scholarly journals Functional brain abnormalities associated with comorbid anxiety in autism spectrum disorder

2020 ◽  
Vol 32 (4) ◽  
pp. 1273-1286
Author(s):  
James Bartolotti ◽  
John A. Sweeney ◽  
Matthew W. Mosconi

AbstractAnxiety disorders are common in autism spectrum disorder (ASD) and associated with social–communication impairment and repetitive behavior symptoms. The neurobiology of anxiety in ASD is unknown, but amygdala dysfunction has been implicated in both ASD and anxiety disorders. Using resting-state functional magnetic resonance imaging, we compared amygdala–prefrontal and amygdala–striatal connections across three demographically matched groups studied in the Autism Brain Imaging Data Exchange (ABIDE): ASD with a comorbid anxiety disorder (N = 25; ASD + Anxiety), ASD without a comorbid disorder (N = 68; ASD-NoAnx), and typically developing controls (N = 139; TD). Relative to ASD-NoAnx and TD controls, ASD + Anxiety individuals had decreased connectivity between the amygdala and dorsal/rostral anterior cingulate cortex (dACC/rACC). The functional connectivity of these connections was not affected in ASD-NoAnx, and amygdala connectivity with ventral ACC/medial prefrontal cortex (mPFC) circuits was not different in ASD + Anxiety or ASD-NoAnx relative to TD. Decreased amygdala–dorsomedial prefrontal cortex (dmPFC)/rACC connectivity was associated with more severe social impairment in ASD + Anxiety; amygdala–striatal connectivity was associated with restricted, repetitive behavior (RRB) symptom severity in ASD-NoAnx individuals. These findings suggest comorbid anxiety in ASD is associated with disrupted emotion-monitoring processes supported by amygdala–dACC/mPFC pathways, whereas emotion regulation systems involving amygdala–ventromedial prefrontal cortex (vmPFC) are relatively spared. Our results highlight the importance of accounting for comorbid anxiety for parsing ASD neurobiological heterogeneity.

2017 ◽  
Vol 47 (14) ◽  
pp. 2513-2527 ◽  
Author(s):  
C. O. Carlisi ◽  
L. Norman ◽  
C. M. Murphy ◽  
A. Christakou ◽  
K. Chantiluke ◽  
...  

BackgroundAutism spectrum disorder (ASD) and obsessive-compulsive disorder (OCD) share abnormalities in hot executive functions such as reward-based decision-making, as measured in the temporal discounting task (TD). No studies, however, have directly compared these disorders to investigate common/distinct neural profiles underlying such abnormalities. We wanted to test whether reward-based decision-making is a shared transdiagnostic feature of both disorders with similar neurofunctional substrates or whether it is a shared phenotype with disorder-differential neurofunctional underpinnings.MethodsAge and IQ-matched boys with ASD (N = 20), with OCD (N = 20) and 20 healthy controls, performed an individually-adjusted functional magnetic resonance imaging (fMRI) TD task. Brain activation and performance were compared between groups.ResultsBoys with ASD showed greater choice-impulsivity than OCD and control boys. Whole-brain between-group comparison revealed shared reductions in ASD and OCD relative to control boys for delayed-immediate choices in right ventromedial/lateral orbitofrontal cortex extending into medial/inferior prefrontal cortex, and in cerebellum, posterior cingulate and precuneus. For immediate-delayed choices, patients relative to controls showed reduced activation in anterior cingulate/ventromedial prefrontal cortex reaching into left caudate, which, at a trend level, was more decreased in ASD than OCD patients, and in bilateral temporal and inferior parietal regions.ConclusionsThis first fMRI comparison between youth with ASD and with OCD, using a reward-based decision-making task, shows predominantly shared neurofunctional abnormalities during TD in key ventromedial, orbital- and inferior fronto-striatal, temporo-parietal and cerebellar regions of temporal foresight and reward processing, suggesting trans-diagnostic neurofunctional deficits.


2019 ◽  
Author(s):  
Valentina Parma ◽  
Nicola Cellini ◽  
Lisa Guy ◽  
Alana McVey ◽  
Keiran Rump ◽  
...  

