Advancing the neuroscience of ADHDStructural Brain Imaging of Attention-Deficit/Hyperactivity Disorder
Section snippets
Historical Background for Hypotheses of Brain Dysfunctions in ADHD
Attention-deficit/hyperactivity disorder was first described 100 years ago as a childhood disorder found mainly in boys, initially called “hyperactivity,” or “hyperkinesis disorder of childhood” (Still 1902). In the 1960s, the (now outmoded) terms “minimal brain damage” or “minimal brain dysfunction” (MBD) were used to suggest this could be a brain disorder. Revisions in the diagnostic construct have been made a number of times over the past century. The most significant shift occurred in the
Structural Brain Imaging in Children and Teenagers with ADHD
There are a number of previous reviews of structural and functional imaging studies of ADHD (Castellanos 1997; Durston 2003; Seidman et al 2004a). This article differs from previous reviews by providing a comprehensive table summarizing the results by anatomic region, proposing in some detail the importance of the cerebellum in ADHD, and providing a critical analysis of structural imaging studies. This review is based on a search through computer data bases, using key words such as “structural
Total and Lateralized Cerebral Volume
Seven of twelve reports (Castellanos et al 1996, Castellanos et al 2001, Castellanos et al 2002; Filipek et al 1997; Kates et al 2002; Mostofsky et al 2002; Hill et al 2003) have shown that in ADHD children through age 19, the total cerebrum, particularly the right hemisphere, is 3%–5% smaller, and one study reported reduced intracranial volume (Durston et al 2004). Studies have also reported smaller total gray and white matter (Castellanos et al 2002; Mostofsky et al 2002). No study reported
Exploratory Brain Regions of Interest
A number of reports have identified abnormalities in ROIs that were not predicted by cognitive models of ADHD. Although it is too soon to know whether these results will be robust, they are important to consider, because a neurodevelopmental etiology of ADHD can account for widespread alterations in the formation of the brain that have yet to be well studied (Nopoulous et al 2000).
Structural Brain Imaging in Adults with ADHD
It is unclear why there is only one structural brain imaging study in adults with ADHD. Because this contrasts sharply with the literature on most psychiatric disorders (for which there are typically numerous imaging studies), we suspect that the lack of research reflects the fact that, until recently, the validity of ADHD in adulthood was questioned. As illustrated by the burgeoning literature in other areas of adults with ADHD (seen in this issue), this tendency is changing. Thus, future
Psychiatric Comorbidity
Children and adults with ADHD frequently have comorbid antisocial, substance abuse, mood, anxiety, or learning disorders (LDs; Biederman et al 1993). A key question is whether these disorders account for the brain abnormalities. Importantly, studies in children and adults showed that neuropsychologic deficits in ADHD remained robust after statistically adjusting for psychiatric comorbidities (Faraone et al 2000; Seidman et al 1998, 2004b). Most of the morphometric MRI studies of children with
Assessing the Effects of Gender on Brain Abnormalities in ADHD
Because severe behavioral disturbances are observed less frequently among ADHD girls, they may be less likely to come to the attention of health care providers (Gaub and Carlson 1997). Depending on the sampling source, ADHD is 2 to 9 times more prevalent among boys than girls. In adults, however, the ratio is closer to 1.5:1.0 (male:female; Biederman 1998). Although it is increasingly recognized that ADHD affects both genders, most of the research literature had been limited to male subjects (
Heterogeneity of ADHD and Brain Abnormalities
A number of other potentially important sources of heterogeneity exist in addition to those described thus far—for example, presence or absence of family history of ADHD, inattentive versus hyperactive-impulsive symptoms, and perinatal complications. Studies indicate that as many as 57% of ADHD adults have at least one first-degree relative with ADHD (Biederman et al 1995). There is preliminary evidence that these individuals are more neuropsychologically impaired than those without a positive
Relationship of Brain Structure and Neuropsychologic Dysfunctions
The analysis of attention and executive functions into subcomponents—and the mapping of attentional functions onto different brain regions—supports the proposition that inhibition and other executive deficits in ADHD will be associated with brain abnormalities. In children, Casey et al (1997) found that performance on three response inhibition tasks correlated only with those anatomic measures of frontostriatal circuitry observed to be abnormal in ADHD (i.e., the PFC, caudate, and pallidum, but
Summary
In summary, many investigators hypothesize that a key brain abnormality in ADHD involves structural and functional abnormalities in frontostriatal circuitry (Castellanos 1997; Faraone and Biederman 1998). Although our review suggests that there is substantial anatomic support for this hypothesis, a growing literature indicates abnormalities in other cortical regions as well as the cerebellum. Because there is only one report of ADHD adults, we must currently rely on results in children with
Microanalysis of ROIs—Example of Cerebellar Anatomy and Connections
The subtle but widespread and developmentally based alterations in the brain in ADHD can be conceptualized as potentially involving dysfunctions of brain connectivity. Although it is beyond the scope of this article to address this in detail, one of the most interesting questions in ADHD is how to understand the role and relationship of cerebellar to frontostriatal abnormalities. The cerebellum is increasingly understood to be important in ADHD, and the precise measurement of cerebellar
Conclusion
The identification of neuroanatomic, neuropsychologic, and functional abnormalities in ADHD, as well as the interrelationship among these abnormalities, is crucial for understanding the neurobiological mechanisms involved in ADHD. Additional research on the neuroanatomy of adult ADHD is needed using high-resolution MRI, and a subsequent meta-analysis would strengthen these findings. This greater knowledge of the ADHD brain is necessary to help clarify the neurodevelopmental evolution of the
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