Decreasing ADHD phenotypic heterogeneity: searching for neurobiological underpinnings of the restrictive inattentive phenotype

Abstract

During the process of developing the DSM-5, a new phenotype of ADHD was proposed-the ADHD restrictive inattentive presentation (ADHD-RI), describing subjects with high endorsement of inattentive symptoms and a low level of hyperactivity. However, this phenotype was not included in the DSM-5 because of the lack of robust neurobiological data. We aimed to assess the specific neurobiological underpinnings of individuals presenting ADHD-RI. We compared a sample of 301 subjects (101 ADHD-Combined; 50 ADHD-RI; 50 ADHD predominantly inattentive type and 100 typically developing subjects) aged 8-15 years, using a complete neuropsychological battery, molecular genetic data (DRD4 and DAT1 most studied polymorphisms) and functional MRI during a Go-No/Go task. Subjects with ADHD-RI had a significantly different neuropsychological profile compared with the other groups, including lower psychomotor speeds, longer reaction times and the worst overall performance in the global neurocognitive index. The proportion of subjects with the presence of DRD4-7 repeat allele was significantly higher in ADHD-RI. The fMRI data suggested that more attention-related posterior brain regions (especially temporo-occipital areas) are activated in ADHD-RI during both Go and No-Go cues compared to TD controls and ADHD predominantly inattentive type. ADHD-RI may represent a different phenotype than other types of ADHD. In addition, our results suggest that reducing the phenotypic heterogeneity may aid in the search for the neurobiological underpinnings of ADHD.

Which neuropsychological functions predict various processing speed components in children with and without attention-deficit/hyperactivity disorder?

“…A child who struggles with executive functioning may respond in a haphazard manner, pay poor attention to detail, and not self-regulate performance well (e.g., have poor pacing and not switch well between symbols), leading to slow and/or inaccurate performance. These results are consistent with past findings on psychomotor slowing in ADHD in that it may be specific to neurodevelopmental impulsivity and less commonly found when comparing other psychiatric groups (i.e., mood, anxiety and oppositional defiant disorders) to controls (Mayes & Calhoun, 2007; Sabri et al, 2016; Walker, Shores, Trollor, Lee & Sachdev, 2000). Alternatively, given that Coding always was administered prior to Coding Copy following the WISC Integrated manual’s procedures, it is possible that children with more efficient working memory were able to encode the symbols better during Coding and, thus, perform better on Coding Copy.…”

A Systematic Review of Imaging Studies in the Combined and Inattentive Subtypes of Attention Deficit Hyperactivity Disorder

“…Task-based studies investigating either the ADHD-C or the ADHD-I subtype, relative to controls, also provide supporting evidence for these aberrant functional differences in ADHD subtypes. Greater activation in the temporo–occipital and posterior brain regions were found in the hypothesized restrictive inattentive ADHD (ADHD-RI) type (Ercan et al, 2016b ) and decreased activation in ADHD-I, relative to ADHD-C, in regions involving the cingulo–frontal–parietal attention (Orinstein and Stevens, 2014 ) has been reported. Studies examining the ADHD-C type showed task-dependent activation differences in regions involving the parietal, temporal lobes and basal ganglia, in line with the findings suggestive of fronto–striatal–thalamic deficits (Silk et al, 2005 ; Vaidya et al, 2005 ; Smith et al, 2006 , 2008 ; Tamm et al, 2006 ; Rubia et al, 2007 ; Stevens et al, 2007 ; Vance et al, 2007 ; Fassbender et al, 2009 ; Iannaccone et al, 2015 ).…”

Advancing the study of sluggish cognitive tempo via DSM, RDoC, and hierarchical models of psychopathology

“…Interestingly, research suggests that atomoxetine reduces SCT symptoms in youth with ADHD [41,42], which aligns with other studies indicating atomoxetine to be effective for youth with ADHD and co-occurring internalizing symptoms [43,44] These findings together suggest that SCT as a possible specifier among children with ADHD is an area worth further examination, particularly if an SCT specifier can inform treatment decisions. In addition, there has recently been some renewed interest in a possible ADHD restrictive inattentive presentation [45], and children with this phenotype may have a different neuropsychological and attentional profile than other children with ADHD, as well as different brain functioning and genetic markers (e.g., presence of the DRD4-7 repeat allele) [46,47]. Integrating SCT within studies of ADHD restrictive inattentive presentation would be advantageous as part of overall efforts to better understand and categorize the phenotypic heterogeneity of ADHD.…”