11C-UCB-J PET imaging is consistent with lower synaptic density in autistic adults.

The neural bases of autism are poorly understood at the molecular level, but evidence from animal models, genetics, post-mortem studies, and single-gene disorders implicate synaptopathology. Here, we use positron emission tomography (PET) to assess the density of synapses with synaptic vesicle glycoprotein 2A (SV2A) in autistic adults using 11C-UCB-J. Twelve autistic (mean (SD) age 25 (4) years; six males), and twenty demographically matched non-autistic individuals (26 (3) years; eleven males) participated in a 11C-UCB-J PET scan. Binding potential, BPND, was the primary outcome measure and computed with the centrum semiovale as the reference region. Partial volume correction with Iterative Yang was applied to control for possible volumetric differences. Mixed-model statistics were calculated for between-group differences. Relationships to clinical characteristics were evaluated based on clinician ratings of autistic features. Whole cortex synaptic density was 17% lower in the autism group (p = 0.01). All brain regions in autism had lower 11C-UCB-J BPND compared to non-autistic participants. This effect was evident in all brain regions implicated in autism. Significant differences were observed across multiple individual regions, including the prefrontal cortex (-15%, p = 0.02), with differences most pronounced in gray matter (p < 0.0001). Synaptic density was significantly associated with clinical measures across the whole cortex (r = 0.67, p = 0.02) and multiple regions (rs = -0.58 to -0.82, ps = 0.05 to <0.01). The first in vivo investigation of synaptic density in autism with PET reveals pervasive and large-scale lower density in the cortex and across multiple brain areas. Synaptic density also correlated with clinical features, such that a greater number of autistic features were associated with lower synaptic density. These results indicate that brain-wide synaptic density may represent an as-yet-undiscovered molecular basis for the clinical phenotype of autism and associated pervasive alterations across a diversity of neural processes.

Whole-genome sequencing reveals Listeria monocytogenes diversity and allows identification of long-term persistent strains in Brazil.

Advances in whole-genome sequencing (WGS) technologies have documented genetic diversity and epidemiology of the major foodborne pathogen Listeria monocytogenes (Lm) in Europe and North America, but data concerning South America are scarce. Here, we examined the population structure and genetic diversity of this major foodborne pathogen collected in Brazil. Based on core genome multilocus sequence typing (cgMLST), isolates from lineages I (n = 22; 63%) and II (n = 13; 37%) were distributed into 10 different sublineages (SLs) and represented 31 new cgMLST types (CTs). The most prevalent SLs were SL9 (n = 9; 26%), SL3 (n = 6; 17%) and SL2 and SL218 (n = 5; 14%). Isolates belonging to CTs L2-SL9-ST9-CT4420 and L1-SL315-ST520-CT4429 were collected 3 and 9 years apart, respectively, revealing long-term persistence of Lm in Brazil. Genetic elements associated with stress survival were present in 60% of isolates (57% SSI-1 and 3% SSI-2). Pathogenic islands were present in 100% (LIPI-1), 43% (LIPI-3) and 6% (LIPI-4) of the isolates. Mutations leading to premature stop codons were detected in the prfA and inlA virulence genes. This study is an important contribution to understanding the genomic diversity and epidemiology of Lm in South America. In addition, the results highlight the importance of using WGS to reveal Lm long-term persistence.

Association of Cognitive Performance with Time at Altitude, Sleep Quality, and Acute Mountain Sickness Symptoms.

OBJECTIVE: It is well documented that cognitive performance may be altered with ascent to altitude, but the association of various cognitive performance tests with symptoms of acute mountain sickness (AMS) is not well understood. Our objective was to assess and compare cognitive performance during a high-altitude expedition using several tests and to report the association of each test with AMS, headache, and quality of sleep. METHODS: During an expedition to Mount Everest, 3 cognitive tests (Stroop, Trail Making, and the real-time cognitive assessment tool, an in-house developed motor accuracy test) were used along with a questionnaire to assess health and AMS. Eight team members were assessed pre-expedition, postexpedition, and at several time points during the expedition. RESULTS: There were no significant differences (P >.05) found among scores taken at 3 time points at base camp and the postexpedition scores for all 3 tests. Changes in the Stroop test scores were significantly associated with the odds of AMS (P <.05). The logistic regression results show that the percent change from baseline for Stroop score (ß = -5.637; P = .032) and Stroop attempts (ß = -5.269; P = .049) are significantly associated with the odds of meeting the criteria for AMS. CONCLUSIONS: No significant changes were found in overall cognitive performance at altitude, but a significant relationship was found between symptoms of AMS and performance in certain cognitive tests. This research shows the need for more investigation of objective physiologic assessments to associate with self-perceived metrics of AMS to gauge effect on cognitive performance.