Objective: Anxiety disorders are common among youth with autism spectrum disorder (ASD). Both anxiety and ASD are associated with differences in physiological activity. To date, few studies have investigated the physiological profile of youth with ASD and even fewer have systematically assessed how the co-occurrence of anxiety disorders and ASD modulates resting physiological activity.Method: The aim of the present study was to evaluate sympathetic and parasympathetic activity at rest in 75 school-aged children and adolescents with ASD, with (ASD+Anxiety = 22, 6F) and without co-occurring anxiety (ASD Alone =15, 6F) and to compare their physiological profile with that of matched typically developing controls (TDC) with (Anxiety Alone = 16, 6F) and without co-occurring anxiety disorders (TDC = 22, 8F).Results: Results indicated reduced sympathetic and parasympathetic activity at rest in ASD as compared to TDC youth without anxiety. The ASD+Anxiety and Anxiety Alone groups showed different sympathetic, but similar parasympathetic, activity. Correlational, multivariate, and regression analyses indicated that the four groups differed among several physiological and subjective measures.Conclusion: These findings suggest that ASD and anxiety are associated with distinct profiles of autonomic nervous system activity that cannot be reduced to either the sympathetic or parasympathetic branch alone. An autonomic profile-based approach is more likely to advance research, diagnosis, and treatment of ASD and anxiety than unidimensional, single-modality approaches.


2020 ◽  
Vol 22 (1) ◽  
pp. 118
Author(s):  
Yuanpeng Zheng ◽  
Tessa A. Verhoeff ◽  
Paula Perez Pardo ◽  
Johan Garssen ◽  
Aletta D. Kraneveld

Autism Spectrum Disorder (ASD) is a spectrum of disorders that are characterized by problems in social interaction and repetitive behavior. The disease is thought to develop from changes in brain development at an early age, although the exact mechanisms are not known yet. In addition, a significant number of people with ASD develop problems in the intestinal tract. A Disintegrin And Metalloproteases (ADAMs) include a group of enzymes that are able to cleave membrane-bound proteins. ADAM10 and ADAM17 are two members of this family that are able to cleave protein substrates involved in ASD pathogenesis, such as specific proteins important for synapse formation, axon signaling and neuroinflammation. All these pathological mechanisms are involved in ASD. Besides the brain, ADAM10 and ADAM17 are also highly expressed in the intestines. ADAM10 and ADAM17 have implications in pathways that regulate gut permeability, homeostasis and inflammation. These metalloproteases might be involved in microbiota-gut–brain axis interactions in ASD through the regulation of immune and inflammatory responses in the intestinal tract. In this review, the potential roles of ADAM10 and ADAM17 in the pathology of ASD and as targets for new therapies will be discussed, with a focus on the gut–brain axis.


2021 ◽  
Author(s):  
Laura E. Quiñones‐Camacho ◽  
Frank A. Fishburn ◽  
Katherine Belardi ◽  
Diane L. Williams ◽  
Theodore J. Huppert ◽  
...  

2021 ◽  
Author(s):  
Pavithra Elumalai ◽  
Yasharth Yadav ◽  
Nitin Williams ◽  
Emil Saucan ◽  
Jürgen Jost ◽  
...  

Autism Spectrum Disorder (ASD) is a set of neurodevelopmental disorders that pose a significant global health burden. Measures from graph theory have been used to characterise ASD-related changes in resting-state fMRI functional connectivity networks (FCNs), but recently developed geometry-inspired measures have not been applied so far. In this study, we applied geometry-inspired graph Ricci curvatures to investigate ASD-related changes in resting-state fMRI FCNs. To do this, we applied Forman-Ricci and Ollivier-Ricci curvatures to compare networks of ASD and healthy controls (N = 1112) from the Autism Brain Imaging Data Exchange I (ABIDE-I) dataset. We performed these comparisons at the brain-wide level as well as at the level of individual brain regions, and further, determined the behavioral relevance of region-specific differences with Neurosynth meta-analysis decoding. We found brain-wide ASD-related differences for both Forman-Ricci and Ollivier-Ricci curvatures. For Forman-Ricci curvature, these differences were distributed across 83 of the 200 brain regions studied, and concentrated within the Default Mode, Somatomotor and Ventral Attention Network. Meta-analysis decoding identified the brain regions showing curvature differences as involved in social cognition, memory, language and movement. Notably, comparison with results from previous non-invasive stimulation (TMS/tDCS) experiments revealed that the set of brain regions showing curvature differences overlapped with the set of brain regions whose stimulation resulted in positive cognitive or behavioural outcomes in ASD patients. These results underscore the utility of geometry-inspired graph Ricci curvatures in characterising disease-related changes in ASD, and possibly, other neurodevelopmental disorders.


2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Jiujun Qiu ◽  
Xuejun Kong ◽  
Jihan Li ◽  
Jie Yang ◽  
Yiting Huang ◽  
...  

