scholarly journals New guidance to seekers of autism biomarkers: an update from studies of identical twins

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
John N. Constantino
Keyword(s):  
Allostatic Load ◽  
Statistical Power ◽  
Environmental Influences ◽  
Autism Spectrum ◽  
Main Body ◽  
Case Control Studies ◽  
Inherited Susceptibility ◽  
Behavioral Predictors ◽  
General Populations ◽  
Mz Twins

Abstract Background The autism spectrum disorders (ASD) are common neuropsychiatric conditions of childhood for which the vast proportion of population risk is attributable to inheritance, and for which there exist few if any replicated biomarkers. Main body This commentary summarizes a set of recent studies involving identical (monozygotic, MZ) twins which, taken together, have significant implications for the search for biomarkers of inherited susceptibility to autism. A first is that variation-in-severity of the condition (above the threshold for clinical diagnosis) appears more strongly influenced by stochastic/non-shared environmental influences than by heredity. Second is that there exist disparate early behavioral predictors of the familial recurrence of autism, which are themselves strongly genetically influenced but largely independent from one another. The nature of these postnatal predictors is that they are trait-like, continuously distributed in the general population, and largely independent from variation in general cognition, thereby reflecting a developmental substructure for familial autism. A corollary of these findings is that autism may arise as a developmental consequence of an allostatic load of earlier-occurring liabilities, indexed by early behavioral endophenotypes, in varying permutations and combinations. The clinical threshold can be viewed as a “tipping point” at which stochastic influences and/or other non-shared environmental influences assert much stronger influence on variation-in-severity (a) than do the genetic factors which contributed to the condition in the first place, and (b) than is observed in typical development. Conclusion Biomarkers identified on the basis of association with clinical symptom severity in ASD may reflect effects rather than causes of autism. The search for biomarkers of pathogenesis may benefit from a greater focus on traits that predict autism recurrence, among both clinical and general populations. In case–control studies, salient developmental liabilities should be systematically measured in both cases and controls, to avoid the erosion in statistical power (i.e., to detect differences) that can occur if control subjects carry sub-clinical aggregations of the same unmeasured traits that exert causal influences on the development of autism.

Highly sensitive adolescent benefits in positive school transitions: Evidence for vantage sensitivity in Japanese high-schoolers

2020 ◽  
Author(s):  
Shuhei Iimura
Keyword(s):  
High School ◽  
Statistical Power ◽  
Environmental Influences ◽  
Differential Susceptibility ◽  
School Transition ◽  
Well Being ◽  
Crossover Point ◽  
Japanese Adolescents ◽  
Highly Sensitive

Some researchers indicate that the transition to high school deflects adolescent developmental trajectories. Others assert it provides a new possibility for the promotion of adolescents’ socioemotional well-being. One critical view missing in such claims is that individual variabilities interact with environmental influences. We employed the framework of Differential Susceptibility Theory, which postulates that individual susceptibilities moderate external influences for better and for worse. In order to clarify the mechanism of adolescents’ differential adjustments, this paper investigated the role of sensory-processing sensitivity using the Japanese version of Highly Sensitive Child Scale for Adolescence (J-HSCS), and tested whether the diathesis-stress model or the differential susceptibility model best describes students’ socioemotional adjustment across their high school transition. The current paper used the two-wave data collected from Japanese adolescents aged from 14 to 15 years (n = 412, 50% girls). In Study 1, we investigated the replicability of psychometric properties of J-HSCS. The results supported previous findings, indicating its validity for the bifactor model. In Study 2, we utilized confirmatory competitive model testing, which maximizes statistical power by parameterizing the crossover point to allow a direct comparison of alternative models. The results indicated that neither the diathesis-stress nor the differential susceptibility models fitted the data. Rather, a strong vantage sensitivity model was revealed, suggesting that highly susceptible adolescents disproportionately benefitted from a positive school transition over their counterparts. This finding signified the role of adolescents’ sensitivity to environmental influences and the importance of considering its moderation under person x environment interactions.

scholarly journals The socioeconomic burden of antibiotic resistance in conflict-affected settings and refugee hosting countries: a systematic scoping review

2021 ◽  
Vol 15 (1) ◽  
Author(s):  
Elsa Kobeissi ◽  
Marilyne Menassa ◽  
Krystel Moussally ◽  
Ernestina Repetto ◽  
Ismail Soboh ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Scoping Review ◽  
Statistical Power ◽  
Data Extraction ◽  
Quality Data ◽  
Sufficient Information ◽  
Socioeconomic Burden ◽  
General Populations ◽  
Global Threat ◽  
The Cost

