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A web-based survey of academic publishers was undertaken in 2021 by a team at Oxford International Centre for Publishing into the state of monograph publication in the arts, humanities, and social sciences. 25 publishing organisations responded, including many of the larger presses, representing approximately 75% of monograph output. Responses to the survey showed that the Covid 19 pandemic has accelerated the existing trend from print to digital dissemination and that Open Access (OA) titles receive substantially greater levels of usage than those published traditionally. Responses also showed that for most publishers OA publication stands at under 25% of output and that fewer than 10% of authors enquire about OA publication options. Continuing problem areas highlighted by respondents were the clearing of rights for OA publication and the standardisation of title and usage metadata. All responding organisations confirmed that they expect to be publishing monographs in ten years’ time, but that they anticipate the format and/or the model will be different, with open access expected to play a key part in the future, perhaps in the context of a mixed economy of OA and ‘toll access’ publication.

Despite advances in identifying rare and common genetic variants conferring risk for ADHD, the lack of a transcriptomic understanding of cortico-striatal brain circuitry has stymied a molecular mechanistic understanding of this disorder. To address this gap, we mapped the transcriptome of the caudate nucleus and anterior cingulate cortex in post-mortem tissue from 60 individuals with and without ADHD. Significant differential expression of genes was found in the anterior cingulate cortex and, to a lesser extent, the caudate. Significant downregulation emerged of neurotransmitter gene pathways, particularly glutamatergic, in keeping with models that implicate these neurotransmitters in ADHD. Consistent with the genetic overlap between mental disorders, correlations were found between the cortico-striatal transcriptomic changes seen in ADHD and those seen in other neurodevelopmental and mood disorders. This transcriptomic evidence points to cortico-striatal neurotransmitter anomalies in the pathogenesis of ADHD, consistent with current models of the disorder.

Human brain mapping 43(1), 37-55 (2022). doi:10.1002/hbm.25029 special issue: "Special Issue: The ENIGMA Consortium: the first 10 years / Issue Edited by: P.M. Thompson, N. Jahanshad, L. Schmaal, J.A. Turner, A. Winkler, S.I. Thomopoulos, G.F. Egan, P. Kochunov", Published by Wiley-Liss, New York, NY

BackgroundPrevious studies identified a strong linkage signal for non-syndromic persistent developmental stuttering on chromosome 3q13.2-3q13.33 in a large consanguineous family. To identify the causative genetic variant at this locus, including we performed further analysis, including whole exome, whole genome, and targeting Sanger sequencing.ResultsWe identified a homozygous rare c.2155G>A variant inZBTB20in individuals who stutter. This mutation encodes Isoleucine in place of a highly conserved Valine at amino acid position 719 in ZBTB20 that co-segregates (LOD = 4.23) with stuttering under a model of recessive inheritance with reduced penetrance in this family. Coding variants in this gene were significantly more frequent in a multiethnic cohort of unrelated individuals who stutter than in individuals in large population databases comprised of our normal control subjects and gnomAD database subjects matched for ethnicity.ZBTB20encodes a zinc-finger transcription factor, and luciferase reporter constructs using genes known to be regulated by ZBTB20 showed that the Ile719 mutant form of the protein displays altered transcriptional regulationin vitro. Although homozygosity for mutations inZBTB20has not previously been observed, dominant mutations inZBTB20have been reported in Primrose syndrome, a rare Mendelian dominant disorder characterized by tall stature, developmental delay, dysgenesis of the corpus callosum, but generally not speech disorders. Clinical re-examination of the affected family members ten years after their original ascertainment revealed only some suggestive signs associated with Primrose syndrome.ConclusionsOur findings support variants inZBTB20as a cause of stuttering in a large family, and rarely in the wider population. Previous studies in mice have demonstrated thatZbtb20is required for the development of astrocytes, a brain cell type previously implicated in an animal model of stuttering. Our findings support our hypothesis that astrocyte pathology is involved in this disorder. Our findings also broaden the medical genetic view of disorders ofZBTB20, and demonstrate that individuals carrying a homozygous mutation in this gene can be viable, and that they can primarily display persistent developmental stuttering.

