Connectome-wide mega-analysis reveals robust patterns of atypical functional connectivity in autism

Neuroimaging studies on functional connectivity (FC) in autism have been hampered by small sample sizes and inconsistent findings with regard to whether connectivity is increased or decreased in individuals with autism, whether these alterations affect focal systems or reflect a brain-wide dysfunction, and whether these are age- and/or sex-dependent. The study included resting-state fMRI and clinical data from the LEAP and the ABIDE I and II initiatives, of 1824 (796 with autism) participants with age range 5-58 years. Between-group differences in FC were assessed, and associations between FC and clinical symptom ratings were investigated through canonical correlation analysis. Autism was associated with a brain-wide pattern of hypo- and hyperconnectivity. Hypoconnectivity predominantly affected sensory and higher-order attentional networks and correlated with social impairments, restrictive and repetitive behavior (RRB), and sensory processing. Hyperconnectivity was observed primarily between the default mode network and the rest of the brain, and between cortical and subcortical systems. This pattern was strongly associated with social impairments and sensory processing. Interactions between diagnosis and age or sex were not statistically significant. The FC alterations observed in this study, which primarily involve hypoconnectivity of primary sensory and attention networks and hyperconnectivity of the DMN and subcortex with the rest of the brain, do not appear to be age or sex-dependent and correlate with clinical dimensions of social difficulties, RRBs, and alterations in sensory processing. These findings suggest that the observed connectivity alterations are stable, trait-like features of autism that are related to the three main symptom domains.

Identity and pathogenicity of fungi associated with root, crown and vascular symptoms related to winter squash yield decline

Winter squash (Cucurbita maxima cv. ‘Golden Delicious’) produced in Oregon’s Willamette Valley for edible seed production has experienced significant yield losses due to a soilborne disease. The symptoms associated with this disease problem include root rot, crown rot and vascular discoloration in the stems leading to a severe late season wilt and plant collapse. Through field surveys, Fusarium oxysporum, F. solani, F. culmorum-like fungi, Plectosphaerella cucumerina, and Setophoma terrestris were identified to be associated with diseased tissues, and each produced symptoms of root rot, crown rot or stem discoloration in preliminary pathogenicity trials. In this study, 219 isolates of these species were characterized by molecular identity analyses using BLAST of the ITS and EF1α genomic regions and by pathogenicity testing in outdoor, large-container trials. Molecular identity analyses confirmed the identity of isolates at 99 to 100% similarity to reference isolates in the database. In pathogenicity experiments, F. solani produced the most severe symptoms, followed by F. culmorum-like fungi, F. oxysporum, P. cucumerina, and S. terrestris. Some treatments of mixed species inoculum produced symptoms above what was expected from individual species. In particular, the mixture of F. culmorum-like fungi, F. oxysporum, and P. cucumerina and the mixture of F. culmorum-like fungi, F. solani, and S. terrestris had equally severe symptom ratings than that of F. solani by itself. Results indicate that this soilborne disease is primarily caused by Fusarium solani, but interactions among the complex of F. solani, F. culmorum-like fungi, F. oxysporum, and P. cucumerina, can exacerbate disease severity.

Responsivity of the striatal dopamine system to methylphenidate – a within-subject I-123-β-CIT-SPECT study in children and adolescents with Attention-Deficit/Hyperactivity Disorder

Background: Methylphenidate (MPH) is the first-line pharmacological treatment of attention-deficit/hyperactivity disorder (ADHD). MPH binds to the dopamine (DA) transporter (DAT), which has high density in the striatum. Assessments of the striatal dopamine transporter by single positron emission computed tomography (SPECT) in childhood and adolescent patients are rare but can provide insight in how effects of MPH affect DAT availability. The aim of our within-subject study was to investigate the effect of MPH on DAT availability and how responsivity to MPH in DAT availability is linked to clinical symptoms and cognitive functioning. Methods: Thirteen adolescent male patients (9-16 years) with diagnosis of ADHD according to DSM-IV and long-term stimulant medication (for at least 6 months) with MPH were assessed twice within 7 days using SPECT after application of I-123-beta-CIT to examine DAT binding potential (DAT BP). SPECT measures took place in on and off-MPH status balanced for order across participants. A virtual-reality continuous-performance test was performed at each time point. Further clinical symptoms were assessed for baseline off-MPH. Results: On-MPH status was associated with a highly significant decrease (-27,6%) of striatal DAT BP as compared to off-MPH (t=4.93, p<0.001). More pronounced decrease in striatal DAT BP was associated with higher off-MPH attentional and externalizing symptom ratings (Pearson r=0.68, p=0.01). Striatal DAT BP off-MPH, but not on- MPH, was associated with higher symptom ratings off-MPH (Pearson r=0.56, p=0.04). In further exploratory analysis in left vs. right striatal sub-regions, stronger decrease in DAT BP in the right caudate nucleus was weakly associated with improved performance in the continuous-performance test (Pearson r= - 0.54, p=0.07). Conclusion: Our findings corroborate previous reports from mainly adult samples that MPH reduces striatal DAT BP availability and suggest higher off-MPH DAT BP, likely reflecting low baseline DA levels, as a marker of symptom severity. More speculatively, regional specific responsivity of DAT BP to MPH may reflect treatment response with respect to cognitive functioning. However, implications from this small patient sample should be treated with caution and warrant replication.

