postcentral gyrus abnormalities contributing to deficits in visuospatial function. Compelling cognitive-behavioral and neurodevelopmental contrasts also exist in these two disorders, for example, aberrant amygdala and fusiform cortex structure and function occurring in the context of contrasting social behavioral phenotypes, and temporal cortical and cerebellar abnormalities potentially underlying differences in language function. Abnormal dendritic development is a shared neurodevelopmental morphologic feature between FraX and Williams syndrome. Commonalities in molecular machinery and processes across FraX and Williams syndrome occur as well - microRNAs involved in translational regulation of major synaptic proteins; scaffolding proteins in excitatory synapses; and proteins involved in axonal development. SUMMARY: Although the genetic variations leading to FraX and Williams syndrome are different, important similarities and contrasts in the phenotype, neurocircuitry, molecular machinery, and cellular processes in these two disorders allow for a unique approach to conceptualizing gene-brain-behavior links occurring in neurodevelopmental disorders.

The impact of autism-related training programs on physician knowledge, self-efficacy, and practice behavior: A systematic review.

LAY ABSTRACT: Autism spectrum disorder is estimated to impact 1.5 million children and almost 5.5 million adults. However, most physicians do not receive training on how to provide care to this increasingly large group of people. After performing a systematic review of the literature and screening over 4,500 unique articles focused on the effectiveness of autism-specific training programs designed for physicians and physician trainees, we determined that 17 studies met the pre-determined criteria for inclusion in this systematic review. The results reported by these studies suggest that by completing specialized training programs related to autism, physicians were more knowledgeable on topics related to the condition, more confident in their ability to provide care to autistic individuals, and more likely to screen their patients for autism spectrum disorder. However, further studies with higher quality data are needed to validate these findings and provide additional insight on the ability of these programs to improve physician behavior and patient outcomes. We are therefore advocating that medical educators develop and evaluate specialized autism training programs with an increased focus on improving physician behavior related to all aspects of providing care to autistic people.

Region-specific associations between gamma-aminobutyric acid A receptor binding and cortical thickness in high-functioning autistic adults.

The neurobiology of autism has been shown to involve alterations in cortical morphology and gamma-aminobutyric acid A (GABAA ) receptor density. We hypothesized that GABAA receptor binding potential (GABAA R BPND ) would correlate with cortical thickness, but their correlations would differ between autistic adults and typically developing (TD) controls. We studied 50 adults (23 autism, 27 TD, mean age of 27 years) using magnetic resonance imaging to measure cortical thickness, and [18 F]flumazenil positron emission tomography imaging to measure GABAA R BPND . We determined the correlations between cortical thickness and GABAA R BPND by cortical lobe, region-of-interest, and diagnosis of autism spectrum disorder (ASD). We also explored potential sex differences in the relationship between cortical thickness and autism characteristics, as measured by autism spectrum quotient (AQ) scores. Comparing autism and TD groups, no significant differences were found in cortical thickness or GABAA R BPND . In both autism and TD groups, a negative relationship between cortical thickness and GABAA R BPND was observed in the frontal and occipital cortices, but no relationship was found in the temporal or limbic cortices. A positive correlation was seen in the parietal cortex that was only significant for the autism group. Interestingly, in an exploratory analysis, we found sex differences in the relationships between cortical thickness and GABAA R BPND , and cortical thickness and AQ scores in the left postcentral gyrus. LAY SUMMARY: The thickness of the brain cortex and the density of the receptors associated with inhibitory neurotransmitter GABA have been hypothesized to underlie the neurobiology of autism. In this study, we found that these biomarkers correlate positively in the parietal cortex, but negatively in the frontal and occipital cortical regions of the brain. Furthermore, we collected preliminary evidence that the correlations between cortical thickness and GABA receptor density are sexdependent in a brain region where sensory inputs are registered.

Thalamocortical connectivity is associated with autism symptoms in high-functioning adults with autism and typically developing adults.

Alterations in sensorimotor functions are common in individuals with autism spectrum disorder (ASD). Such aberrations suggest the involvement of the thalamus due to its key role in modulating sensorimotor signaling in the cortex. Although previous research has linked atypical thalamocortical connectivity with ASD, investigations of this association in high-functioning adults with autism spectrum disorder (HFASD) are lacking. Here, for the first time, we investigated the resting-state functional connectivity of the thalamus, medial prefrontal, posterior cingulate, and left dorsolateral prefrontal cortices and its association with symptom severity in two matched cohorts of HFASD. The principal cohort consisted of 23 HFASD (mean[SD] 27.1[8.9] years, 39.1% female) and 20 age- and sex-matched typically developing controls (25.1[7.2] years, 30.0% female). The secondary cohort was a subset of the ABIDE database consisting of 58 HFASD (25.4[7.8] years, 37.9% female) and 51 typically developing controls (24.4[6.7] years, 39.2% female). Using seed-based connectivity analysis, between-group differences were revealed as hyperconnectivity in HFASD in the principal cohort between the right thalamus and bilateral precentral/postcentral gyri and between the right thalamus and the right superior parietal lobule. The former was associated with autism-spectrum quotient in a sex-specific manner, and was further validated in the secondary ABIDE cohort. Altogether, we present converging evidence for thalamocortical hyperconnectivity in HFASD that is associated with symptom severity. Our results fill an important knowledge gap regarding atypical thalamocortical connectivity in HFASD, previously only reported in younger cohorts.

