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      Structural brain imaging correlates of ASD and ADHD across the lifespan: a hypothesis-generating review on developmental ASD–ADHD subtypes

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          Abstract

          We hypothesize that it is plausible that biologically distinct developmental ASD–ADHD subtypes are present, each characterized by a distinct time of onset of symptoms, progression and combination of symptoms. The aim of the present narrative review was to explore if structural brain imaging studies may shed light on key brain areas that are linked to both ASD and ADHD symptoms and undergo significant changes during development. These findings may possibly pinpoint to brain mechanisms underlying differential developmental ASD–ADHD subtypes. To this end we brought together the literature on ASD and ADHD structural brain imaging symptoms and particularly highlight the adolescent years and beyond. Findings indicate that the vast majority of existing MRI studies has been cross-sectional and conducted in children, and sometimes did include adolescents as well, but without explicitly documenting on this age group. MRI studies documenting on age effects in adults with ASD and/or ADHD are rare, and if age is taken into account, only linear effects are examined. Data from various studies suggest that a crucial distinctive feature underlying different developmental ASD–ADHD subtypes may be the differential developmental thinning patterns of the anterior cingulate cortex and related connections towards other prefrontal regions. These regions are crucial for the development of cognitive/effortful control and socio-emotional functioning, with impairments in these features as key to both ASD and ADHD.

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          Most cited references77

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          Attention-deficit/hyperactivity disorder is characterized by a delay in cortical maturation.

          There is controversy over the nature of the disturbance in brain development that underpins attention-deficit/hyperactivity disorder (ADHD). In particular, it is unclear whether the disorder results from a delay in brain maturation or whether it represents a complete deviation from the template of typical development. Using computational neuroanatomic techniques, we estimated cortical thickness at >40,000 cerebral points from 824 magnetic resonance scans acquired prospectively on 223 children with ADHD and 223 typically developing controls. With this sample size, we could define the growth trajectory of each cortical point, delineating a phase of childhood increase followed by adolescent decrease in cortical thickness (a quadratic growth model). From these trajectories, the age of attaining peak cortical thickness was derived and used as an index of cortical maturation. We found maturation to progress in a similar manner regionally in both children with and without ADHD, with primary sensory areas attaining peak cortical thickness before polymodal, high-order association areas. However, there was a marked delay in ADHD in attaining peak thickness throughout most of the cerebrum: the median age by which 50% of the cortical points attained peak thickness for this group was 10.5 years (SE 0.01), which was significantly later than the median age of 7.5 years (SE 0.02) for typically developing controls (log rank test chi(1)(2) = 5,609, P < 1.0 x 10(-20)). The delay was most prominent in prefrontal regions important for control of cognitive processes including attention and motor planning. Neuroanatomic documentation of a delay in regional cortical maturation in ADHD has not been previously reported.
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            Longitudinal development of human brain wiring continues from childhood into adulthood.

            Healthy human brain development is a complex process that continues during childhood and adolescence, as demonstrated by many cross-sectional and several longitudinal studies. However, whether these changes end in adolescence is not clear. We examined longitudinal white matter maturation using diffusion tensor tractography in 103 healthy subjects aged 5-32 years; each volunteer was scanned at least twice, with 221 total scans. Fractional anisotropy (FA) and mean diffusivity (MD), parameters indicative of factors including myelination and axon density, were assessed in 10 major white matter tracts. All tracts showed significant nonlinear development trajectories for FA and MD. Significant within-subject changes occurred in the vast majority of children and early adolescents, and these changes were mostly complete by late adolescence for projection and commissural tracts. However, association tracts demonstrated postadolescent within-subject maturation of both FA and MD. Diffusion parameter changes were due primarily to decreasing perpendicular diffusivity, although increasing parallel diffusivity contributed to the prolonged increases of FA in association tracts. Volume increased significantly with age for most tracts, and longitudinal measures also demonstrated postadolescent volume increases in several association tracts. As volume increases were not directly associated with either elevated FA or reduced MD between scans, the observed diffusion parameter changes likely reflect microstructural maturation of brain white matter tracts rather than just gross anatomy.
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              Sexual dimorphism of brain developmental trajectories during childhood and adolescence.

              Human total brain size is consistently reported to be approximately 8-10% larger in males, although consensus on regionally specific differences is weak. Here, in the largest longitudinal pediatric neuroimaging study reported to date (829 scans from 387 subjects, ages 3 to 27 years), we demonstrate the importance of examining size-by-age trajectories of brain development rather than group averages across broad age ranges when assessing sexual dimorphism. Using magnetic resonance imaging (MRI) we found robust male/female differences in the shapes of trajectories with total cerebral volume peaking at age 10.5 in females and 14.5 in males. White matter increases throughout this 24-year period with males having a steeper rate of increase during adolescence. Both cortical and subcortical gray matter trajectories follow an inverted U shaped path with peak sizes 1 to 2 years earlier in females. These sexually dimorphic trajectories confirm the importance of longitudinal data in studies of brain development and underline the need to consider sex matching in studies of brain development.
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                Author and article information

                Contributors
                n.lambregts-rommelse@psy.umcn.nl
                Journal
                J Neural Transm (Vienna)
                J Neural Transm (Vienna)
                Journal of Neural Transmission
                Springer Vienna (Vienna )
                0300-9564
                1435-1463
                21 December 2016
                21 December 2016
                2017
                : 124
                : 2
                : 259-271
                Affiliations
                [1 ]ISNI 0000 0004 0444 9382, GRID grid.10417.33, Department of Psychiatry, Donders Institute for Brain, Cognition and Behavior, , Radboud University Medical Center, ; Nijmegen, The Netherlands
                [2 ]Karakter, Child and Adolescent Psychiatry University Center, Nijmegen, The Netherlands
                [3 ]ISNI 0000 0004 0444 9382, GRID grid.10417.33, Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition and Behavior, , Radboud University Medical Center, ; Nijmegen, The Netherlands
                [4 ]ISNI 0000 0004 0407 1981, GRID grid.4830.f, Department of Psychiatry, Interdisciplinary Center of Psychopathology and Emotion Regulation (ICPE) & Research School of Behavioral and Cognitive Neuroscience, University Medical Center Groningen, , University of Groningen, ; Groningen, The Netherlands
                Article
                1651
                10.1007/s00702-016-1651-1
                5285408
                28000020
                517c594d-50cb-41b9-9d83-6687c21274cf
                © The Author(s) 2016

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

                History
                : 25 June 2016
                : 11 November 2016
                Categories
                High Impact Review in Neuroscience, Neurology or Psychiatry - Review Article
                Custom metadata
                © Springer-Verlag Wien 2017

                autism spectrum disorder,attention-deficit/hyperactivity disorder,comorbidity,life span,mri,brain,adults,adolescence,anterior cingulate cortex,prefrontal

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