Adults with attention-deficit/hyperactivity disorder — A diffusion-tensor imaging study of the corpus callosum
Introduction
Attention-Deficit/Hyperactivity Disorder (ADHD) is a neurodevelopmental disorder with symptoms of inattention, impulsivity, and hyperactivity (American Psychiatric Association, 2000). According to a worldwide estimation, 5.3% of children and adolescents are diagnosed with ADHD (Polanczyk et al., 2007), but great variations in prevalence are reported (Skounti et al., 2007). Approximately 65% of children with ADHD show persistent symptoms and impaired function into adulthood (Faraone et al., 2006), even if the estimates vary (Mannuzza et al., 2003). The maturation of the cerebral cortex is delayed in children with ADHD (Shaw et al., 2006, Shaw et al., 2007), but children who improve clinically, show partial normalization of cortical thickness (Shaw et al., 2006). However, the majority of affected children continue to have symptoms into adulthood, leading to functional impairment (Biederman and Faraone, 2005, Biederman et al., 2006). Adults with ADHD may represent a subgroup with neurobiological dysfunctions other than late maturation of the cortex, such as dysregulation of the dopamine system (Staller and Faraone, 2007, Genro et al., 2010), or a hypoglutamatergic prefrontal condition (Carlsson, 2001).
The corpus callosum (CC) is the main commissural white matter bundle interconnecting the two cerebral hemispheres in a dynamic and flexible interaction (Innocenti, 2009). The number of callosal fibers is determined prenatally, but throughout childhood and adolescence the CC area changes due to axonal myelination, redirection, and pruning (LaMantia and Rakic, 1990, Luders et al., 2010, Westerhausen et al., 2011b). The size of the CC increases into the late twenties, along with an age-related decrease of T1 image signal intensities, which may reflect a maturation of the axonal cytoskeleton with a decrease in the microtubular density (Pujol et al., 1993, Keshavan et al., 2002). Transcallosal conduction time seems to increase in larger brains, and this interhemispheric transfer delay may relate to hemispheric specialization (Ringo et al., 1994, Aboitiz and Montiel, 2003). Forebrain volume correlates inversely to the midsagittal size of the CC in both children and adults (Ringo et al., 1994, Jancke et al., 1999), supporting the theory of increased lateralization in larger brains. Lateralization processes may be of importance in the pathophysiology of ADHD (Roessner et al., 2004), and impaired development of the normal cortical asymmetry is reported in a longitudinal study of children with ADHD (Shaw et al., 2009).
Two meta-analyses suggest that a reduction of the posterior region including the splenium of the CC (Seidman, 2005, Valera et al., 2007) is one of the most replicated structural neuroimaging findings in the CC in children with ADHD. Subsequent studies have revealed inconsistent results (Luders et al., 2009, Cao et al., 2010, McNally et al., 2010). The results, however, may be difficult to compare because of methodological differences. The only structural magnetic resonance imaging (MRI) study of the CC in adults with ADHD (Rüsch et al., 2007) found a reduction of the region including the isthmus. This study included women with ADHD and a concurrent borderline personality disorder, and it is thus impossible to estimate the impact of ADHD itself.
When exploring the role of the CC in a psychiatric disorder, it is relevant to examine microstructural characteristics besides its macro-anatomical features. Diffusion tensor imaging (DTI) is an MRI technique using the properties of water diffusion within white matter tracts to obtain information about the microstructural architecture of these tracts (Mori and van Zijl, 2002, Jones, 2008, Mori et al., 2009). Different diffusion parameters have been developed to characterize the diffusion process and to quantify micro-architectonical properties of the brain white matter. Fractional anisotropy (FA) indicates the directionality of the diffusion process, and can be taken to indicate the alignment and density of axons within a fiber tract. Three DTI studies with focus on the CC in children with ADHD have so far been published. One article found no group differences in FA in the CC (Hamilton et al., 2008), whereas the two others observed reduced FA in the genu (Chao et al., 2009) and isthmus (Cao et al., 2010) in children with ADHD compared with healthy controls. To our knowledge, no studies have earlier studied FA values in the CC of adults with ADHD. The only DTI study of adults with ADHD (Rusch et al., 2010) did not examine FA values, but used measures of tractography, reconstructing the fiber bundles, and reported a decreased number of reconstructed fiber tracts through the anterior region of the CC in adults with ADHD. Moreover, this study included only women, and all participants with ADHD had a comorbid borderline personality disorder, which makes it impossible to draw firm conclusions concerning the impact of microstructural features of the CC in adults with ADHD only.
