Imaging-Genetics in Autism Spectrum Disorder: Advances, Translational Impact, and Future Directions

Autism Spectrum Disorder (ASD) refers to a group of heterogeneous neurodevelopmental disorders that are unified by impairments in reciprocal social communication and a pattern of inflexible behaviors. Recent genetic advances have resolved some of the complexity of the genetic architecture underlying ASD by identifying several genetic variants that contribute to the disorder. Different etiological pathways associated with ASD may converge through effects on common molecular mechanisms, such as synaptogenesis, neuronal motility, and axonal guidance. Recently, with more sophisticated techniques, neuroimaging, and neuropathological studies have provided some consistency of evidence that altered structure, activity, and connectivity within complex neural networks is present in ASD, compared to typically developing children. The imaging-genetics approach promises to help bridge the gap between genetic variation, resultant biological effects on the brain, and production of complex neuropsychiatric symptoms. Here, we review recent findings from the developing field of imaging-genetics applied to ASD. Studies to date have indicated that relevant risk genes are associated with alterations in circuits that mediate socio-emotional, visuo-spatial, and language processing. Longitudinal studies ideally focused on early development, in conjunction with investigation for gene–gene, and gene–environment interactions may move the promise of imaging-genetics in ASD closer to the clinical domain

Evaporite-bearing sequences in the Zechstein and Salina Basins, with a discussion on the origin of their cyclic features

Factors controlling cyclic sedimentation are discussed in a parallel study of two evaporite-bearing sequence, the Zechstein of Germany and the Silurian Salina Group of the Appalachian Basin. The Zechstein sequence was deposited in a basin that had received the debris swept in from the Variscan orogenic zone. The deposition of the evaporite-bearing sequence took place during a period of tectonic calm, preceded and succeeded by mild late Variscan movements. The sequence is divided into four major cycles by shale horizons accompanied and basinwards partially replaced by dolomites and anhydrites. Halite is the dominant sediment, it contains beds of anhydrite and potash salts, less commonly of shale, forming with the halite sedimentary cycles of diverse magnitudes. The Salina Group has been deposited in a basin that had previously received debris from the Taconic orogenic zone. The last orogenic movements had virtually ceased before the deposition of evaporites commenced. The evaporite-bearing sequence is divided into three major cycles by shale suites related to alluvial, fans of debris swept in from the previous orogenic zone. The shale beds are accompanied by dolomite beds containing stromatolitic horizons. The salt contains shale and dolomite beds of diverse thicknesses, giving rise to cycles of varied magnitudes. With increasing distance from the orogenic zone, the thinner shale interbeds in the salt grade into anhydrite. In contrast to the Zechstein sequence, in the Salina Group thicker anhydrite beds are rare and no potash zones have been found. The anhydrite deficiency is attributed by the author to bacterial reduction of the CaSO₄. The H₂S thus formed is in part retained in the sediments, in part it deposited FeS₂ or re-oxidized. The lack of potassium salts indicates a less inhibited communication with the open sea, as also witnessed by repeated incursions of marine fauna. In both sequences, most sedimentary cycles are controlled by the periodic entrance of diluted waters into the basin. Rain water enters directly as well as in the form of terrestrial run-off from the adjacent mountains, introducing mud and foreign ions, diluting and changing the ion ratios of the brines. Sea water enters the basin continuously or periodically, the concentration increases caused by the concomitant inflow of dissolved salts are mitigated by the reflux of more concentrated brines. Abrupt dilution of the brines by sea water followed by slow evaporation produces cycles of progressive solubility in the sediments resembling experimental successions. The periodic entrance of rain and sea water can be controlled by several factors. Increases in rainfall, particularly in the detritus source area, may reflect morphologically or astronomically induced climatic changes; the morphologic factors may in turn be controlled by tectonism, erosion and sediment accumulation. The ingress of sea water can be caused by intermittent subsidence in the bar area, or by a rise of sea level induced tectonically, glacio-eustatically, or simply by a change in wind direction. A few models involving parallel control of terrestrial and marine inflow are presented at the end

Suicidal behaviours among adolescents from 90 countries: A pooled analysis of the global school-based student health survey

