Metabolite Concentrations Shed Light on Autistic Brain Structure

IRVINE, CALIF. — Children with autism and pervasive developmental disorder show abnormalities in brain structure and chemistry early in their life, Seth Friedman, Ph.D., said at the annual conference of the EEG and Clinical Neuroscience Society.

Brain-volume increases in autism are likely not present at birth but begin to develop in infancy, grow most marked by 3–4 years of age, and level off somewhat by age 6–7 years, a theory championed by Eric Courchesne, Ph.D., of the University of California, San Diego. These changes may reflect deficits in cortical volume and organization relative to that seen in children who are developing more typically, said Dr. Friedman, of the University of Washington, Seattle.

With his colleagues, Dr. Friedman compared magnetic resonance images from 45 children with autism or pervasive developmental disorder not otherwise specified (PDD-NOS) and from 14 children with other types of developmental delays (DD) with images from 26 typically developing (TD) children. All subjects were 3–4 years old.

The children in the autistic and PDD-NOS groups had significantly larger cerebral volumes than the other two groups. Their cerebellar, amygdala, and hippocampal volumes were also larger but were proportionate to the overall increase in cerebral size. However, the amygdala was disproportionately large in a subgroup of children with strictly defined autism. The findings were generally similar for boys and girls. Children with DD had smaller amygdalas (Neurology 2002;59:184–92).

Consistent with the findings of other studies, larger-than-average brains in the University of Washington autism sample leveled off in size over time, Dr. Friedman said. Some researchers have suggested that this early increase might be caused by a large number of neurons densely packed into the cortex.

To test this hypothesis, he and his associates evaluated regional brain chemistry in the same 45 children with autism and PDD-NOS, as well as 15 children with DD (the original 14 plus 1 more), and 13 of the original children in the TD group.

They used dual-proton echoplanar spectroscopic imaging to measure brain metabolite concentrations. They also measured each metabolite's relaxation time—the approximate time it takes a chemical system to return to its original state after being perturbed by an outside force, such as a change in temperature, pressure, or—in the case of magnetic resonance—radio waves. In this study, the relative measures of transverse relaxation (T2r) were calculated from the paired echoes to provide a picture of the metabolic activity within the subjects' gray matter.

Compared with the TD children, those with autism and PDD-NOS had T2r values of myoinositol, N-acetylaspartate, and creatine that were 13%, 10%, and 8% lower, respectively. These significant differences suggest there is a lower concentration of these metabolites in the gray matter. However, compared with those of the DD subjects, their T2r values for choline and creatine were 10% and 9% higher, respectively (Neurology 2003;60:100–7).

These data contradict the idea that people with autism experience dense neuronal packing early in the life, Dr. Friedman said. They may support a theory advanced by Manuel F. Casanova, M.D., of the University of Louisville (Ky.), that cortical minicolumns, self-contained organizational neuronal units found throughout the brain, are more numerous but smaller and less organized in these patients.

IRVINE, CALIF. — Children with autism and pervasive developmental disorder show abnormalities in brain structure and chemistry early in their life, Seth Friedman, Ph.D., said at the annual conference of the EEG and Clinical Neuroscience Society.

Brain-volume increases in autism are likely not present at birth but begin to develop in infancy, grow most marked by 3–4 years of age, and level off somewhat by age 6–7 years, a theory championed by Eric Courchesne, Ph.D., of the University of California, San Diego. These changes may reflect deficits in cortical volume and organization relative to that seen in children who are developing more typically, said Dr. Friedman, of the University of Washington, Seattle.

With his colleagues, Dr. Friedman compared magnetic resonance images from 45 children with autism or pervasive developmental disorder not otherwise specified (PDD-NOS) and from 14 children with other types of developmental delays (DD) with images from 26 typically developing (TD) children. All subjects were 3–4 years old.

The children in the autistic and PDD-NOS groups had significantly larger cerebral volumes than the other two groups. Their cerebellar, amygdala, and hippocampal volumes were also larger but were proportionate to the overall increase in cerebral size. However, the amygdala was disproportionately large in a subgroup of children with strictly defined autism. The findings were generally similar for boys and girls. Children with DD had smaller amygdalas (Neurology 2002;59:184–92).

