Probing the overarching continuum theory: data-driven phenotypic clustering of children with ASD or ADHD

The clinical validity of the distinction between ADHD and ASD is a longstanding discussion. Recent advances in the realm of data-driven analytic techniques now enable us to formally investigate theories aiming to explain the frequent co-occurrence of these neurodevelopmental conditions. In this study, we probe different theoretical positions by means of a pre-registered integrative approach of novel classification, subgrouping, and taxometric techniques in a representative sample (N = 434), and replicate the results in an independent sample (N = 219) of children (ADHD, ASD, and typically developing) aged 7–14 years. First, Random Forest Classification could predict diagnostic groups based on questionnaire data with limited accuracy—suggesting some remaining overlap in behavioral symptoms between them. Second, community detection identified four distinct groups, but none of them showed a symptom profile clearly related to either ADHD or ASD in neither the original sample nor the replication sample. Third, taxometric analyses showed evidence for a categorical distinction between ASD and typically developing children, a dimensional characterization of the difference between ADHD and typically developing children, and mixed results for the distinction between the diagnostic groups. We present a novel framework of cutting-edge statistical techniques which represent recent advances in both the models and the data used for research in psychiatric nosology. Our results suggest that ASD and ADHD cannot be unambiguously characterized as either two separate clinical entities or opposite ends of a spectrum, and highlight the need to study ADHD and ASD traits in tandem.</p

Clinical subtyping using community detection: Limited utility?

ObjectivesTo discover psychiatric subtypes, researchers are adopting a method called community detection. This method was not subjected to the same scrutiny in the psychiatric literature as traditional clustering methods. Furthermore, many community detection algorithms have been developed without psychiatric sample sizes and variable numbers in mind. We aim to provide clarity to researchers on the utility of this method.MethodsWe provide an introduction to community detection algorithms, specifically describing the crucial differences between correlation-based and distance-based community detection. We compare community detection results to results of traditional methods in a simulation study representing typical psychiatry settings, using three conceptualizations of how subtypes might differ.ResultsWe discovered that the number of recovered subgroups was often incorrect with several community detection algorithms. Correlation-based community detection fared better than distance-based community detection, and performed relatively well with smaller sample sizes. Latent profile analysis was more consistent in recovering subtypes. Whether methods were successful depended on how differences were introduced.ConclusionsTraditional methods like latent profile analysis remain reasonable choices. Furthermore, results depend on assumptions and theoretical choices underlying subtyping analyses, which researchers need to consider before drawing conclusions on subtypes. Employing multiple subtyping methods to establish method dependency is recommended

Modern Views of Machine Learning for Precision Psychiatry

In light of the NIMH's Research Domain Criteria (RDoC), the advent of functional neuroimaging, novel technologies and methods provide new opportunities to develop precise and personalized prognosis and diagnosis of mental disorders. Machine learning (ML) and artificial intelligence (AI) technologies are playing an increasingly critical role in the new era of precision psychiatry. Combining ML/AI with neuromodulation technologies can potentially provide explainable solutions in clinical practice and effective therapeutic treatment. Advanced wearable and mobile technologies also call for the new role of ML/AI for digital phenotyping in mobile mental health. In this review, we provide a comprehensive review of the ML methodologies and applications by combining neuroimaging, neuromodulation, and advanced mobile technologies in psychiatry practice. Additionally, we review the role of ML in molecular phenotyping and cross-species biomarker identification in precision psychiatry. We further discuss explainable AI (XAI) and causality testing in a closed-human-in-the-loop manner, and highlight the ML potential in multimedia information extraction and multimodal data fusion. Finally, we discuss conceptual and practical challenges in precision psychiatry and highlight ML opportunities in future research

From pattern classification to stratification: towards conceptualizing the heterogeneity of Autism Spectrum Disorder

Pattern classification and stratification approaches have increasingly been used in research on Autism Spectrum Disorder (ASD) over the last ten years with the goal of translation towards clinical applicability. Here, we present an extensive scoping literature review on those two approaches. We screened a total of 635 studies, of which 57 pattern classification and 19 stratification studies were included. We observed large variance across pattern classification studies in terms of predictive performance from about 60% to 98% accuracy, which is among other factors likely linked to sampling bias, different validation procedures across studies, the heterogeneity of ASD and differences in data quality. Stratification studies were less prevalent with only two studies reporting replications and just a few showing external validation. While some identified strata based on cognition and intelligence reappear across studies, biology as a stratification marker is clearly underexplored. In summary, mapping biological differences at the level of the individual with ASD is a major challenge for the field now. Conceptualizing those mappings and individual trajectories that lead to the diagnosis of ASD, will become a major challenge in the near future