Background Recommendations for promoting mental health during the COVID-19 pandemic include maintaining social contact, through virtual rather than physical contact, moderating substance/alcohol use, and limiting news and media exposure. We seek to understand if these pandemic-related behaviors impact subsequent mental health. Methods Daily online survey data were collected on adults during May/June 2020. Measures were of daily physical and virtual (online) contact with others; substance and media use; and indices of psychological striving, struggling and COVID-related worry. Using random-intercept cross-lagged panel analysis, dynamic within-person cross-lagged effects were separated from more static individual differences. Results In total, 1148 participants completed daily surveys [657 (57.2%) females, 484 (42.1%) males; mean age 40.6 (s.d. 12.4) years]. Daily increases in news consumed increased COVID-related worrying the next day [cross-lagged estimate = 0.034 (95% CI 0.018–0.049), FDR-adjusted p = 0.00005] and vice versa [0.03 (0.012–0.048), FDR-adjusted p = 0.0017]. Increased media consumption also exacerbated subsequent psychological struggling [0.064 (0.03–0.098), FDR-adjusted p = 0.0005]. There were no significant cross-lagged effects of daily changes in social distancing or virtual contact on later mental health. Conclusions We delineate a cycle wherein a daily increase in media consumption results in a subsequent increase in COVID-related worries, which in turn increases daily media consumption. Moreover, the adverse impact of news extended to broader measures of psychological struggling. A similar dynamic did not unfold between the daily amount of physical or virtual contact and subsequent mental health. Findings are consistent with current recommendations to moderate news and media consumption in order to promote mental health.

While childhood attention-deficit/hyperactivity disorder (ADHD) is more prevalent in males than females, genetic contributors to this effect have not been established. Here, we explore sex differences in the contribution of common and/or rare genetic variants to ADHD. Participants were from the Adolescent Brain and Cognitive Development study (N = 1253 youth meeting DSM-5 criteria for ADHD [mean age = 11.46 years [SD = 0.87]; 31% female] and 5577 unaffected individuals [mean age = 11.42 years [SD = 0.89]; 50% female], overall 66% White, non-Hispanic (WNH), 19% Black/African American, and 15% other races. Logistic regression tested for interactions between sex (defined genotypically) and both rare copy number variants (CNV) and polygenic (common variant) risk in association with ADHD. There was a significant interaction between sex and the presence of a CNV deletion larger than 200 kb, both in the entire cohort (β = -0.74, CI = [-1.27 to -0.20], FDR-corrected p = 0.048) and, at nominal significance levels in the WNH ancestry subcohort (β = -0.86, CI = [-1.51 to -0.20], p = 0.010). Additionally, the number of deleted genes interacted with sex in association with ADHD (whole cohort. β = -0.13, CI = [-0.23 to -0.029], FDR-corrected p = 0.048; WNH. β = -0.17, CI = [-0.29 to -0.050], FDR-corrected p = 0.044) as did the total length of CNV deletions (whole cohort. β = -0.12, CI = [-0.19 to -0.044], FDR-corrected p = 0.028; WNH. β = -0.17, CI = [-0.28 to -0.061], FDR-corrected p = 0.034). This sex effect was driven by increased odds of childhood ADHD for females but not males in the presence of CNV deletions. No similar sex effect was found for CNV duplications or polygenic risk scores. The association between CNV deletions and ADHD was partially mediated by measures of cognitive flexibility. In summary, CNV deletions were associated with increased odds for childhood ADHD in females, but not males.

Recent research has shown the mental health consequence of social distancing during the COVID-19 pandemic, but longitudinal data are relatively scarce. It is unclear whether the pattern of isolation and elevated stress seen at the beginning of the pandemic persists over time. This study evaluates change in social interaction over six months and its mental health impact among older adults. We drew data from a panel study with six repeated assessments of social interaction and mental health conducted monthly May through October 2020. The sample included a total of 380 White, Black and Hispanic participants aged 50 and over, of whom 33% had low income, who residing in fourteen U.S. states with active stay-at-home orders in May 2020. The analysis examined how change in living arrangement, in-person interaction outside the household, quality of relationship with family and friends, and perceived social support affected trajectories of isolation stress, COVID worry and sadness. While their living arrangements and relationship quality remained stable, older adults experienced fluctuations in perceived social support and increases in in-person conversations outside the household. Living with a spouse/partner stabilized isolation stress and COVID worry over time. Individuals with better relationship quality with friends became happier over time. Changes in social support were associated with greater fluctuations in isolation stress and COVID worry. During the pandemic, social interactions are protective and lack of stability in feeling supported makes older adults vulnerable to stress. Efforts should focus on (re)building and maintaining companionship and support to mitigate the pandemic’s negative impact.

