بزرگسالان مبتلا به اختلال نقص توجه/بیش فعالی: یک مطالعه تصویربرداری کشیدگی تانسور جسم پینه ای

The objective of the present study was to investigate the microstructure and the macrostructure of the corpus callosum (CC) in adults with Attention-Deficit/Hyperactivity Disorder (ADHD) by means of magnetic resonance imaging (MRI). Twenty-nine participants with ADHD and 37 controls were included from the Norwegian ADHD project in Bergen. We measured the fractional anisotropy (FA) values, as well as the size of different subdivisions of the CC, using diffusion tensor imaging (DTI) and anatomical MRI. The isthmus/splenium part of the CC in the ADHD group showed reduced FA values compared to the control group, whereas the size of the CC did not differ across groups. Our findings thus demonstrate a divergence between microstructural and macrostructural measures in the CC of adults with ADHD. This contrasts with findings in children demonstrating callosal abnormalities in both microstructure and macrostructure. Our results may indicate that adults with ADHD in part have succeeded in passing by an earlier developmental delay of the CC, resulting in a normalization of callosal macrostructure into adulthood. However, microstructural differences are still present in adults, which may point to an abnormal lateralization in adults with ADHD, or could be a sign of a persisting impairment.

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 and 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 and 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 and 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 and 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 and 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 and Aboitiz and Montiel, 2003). Forebrain volume correlates inversely to the midsagittal size of the CC in both children and adults (Ringo et al., 1994 and 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 and 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 and 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 and 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.

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 lateralization in the auditory and parietal cortices in adults with ADHD, according to the findings of an inverse relationship between callosal connectivity and brain lateralization (Aboitiz and Montiel, 2003). Studies of lateralization processes (Shaw et al., 2009), however, have reported disruption of the development of cortical asymmetry prefrontally, but not in the temporo-occipital lobes, in young adults with ADHD compared to controls. Studies of lateralization processes in ADHD are still few, and firm conclusions are not possible to draw. Moreover, our findings are preliminary, and it would be crucial in the future to include younger and older participants with ADHD in the same study, preferably in a longitudinal design to confirm our understanding of the developmental trajectory of brain lateralization and, more specifically, of the CC in individuals with ADHD.