Aim of project

The aim is to longitudinally study brain development in children with ADHD and controls. Both gross development of brain structures (using structural Magnetic Resonance Imaging, sMRI) and the development of white matter tracks (using Diffusion Tensor Imaging, DTI) will be studied. Of particular interest are the influences of genetic and cognitive factors on this development.

Theoretical Background 

Attention Deficit Hyperactivity Disorder (ADHD) is a common and impairing neuropsychiatric disorder of childhood, occurring in 3 to 5% of all school-age children (American Psychiatric Association, 1994). This disorder is associated with greater risks for low academic achievement, school dropouts, poor family and peer relations, aggression, substance abuse, driving accidents and chronic problems in adult adaptation (Barkley, 1990; Weiss & Hechtman, 1993). As such, it has an enormous impact on the utilization of medical and health care services, and the direct and indirect costs of this disorder are high. However, in a large number of children symptoms dissipate as they grow up and they go on to function normally and lead typical lives (Barkley, 1990; Weiss & Hechtman, 1993). This has lead to speculation that ADHD may not so much represent a disruption, as a delay of brain development. The aim of this study is to address this issue.

There is a growing body of research supporting the existence of deficits in brain anatomy associated with ADHD, with evidence of reductions in overall brain size, cortical grey matter and subcortical structures (Durston, 2003; Seidman et al., 2005; Valera et al., 2006). However, reported effect sizes are small and results not always consistent. Typically, studies of brain anatomy in ADHD have included small, cross-sectional samples and have focused on volumetric measures of areas of theoretical interest. Such studies are easily confounded, as brain development is complex and associated with both progressive and regressive changes in brain anatomy. The first longitudinal studies of brain development in ADHD (Castellanos et al., 2001; 2002) have included large samples of subjects, but have largely considered volumetric measures. In this study, we are combining longitudinal data from a large cohort of children and adolescents with state-of-the-art imaging methods (including DTI and Voxelbased Morphometry, VBM) to investigate brain development in ADHD. This will allow us to address the question whether ADHD represents a disruption or a delay of brain development. Furthermore, DNA will be acquired of children and their parents to allow for a preliminary investigation of the involvement of known ADHD risk genes in aberrant brain development in this disorder. Additionally, we will acquire cognitive characteristics of our participants with proven differential association with ADHD in order to investigate how brain development and cognitive development relate in this disorder.

Approach to the research aims 

Longitudinal sMRI (volumetric analysis and VBM) and DTI, DNA genotyping of ADHD risk genes (e.g. DAT1, DRD4) and cognitive testing.

References

American Psychiatric Association. (1994). Diagnostic and Statistical Manual of Mental Disorders (4^th ed.). Washington DC.

Barkley, R.A. (1990). Attention Deficit Hyperactivity Disorder. New York: Guilford Press.

Castellanos, F. X., Lee, P. P., Sharp, W., Jeffries, N. O., Greenstein, D. K., Clasen, L. S., et al. (2002). Developmental trajectories of brain volume abnormalities in children and adolescents with attention-deficit/hyperactivity disorder. JAMA, 288(14), 1740.

Durston, S. (2003). A review of the biological bases of ADHD: What have we learned from imaging studies? Mental Retardation and Developmental Disabilities Research, 9(3), 184.

Seidman, L. J., Valera, E. M., & Makris, N. (2005). Structural brain imaging of attention-deficit/hyperactivity disorder. Biological Psychiatry, 57(11), 1263-1272.

Valera, E. M., Faraone, S. V., Murray, K. E., & Seidman, L. J. (2006). Meta-analysis of structural imaging findings in attention-deficit/hyperactivity disorder. Biological Psychiatry.

Weiss, G., & Hechtman, L. (1993) Hyperactive children grown up. New York: Guilford Press.