Predictive processing accounts of autism posit that autistic individuals' perception is less biased by expectations than nonautistic individuals', perhaps through stronger precision‐weighting of ...prediction errors. Since precision‐weighting is fundamental to all information processing, under this theory, the differences between autistic and nonautistic individuals should be domain‐general and observable in both behavior and brain responses. This study used EEG, behavioral responses, and eye‐tracking co‐registration during gaze‐direction adaptation, to investigate whether increased precision‐weighting of prediction errors is evident through smaller adaptation after‐effects in autistic adolescents compared with nonautistic peers. Multilevel modeling showed that autistic and nonautistic adolescents' responses were consistent with behavioral adaptation, with Bayesian statistics providing extremely strong evidence for the absence of a group difference. Cluster‐based permutation testing of ERP responses did not show the expected adaptation after‐effect but did show habituation to repeated stimulus presentation, and no group difference was detected, a result not consistent with the theoretical account. Combined with the few other available studies, the current findings raise challenges for the theory, suggesting no fundamental difference in precision‐weighting of prediction errors in autism.
Lay Summary
Some researchers claim that we never see the world exactly as it is, but instead we always interpret things based on what we have seen before. Recently, some researchers have tried to explain autism as the result of differences in this system of interpreting the world based on what we have seen before. This experiment used a visual illusion to test this idea, because the strength of the illusion can show us how much participants are interpreting pictures based on what they have seen before. We used this illusion to test whether autistic teenagers were influenced less by the previous pictures we had showed them than nonautistic teenagers were. We found very strong evidence that the autistic and nonautistic teenagers were equally influenced by what they had seen before, which does not support the theory, and we ask for updates to the theory.
Attention-deficit/hyperactivity disorder (ADHD) is associated with functional impairments in different areas of daily life. One such area is social functioning. The purpose of this paper is to ...critically review research on social dysfunctioning in children with ADHD. Children with ADHD often have conflicts with adults and peers, and suffer from unpopularity, rejection by peers, and a lack of friendships, in part as a consequence of their ADHD symptoms. Comorbid oppositional defiant or conduct disorder aggravates these impairments. In some cases the inadequate social behavior of children with ADHD may be phenomenologically and etiologically related to pervasive developmental disorders (PDD). However, the causes and consequences of PDD symptoms in ADHD are understudied. Also, the relative contributions of ADHD, on the one hand, and comorbid disorders, on the other, to the course of social impairments are unknown. Social dysfunctioning in children with ADHD appears to increase their risk of later psychopathology other than ADHD. Thus far effective treatment for social dysfunctioning is lacking. Future research should address the exact nature and long-term consequences of social dysfunctioning in children with ADHD, and focus on development of effective treatment strategies.
Molecular Landscape of Tourette's Disorder Widomska, Joanna; De Witte, Ward; Buitelaar, Jan K ...
International journal of molecular sciences,
01/2023, Letnik:
24, Številka:
2
Journal Article
Recenzirano
Odprti dostop
Tourette's disorder (TD) is a highly heritable childhood-onset neurodevelopmental disorder and is caused by a complex interplay of multiple genetic and environmental factors. Yet, the molecular ...mechanisms underlying the disorder remain largely elusive. In this study, we used the available omics data to compile a list of TD candidate genes, and we subsequently conducted tissue/cell type specificity and functional enrichment analyses of this list. Using genomic data, we also investigated genetic sharing between TD and blood and cerebrospinal fluid (CSF) metabolite levels. Lastly, we built a molecular landscape of TD through integrating the results from these analyses with an extensive literature search to identify the interactions between the TD candidate genes/proteins and metabolites. We found evidence for an enriched expression of the TD candidate genes in four brain regions and the pituitary. The functional enrichment analyses implicated two pathways ('cAMP-mediated signaling' and 'Endocannabinoid Neuronal Synapse Pathway') and multiple biological functions related to brain development and synaptic transmission in TD etiology. Furthermore, we found genetic sharing between TD and the blood and CSF levels of 39 metabolites. The landscape of TD not only provides insights into the (altered) molecular processes that underlie the disease but, through the identification of potential drug targets (such as FLT3, NAALAD2, CX3CL1-CX3CR1, OPRM1, and HRH2), it also yields clues for developing novel TD treatments.