Recently, transcranial direct current stimulation (tDCS) has been applied to relieve symptoms in individuals with autism spectrum disorder (ASD). In this prospective, parallel, single-blinded, randomized study, we investigate the modulation effect of three-week tDCS treatment at the left dorsal lateral prefrontal cortex (DLPFC) in children with ASD. 47 children with ASD were enrolled, and 40 (20 in each group) completed the study. The primary outcomes are Childhood Autism Rating Scale (CARS), Aberrant Behavior Checklist (ABC), and the Repetitive Behavior Scale-Revised (RBS-R). We found that children with ASD can tolerate three-week tDCS treatment with no serious adverse events detected. A within-group comparison showed that real tDCS, but not sham tDCS, can significantly reduce the scores of CARS, Children’s Sleep Habits Questionnaire (CSHQ), and general impressions in CARS (15th item). Real tDCS produced significant score reduction in the CSHQ and in CARS general impressions when compared to the effects of sham tDCS. The pilot study suggests that three-week left DLPFC tDCS is well-tolerated and may hold potential in relieving some symptoms in children with ASD.


Author(s):  
Michael Ellis

The assessment and diagnosis phase of autism spectrum disorder (ASD) is a very difficult time for the parent. You will likely feel completely bewildered. You will be filled with many mixed emotions such as love for your child and fear for your child’s future. You may feel like your heart is breaking. But I can tell you, you are going to make it through this—just like I have. You will likely have to overcome significant denial to even discuss the unusual signs or symptoms that you have noticed in your young child. You may be afraid to hear the term “autism” come from your pediatrician’s mouth. However, you are about to start a very important journey with your child. You have to be strong in order to obtain for your child vital treatments and therapies that can dramatically improve your child’s life and future. Theoretically, ASD is not difficult to recognize and diagnose. However, in practice, it can be challenging. The full spectrum of symptoms included in ASD is quite wide. One child may appear quite typical with only minor eccentricities while another has significant intellectual disability, social impairment, self-injurious behavior, and aggression. No two individuals with ASD are exactly alike. In fact, individuals with autism are often more different than similar. We cannot easily pigeonhole or stereotype our children. Further complicating diagnosis, professionals often have little training in ASD, even in fields that have autism within their scope of practice. Furthermore, children with more subtle ASD symptoms or those who are “high-functioning” (more verbal and with more capabilities in general) do not always have symptoms that are evident at a very young age. At times, autism symptoms may not be identifiable until social problems become more significant as the child grows older. Primary care physicians are not typically able to spend long enough with your child during visits to pick up on the sometimes subtle signs needed to alert them to a possible ASD diagnosis.


2018 ◽  
Vol 2 (S1) ◽  
pp. 21-22
Author(s):  
Carla J. Ammons ◽  
Mary-Elizabeth Winslett ◽  
Rajesh K. Kana

OBJECTIVES/SPECIFIC AIMS: Autism spectrum disorder (ASD) affects 1 in 68 people and includes restricted, repetitive behavior, and social communication deficits. Aspects of face processing (i.e., identity, emotion perception) are impaired in some with ASD. Neuroimaging studies have shown aberrant patterns of brain activation and connectivity of face processing regions. However, small sample sizes and inconsistent results have hindered clinical utility of these findings. The study aims to establish consistent patterns of brain responses to faces in ASD and provide directions for future research. METHODS/STUDY POPULATION: Neuroimaging studies were identified through a multi-database search according to PRISMA guidelines. In total, 23 studies were retained for a sample size of 383 healthy controls and 345 ASD. Peak coordinates were extracted for activation likelihood estimation (ALE) in GingerALE v2.3.6. Follow-up ALE analyses investigated directed Versus undirected gaze, static Versus dynamic, emotional Versus neutral, and familiar Versus unfamiliar faces. RESULTS/ANTICIPATED RESULTS: Faces produced bilateral activation of the fusiform gyrus (FG) in healthy controls (−42 −52 −20; 22 −74 −12, p<0.05, FDR) and left FG activation in ASD (−42 −54 −16, p<0.05, FDR). Activation in both groups was lateral to the mid-fusiform sulcus. Follow-up results pending. DISCUSSION/SIGNIFICANCE OF IMPACT: Reduced right FG activation to faces may inform biomarker or response to intervention studies. Mid-fusiform sulcus proved a reliable predictor of functional divides should be investigated on a subject-specific level.


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