Few studies have focused on the morphometry of the CC in adults with ADHD, and to our knowledge, no reports exist that combine structural MRI and measures of FA values in adults with ADHD. We thus compared the CC in adults with ADHD with a group of healthy controls using anatomical MRI and DTI. Based on earlier studies of children, we expected a reduction of the CC size in the ADHD group compared with the controls as our first hypothesis. Secondly, because FA may be an expression of fiber density or thickness, reflected by the size of the CC, we expected a reduction of FA values in the ADHD group.
Section snippets
Participants
Twenty-nine participants with ADHD and 37 controls were selected from the Norwegian ADHD project in Bergen. The recruitment procedure is described in detail in other publications (Johansson et al., 2008, Halleland et al., 2009, Halmoy et al., 2009). The Norwegian ADHD project in Bergen included participants with ADHD diagnosed according to ICD-10 or DSM-IV criteria for hyperkinetic disorder/ADHD by psychiatrists or psychologists, whereas controls were recruited from the database of the Medical
CC measurement on anatomical images
The ANCOVA of the CC size did not reveal any difference between ADHD and controls (Table 1). This result was independent of whether CC size was adjusted for FBV or whether we used the uncorrected size of the CC. Sex had a significant influence on CC size not corrected for FBV, with the CC being larger in men than in women, whereas the influence of sex disappeared when corrected CC size was used as dependent variable. Age as a main effect did not reach a statistically significant level, and we
Discussion
We did not discern any anatomical differences in mean size or subdivisions of the CC between the two groups, and these findings did not support our first hypothesis. This contrasts to results originating from studies including children with ADHD that detected reduced area of the posterior part of the CC in children with ADHD (Seidman, 2005, Valera et al., 2007, Cao et al., 2010). We could, however, confirm our second hypothesis in that FA values were reduced in the intersection of the isthmus
Conclusion
The reduction of FA values in the posterior part of the CC in adults with ADHD did not correspond to a reduction of CC size, and this discrepancy between the microstructure and the macrostructure in adults with ADHD may be an expression of partial normalization of developmental delay of interhemispheric connections. The finding of reduced FA values in the posterior part of the CC in adults with ADHD may be an expression of abnormal lateralization in ADHD, possibly with an increase of
Acknowledgments
The research was supported by grants from Division of Psychiatry, Haukeland University Hospital, The Research Council of Norway, Western Norway Regional Health Authority, National Resource Unit for AD/HD, Tourette Syndrome and Narcolepsy. We would like to thank Roger Barndon, Turid Randa, and Eva Øksnes for their contributions to the study.
References (55)
- et al.
Attention-deficit hyperactivity disorder
The Lancet
(2005) - et al.
Sex differences in the human corpus callosum: myth or reality?
Neuroscience and Biobehavioral Reviews
(1997) - et al.
The macrostructural and microstructural abnormalities of corpus callosum in children with attention deficit/hyperactivity disorder: a combined morphometric and diffusion tensor MRI study
Brain Research
(2010) On the role of prefrontal cortex glutamate for the antithetical phenomenology of obsessive compulsive disorder and attention deficit hyperactivity disorder
Progress in Neuro-Psychopharmacology & Biological Psychiatry
(2001)- et al.
