Shared Brain Connectivity Issues, Symptoms, and Comorbidities in Autism Spectrum Disorder, Attention Deficit/Hyperactivity Disorder, and Tourette Syndrome

Abstract

The prevalence of neurodevelopmental disorders, including autism spectrum disorder (ASD), attention deficit/hyperactivity disorder (ADHD), and Tourette syndrome (TS), has increased over the past two decades. Currently, about one in six children in the United States is diagnosed as having a neurodevelopmental disorder. Evidence suggests that ASD, ADHD, and TS have similar neuropathology, which includes long-range underconnectivity and short-range overconnectivity. They also share similar symptomatology with considerable overlap in their core and associated symptoms and a frequent overlap in their comorbid conditions. Consequently, it is apparent that ASD, ADHD, and TS diagnoses belong to a broader spectrum of neurodevelopmental illness. Biologically, long-range underconnectivity and short-range overconnectivity are plausibly related to neuronal insult (e.g., neurotoxicity, neuroinflammation, excitotoxicity, sustained microglial activation, proinflammatory cytokines, toxic exposure, and oxidative stress). Therefore, these disorders may a share a similar etiology. The main purpose of this review is to critically examine the evidence that ASD, ADHD, and TS belong to a broader spectrum of neurodevelopmental illness, an abnormal connectivity spectrum disorder, which results from neural long-range underconnectivity and short-range overconnectivity. The review also discusses the possible reasons for these neuropathological connectivity findings. In addition, this review examines the role and issue of axonal injury and regeneration in order to better understand the neuropathophysiological interplay between short- and long-range axons in connectivity issues.

What can autism teach us about the role of sensorimotor systems in higher cognition? New clues from studies on language, action semantics, and abstract emotional concept processing

“…The neural substrates of motor dysfunction in DCD, ADHD and SLI have not received quite as much attention: there are many hypotheses regarding DCD but few with neurobiological support from brain imaging (see reviews by Brown-Lum &Zwicker, 2015, andGomez &Sirigu, 2015: of these, the corpus callosum, cerebellum, parietal lobe and basal ganglia are highlighted, but studies contain extremely small samples); studies of SLI have mainly focused on perisylvian language cortices (see Mayes, Reilly, & Morgan, 2015 for review, but note that these authors admit the confusion regarding classification of this condition across studies). ADHD and autism are commonly comorbid, both more commonly diagnosed in males 10 and seem to both be characterized by abnormal connectivity (Kern et al, 2015;Konrad & Eickhoff, 2010); they may be set apart by the concentration of dysconnectivity in particular regions. We are not however aware of studies focussing on the neural substrates of motor dysfunction and connectivity related to movement in ADHD, presumably as this is a less salient feature of this condition.…”

ASD Validity

“…There are many forms of genetic syndromic ASD (Cederlöf et al 2014;Kern et al 2015;Plasschaert et al 2015;Poot 2015;Richards et al 2015). The fact that many different genetic syndromes do yield ASD diagnostic symptoms is the result of locus heterogeneity, wherein different gene variants produce the same phenotype, or the same phenotypic trait or symptom.…”

Abnormal Brain Connectivity Spectrum Disorders Following Thimerosal Administration

“…1 Evidence suggests these children share similar neuropathology, symptomatology, and comorbid conditions. Moreover, these disorders present with a similar pattern of abnormal brain connectivity of long-range underconnectivity and short-range overconnectivity.…”

“…Moreover, these disorders present with a similar pattern of abnormal brain connectivity of long-range underconnectivity and short-range overconnectivity. 1 As a consequence, it was suggested that these disorders may be subsets in what could be termed an abnormal connectivity spectrum disorder (ACSD).…”

“…1 Certain neurotoxicants, including mercury (Hg), show neuropathological evidence of loss of long-range connections and a resultant increase in short-range connections. 1 …”