Twin pairs discordant for ADHD, as defined by DSM-IV, were recruited nationally as described elsewhere in detail (2). Exclusion criteria were a full-scale IQ less than 80, medical or neurological disorders determined from examination or history, and other primary axis I psychiatric disorders. The study was conducted at the Child Psychiatry Branch of the National Institute of Mental Health (NIMH) in Bethesda, Md., between 1996 and 2001. The NIMH institutional review board approved the research protocol, and written informed consent and assent were obtained from parents and children, respectively.
All subjects were studied on the same 1.5-T GE Signa scanner (GE Medical Systems, Milwaukee). T1-weighted images with contiguous 1.5-mm axial and 2.0-mm coronal slices were obtained by using three-dimensional spoiled gradient recalled echo in the steady state with echo time=5 msec, repetition time=24 msec, flip angle=45°, acquisition matrix=256×192, number of excitations=1, and field of view=24 cm. Head placement was standardized as previously described (3). T2-weighted images were obtained for evaluation by a clinical neuroradiologist. Quantification of MRI images was performed by means of a highly reliable fully automated process that determines gray and white matter volumes for the frontal, temporal, parietal, and occipital lobes as well as caudate and cerebellum volumes, as described elsewhere (4). The minimum and maximum Talairach (x, y, z) coordinates that defined the left caudate were –20, –28, –12 and –3, 23, 27, respectively; the corresponding values for the right caudate were 5, –24, –10 and 20, 23, 26. Although the algorithm provided volumes for the right and left caudate, these did not accord well with values determined by hand tracing; the intraclass correlation coefficient (ICC) was <0.40. By contrast, the total caudate volumes were highly concordant with values derived by hand tracing of the caudate head plus body (N=17, ICC=0.91).
Paired t tests contrasting the affected and unaffected co-twins and Pearson correlations representing twin-twin differences in brain volumes and symptom severity ratings were performed by using SPSS 10.0 for Windows (5). Two-tailed significance levels were used, and the criterion for significance was p≤0.05.