Abstract Background Antibiotic resistance (ABR) is a major global threat. Armed and protracted conflicts act as multipliers of infection and ABR, thus leading to increased healthcare and societal costs. We aimed to understand and describe the socioeconomic burden of ABR in conflict-affected settings and refugee hosting countries by conducting a systematic scoping review. Methods A systematic search of PubMed, Medline (Ovid), Embase, Web of Science, SCOPUS and Open Grey databases was conducted to identify all relevant human studies published between January 1990 and August 2019. An updated search was also conducted in April 2020 using Medline/Ovid. Independent screenings of titles/abstracts followed by full texts were performed using pre-defined criteria. The Newcastle-Ottawa Scale was used to assess study quality. Data extraction and analysis were based on the PICOS framework and following the PRISMA-ScR guideline. Results The search yielded 8 studies (7 publications), most of which were single-country, mono-center and retrospective studies. The studies were conducted in Lebanon (n = 3), Iraq (n = 2), Jordan (n = 1), Palestine (n = 1) and Yemen (n = 1). Most of the studies did not have a primary aim to assess the socioeconomic impact of ABR and were small studies with limited statistical power that could not demonstrate significant associations. The included studies lacked sufficient information for the accurate evaluation of the cost incurred by antibiotic resistant infections in conflict-affected countries. Conclusion This review highlights the scarcity of research on the socioeconomic burden of ABR on general populations in conflict-affected settings and on refugees and migrants in host countries, and lists recommendations for consideration in future studies. Further studies are needed to understand the cost of ABR in these settings to develop and implement adaptable policies.

scholarly journals Dissecting autism and schizophrenia through neuroimaging genomics

Brain ◽  
2021 ◽  
Author(s):  
Clara A Moreau ◽  
Armin Raznahan ◽  
Pierre Bellec ◽  
Mallar Chakravarty ◽  
Paul M Thompson ◽  
...  
Keyword(s):  
High Risk ◽  
Psychiatric Symptoms ◽  
Clinical Manifestations ◽  
Autism Spectrum ◽  
Case Control ◽  
Effect Sizes ◽  
Case Control Studies ◽  
Top Down ◽  
Bottom Up ◽  
Genomic Variants

Abstract Neuroimaging genomic studies of autism spectrum disorder and schizophrenia have mainly adopted a ‘top-down’ approach, starting with the behavioural diagnosis, and moving down to intermediate brain phenotypes and underlying genetic factors. Advances in imaging and genomics have been successfully applied to increasingly large case-control studies. As opposed to diagnostic-first approaches, the bottom-up strategy starts at the level of molecular factors enabling the study of mechanisms related to biological risk, irrespective of diagnoses or clinical manifestations. The latter strategy has emerged from questions raised by top-down studies: Why are mutations and brain phenotypes over-represented in individuals with a psychiatric diagnosis? Are they related to core symptoms of the disease or to comorbidities? Why are mutations and brain phenotypes associated with several psychiatric diagnoses? Do they impact a single dimension contributing to all diagnoses? In the review, we aimed at summarizing imaging genomic findings in autism and schizophrenia as well as neuropsychiatric variants associated with these conditions. Top-down studies of autism and schizophrenia identified patterns of neuroimaging alterations with small effect-sizes and an extreme polygenic architecture. Genomic variants and neuroimaging patterns are shared across diagnostic categories suggesting pleiotropic mechanisms at the molecular and brain network levels. Although the field is gaining traction; characterizing increasingly reproducible results, it is unlikely that top-down approaches alone will be able to disentangle mechanisms involved in autism or schizophrenia. In stark contrast with top-down approaches, bottom-up studies showed that the effect-sizes of high-risk neuropsychiatric mutations are equally large for neuroimaging and behavioural traits. Low specificity has been perplexing with studies showing that broad classes of genomic variants affect a similar range of behavioral and cognitive dimensions, which may be consistent with the highly polygenic architecture of psychiatric conditions. The surprisingly discordant effect sizes observed between genetic and diagnostic first approaches underscore the necessity to decompose the heterogeneity hindering case-control studies in idiopathic conditions. We propose a systematic investigation across a broad spectrum of neuropsychiatric variants to identify putative latent dimensions underlying idiopathic conditions. Gene expression data on temporal, spatial and cell type organization in the brain have also considerable potential for parsing the mechanisms contributing to these dimensions phenotypes. While large neuroimaging genomic datasets are now available in unselected populations, there is an urgent need for data on individuals with a range of psychiatric symptoms and high-risk genomic variants. Such efforts together with more standardized methods will improve mechanistically informed predictive modeling for diagnosis and clinical outcomes.