We sought to identify resting-state characteristics related to attention deficit/hyperactivity disorder, both as a categorical diagnosis and as a trait feature, using large-scale samples which were processed according to a standardized pipeline. In categorical analyses, we considered 1301 subjects with diagnosed ADHD, contrasted against 1301 unaffected controls (total N = 2602; 1710 males (65.72%); mean age = 10.86 years, sd = 2.05). Cases and controls were 1:1 nearest neighbor matched on in-scanner motion and key demographic variables and drawn from multiple large cohorts. Associations between ADHD-traits and resting-state connectivity were also assessed in a large multi-cohort sample (N = 10,113). ADHD diagnosis was associated with less anticorrelation between the default mode and salience/ventral attention (B = 0.009, t = 3.45, p-FDR = 0.004, d = 0.14, 95% CI = 0.004, 0.014), somatomotor (B = 0.008, t = 3.49, p-FDR = 0.004, d = 0.14, 95% CI = 0.004, 0.013), and dorsal attention networks (B = 0.01, t = 4.28, p-FDR 0.001, d = 0.17, 95% CI = 0.006, 0.015). These results were robust to sensitivity analyses considering comorbid internalizing problems, externalizing problems and psychostimulant medication. Similar findings were observed when examining ADHD traits, with the largest effect size observed for connectivity between the default mode network and the dorsal attention network (B = 0.0006, t = 5.57, p-FDR 0.001, partial-r = 0.06, 95% CI = 0.0004, 0.0008). We report significant ADHD-related differences in interactions between the default mode network and task-positive networks, in line with default mode interference models of ADHD. Effect sizes (Cohen's d and partial-r, estimated from the mega-analytic models) were small, indicating subtle group differences. The overlap between the affected brain networks in the clinical and general population samples supports the notion of brain phenotypes operating along an ADHD continuum.

While attention-deficit/hyperactivity disorder (ADHD) has been associated with differences in the structural connections formed by the brain's white matter tracts, studies of such differences have yielded inconsistent findings, likely reflecting small sample sizes. Thus, we conducted a mega-analysis on in vivo measures of white matter microstructure obtained through diffusion tensor imaging of more than 6000 participants from 5 cohorts.In a mega-analysis, linear mixed models were used to test for associations between the fractional anisotropy of 42 white matter tracts and ADHD traits and diagnosis. Contrasts were made against measures of mood, anxiety, and other externalizing problems.Overall, 6993 participants (ages 6-18 years, mean age 10.62 years [SD 1.99]; 3368 girls, 3625 boys; 764 African American, 4146 non-Hispanic White, and 2083 other race/ethnicities) had measures of ADHD and other emotional/behavioral symptoms (N = 6933) and/or enough clinical data to allow a diagnosis of ADHD (n = 951) or its absence (n = 4884). Both the diagnosis and symptoms of ADHD were associated with lower fractional anisotropy of the inferior longitudinal and left uncinate fasciculi (at a false discovery rate-adjusted p.05). Associated effect sizes were small (the strongest association with ADHD traits had an effect size of partial r = -0.14, while the largest case-control difference was associated with an effect size of d = -0.3). Similar microstructural anomalies were not present for anxiety, mood, or externalizing problems. Findings held when ADHD cases and control subjects were matched on in-scanner motion.While present across cohorts, ADHD-associated microstructural differences had small effects, underscoring the limited clinical utility of this imaging modality used in isolation.

