Lingering
doubts have persisted among skeptics that attention-deficit/hyperactivity
disorder (ADHD) is not a real phenomenon but instead the creation
of overly protective or reluctantly disciplinarian parents, or of
a pharmaceutical industry wanting to justify sales of drugs to the
last remaining new demographic in the pharmaceutical marketplace,
children.
This
paper should dispel those doubts resoundingly. Castellanos et
al. show that the brains of children with attention-deficit/hyperactivity
disorder (ADHD) average smaller than children without ADHD.
Their study provides compelling evidence that ADHD is a real,
biologically-based phenomenon not imagined by parents nor teachers
nor caused by medical treatment for the condition.
From
the earliest age studied, the trajectory of brain growth in ADHD
children paralleled that of normal children, but at each
age brain size overall, and that of most brain subregions, were
smaller than normal.
Children
diagnosed with ADHD but not receiving medical treatment also had
reduced brain size.
Because
differences between ADHD children and controls were apparent even
at the youngest age (ages ranged from 5 to 18) Castellano's research
does reveal when the differences in brain growth initially arose.
They could arise from genetic differences, they could involve
prenatal interference with brain development, or they could appear
in early childhood.
What
did they do? Castellanos et al. used magnetic
resonance imaging equipment (MRI) to scan the brains of 152
children (89 male; 63 female) diagnosed with ADHD and compared measured
brain volumes with 139 unrelated healthy children (83 male; 56 female).
Some of the subjects were scanned up to 4 times over the course
of the 10-year study. Their MRI scanner allowed them to examine
not only overall brain volume, but also the sizes of different brain
subregions, and to calculate the volumes of gray and white matter
compartments in frontal, temporal, parietal and occiptal lobes,
as well as basal ganglia and cerebellum.
The
research team then used statistical procedures that allowed them
to test for differences between ADHD and normal children, and within
ADHD for the effects of medical treatment. These procedures adjusted
for variables such as differences in overall body size, gender,
age, etc.
What
did they find? Brain volume was slightly smaller in ADHD
patients. On average, after controlling for size and other variables,
cerebral and cerebellar volumes were 3.2% and 3.5% smaller in ADHD
patients. These differences were highly significant statistically.
The largest difference observed was a 9.2% decline in temporal white
matter.
Using
an additional statistical step Castellanos et al. determined
that the cerebellum decreased disproportionately more than other
brain parts.
And
looking at the effect of medication, Castellanos' team observed
that unmedicated ADHD total cerebral and cerebellar volumes were
smaller than controls, but indistinguishable from medicated ADHD
patients. Hence the brain volume differences observed between
ADHD and controls are not caused by medication.
While
medicated
ADHD patients did not differ from controls on any white matter measures,
"robust differences from controls remained for all gray matter
measures."
Examining
changes in brain volume over time, the scientists found that for
all but one region studied, differences observed in the youngest
patients continued through teenage years. In other words, there
was no acceleration in brain volume growth that might have allowed
the ADHD volumes to "catch up" to normal brain size. Equally
important, these data on developmental trends establish that the
volumetric differences are evident at the youngest ages measured.
This indicates that ADHD begins very early in life, possibly even
in the womb.

More
detailed analysis revealed that measured brain subregions were smaller
in ADHD patients than controls at all ages, with one exception in
later teenage years.
The
exception involved the caudate region, where volume normally peaks
around the age of ten and then declines. This is shown in the left
graph, below. ADHD caudate volume tracked beneath that of controls
at the peak and then on through early-teenage years. In mid-teenage
years and beyond, however, caudate volume in ADHD patients did not
fall proportionately as far as normal caudate volume. The greater
decline in normal caudate volume then led to convergence of normal
brains with ADHD brains in this one parameter.

By
comparison (right), cerebellar volume continues to grow throughout
the ages studied. At each stage in development, ADHD volume is lower
than control volume. It would appear that ADHD cerebellar growth
may approach a plateau during teenage years more rapidly than that
of the controls.
What
does it mean?
The
volume measurements reported by Castellanos et al. clearly
indicate that that brains of control and ADHD patients differ. This
is important, because it demonstrates that ADHD has a biological
basis with measurable physical manifestations. Their work also shows
ADHD is not caused by caused by medication. Instead it is related
to changes in patterns brain growth initiated in early childhood,
or in the womb. These changes persist throughough childhood and
teenage years.
The
results reveal little about the detailed structural changes that
almost certainly underlie the volume differences. It therefore remains
impossible to say what stimulates the changes in growth or what
mechanisms link the overt changes in brain volume reported here
with the behavioral manifestations of ADHD.
Interviewed
by the Los
Angeles Times, the scientists said that they believe the data
indicate ADHD is caused prenatally.
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