The Influence of Depression on Biased Diagnosis of Premenstrual Syndrome and Premenstrual Dysphoric Disorder by the PSST Inventory

The diagnosis of premenstrual syndrome (PMS) and premenstrual dysphoric disorder (PMDD) poses a challenge for clinicians due to the overdiagnosis of retrospective methods and overlapping symptoms with depression. The present study utilized an Item Response Theory analysis to examine the predictive utility of the Premenstrual Symptom Screening Tool (PSST) in women with and without depression. Two hundred and fifteen women aged 20–35 completed the PSST, a daily symptom calendar, SCID-I, and CES-D for two consecutive menstrual cycles. PSST items: fatigue, depressed mood, feeling overwhelmed, anxiety/tension, and decreased interest in everyday activities were the best predictors of PMS. Unlike the daily symptom ratings, the PSST over-diagnosed PMS/PMDD in the depressed group but not in the group of women without PMS/PMDD. While diagnosing premenstrual disorders, clinicians should be aware that a retrospective diagnosis with PSST can be more sensitive to mood disorders and cycle phases than a prospective diagnosis with a daily symptoms calendar.

Effects of cannabis ingestion on endometriosis-associated pelvic pain and related symptoms.

Background The use of cannabis for symptoms of endometriosis was investigated utilising retrospective archival data from Strainprint Technologies Ltd., a Canadian data technology company with a mobile phone application that tracks a range of data including dose, mode of administration, chemovar and their effect on various self-reported outcomes, including pelvic pain. Methods A retrospective, electronic record-based cohort study of Strainprint™ users with self-reported endometriosis was conducted. Self-rated cannabis efficacy, defined as a function of initial and final symptom ratings, was investigated across the included symptom clusters of cramps, pelvic pain, gastrointestinal pain, nausea, depression, and low libido. Cannabis dosage form, dose and cannabinoid ratio information was also recorded. Results A total number of 252 participants identifying as suffering endometriosis recorded 16193 sessions using cannabis between April 2017 and February 2020. The most common method of ingestion was inhalation (n = 10914, 67.4%) with pain as the most common reported symptom being treated by cannabis (n = 9281, 57.3%). Gastrointestinal symptoms, though a less common reason for cannabis usage (15.2%), had the greatest self-reported improvement after use. Inhaled forms had higher efficacy for pain, while oral forms were superior for mood and gastrointestinal symptoms. Dosage varied across ingestion methods, with a median dose of 9 inhalations (IQR 5 to 11) for inhaled dosage forms and 1 mg/mL (IQR 0.5 to 2) for other ingested dosage forms. The ratio of THC to CBD had a statistically significant, yet clinically small, differential effect on efficacy, depending on method of ingestion. Conclusions Cannabis appears to be effective for pelvic pain, gastrointestinal issues and mood, with effectiveness differing based on method of ingestion. The greater propensity for use of an inhaled dosage delivery may be due to the rapid onset of pain-relieving effects versus the slower onset of oral products. Oral forms appeared to be superior compared to inhaled forms in the less commonly reported mood or gastrointestinal categories. Clinical trials investigating the tolerability and effectiveness of cannabis for endometriosis pain and associated symptoms are urgently required.

Investigating the Response Scale of the Eortc Qlq-C30 in German Cancer Patients and a Population Survey – A Case of Quality Control in Patient-Reported Outcomes Research

Background: The European Organization for research and Treatment of Cancer (EORTC) Core Quality of Life Questionnaire (QLQ-C30) scales are scored on a 4-point response scale, ranging from not at all to very much. Previous studies have shown that the German translation of the response option quite a bit as mäßig violates interval scale assumptions, and that ziemlich is a more appropriate translation. The present studies investigated differences between the two questionnaire versions and were based on the hypothesis that the conventional version yielded lower functioning and higher symptom ratings than the optimized version, particularly in respondents with a higher health burden.Methods: The first study employed a balanced cross-over design and included 450 patients with different types of cancer from three German-speaking countries. The second study was a representative survey in Germany including 2033 respondents. Half of the participants filled in the mäßig, the other half the ziemlich version of the questionnaire.Results: In accordance with our hypothesis, the adjusted summary score was lower in the mäßig than in the ziemlich version; Study 1: -4.5 (95% CI -7.8 to -1.3), p = 0.006, Study 2: -3.1 (95% CI - 4.6 to -1.5), p < 0.001. In both studies, this effect was pronounced in respondents with a higher health burden; Study 1: -6.8 (95% CI -12.2 to -1.4), p = 0.013; Study 2: -4.5 (95% CI -7.3 to -1.7), p = 0.002.Conclusions: We found subtle but consistent differences between the two questionnaire versions. The optimized response option should be used for the EORTC QLQ-C30 as well as for all other German modules.Trial registration: The study was retrospectively registered on the German Registry for Clinical Studies (reference number DRKS00012759, 04th August 2017, https://www.drks.de/DRKS00012759).

