Neural Correlates of Attention-Deficit/Hyperactivity Disorder in Adulthood

Abstract

dults with traits of attention-deficit/hyperactivity disorder(ADHD) have been described for centuries. A notableexample is Lelie, a character in Moliere's 1653 comedyL'etourdi ou les Contretemps, who, among other things, constantlyinterrupts others, fidgets with his feet, and has difficulty payingattention and following instructions. Despite many informalaccounts and even formal scientific reports dating back to theearly 20th century suggesting that ADHD traits may persist intoadulthood, the erroneous notion that ADHD is mainly a childhooddisorder has been difficult to shake (1). It is now recognized,however, that a substantial proportion of children with ADHDhave symptoms that persist into adulthood (2,3) and that ADHD isa serious medical condition with potential long-term individualand societal consequences ranging from loss of productivity tocriminality (4). Recent years have witnessed a substantial increasein the number of studies of ADHD in adults. In fact, in the last fewyears in Europe and North America, more studies on long-termoutcomes (i.e., studies of at least 2 years in duration) of ADHDhave been conducted in adults than in children or adolescents (1).Nonetheless, with the exception of a few predictors like comorbidchildhood psychopathology (5), little has been garnered aboutthe factors associated with the persistence or remission of ADHDin adulthood. In the current issue of Biological Psychiatry, twooriginal and complementary studies are published that explorethe matter.In this issue, Shaw et al. (6) analyzed a unique longitudinaldataset that includes a combination of repeated clinical assess-ments from childhood to adulthood with repeated structuralmagnetic resonance imaging scans on the same subjects. One ofthe aims of the work was to identify regions where thedevelopmental trajectory in cortical thickness was associatedwith adult signs and symptoms of ADHD and to compare thetrajectories of subjects that had persistent ADHD with those ofsubjects who no longer met the criteria for ADHD. As shownpreviously by this group (7), cortical developmental trajectoriesyield valuable information that cross-sectional analyses cannotprovide.Specifically, Shaw et al. (6) analyzed data on 92 participantsthat had been diagnosed with childhood ADHD and contrastedfindings with 184 typically developing matched control subjects.Of the 92 subjects with childhood ADHD, 37 still met criteria forADHD as adults. Typically, for the age range under study, thecortex tends to thin gradually over time. Whereas no associationswere found between cortical thickness in the baseline scan andsymptoms of adult ADHD, it was shown that higher rates ofcortical thinning in specific regions are associated with a greaternumber of ADHD symptoms persisting into adulthood. Thesefindings were driven by the number of symptoms of inattentionand the relevant regions included, bilaterally, the cingulate gyrus,medial prefrontal cortex, and precuneus, as well as the rightdorsolateral prefrontal cortex. Further, a significant difference inrate of cortical thinning was shown in these regions betweenthose adults that remitted and those that had persistent symp-toms. Intriguingly, those that remitted exhibited a slower rate ofcortical thinning than typically developing control subjects. Infact, some of the subjects that remitted even displayed a degreeof cortical thickening. Overall, this resulted in an essentially equalthickness in the above regions, in adulthood, for remitters andcontrol subjects. Importantly, although the rate of psychostimu-lant use was greater at final assessment in those with persistentADHD, the authors report that results held when analyses werelimited to subjects not medicated at final assessment. Further, nodifference in the proportion of time on psychostimulants duringthe study was found between ADHD groups. This being said, theauthors concede that this measure did not include estimates oftotal lifetime medication dose and was based on participantreports.In a second study in this issue, Cortese et al. (8), the authorsused diffusion-weighted imaging to study white-matter connec-tivity and focused on ADHD as a consequence of altered brainconnectivity. They compared fractional anisotropy (FA), a metricsensitive to white matter structural properties, in adult malesubjects diagnosed with childhood ADHD with that of matchedcontrol subjects. As in Shaw et al. (6), they compared those thathad persistent ADHD into adulthood with those that no longermet criteria for ADHD. They first contrasted FA in 51 male subjectsaged 41 years that had been diagnosed with childhood ADHDabout 33 years earlier (probands) with FA from 66 male controlsubjects matched for age, social class, and geographic residence.The probands exhibited lower FA (presumed to reflect poorerconnectivity) than control subjects in tracts such as the sagittalstratum, the retrolenticular internal capsule, and the superiorlongitudinal fasciculus. These tracts link regions known to beinvolved in attention set shifting, focused attention, and spatialworking memory, among others. The results also showed lowerFA for probands in multiple tracts involved in visual processing, afinding that the authors suggest has generally been overlookedin prior studies, in part, perhaps because of the strong focus onfrontostriatal dysfunctions. As both probands and control subjectsincluded subjects with diagnoses of ADHD Not OtherwiseSpecified, further analyses excluded these subjects. This resultedin a group of 40 probands (15 still meeting ADHD criteria asadults) and 47 non-ADHD control subjects. Probands withpersistent ADHD exhibited lower FA than control subjects inmany of the tracts noted above. Interestingly, lower FA wasobserved in probands regardless of current ADHD status. Further,no differences were found between probands with persistentsymptoms and those that had a remission of symptoms inadulthood. However, as acknowledged by the authors, this maybe due to small subsamples and hence limited statistical power.This last finding sharply contrasts with Shaw et al. (6), who didfind differences between those with persistent ADHD and thosewith a remission of symptoms. However, it is noteworthy that