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Neuropsychopharmacology: The Fifth Generation of Progress

TABLE 43.2. FUNCTIONAL NEUROIMAGING STUDIES OF ADHD

Study

Diagnosis

Method

Findings

Lou et al. (201) Lou et al. (216)

ADD ADHD

rCBF rCBF

Hypoperfusion in frontal cortex and caudate, hyperperfusion in occipital cortex Hypoperfusion in right striatal region, hyperperfusion in occipital cortex, left

Lou et al. (217)

ADHD

rCBF

sensorimotor, and primary auditory regions Hypoperfusion in striatal and posterior periventricular regions; hyperperfusion in

Zametkin et al. (66)

ADHD

PET

occipital cortex, left sensorimoter, and primary auditory regions Lower glucose metabolism in premotor and superior prefrontal cortex, right

Ernst et al. (62)

ADHD

PET

thalamus, right caudate, right hippocampus, and right cingulate ADHD girls (but not boys) show lower glucose metabolism in right prefrontal

Amen et al. (218) Rubia et al. (219)

ADHD ADHD

SPECT fMRI

cortex, right temporal cortex, right and left posterior putamen, and middle cingulate Decreased perfusion in prefrontal cortex Lower activation in right mesial prefrontal cortex, right inferior prefrontal cortex,

Baving et al. (63)

ADHD

EEG

and left caudate Boys show a less right-lateralized frontal activation pattern; girls show a more

Schweitzer et al. (220)

ADHD

rCBF

right-lateralized frontal activation pattern than healthy control girls Task-related changes in rCBF in non-ADHD men without ADHD were prominent

Silberstein et al. (221)

ADHD

EEG

in frontal and temporal regions; changes in ADHD men were more widespread, suggesting the use of compensatory mental and neural strategies Increased speed of prefrontal processing in non-ADHD children, ADHD following

Vaidya et al. (222)

ADHD

fMRI

priming stimulus, and a deficit in such processes in ADHD children ADHD is characterized by atypical frontal-striatal function, and methylphenidate

Ernst et al. (223)

ADHD

PET

affects striatal activation differently in ADHD than in healthy children More accumulation of [18F]DOPA in the right midbrain correlated with symptom

Bush et al. (65)

ADHD

fMRI

severity ADHD adults show weak activation of anterior cingulate cognitive division

Dougherty et al. (67)

ADHD

SPECT

during counting Stroop task Dopamine transporter density in striatum greater in ADHD adults

ADD, DSM-III attention-def magnetic resonance imagi tomography.

icit disorder; ADHD, DSM-III-R attention-deficit hyperactivity disorder; EEG, Electroencephalogram; fMRI, functional ng; PET, position emission tomography, rCBF, regional cerebral blood flow; SPECT, photon emission computed

pothesis of ADHD in showing the DAT to be elevated by about 70% in adults with ADHD.

The functional studies are consistent with the structural studies in implicating frontosubcortical system in the patho- physiology of ADHD. Taken together, the brain imaging studies fit well with the idea that dysfunction in frontosub- cortical pathways occurs in ADHD. They are also consistent with the report of a father and son, both having methyl- phenidate-responsive ADHD secondary to frontal lobe epi- lepsy (68). Notably, the frontosubcortical systems that con- trol attention and motor behavior are rich in catecholamines, which have been implicated in ADHD by the mechanism of action of stimulants.

al. assayed four brain abnormalities believed to occur before birth: neural migration anomalies, corpus callosum agenesis or partial agenesis, enlarged cavum septi pellucidi, and mal- formations of the posterior fossa (70). Neural migration anomalies and malformations of the posterior fossa were more common among patients with ADHD compared with control subjects. Both these abnormalities were rare. How- ever, given that several other studies showed partial agenesis of the corpus callosum or anomalies of the cerebellar vermis (also formed before birth), it seems reasonable to conclude that at least some children with ADHD have a very early onset of brain abnormalities.

In a novel approach to assessing brain regions implicated in ADHD, Herskovits et al. used magnetic resonance imag- ing to assess the spatial distribution of lesions in children who developed ADHD after closed-head injuries (69). Compared with head-injured children who did not develop ADHD, the children with ADHD had more lesions in the right putamen and a trend for more lesions in the right caudate nucleus and right globus pallidus.

Very little is known about when ADHD-related brain abnormalities emerge. To address this issue, Nopoulos et

GENETICS Family Studies

Figure 43.1A shows rates of hyperactivity among the sib- lings of hyperactive probands (71–75). Figure 43.1B shows an elevated prevalence of ADHD among mothers and fa- thers of children with ADHD that provides further support for the familiality of the disorder and evidence that the adult diagnosis is valid. These studies leave no doubt that ADHD

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