Global gene expression profiling of healthy human brain and its application in studying neurological disorders

The human brain is the most complex structure known to mankind and one of the greatest challenges in modern biology is to understand how it is built and organized. The power of the brain arises from its variety of cells and structures, and ultimately where and when different genes are switched on and off throughout the brain tissue. In other words, brain function depends on the precise regulation of gene expression in its sub-anatomical structures. But, our understanding of the complexity and dynamics of the transcriptome of the human brain is still incomplete. To fill in the need, we designed a gene expression model that accurately defines the consistent blueprint of the brain transcriptome; thereby, identifying the core brain specific transcriptional processes conserved across individuals. Functionally characterizing this model would provide profound insights into the transcriptional landscape, biological pathways and the expression distribution of neurotransmitter systems. Here, in this dissertation we developed an expression model by capturing the similarly expressed gene patterns across congruently annotated brain structures in six individual brains by using data from the Allen Brain Atlas (ABA). We found that 84% of genes are expressed in at least one of the 190 brain structures. By employing hierarchical clustering we were able to show that distinct structures of a bigger brain region can cluster together while still retaining their expression identity. Further, weighted correlation network analysis identified 19 robust modules of coexpressing genes in the brain that demonstrated a wide range of functional associations. Since signatures of local phenomena can be masked by larger signatures, we performed local analysis on each distinct brain structure. Pathway and gene ontology enrichment analysis on these structures showed, striking enrichment for brain region specific processes. Besides, we also mapped the structural distribution of the gene expression profiles of genes associated with major neurotransmission systems in the human. We also postulated the utility of healthy brain tissue gene expression to predict potential genes involved in a neurological disorder, in the absence of data from diseased tissues. To this end, we developed a supervised classification model, which achieved an accuracy of 84% and an AUC (Area Under the Curve) of 0.81 from ROC plots, for predicting autism-implicated genes using the healthy expression model as the baseline. This study represents the first use of healthy brain gene expression to predict the scope of genes in autism implication and this generic methodology can be applied to predict genes involved in other neurological disorders

An assessment of the autism neuroimaging literature for the prospects of re-executability

Background: The degree of reproducibility of the neuroimaging literature in psychiatric application areas has been called into question and the issues that relate to this reproducibility are extremely complex. Some of these complexities have to do with the underlying biology of the disorders that we study and others arise due to the technology we apply to the analysis of the data we collect. Ultimately, the observations we make get communicated to the rest of the community through publications in the scientific literature. Methods: We sought to perform a ‘re-executability survey’ to evaluate the recent neuroimaging literature with an eye toward seeing if the technical aspects of our publication practices are helping or hindering the overall quest for a more reproducible understanding of brain development and aging. The topic areas examined include availability of the data, the precision of the imaging method description and the reporting of the statistical analytic approach, and the availability of the complete results. We applied the survey to 50 publications in the autism neuroimaging literature that were published between September 16, 2017 to October 1, 2018. Results: The results of the survey indicate that for the literature examined, data that is not already part of a public repository is rarely available, software tools are usually named but versions and operating system are not, it is expected that reasonably skilled analysts could approximately perform the analyses described, and the complete results of the studies are rarely available. Conclusions: We have identified that there is ample room for improvement in research publication practices. We hope exposing these issues in the retrospective literature can provide guidance and motivation for improving this aspect of our reporting practices in the future

Prediksi Gejala Autism Spectrum Disorders pada Remaja Menggunakan Optimasi Particle Swarm Optimization dan Algoritma Support Vector Machine

