Abstract:

Autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) exhibit a high rate of comorbidity. This paper systematically reviews existing studies at different levels to summarize the common pathological mechanisms underlying the comorbidity of ASD and ADHD. Specifically: (1) Both diseases exhibit abnormal synaptic pruning, leading to a further aggravation of abnormal brain structure in patients with the comorbidity; (2) Dysfunction of the default mode network and executive control network constitutes important neurobiological evidence for the comorbidity of the two disorders; (3) The abnormal signaling pathways implicated in ASD and ADHD mainly involve the dopamine, Wnt, GABA, mTOR, and inflammation-related pathways, all of which are closely associated with the stability of synapse numbers; (4) Abnormal synaptic pruning leads to excitatory/inhibitory (E/I) imbalance, which may provide the physiological basis for abnormal functional connectivity of brain networks and altered cortical thickness and volume in higher cognitive regions such as the prefrontal cortex. Moreover, by computational neural network modeling and molecular network modeling, it is expected to advance the understanding of the co-morbidity mechanism of autism and attention deficit hyperactivity disorder. In this review, we elucidate the pathological mechanism of comorbidity in two typical diseases related to neurodevelopmental disorders from different perspectives, and may provide a theoretical basis for early intervention and precise treatment in comorbid patients.

Key words: autism spectrum disorder, attention deficit hyperactivity disorder, biophysical mechanism, signaling pathway, synaptic pruning, theoretical modeling