Association of serum allopregnanolone with restricted and repetitive behaviors in adult males with autism.

Autism spectrum disorder (ASD) has been associated with imbalance between excitatory and inhibitory (E/I) neurotransmission systems, as well as with neuroinflammation. Sitting at the crossroads between E/I imbalance and neuroinflammation is a class of endogenous hormones known as neurosteroids. Current literature points to dysregulated steroid metabolism and atypical neurosteroid levels in ASD as early as in utero. However, due to the complexity of neurosteroid metabolomics, including possible sex differences, the impact of neurosteroids on ASD symptomatology remains unclear. In this study, we assessed neurosteroid levels and ASD symptom severity of 21 males with ASD and 20 full-scale-IQ-matched typically developing (TD) males, all aged 18-39. Using liquid chromatography-tandem mass spectrometry, concentrations of allopregnanolone, cortisol, dehydroepiandrosterone, progesterone, and testosterone were measured in saliva and serum. With the exception of cortisol's, all neurosteroids' concentrations were found to have ASD vs. TD group differences in distribution, where one group was normally distributed and the other non-normally distributed. Serum allopregnanolone levels in males with ASD were found to negatively correlate with clinician-rated measures of restricted and repetitive behavior measures (ADOS-2 RRB and ADI-R RRSB domain scores). Additionally, lower serum allopregnanolone levels were found to predict more negative camouflaging scores, which represent greater differences in self- and clinician-rated symptom severity, of both ASD symptomatology overall and repetitive behaviors in particular. Taken together, our findings demonstrate that in adult males with ASD, decreased serum allopregnanolone levels are associated with more severe restricted and repetitive behaviors and with less insight into the severity of these behaviors.

Design, synthesis and evaluation of constrained tetrahydroimidazopyrimidine derivatives as antagonists of corticotropin-releasing factor type 1 receptor (CRF1R).

Several tetrahydroimidazopyrimidines were prepared using silver assisted cyclization as the key step. The binding affinities of compounds thus prepared were evaluated in vitro toward hCRF(1)R. Initial lead compound 16 (K(i)=32 nM) demonstrated modest putative anxiolytic effects in the mouse canopy test. Further optimization using parallel synthesis provided compounds with K(i)'s <50 nM.

Implementing Digital Dentistry into Your Esthetic Dental Practice.

The use of digital dentistry is on the increase as costs to acquire digital technology have gone down dramatically and allowed for more practitioners to integrate digital equipment with reduced investment. One of the most significant benefits of digital technology in dentistry is the ability to streamline processes that can be cumbersome via the analog way. In digital dentistry, it is important to understand the advantages and disadvantages of each device or system available.

Adjunctive use of lithium carbonate for the management of neutropenia in clozapine-treated children.

OBJECTIVE: Clozapine, a dibenzodiazepine antipsychotic, is the most effective medication for treatment-resistant schizophrenia. However, its use has been limited by the high risk of neutropenia. In children, the rate of neutropenia is higher when compared to adults. We decided to explore the use of lithium to manage neutropenia in childhood-onset schizophrenia (COS) through a systematic audit of COS cases. METHODS: Medical records were reviewed for patients with COS who had been treated with the combination of clozapine and lithium carbonate. RESULTS: Seven patients were found to have been treated with both clozapine and lithium. After initiation of lithium, ANC increased significantly in six out of seven subjects by 29 to 106% with a mean of 66%. In addition, six out of seven subjects continued using both clozapine and lithium for over 2 years (range: 2.0-7.2 years) and do not have immediate plans for discontinuation of either medications. CONCLUSIONS: Our study bolsters support for the use of lithium in the management of neutropenia in children treated with clozapine. Although the coadministration of lithium and clozapine appears effective in the management of neutropenia, it is not without its risks and clinicians must be diligent in their joint use of these medications.

Brief Report: Sex/Gender Differences in Symptomology and Camouflaging in Adults with Autism Spectrum Disorder.