Social Support and Parental Conflict as Predictors of Outcomes of Group Cognitive Behavioral Therapy for Adolescent Depression.

Group cognitive behavioral therapy (CBT) is an effective treatment for adolescent depression, but outcomes vary. Our goal was to examine interpersonal factors that predict response to group CBT for adolescent depression using a broad range of outcomes, including depressive symptoms, session attendance, treatment completion, engagement, and improvement. Seventy adolescents (age 14-18) with depression completed self-report measures of social support and parental conflict and were offered an established 16-session group CBT program. Correlation and regression analyses were conducted for interpersonal predictors and CBT outcomes. Accounting for pre-treatment depressive symptoms, fewer social supports predicted lower likelihood of finishing treatment and less clinician-rated improvement. Greater pre-treatment parental conflict predicted fewer sessions attended, lower clinician-rated engagement, and less clinician-rated improvement. Results highlight the need to consider interpersonal difficulties in CBT, as they may present a barrier to treatment attendance, engagement, and improvement.

Investigating the Face Inversion Effect in Autism Across Behavioral and Neural Measures of Face Processing: A Systematic Review and Bayesian Meta-Analysis.

Importance: Face processing is foundational to human social cognition, is central to the hallmark features of autism spectrum disorder (ASD), and shapes neural systems and social behavior. Highly efficient and specialized, the face processing system is sensitive to inversion, demonstrated by reduced accuracy in recognition and altered neural response to inverted faces. Understanding at which mechanistic level the autistic face processing system may be particularly different, as measured by the face inversion effect, will improve overall understanding of brain functioning in autism. Objective: To synthesize data from the extant literature to determine differences of the face processing system in ASD, as measured by the face inversion effect, across multiple mechanistic levels. Data Sources: Systematic searches were conducted in the MEDLINE, Embase, Web of Science, and PubMed databases from inception to August 11, 2022. Study Selection: Original research that reported performance-based measures of face recognition to upright and inverted faces in ASD and neurotypical samples were included for quantitative synthesis. All studies were screened by at least 2 reviewers. Data Extraction and Synthesis: This systematic review and meta-analysis was conducted according to the 2020 Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline. Multiple effect sizes were extracted from studies to maximize information gain and statistical precision and used a random-effects, multilevel modeling framework to account for statistical dependencies within study samples. Main Outcomes and Measures: Effect sizes were calculated as a standardized mean change score between ASD and neurotypical samples (ie, Hedges g). The primary outcome measure was performance difference between upright and inverted faces during face recognition tasks. Measurement modality, psychological construct, recognition demand, sample age, sample sex distribution, and study quality assessment scores were assessed as moderators. Results: Of 1768 screened articles, 122 effect sizes from 38 empirical articles representing data from 1764 individual participants (899 ASD individuals and 865 neurotypical individuals) were included in the meta-analysis. Overall, face recognition performance differences between upright and inverted faces were reduced in autistic individuals compared with neurotypical individuals (g = -0.41; SE = 0.11; 95% credible interval [CrI], -0.63 to -0.18). However, there was considerable heterogeneity among effect sizes, which were explored with moderator analysis. The attenuated face inversion effect in autistic individuals was more prominent in emotion compared with identity recognition (b = 0.46; SE = 0.26; 95% CrI, -0.08 to 0.95) and in behavioral compared with electrophysiological measures (b = 0.23; SE = 0.24; 95% CrI, -0.25 to 0.70). Conclusions and Relevance: This study found that on average, face recognition in autism is less impacted by inversion. These findings suggest less specialization or expertise of the face processing system in autism, particularly in recognizing emotion from faces as measured in behavioral paradigms.