Abstrak: Telah ada peningkatan prevalensi diagnosis Autism Spectrum Disorder (ASD) secara global selama dekade terakhir. Perkiraan prevalensi ASD yang diperbarui dan keseluruhan di Asia akan membantu para profesional kesehatan untuk mengembangkan strategi kesehatan masyarakat yang relevan. Dalam penelitian ini, mengusulkan metode untuk prediksi gejala ASD menggunakan teknik integrasi seleksi fitur PSO dan algoritma Support Vector Machine. Penelitian ini menggunakan dataset dari UCI repository. Model yang diusulkan meliputi penerapan seleksi fitur menggunakan&nbsp; particle swarm optimization (PSO), dengan algoritma pengklasifikasi. Hasil akhir akan dilakukan perbandingan pengujian dan analisa terhadap model prediksi yang memiliki tingkat akurasi tertinggi atau terbaik dalam prediksi gejala ASD. Dalam penelitian ini menggunakan dataset UCI repository yaitu data ASD pada remaja, data tersebut memiliki jumlah data sebanyak 104 instance dan 21 atribut, 41 orang tidak menderita ASD dan 63 orang menderita ASD, tools yang digunakan untuk menerapkan model usulan menggunakan aplikasi Weka versi 3.8.4. Untuk mengetahui model usulan yang diajukan pada penelitian ini, pertama menguji dengan klasifikasi tunggal SVM, dan kedua, menguji dengan seleksi fitur PSO dan algoritma klasifikasi SVM. Untuk mengetahui apakah seleksi fitur PSO berpengaruh terhadap performa algoritma klasifikasi SVM. Pengujian pertama, nilai akurasi yang dihasilkan oleh algoritma klasifikasi SVM adalah sebesar 89.42%, dan nilai AUC sebesar 0.891. Berdasarkan pengujian yang kedua yaitu menggunakan seleksi fitur PSO, seleksi fitur PSO dapat meningkatkan performa algoritma klasifikasi SVM sebesar 2,88% dan nilai AUC sebesar 0,024. &nbsp; Kata kunci: Autism Spectrum Disorder, Particle Swarm Optimizatio, Support Vector Machine &nbsp; Abstract:&nbsp;There has been an increase in the prevalence of diagnoses of Autism Spectrum Disorder (ASD) globally over the past decade. Updated and overall ASD prevalence estimates in Asia will help health professionals to develop relevant public health strategies. In this study, proposing a method for ASD symptom prediction using PSO feature selection integration techniques and the Support Vector Machine algorithm. This study uses a dataset from the UCI repository. The proposed model includes the application of feature selection using particle swarm optimization (PSO), with the classification algorithm. The final result will be a comparison test and analysis of prediction models that have the highest or best accuracy in predicting ASD symptoms. In this study using the UCI repository dataset, ASD data on adolescents, the data has 104 data and 21 attributes, 41 people do not suffer from ASD and 63 people suffer from ASD, tools used to implement the proposed model using the Weka application version 3.8.4 . To find out the proposed model proposed in this study, firstly testing with SVM single classification, and secondly, testing with PSO feature selection and SVM classification algorithm. To find out whether the PSO feature selection affects the performance of the SVM classification algorithm. The first test, the accuracy value generated by the SVM classification algorithm is 89.42%, and the AUC value is 0.891. Based on the second test using PSO feature selection, PSO feature selection can improve the performance of the SVM classification algorithm by 2.88% and the AUC value of 0.024. &nbsp; Keywords: Autism Spectrum Disorder, Particle Swarm Optimizatio, Support Vector Machine

Transdiagnostic profiles of behaviour and communication relate to academic and socioemotional functioning and neural white matter organisation

Background: Behavioural and language difficulties co-occur in multiple neurodevelopmental conditions. Our understanding of these problems has arguably been slowed by an overreliance on study designs that compare diagnostic groups and fail to capture the overlap across different neurodevelopmental disorders and the heterogeneity within them. Methods: We recruited a large transdiagnostic cohort of children with complex needs (N = 805) to identify distinct subgroups of children with common profiles of behavioural and language strengths and difficulties. We then investigated whether and how these data-driven groupings could be distinguished from a comparison sample (N = 158) on measures of academic and socioemotional functioning and patterns of global and local white matter connectome organisation. Academic skills were assessed via standardised measures of reading and maths. Socioemotional functioning was captured by the parent-rated version of the Strengths and Difficulties Questionnaire. Results: We identified three distinct subgroups of children, each with different levels of difficulties in structural language, pragmatic communication, and hot and cool executive functions. All three subgroups struggled with academic and socioemotional skills relative to the comparison sample, potentially representing three alternative but related developmental pathways to difficulties in these areas. The children with the weakest language skills had the most widespread difficulties with learning, whereas those with more pronounced difficulties with hot executive skills experienced the most severe difficulties in the socioemotional domain. Each data-driven subgroup could be distinguished from the comparison sample based on both shared and subgroup-unique patterns of neural white matter organisation. Children with the most pronounced deficits in language, cool executive, or hot executive function were differentiated from the comparison sample by altered connectivity in predominantly thalamocortical, temporal-parietal-occipital, and frontostriatal circuits, respectively. Conclusions: These findings advance our understanding of commonly co-morbid behavioural and language problems and their relationship to behavioural outcomes and neurobiological substrates