Distinguishing autism from co-existing conditions: a behavioural profiling investigation

2016 ◽  
Vol 2 (1) ◽  
pp. 41-54
Author(s):  
Ashleigh Saunders ◽  
Karen E. Waldie
Keyword(s):  
Statistical Power ◽  
Psychiatric Comorbidity ◽  
Adaptive Functioning ◽  
Autism Spectrum ◽  
Small Sample ◽  
Comorbid Conditions ◽  
Sample Sizes ◽  
Content Type ◽  
Small Sample Sizes ◽  
Comorbid Adhd

Purpose – Autism spectrum disorder (ASD) is a lifelong neurodevelopmental condition for which there is no known cure. The rate of psychiatric comorbidity in autism is extremely high, which raises questions about the nature of the co-occurring symptoms. It is unclear whether these additional conditions are true comorbid conditions, or can simply be accounted for through the ASD diagnosis. The paper aims to discuss this issue. Design/methodology/approach – A number of questionnaires and a computer-based task were used in the current study. The authors asked the participants about symptoms of ASD, attention deficit hyperactivity disorder (ADHD) and anxiety, as well as overall adaptive functioning. Findings – The results demonstrate that each condition, in its pure form, can be clearly differentiated from one another (and from neurotypical controls). Further analyses revealed that when ASD occurs together with anxiety, anxiety appears to be a separate condition. In contrast, there is no clear behavioural profile for when ASD and ADHD co-occur. Research limitations/implications – First, due to small sample sizes, some analyses performed were targeted to specific groups (i.e. comparing ADHD, ASD to comorbid ADHD+ASD). Larger sample sizes would have given the statistical power to perform a full scale comparative analysis of all experimental groups when split by their comorbid conditions. Second, males were over-represented in the ASD group and females were over-represented in the anxiety group, due to the uneven gender balance in the prevalence of these conditions. Lastly, the main profiling techniques used were questionnaires. Clinical interviews would have been preferable, as they give a more objective account of behavioural difficulties. Practical implications – The rate of psychiatric comorbidity in autism is extremely high, which raises questions about the nature of the co-occurring symptoms. It is unclear whether these additional conditions are true comorbid conditions, or can simply be accounted for through the ASD diagnosis. Social implications – This information will be important, not only to healthcare practitioners when administering a diagnosis, but also to therapists who need to apply evidence-based treatment to comorbid and stand-alone conditions. Originality/value – This study is the first to investigate the nature of co-existing conditions in ASD in a New Zealand population.

scholarly journals Genetic and environmental influences on structural brain measures in twins with autism spectrum disorder

2019 ◽  
Vol 25 (10) ◽  
pp. 2556-2566 ◽  
Author(s):  
John P. Hegarty ◽  
Luiz F. L. Pegoraro ◽  
Laura C. Lazzeroni ◽  
Mira M. Raman ◽  
Joachim F. Hallmayer ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Environmental Factors ◽  
Cortical Thickness ◽  
Genetic Factors ◽  
Brain Size ◽  
Environmental Influences ◽  
Autism Spectrum ◽  
Growth Patterns ◽  
Spectrum Disorder ◽  
Structural Brain

Abstract Atypical growth patterns of the brain have been previously reported in autism spectrum disorder (ASD) but these alterations are heterogeneous across individuals, which may be associated with the variable effects of genetic and environmental influences on brain development. Monozygotic (MZ) and dizygotic (DZ) twin pairs with and without ASD (aged 6–15 years) were recruited to participate in this study. T1-weighted MRIs (n = 164) were processed with FreeSurfer to evaluate structural brain measures. Intra-class correlations were examined within twin pairs and compared across diagnostic groups. ACE modeling was also completed. Structural brain measures, including cerebral and cerebellar gray matter (GM) and white matter (WM) volume, surface area, and cortical thickness, were primarily influenced by genetic factors in TD twins; however, mean curvature appeared to be primarily influenced by environmental factors. Similarly, genetic factors accounted for the majority of variation in brain size in twins with ASD, potentially to a larger extent regarding curvature and subcortical GM; however, there were also more environmental contributions in twins with ASD on some structural brain measures, such that cortical thickness and cerebellar WM volume were primarily influenced by environmental factors. These findings indicate potential neurobiological outcomes of the genetic and environmental risk factors that have been previously associated with ASD and, although preliminary, may help account for some of the previously outlined neurobiological heterogeneity across affected individuals. This is especially relevant regarding the role of genetic and environmental factors in the development of ASD, in which certain brain structures may be more sensitive to specific influences.

