Macrocephaly refers to an abnormally large head size and includes the scalp, the cranial bones and brain size.

Relevance to autism:

Leo Kanner first reported a larger-than-normal head size as feature of autism in his classic paper describing the first case of autism1.

Subsequent studies show that approximately 20 percent of children with autism have enlarged heads2.

At the 2010 International Meeting for Autism Research, Eric Courchesne presented unpublished data from a study of postmortem tissue from nine children aged 2 to 15 years with autism. His team found 65 percent more neurons in the dorsolateral prefrontal cortex and 25 percent more neurons in the medial prefrontal cortex in the autism group compared with brains from age-matched controls.

What causes this peculiar pattern of brain growth in autism is as yet unknown. Greater numbers of neurons or glial cells, the supporting cells of the nervous system, alterations in the formation of a myelin sheath around nerve fibers, and aberrant formation or pruning of synapses are all logical suspects.

Researchers speculate that if damaged neurons are not pruned, they proliferate in the brain, possibly driving their over-abundance, and the overgrowth of connecting fibers. This may lead to faulty connections between different brains regions, which is believed to be one of the deficits underlying autism.

Growth trajectory:

In a 2005 meta-analysis, researchers first introduced a hypothesis about the trajectory of brain growth in autism: Babies with autism have normal head size at birth, followed by rapidly increasing brain size until 2 years of age and ending abruptly by age 4, when the brain slowly begins to decrease in size3.

Since then, several studies have confirmed this hypothesis. An October 2010 brain imaging study looks at magnetic resonance imaging scans of more than 250 participants with autism ranging in age from 2 to 50 years and an equal number of controls4.

The researchers report that brains of people with autism show three distinct periods of abnormal development — overgrowth in infancy, prematurely arrested growth in childhood, and shrinking between adolescence and middle age.

In typically developing children, the cortex — layered neural tissue that plays a key role in memory, attention, language and consciousness — thickens steadily from age 5 or 6 through puberty, as their brains forge new connections through learning and experience. In this same period, brain growth prematurely halts in children with autism. In both groups, the cortex thins with age, but in people with autism that process begins sooner and appears to advance more rapidly.

In another imaging study of 41 teenagers with autism and 41 controls, researchers saw a thinning of the cortex beginning at around age 15 and accelerating at 175. The results are especially pronounced in the temporal and parietal cortex, areas involved in processing language and sensory information. In participants aged 20 and above, the researchers also saw more thinning in the left fusiform gyri, a brain region involved in face processing and perception of emotion in faces.

A May 2010 brain imaging study suggests that the brain overgrowth occurs before children reach 2 years of age. It shows that the brains of 38 children with autism grow at the same rate as those of controls between ages 2 and 46.

Conflicting results:

Some studies, however, report no difference in head size between children with autism and controls. Working with data from the Early Childhood Longitudinal Study Birth Cohort a U.S. Department of Education initiative, researchers at Baylor University in Texas looked at head circumference in 9,000 children born in the U.S. in 20017.

They found no indications of head circumference greater than two standard deviations from the average in the 100 children diagnosed with autism by age 3 in the sample. At 9 months of age, the researchers observed a slight bump in head size, but it did not achieve statistical significance.

Critiques of this study include the fact children were assigned to the autism category based solely on a parent’s report that a ‘professional’ had diagnosed the child with autism.

Brain size:

Although the head overall is bigger in some children with autism, researchers have found more informative differences in size — some smaller, some larger — across regions of the brain.

For example, one study showed that the volume of the striatum, the large cluster of nerve cells that controls movement, increases with age in individuals with autism, but decreases in typically developing individuals8. Another study found that the corpus callosum, the thick band of white matter that connects brain hemispheres, is smaller in individuals with autism compared with healthy controls9.

  1. Kanner L. Nervous Child 2, 217-250 (1943)
  2. Fombonne E. et al. J. Autism Dev. Disord. 29, 113-119 (1999) PubMed
  3. Redcay E. and E. Courchesne Biol. Psychiatry 58, 1-9 (2005) PubMed
  4. Courchesne E. et al. Brain Res. 164, Epub ahead of print (2010) PubMed
  5. Wallace G.L. et al. Brain 133, 3745-3754 (2010) PubMed
  6. Hazlett H.C. et al. Arch. Gen. Psychiatry 68, 467-476 (2011) PubMed
  7. Langen M. et al. Biol. Psychiatry 66, 327-333 (2009) PubMed
  8. Freitag C.M. et al. Biol. Psychiatry 66, 316-319 (2009) PubMed
  9. Bernard-Brak L. et al. Pediatr. Neurol. 44, 97-100 (2011) PubMed