Consistent with the findings of other studies, larger-than-average brains in the University of Washington autism sample leveled off in size over time, Dr. Friedman said. Some researchers have suggested that this early increase might be caused by a large number of neurons densely packed into the cortex.

To test this hypothesis, he and his associates evaluated regional brain chemistry in the same 45 children with autism and PDD-NOS, as well as 15 children with DD (the original 14 plus 1 more), and 13 of the original children in the TD group.

They used dual-proton echoplanar spectroscopic imaging to measure brain metabolite concentrations. They also measured each metabolite's relaxation time—the approximate time it takes a chemical system to return to its original state after being perturbed by an outside force, such as a change in temperature, pressure, or—in the case of magnetic resonance—radio waves. In this study, the relative measures of transverse relaxation (T2r) were calculated from the paired echoes to provide a picture of the metabolic activity within the subjects' gray matter.

Compared with the TD children, those with autism and PDD-NOS had T2r values of myoinositol, N-acetylaspartate, and creatine that were 13%, 10%, and 8% lower, respectively. These significant differences suggest there is a lower concentration of these metabolites in the gray matter. However, compared with those of the DD subjects, their T2r values for choline and creatine were 10% and 9% higher, respectively (Neurology 2003;60:100–7).

These data contradict the idea that people with autism experience dense neuronal packing early in the life, Dr. Friedman said. They may support a theory advanced by Manuel F. Casanova, M.D., of the University of Louisville (Ky.), that cortical minicolumns, self-contained organizational neuronal units found throughout the brain, are more numerous but smaller and less organized in these patients.

IRVINE, CALIF. — Children with autism and pervasive developmental disorder show abnormalities in brain structure and chemistry early in their life, Seth Friedman, Ph.D., said at the annual conference of the EEG and Clinical Neuroscience Society.

Brain-volume increases in autism are likely not present at birth but begin to develop in infancy, grow most marked by 3–4 years of age, and level off somewhat by age 6–7 years, a theory championed by Eric Courchesne, Ph.D., of the University of California, San Diego. These changes may reflect deficits in cortical volume and organization relative to that seen in children who are developing more typically, said Dr. Friedman, of the University of Washington, Seattle.

With his colleagues, Dr. Friedman compared magnetic resonance images from 45 children with autism or pervasive developmental disorder not otherwise specified (PDD-NOS) and from 14 children with other types of developmental delays (DD) with images from 26 typically developing (TD) children. All subjects were 3–4 years old.

The children in the autistic and PDD-NOS groups had significantly larger cerebral volumes than the other two groups. Their cerebellar, amygdala, and hippocampal volumes were also larger but were proportionate to the overall increase in cerebral size. However, the amygdala was disproportionately large in a subgroup of children with strictly defined autism. The findings were generally similar for boys and girls. Children with DD had smaller amygdalas (Neurology 2002;59:184–92).

Consistent with the findings of other studies, larger-than-average brains in the University of Washington autism sample leveled off in size over time, Dr. Friedman said. Some researchers have suggested that this early increase might be caused by a large number of neurons densely packed into the cortex.

To test this hypothesis, he and his associates evaluated regional brain chemistry in the same 45 children with autism and PDD-NOS, as well as 15 children with DD (the original 14 plus 1 more), and 13 of the original children in the TD group.

They used dual-proton echoplanar spectroscopic imaging to measure brain metabolite concentrations. They also measured each metabolite's relaxation time—the approximate time it takes a chemical system to return to its original state after being perturbed by an outside force, such as a change in temperature, pressure, or—in the case of magnetic resonance—radio waves. In this study, the relative measures of transverse relaxation (T2r) were calculated from the paired echoes to provide a picture of the metabolic activity within the subjects' gray matter.

Compared with the TD children, those with autism and PDD-NOS had T2r values of myoinositol, N-acetylaspartate, and creatine that were 13%, 10%, and 8% lower, respectively. These significant differences suggest there is a lower concentration of these metabolites in the gray matter. However, compared with those of the DD subjects, their T2r values for choline and creatine were 10% and 9% higher, respectively (Neurology 2003;60:100–7).

These data contradict the idea that people with autism experience dense neuronal packing early in the life, Dr. Friedman said. They may support a theory advanced by Manuel F. Casanova, M.D., of the University of Louisville (Ky.), that cortical minicolumns, self-contained organizational neuronal units found throughout the brain, are more numerous but smaller and less organized in these patients.