Background: Understanding the burden and determinants of suicide during adolescence is key to achieving global health goals. We examined the prevalence and determinants of self-reported suicidal ideation and attempts among younger (13-15 years) and older adolescents (16-17 years).Methods: Pooled prevalence estimates with 95% confidence interval, were calculated for suicide ideation and attempts for 118 surveys from 90 countries that administered the Global School-based Student Health Survey (GSHS) to adolescents (13-17 years of age) from 2003 to 2017. Indicators (including individual and social factors) associated with suicidal ideation and attempts were determined from multivariable linear regressions on key outcomes.Results: The prevalence of suicidal ideation representing 397,299 adolescents (51.3% female) was significantly higher among girls than boys whereas attempts did not differ by age or sex. Being bullied, or having no close friends was associated with suicidal ideation among girls 13-15 years and 16-17 years, respectively. Among all boys, being in a fight and having no close friends was associated with suicidal ideation with the addition of serious injury for boys 13-15 years. Common to all younger adolescents was an association of suicide attempt with being bullied and having had a serious injury. Among young boys, having no close friends was an additional indicator for suicide attempt. Having no close friends was associated with suicide attempt in older adolescents with the addition to being bullied in older girls and serious injury in older boys.Conclusions: Building positive social relationships with peers and avoiding serious injury appear key to suicide prevention strategies for vulnerable adolescents. Targeted programs by age group and sex for such indicators could improve mental health during adolescence in low and middle-income countries, given the diverse risk profiles for suicidal ideation and attempts

Mental, behavioral and neurodevelopmental disorders in the ICD-11 : An international perspective on key changes and controversies

The Author(s). 2020Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, andreproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link tothe Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver(http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.An update of the chapter on Mental, Behavioral and Neurodevelopmental Disorders in the International Classification of Diseases and Related Health Problems (ICD) is of great interest around the world. The recent approval of the 11th Revision of the ICD (ICD-11) by the World Health Organization (WHO) raises broad questions about the status of nosology of mental disorders as a whole as well as more focused questions regarding changes to the diagnostic guidelines for specific conditions and the implications of these changes for practice and research. This Forum brings together a broad range of experts to reflect on key changes and controversies in the ICD-11 classification of mental disorders. Taken together, there is consensus that the WHO's focus on global applicability and clinical utility in developing the diagnostic guidelines for this chapter will maximize the likelihood that it will be adopted by mental health professionals and administrators. This focus is also expected to enhance the application of the guidelines in non-specialist settings and their usefulness for scaling up evidence-based interventions. The new mental disorders classification in ICD-11 and its accompanying diagnostic guidelines therefore represent an important, albeit iterative, advance for the field.Peer reviewedFinal Published versio

Toward precision therapeutics: general and specific factors differentiate symptom change in depressed adolescents.

BACKGROUND: The longitudinal course of multiple symptom domains in adolescents treated for major depression is not known. Revealing the temporal course of general and specific psychopathology factors, including potential differences between psychotherapies, may aid therapeutic decision-making. METHODS: Participants were adolescents with major depressive disorder (aged 11-17; 75% female; N = 465) who were part of the IMPACT trial, a randomized controlled trial comparing cognitive behavioral therapy, short-term psychoanalytic psychotherapy, and brief psychosocial intervention. Self-reported symptoms at baseline and 6, 12, 36, 52, and 86 weeks postrandomization were analyzed with bifactor modeling. RESULTS: General psychopathology factor scores decreased across treatment and one-year follow-up. Specific melancholic features and depressive cognitions factors decreased from baseline to 6 weeks. Conduct problems decreased across treatment and follow-up. Anxiety increased by 6 weeks and then reverted to baseline levels. Obsessions-compulsions did not change. Changes in general and specific factors were not significantly different between the three psychotherapies during treatment. During follow-up, however, conduct problems decreased more in brief psychosocial intervention versus cognitive behavioral therapy (1.02, 95% Bayes credible interval 0.25, 1.96), but not versus short-term psychoanalytic psychotherapy. CONCLUSIONS: The clinical response signature in this trial is best revealed by rapid reductions in depression symptoms and general psychopathology. Protracted improvements in general psychopathology and conduct problems subsequently occur. Psychosocial treatments for adolescent depression have comparable effects on general and specific psychopathology, although a psychoeducational, goal-focused approach may be indicated for youth with comorbid conduct problems

The Jeremoabo transpressional transfer fault, Rec?ncavo-Tucano Rift, NE Brazil.

The Jeremoabo fault, located in the Early Cretaceous Rec?ncavo?Tucano Rift, northeastern Brazil, represents an example of transfer fault. A field-based structural analysis along 20 km of exposures revealed an E?W-trending and steeply dipping reverse-sinistral fault that resulted from transpressional reactivation of a pre-existent weak zone. The fault is associated with a 5-km-wide footwall deformation zone, in which sandstone layers are folded and locally overturned becoming parallel to the fault. The deformation zone contains a pervasive system of NE- and NNW-trending conjugate Riedel shear fractures of outcrop to kilometer scale. A paleostress analysis based on these Riedel fractures indicated ?1 and ?3 trending, respectively, 016? and 108?, and ?2 subvertical, consistent with transpression and local switch between ?1 and ?2 relative to the regional paleostress field. The Jeremoabo fault links smaller rift border faults and has sense of slip consistent with the mapped offset of the basin border. Its transfer function is attested by linkage with a major dextral transfer fault and a transfer zone during the rifting period. By acting together these structures accommodated the change in asymmetry between the two major half-grabens of the rift