One neurodevelopmental theory hypothesizes remission of attention-deficit/hyperactivity disorder (ADHD) to result from improved prefrontal top-down control, while ADHD, independent of the current ...diagnosis, is characterized by stable non-cortical deficits (Halperin & Schulz, 2006). We tested this theory using resting state functional MRI (fMRI) data in a large sample of adolescents with remitting ADHD, persistent ADHD, and healthy controls.
Participants in this follow-up study were 100 healthy controls and 129 adolescents with ADHD combined type at baseline (mean age at baseline 11.8 years; at follow-up 17.5 years). Diagnostic information was collected twice and augmented with magnetic resonance imaging (MRI) scanning at follow-up. We used resting state functional connectivity (RSFC) of the executive control network to investigate whether improved prefrontal top-down control was related to a developmental decrease in ADHD symptoms. In addition, we tested whether non-cortical RSFC, i.e., cerebellar and striatal RSFC, was aberrant in persistent and/or remittent ADHD compared to controls.
Higher connectivity within frontal regions (anterior cingulate cortex) of the executive control network was related to decreases in ADHD symptoms. This association was driven by change in hyperactive/impulsive symptoms and not by change in inattention. Participants with remitting ADHD showed stronger RSFC than controls within this network, while persistent ADHD cases exhibited RSFC strengths intermediate to remittent ADHD cases and controls. Cerebellar and subcortical RSFC did not differ between participants with ADHD and controls.
In line with the neurodevelopmental theory, symptom recovery in ADHD was related to stronger integration of prefrontal regions in the executive control network. The pattern of RSFC strength across remittent ADHD, persistent ADHD, and healthy controls potentially reflects the presence of compensatory neural mechanisms that aid symptomatic remission.
We propose to bring together the hitherto rather separate research fields of autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD), and argue that by contrasting and ...combining findings of the endophenotypes of ASD and ADHD new insights can be gained into the etiology and pathophysiology of these two disorders. Given the highly heritable nature of both disorders, studies of the genes explaining the shared origins of the two neurodevelopmental disorders seem particularly called for. Instead of the clinical diagnosis, using neurocognitive measures as (endo)phenotypes that index genetic liability appears a powerful tool in gene finding. We, therefore, extensively reviewed the literature and not only included research wherein ASD and ADHD were compared within a single study, but extended our search also to the separate lines of cognitive neuroscience research. We discuss which cognitive and brain measures will be useful in future genetic studies targeting pleiotropic genes for ASD and ADHD. By specifying the most promising endophenotypic measures we chart the future course for endophenotypic research in ASD and ADHD. We also discuss the various models that may explain the frequent co-occurrence of ASD and ADHD.
•Emotion dysregulation predicts change in ADHD severity.•Nodal efficiency in emotion-related brain networks impacts change in ADHD severity.•Strongest link between change in ADHD severity and nodal ...efficiency in OFC.
The course of attention deficit hyperactivity disorder (ADHD) from adolescence into adulthood shows large variations between individuals; nonetheless determinants of interindividual differences in the course are not well understood. A frequent problem in ADHD, associated with worse outcomes, is emotion dysregulation. We investigated whether emotion dysregulation and integration of emotion-related functional brain networks affect interindividual differences in ADHD severity change. ADHD severity and resting state neuroimaging data were measured in ADHD and unaffected individuals at two points during adolescence and young adulthood. Bivariate latent change score models were applied to investigate whether emotion dysregulation and network integration affect ADHD severity changes. Emotion dysregulation was gauged from questionnaire subscales for conduct problems, emotional problems and emotional lability. Better emotion regulation was associated with a better course of ADHD (104 participants, 44 females, age range: 12–27). Using graph analysis, we determined network integration of emotion-related functional brain networks. Network integration was measured by nodal efficiency, i.e., the average inverse path distance from one node to all other nodes. A pattern of low nodal efficiency of cortical regions associated with emotion processing and high nodal efficiency in subcortical areas and cortical areas involved in implicit emotion regulation predicted a better ADHD course. Larger nodal efficiency of the right orbitofrontal cortex was related to a better course of ADHD (99 participants, 42 females, age range: 10–29). We demonstrated that neural and behavioral covariates associated with emotion regulation affect the course of ADHD severity throughout adolescence and early adulthood beyond baseline effects of ADHD severity.