Autism spectrum disorder (ASD) is more prevalent in males than females. Previous research indicates females camouflage ASD symptoms more than males, potentially contributing to the difference in prevalence. This study investigated sex/gender differences in behavioral phenotypes in 17 males and 11 females with ASD, as well camouflaging in ASD, in an attempt to partially replicate findings from Lai et al. (Autism 21(6):690-702, 2017). Overall ASD symptoms were measured by the autism spectrum quotient (AQ). Mean AQ in females with ASD was higher than males with ASD, with the difference approaching statistical significance. Camouflaging was found to be more common in females with ASD, and not associated to social phobia. Furthermore, camouflaging correlated negatively with emotional expressivity in females, but not males, with ASD. These findings strengthen previous findings regarding camouflaging being more common in females and add to the literature on how camouflaging may be different in females versus males.

A randomized placebo-controlled pilot trial shows that intranasal vasopressin improves social deficits in children with autism.

The social impairments of autism spectrum disorder (ASD) have a major impact on quality of life, yet there are no medications that effectively treat these core social behavior deficits. Preclinical research suggests that arginine vasopressin (AVP), a neuropeptide involved in promoting mammalian social behaviors, may be a possible treatment for ASD. Using a double-blind, randomized, placebo-controlled, parallel study design, we tested the efficacy and tolerability of a 4-week intranasal AVP daily treatment in 30 children with ASD. AVP-treated participants aged 6 to 9.5 years received the maximum daily target dose of 24 International Units (IU); participants aged 9.6 to 12.9 years received the maximum daily target dose of 32 IU. Intranasal AVP treatment compared to placebo enhanced social abilities as assessed by change from baseline in this phase 2 trial's primary outcome measure, the Social Responsiveness Scale, 2nd Edition total score (SRS-2 T score; F 1,20 = 9.853; P = 0.0052; ηp 2 = 33.0%; Cohen's d = 1.40). AVP treatment also diminished anxiety symptoms and some repetitive behaviors. Most of these findings were more pronounced when we accounted for pretreatment AVP concentrations in blood. AVP was well tolerated with minimal side effects. No AVP-treated participants dropped out of the trial, and there were no differences in the rate of adverse events reported between treatment conditions. Last, no changes from baseline were observed in vital signs, electrocardiogram tracings, height and body weight, or clinical chemistry measurements after 4 weeks of AVP treatment. These preliminary findings suggest that AVP has potential for treating social impairments in children with ASD.

Aminoquinazolines as TRPV1 antagonists: modulation of drug-like properties through the exploration of 2-position substitution.

A focused SAR exploration of the lead 4-aminoquinazoline TRPV1 antagonist 2 led to the discovery of compound 18. In rats, compound 18 is readily absorbed following oral dosing and demonstrates excellent in vivo potency and efficacy in an acute inflammatory pain model.

A sterile animal model for neuroinflammation?

MRI-guided pulsed focused ultrasound combined with systemic infusion of contrast agent microbubbles induces local neuroinflammation in the rat.

Linkage of traffic crash and hospitalization records with limited identifiers for enhanced public health surveillance.

BACKGROUND: Motor vehicle traffic (MVT) crashes kill or seriously injure approximately 4250 people in New York City (NYC) each year. Traditionally, NYC surveillance practices use hospitalization and crash data separately to monitor trends in MVT-related injuries, but key information linking crash circumstances to health outcomes is lost when analyzing these data sources in isolation. Our objective was to match crash reports to hospitalization records to create a traffic injury surveillance dataset that can be used to describe crash circumstances and related injury outcomes. The linkage of the two systems presents a unique challenge since the system tracking crashes and the system tracking hospitalizations and emergency department (ED) visits lack key identifying data such as names and dates of birth. METHODS: NYC Department of Transportation provided electronic records based on reports of motor vehicle crashes submitted to the New York State Department of Motor Vehicles for all crashes occurring in NYC from 2009 to 2013. New York Statewide Planning and Research Cooperative System (SPARCS) ED and hospitalization administrative data from NYC hospitals were used to identify unintentional MVT-related injuries using external cause of injury codes. Since the two systems do not share unique individual identifiers, probabilistic record linkage was conducted using LinkSolv9.0. Sensitivity/specificity calculations and chi-square analyses of linkage rates were conducted to assess linkage results. RESULTS: From 2009-2013, there were 1,054,344 individuals involved in MVT crashes in NYC and 280,340 ED visits and hospitalizations from MVT-related injuries. There were 145,003 linked pairs, giving a linkage rate of 52% of the total MVT-related hospital records. This linkage had a sensitivity of 74% and a specificity of 93%. Linkage rates were comparable by age, sex, crash role, collision type, hospital county, injury location, hospital type, and hospital status, indicating no apparent biases in the match by these variables. CONCLUSIONS: Performing a probabilistic linkage between MVT crash reports and hospitalization records is possible with a limited set of identifying variables. These linked data will inform traffic safety policies by providing new information on how crash circumstances translate to health outcomes.