scholarly journals May the best friend be an enemy if not recognized early: possible role of omega-3 against cardiovascular abnormalities due antipsychotics in the treatment of autism

2009 ◽  
Vol 67 (3b) ◽  
pp. 922-926 ◽  
Author(s):  
Roberta M. Cysneiros ◽  
Vera C. Terra ◽  
Hélio R. Machado ◽  
Ricardo M. Arida ◽  
José Salomão Schwartzman ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Sudden Cardiac Death ◽  
Cardiac Death ◽  
Protective Role ◽  
Autism Spectrum ◽  
Antipsychotic Treatment ◽  
Omega 3 Fatty Acids ◽  
Omega 3 ◽  
Case Control Studies ◽  
Qt Interval Prolongation

Autism spectrum disorders (ASD) are neurodevelopment disorders that cause severe and pervasive impairment in socialization, communication, and behavior. Although the availability of antipsychotic treatment in ASD has expanded, we will be very careful with side effects of these pharmacological agents. Following this reasoning, emerging data indicate that some antipsychotics may be associated with cardiovascular adverse events (e.g., QT interval prolongation), suggesting that this could be correlated to sudden death. Quite interesting, substantial evidence from epidemiological and case-control studies indicates that omega-3 reduces the risk of cardiovascular mortality, particularly sudden cardiac death. In accordance to the above mentioned findings, as omega-3 fatty acids per se have a direct cardiovascular protective role, our paper hypothesized that omega-3 fatty acids supplementation in ASD patients treated with atypical antipsychotic drugs may reduce cardiac arrhythmias and hence sudden cardiac death.

scholarly journals Bayesian Variable Selection Methods for Matched Case-Control Studies

2017 ◽  
Vol 13 (1) ◽  
Author(s):  
Josephine Asafu-Adjei ◽  
Mahlet G. Tadesse ◽  
Brent Coull ◽  
Raji Balasubramanian ◽  
Michael Lev ◽  
...  
Keyword(s):  
Variable Selection ◽  
Statistical Power ◽  
High Efficiency ◽  
Massachusetts General Hospital ◽  
Imaging Study ◽  
Bayesian Variable Selection ◽  
Case Control ◽  
Selection Methods ◽  
Case Control Studies ◽  
Matched Case

AbstractMatched case-control designs are currently used in many biomedical applications. To ensure high efficiency and statistical power in identifying features that best discriminate cases from controls, it is important to account for the use of matched designs. However, in the setting of high dimensional data, few variable selection methods account for matching. Bayesian approaches to variable selection have several advantages, including the fact that such approaches visit a wider range of model subsets. In this paper, we propose a variable selection method to account for case-control matching in a Bayesian context and apply it using simulation studies, a matched brain imaging study conducted at Massachusetts General Hospital, and a matched cardiovascular biomarker study conducted by the High Risk Plaque Initiative.

scholarly journals Autism spectrum disorders: weighing the risk of SSRI exposure in pregnancy

2014 ◽  
Vol 23 (3) ◽  
pp. 231-233 ◽  
Author(s):  
G. Ostuzzi ◽  
C. Barbui
Keyword(s):  
Autism Spectrum Disorders ◽  
Selective Serotonin Reuptake Inhibitors ◽  
Autism Spectrum ◽  
Case Control Studies ◽  
Confounding By Indication ◽  
Increased Risk ◽  
Exposure During Pregnancy ◽  
Spectrum Disorders ◽  
Development Outcomes ◽  
Recent Cohort

A possible link between prenatal exposure to the selective serotonin reuptake inhibitors (SSRIs) and development of autism spectrum disorders (ASDs), previously suggested by two case-control studies, was not confirmed by a recent cohort study that followed for 5–10 years more than 600,000 births. However, this study failed to demonstrate that SSRI exposure during pregnancy is safe in terms of child development outcomes, as an increased risk of ASDs cannot be completely ruled out. In the present article, the main strengths and weaknesses of this study are briefly analysed, including a possibility of confounding by indication.

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