Effects of interpolation methods in spatial normalization of diffusion tensor imaging data on group comparison of fractional anisotropy
Magnetic Resonance Imaging
(2009) - et al.
Cognitive control in adults with attention-deficit/hyperactivity disorder
Psychiatry Research
(2011) - et al.
Topography of the human corpus callosum revisited–comprehensive fiber tractography using diffusion tensor magnetic resonance imaging
NeuroImage
(2006) Studying connections in the living human brain with diffusion MRI
Cortex
(2008)- et al.
Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version (K-SADS-PL): initial reliability and validity data
Journal of the American Academy of Child and Adolescent Psychiatry
(1997) - et al.
Development of the corpus callosum in childhood, adolescence and early adulthood
Life Sciences
(2002)
Decreased callosal thickness in attention-deficit/hyperactivity disorder
Biological Psychiatry
Reduced interhemispheric structural connectivity between anterior cingulate cortices in borderline personality disorder
Psychiatry Research
Structural brain imaging of attention-deficit/hyperactivity disorder
Biological Psychiatry
Threshold-free cluster enhancement: addressing problems of smoothing, threshold dependence and localisation in cluster inference
NeuroImage
Tract-based spatial statistics: voxelwise analysis of multi-subject diffusion data
NeuroImage
Meta-analysis of structural imaging findings in attention-deficit/hyperactivity disorder
Biological Psychiatry
Effects of handedness and gender on macro- and microstructure of the corpus callosum and its subregions: a combined high-resolution and diffusion-tensor MRI study
Cognitive Brain Research
A critical re-examination of sexual dimorphism in the corpus callosum microstructure
NeuroImage
One hundred million years of interhemispheric communication: the history of the corpus callosum
Brazilian Journal of Medical and Biological Research
Diagnostic and statistical manual of mental disorders : DSM-IV-TR. Vol
New developments in the treatment of ADHD
The Journal of Clinical Psychiatry
Why IQ is not a covariate in cognitive studies of neurodevelopmental disorders
Journal of the International Neuropsychological Society
The age-dependent decline of attention deficit hyperactivity disorder: a meta-analysis of follow-up studies
Psychological Medicine
Attention-deficit/hyperactivity disorder and the dopaminergic hypotheses
Expert Review of Neurotherapeutics
Development of the human corpus callosum during childhood and adolescence: a longitudinal MRI study
Progress in Neuro-Psychopharmacology & Biological Psychiatry
Association between catechol O-methyltransferase (COMT) haplotypes and severity of hyperactivity symptoms in adults
American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics
Occupational outcome in adult ADHD: impact of symptom profile, comorbid psychiatric problems, and treatment: a cross-sectional study of 414 clinically diagnosed adult ADHD patients
Journal of Attention Disorders
Cited by (55)
Attention-deficit/hyperactivity disorder
2022, Neurobiology of Brain Disorders: Biological Basis of Neurological and Psychiatric Disorders, Second EditionWhite Matter Microstructural Properties Associated with Impaired Attention in Chronic Schizophrenia: A Multi-Center Study
2020, Psychiatry Research - NeuroimagingUpdated European Consensus Statement on diagnosis and treatment of adult ADHD
2019, European PsychiatryGrowing out of attention deficit hyperactivity disorder: Insights from the ‘remitted’ brain
2018, Neuroscience and Biobehavioral ReviewsCitation Excerpt :Diffusion tensor imaging (DTI) can provide measures of the microstructure of these white matter tracts, such as fractional anisotropy and more focused measures of diffusion parallel (axial diffusivity) and perpendicular (radial diffusivity) to axons (Basser and Pierpaoli, 1996). Microstructural anomalies in white matter tracts have been reported in some of these tracts in adolescents and adults with ADHD (Casey et al., 2007; Chuang et al., 2013; Dramsdahl et al., 2012; Helpern et al., 2011; Konrad et al., 2010; Onnink et al., 2015). Here we focus here on studies that examine white matter tract microstructure in adult remitters.