The Multidimensional Research Progress in Attention-deficit/Hyperactivity Disorder Comorbid With Dyslexia: From Gene, Brain to Behavior

Attention-deficit/hyperactivity disorder (ADHD) and Developmental dyslexia (DD) are two common neurodevelopmental disorders, the comorbidity rate of them is as high as 25% similar to 48%. In this paper, we reviewed and summarized the research progresses of ADHD comorbid with DD from multiple dimensions including cognitive psychology, neurophysiology (brain imaging) and molecular genetics. Three main theoretical models have been yielded for the neuropathological mechanisms of ADHD comorbid with DD, including phenocopy hypothesis, cognitive subtype hypotheses and common etiology hypothesis; whereas most of the evidence from the existing literature supported the common etiological hypothesis. Results in cognitive psychology indicated that the shared cognitive impairment in ADHD and DD might be the deficit of processing speed, which should be closely related to the comorbid status. The key imaging features related to ADHD comorbid with DD might include the structural and functional alteration in frontal lobes (especially the dorsal lateral prefrontal cortex), caudate nucleus and anterior cingulate gyrus, and hemispheric asymmetry. For genetics, linkage studies suggested the potential association of the chromosome region of 6p21-22 with both ADHD and DD. In this region, two key genes, DCDC2 and KIAA0319, have attracted much attention and were studied as important candidate genes for ADHD and DD. Several other candidate genes would be also worthy of exploration to illustrate the common and shared genetic background of these two disorders, such as ADRA2A, DYX1C1, DRD4. It is worth noting that the shared genetic factors of DD and ADHD may mainly affect the inattentive symptom and reading ability simultaneously, rather than hyperactive/impulsive symptoms. To further illustrate the neuropathologic mechanisms of ADHD comorbid with DD clearly and comprehensively, further multidimensional studies are needed to elucidate how the genetic susceptibility factors influence the brain structure and function, affect the cognition functions (e.g. processing speed) subsequently and lead to the occurrence of ADHD clinical symptoms finally. Another important challenge should be addressed for the studies on ADHD with DD. In China, most studies only recruited ADHD comorbid with learning disabilities, which is mainly due to the lack of the standard clinical diagnosis criteria of Chinese DD. The establishment of a standard and unified diagnostic criteria for DD in Chinese background will promote the study progress and clinical intervention of ADHD comorbid with DD substantially.