Attention-deficit/hyperactivity disorder (ADHD) is a persistent neurodevelopmental disorder that affects 5% of children and adolescents and 2.5% of adults worldwide. Throughout an individual's ...lifetime, ADHD can increase the risk of other psychiatric disorders, educational and occupational failure, accidents, criminality, social disability and addictions. No single risk factor is necessary or sufficient to cause ADHD. In most cases ADHD arises from several genetic and environmental risk factors that each have a small individual effect and act together to increase susceptibility. The multifactorial causation of ADHD is consistent with the heterogeneity of the disorder, which is shown by its extensive psychiatric co-morbidity, its multiple domains of neurocognitive impairment and the wide range of structural and functional brain anomalies associated with it. The diagnosis of ADHD is reliable and valid when evaluated with standard criteria for psychiatric disorders. Rating scales and clinical interviews facilitate diagnosis and aid screening. The expression of symptoms varies as a function of patient developmental stage and social and academic contexts. Although there are no curative treatments for ADHD, evidenced-based treatments can markedly reduce its symptoms and associated impairments. For example, medications are efficacious and normally well tolerated, and various non-pharmacological approaches are also valuable. Ongoing clinical and neurobiological research holds the promise of advancing diagnostic and therapeutic approaches to ADHD. For an illustrated summary of this Primer, visit: http://go.nature.com/J6jiwl.
Compulsivity and impulsivity are cross-disorder traits observed in autism spectrum disorders (ASD), attention deficit hyperactivity disorder (ADHD) and obsessive compulsive disorder (OCD). Aberrant ...fronto-striatal glutamatergic signalling is core to the understanding of compulsive and impulsive disorders. In this review, the glutamate (Glu) neurochemistry of fronto-striatal circuits in paediatric and adult ASD, ADHD and OCD, as described in 59 studies, is outlined from the perspective of proton magnetic resonance spectroscopy ((1)H MRS). Despite the methodological inconsistencies between studies, two observations stand out that form possible hypotheses for future studies. Firstly, a possible increase in Glx (combination of Glu, glutamine and GABA) in the striatum across ADHD, OCD and ASD. Secondly, an increased Glx signal in the anterior cingulate cortex in paediatric ASD and ADHD but a lower Glx signal in adult ASD and ADHD. This suggests neurodevelopmental changes in fronto-striatal glutamatergic circuits across the lifespan. Future studies should incorporate more homogeneous samples, perform MRS at field strengths of at least 3 Tesla and provide much more precise and standardized information on methods to improve our understanding of fronto-striatal glutamatergic transmission in compulsive and impulsive syndromes.
The prevalence of somatic insulinopathies, like metabolic syndrome (MetS), obesity, and type 2 diabetes mellitus (T2DM), is higher in Alzheimer's disease (AD), autism spectrum disorder (ASD), and ...obsessive-compulsive disorder (OCD). Dysregulation of insulin signalling has been implicated in these neuropsychiatric disorders, and shared genetic factors might partly underlie this observed multimorbidity. We investigated the genetic overlap between AD, ASD, and OCD with MetS, obesity, and T2DM by estimating pairwise global genetic correlations using the summary statistics of the largest available genome-wide association studies for these phenotypes. Having tested these hypotheses, other potential brain "insulinopathies" were also explored by estimating the genetic relationship of six additional neuropsychiatric disorders with nine insulin-related diseases/traits. Stratified covariance analyses were then performed to investigate the contribution of insulin-related gene sets. Significant negative genetic correlations were found between OCD and MetS (r
= -0.315, p = 3.9 × 10
), OCD and obesity (r
= -0.379, p = 3.4 × 10
), and OCD and T2DM (r
= -0.172, p = 3 × 10
). Significant genetic correlations with insulin-related phenotypes were also found for anorexia nervosa (AN), attention-deficit/hyperactivity disorder (ADHD), major depressive disorder, and schizophrenia (p < 6.17 × 10
). Stratified analyses showed negative genetic covariances between AD, ASD, OCD, ADHD, AN, bipolar disorder, schizophrenia and somatic insulinopathies through gene sets related to insulin signalling and insulin receptor recycling, and positive genetic covariances between AN and T2DM, as well as ADHD and MetS through gene sets related to insulin processing/secretion (p < 2.06 × 10
). Overall, our findings suggest the existence of two clusters of neuropsychiatric disorders, in which the genetics of insulin-related diseases/traits may exert divergent pleiotropic effects. These results represent a starting point for a new research line on "insulinopathies" of the brain.
PDF