A - 29 Language Differences in Neurocognitive Scores and Symptom Report in Professional Football Players

Objective The purpose of this study was to investigate the role of language on neurocognitive test outcomes and concussion symptom ratings in professional football players. Methods Design/Setting - A retrospective cross-section analysis of 1546 male Canadian Football League (CFL) athletes was conducted using baseline data collected from the Immediate Post-Concussion Assessment and Cognitive Test (ImPACT) across the 2016–18 competitive seasons. Independent Variables - Participants (1546) were divided into three language categories, native English-speaking, bilingual – whose first language was English, and English as a second language (ESL). Years of education, age, and concussion history were entered as co-variates. Outcome Measure -The 5 Composite scores from ImPACT and the 22 symptoms from the post-concussion symptom scale (PCSS). Results Results of the MANCOVA showed no significant differences between language groups on any of the five ImPACT composite scores F(10, 3072) = 1.09, p = 0.36. The Kruskall-Wallis test revealed significant differences were found in three symptoms including dizziness [X2(2, 1486) = 32.85, p &lt; 0.001)], sadness [X2(2, 1486) = 6.505, p = 0.04], and concentration [X2(2, 1486) = 11.01, p = 0.004)] with the bilingual and non-native English speakers having higher scores. Conclusions This study suggests that cultural and linguistic differences should be considered when administering CNTs. While differences in cognitive outcomes have not been consistently found across studies, differences in baseline symptom reports have been consistently demonstrated. Information pertaining to a patient’s level of acculturation and language proficiency is important for examiners when working with diverse populations. Continuing to develop language-specific normative databases is encouraged.

Susceptibility-Weighted Magnetic Resonance Imaging (MRI) of Microbleeds in Pediatric Concussion

Objective: The long-term consequences of pediatric concussion on brain structure are poorly understood. This study aimed to evaluate the presence and clinical significance of cerebral microbleeds several years after pediatric concussion. Methods: Children and adolescents 8-19 years of age with either a history of concussion (n = 35), or orthopedic injury (n = 20) participated. Mean time since injury for the sample was 30.4 months (SD = 19.6). Participants underwent susceptibility-weighted imaging, rated their depression and postconcussion symptoms, and completed cognitive testing. Parents of participants also completed symptom ratings for their child. Hypointensities in susceptibility-weighted images indicative of cerebral microbleeds were calculated as a measure of hypointensity burden. Results: Hypointensity burden did not differ significantly between participants with a history of concussion and those with a history of orthopedic injury. Depression ratings (self and parent report), postconcussion symptom ratings (self and parent report), and cognitive performance did not significantly correlate with hypointensity burden in the concussion group. Conclusions: These findings suggest that at approximately 2.5 years postinjury, children and adolescents with prior concussion do not have a greater amount of cerebral microbleeds compared to those with orthopedic injury. Future research should use longitudinal study designs and investigate children with persistent postconcussive symptoms to gain better insight into the long-term effects of concussion on cerebral microbleeds.

The Accuracy of Retrospective Recall of Childhood ADHD: Results from a Longitudinal Study

Attention-deficit/hyperactivity disorder (ADHD) is a childhood-onset condition that may continue into adulthood. When assessing adult patients, clinicians usually rely on retrospective reports of childhood symptoms to evaluate the age-of-onset criterion. Since inaccurate symptom recall may impede the diagnosis and treatment of ADHD, knowledge about the factors influencing retrospective reports is needed. This longitudinal study investigated (a) the accuracy of retrospective symptom ratings by adult participants with a childhood diagnosis of ADHD (self-ratings) and parents or significant others (proxy ratings), and (b) the influence of current ADHD symptom severity and ADHD-associated impairments on retrospective symptom ratings. Participants (N = 55) were members of the Cologne Adaptive Multimodal Treatment (CAMT) study who had been referred and treated for ADHD in childhood and were reassessed in adulthood (average age 27 years). Participants’ retrospective self-ratings were substantially lower than, and did not correlate with, parents’ ADHD symptom ratings provided at study entry, while retrospective symptom ratings provided by proxy respondents correlated moderately with parents’ childhood ratings. In addition, participants were more likely to underreport childhood symptoms (79%) and more frequently denied the presence of three or more childhood symptoms (17%) compared to proxy respondents (65% underreporting, 10% false-negative recall). Proxy respondents’ symptom recall was best predicted by childhood ADHD, while participants’ symptom recall was best predicted by current ADHD symptom severity. ADHD-associated impairments were not correlated with symptom recall after controlling for childhood ADHD. Together, these findings suggest a recall bias in adult patients and question the validity of retrospective reports, even in clinical samples.