Background Twin studies show that age-related change in symptoms of attention-deficit/hyperactivity disorder (ADHD) is heritable. However, we do not know the heritability of the development of the neural substrates underlying the disorder. Here, we estimated the heritability of developmental change in white matter tracts and the brain’s intrinsic functional connectivity using longitudinal data. We further determined associations with change in ADHD symptoms. Methods The study reports on 288 children, which included 127 siblings, 19 cousins, and 142 singletons; 150 (52%) had a diagnosis of ADHD (determined by clinician interview with parent); 188 were male. All had two clinical assessments (overall baseline mean age: 9.4 ± 2.4 years; follow-up: 12.5 ± 2.6 years). Diffusion tensor imaging estimated microstructural properties of white matter tracts on 252 participants. Resting-state functional magnetic resonance imaging estimated intrinsic connectivity within and between major brain networks on 226 participants. Total additive genetic heritability (h2) of the annual rate of change in these neural phenotypes was calculated using SOLAR (Sequential Oligogenic Linkage Analysis Routines). Results Significant heritability was found for the rates of change of 6 white matter tract microstructural properties and for change in the connectivity between the ventral attention network and both the cognitive control and dorsal attention networks. Change in hyperactivity-impulsivity was associated with heritable change in white matter tracts metrics and change in the connectivity between the ventral attention and cognitive networks. Conclusions The relatively small number of heritable, ADHD-associated developmental neural phenotypes can serve as phenotypes for future gene discovery and understanding.

BackgroundFrustration, the response to blocked goal attainment, is a universal affective experience, but how the brain embodies frustration is not known. Understanding brain network dynamics during frustration may provide insight into pediatric irritability, one of the most frequent reasons for psychiatric consultation in youth and a risk factor for affective disorders and suicidality.MethodsUsing fMRI, we investigated changes in neural network architecture from a baseline resting-state, through a task that included frustrative nonreward (FNR) and anticipation of new feedback following FNR (FNR+1), to a post-task resting-state in a transdiagnostic sample of 66 youth (33 female, mean age 14 years). Using a train/test/held-out procedure, we aimed to predict past-week irritability from the global efficiency (i.e., Eglob, capacity for parallel information processing) of brain networks before, during, and after frustration.ResultsCompared to pre-task resting state, FNR+1 and the post-state resting state were uniquely associated with a more segregated brain network organization. Nodes that were originally affiliated with the default-mode-temporal-limbic and fronto-parietal networks contributed most to this reconfiguration. Solely Eglob of brain networks that emerged after the frustrating task predicted self- and observer-rated irritability in previously unseen data. Self-reported irritability was predicted by Eglob of a fronto-temporal-limbic module, while observer-rated irritability was predicted by Eglob of motor-parietal and ventral-prefrontal-subcortical modules.DiscussionWe characterize frustration as an evolving brain network process and demonstrate the importance of the post-frustration recovery period for the pathophysiology of irritability; an insight that, if replicated, suggests specific intervention targets for irritability.

Objective Some studies have suggested alterations of structural brain asymmetry in attention-deficit/hyperactivity disorder (ADHD), but findings have been contradictory and based on small samples. Here, we performed the largest ever analysis of brain left-right asymmetry in ADHD, using 39 datasets of the ENIGMA consortium. Methods We analyzed asymmetry of subcortical and cerebral cortical structures in up to 1,933 people with ADHD and 1,829 unaffected controls. Asymmetry Indexes (AIs) were calculated per participant for each bilaterally paired measure, and linear mixed effects modeling was applied separately in children, adolescents, adults, and the total sample, to test exhaustively for potential associations of ADHD with structural brain asymmetries. Results There was no evidence for altered caudate nucleus asymmetry in ADHD, in contrast to prior literature. In children, there was less rightward asymmetry of the total hemispheric surface area compared to controls (t = 2.1, p = .04). Lower rightward asymmetry of medial orbitofrontal cortex surface area in ADHD (t = 2.7, p = .01) was similar to a recent finding for autism spectrum disorder. There were also some differences in cortical thickness asymmetry across age groups. In adults with ADHD, globus pallidus asymmetry was altered compared to those without ADHD. However, all effects were small (Cohen’s d from −0.18 to 0.18) and would not survive study-wide correction for multiple testing. Conclusion Prior studies of altered structural brain asymmetry in ADHD were likely underpowered to detect the small effects reported here. Altered structural asymmetry is unlikely to provide a useful biomarker for ADHD, but may provide neurobiological insights into the trait., Journal of Child Psychology and Psychiatry, 62 (10), ISSN:0021-9630, ISSN:1469-7610