Structural neuroimaging correlates of social deficits are similar in autism spectrum disorder and attention-deficit/hyperactivity disorder: analysis from the POND Network

Autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), and obsessive-compulsive disorder (OCD) have been associated with difficulties recognizing and responding to social cues. Neuroimaging studies have begun to map the social brain; however, the specific neural substrates contributing to social deficits in neurodevelopmental disorders remain unclear. Three hundred and twelve children underwent structural magnetic resonance imaging of the brain (controls = 32, OCD = 44, ADHD = 77, ASD = 159; mean age = 11). Their social deficits were quantified on the Social Communication Questionnaire (SCQ) and the Reading the Mind in the Eyes Test (RMET). Multivariable regression models were used to examine the structural neuroimaging correlates of social deficits, with both a region of interest and a whole-brain vertex-wise approach. For the region of interest analysis, social brain regions were grouped into three networks: (1) lateral mentalization (e.g., temporal–parietal junction), (2) frontal cognitive (e.g., orbitofrontal cortex), and (3) subcortical affective (e.g., limbic system) regions. Overall, social communication deficits on the SCQ were associated with thinner cortices in the left lateral regions and the right insula, and decreased volume in the ventral striatum, across diagnostic groups (p = 0.006 to \u3c0.0001). Smaller subcortical volumes were associated with more severe social deficits on the SCQ in ASD and ADHD, and less severe deficits in OCD. On the RMET, larger amygdala/hippocampal volumes were associated with fewer deficits across groups. Overall, patterns of associations were similar in ASD and ADHD, supporting a common underlying biology and the blurring of the diagnostic boundaries between these disorders

Coping, fostering resilience, and driving care innovation for autistic people and their families during the COVID-19 pandemic and beyond

Abstract: The new coronavirus disease (COVID-19) pandemic is changing how society operates. Environmental changes, disrupted routines, and reduced access to services and social networks will have a unique impact on autistic individuals and their families and will contribute to significant deterioration in some. Access to support is crucial to address vulnerability factors, guide adjustments in home environments, and apply mitigation strategies to improve coping. The current crisis highlights that our regular care systems are not sufficient to meet the needs of the autism communities. In many parts of the world, people have shifted to online school and increased use of remote delivery of healthcare and autism supports. Access to these services needs to be increased to mitigate the negative impact of COVID-19 and future epidemics/pandemics. The rapid expansion in the use of telehealth platforms can have a positive impact on both care and research. It can help to address key priorities for the autism communities including long waitlists for assessment and care, access to services in remote locations, and restricted hours of service. However, system-level changes are urgently needed to ensure equitable access and flexible care models, especially for families and individuals who are socioeconomically disadvantaged. COVID-19 mandates the use of technology to support a broader range of care options and better meet the diverse needs of autistic people and their families. It behooves us to use this crisis as an opportunity to foster resilience not only for a given individual or their family, but also the system: to drive enduring and autism-friendly changes in healthcare, social systems, and the broader socio-ecological contexts

Physical health of autistic girls and women: a scoping review.

BACKGROUND: There is a growing recognition of sex and gender influences in autism. Increasingly, studies include comparisons between sexes or genders, but few have focused on clarifying the characteristics of autistic girls'/women's physical health. METHODS: A scoping review was conducted to determine what is currently known about the physical health of autistic girls/women. We screened 1112 unique articles, with 40 studies meeting the inclusion criteria. We used a convergent iterative process to synthesize this content into broad thematic areas. RESULTS: Autistic girls/women experience more overall physical health challenges compared to non-autistic girls/women and to autistic boys/men. Emerging evidence suggests increased prevalence of epilepsy in autistic girls/women compared to non-autistic girls/women and to autistic boys/men. The literature also suggests increased endocrine and reproductive health conditions in autistic girls/women compared to non-autistic girls/women. Findings regarding gastrointestinal, metabolic, nutritional, and immune-related conditions are preliminary and inconsistent. LIMITATIONS: The literature has substantial heterogeneity in how physical health conditions were assessed and reported. Further, our explicit focus on physical health may have constrained the ability to examine interactions between mental and physical health. The widely differing research aims and methodologies make it difficult to reach definitive conclusions. Nevertheless, in keeping with the goals of a scoping review, we were able to identify key themes to guide future research. CONCLUSIONS: The emerging literature suggests that autistic girls/women have heightened rates of physical health challenges compared to non-autistic girls/women and to autistic boys/men. Clinicians should seek to provide holistic care that includes a focus on physical health and develop a women's health lens when providing clinical care to autistic girls/women