Autism’s home in the brain

To the Editor:

Thank you for the interesting articles on autism by Rapin,1 DeLong,2 Minshew et al.,3 and Courchesne et al.4 I would like to bring up for discussion the possibility that dysgenesis of temporal and frontal lobes, abnormalities of the cerebellar vermis, oculomotor signs, and a disorder of serotonergic neurotransmission could result from perinatal disruption of aerobic metabolism. Anoxia, infections, or exposure to toxic substances during gestation or early postnatal development may impair brainstem nuclei of high metabolic rate in a Wernicke encephalopathy–type symmetric bilateral pattern, whether visible damage is apparent.5 Reports of brainstem damage in infants who died during the perinatal period demonstrate that this kind of pathology occurs.6 Less severe submicroscopic involvement of brainstem nuclei could alter the biochemical processes required for normal development of later maturing areas of the cerebral cortex.

It might be worth considering whether autism spectrum disorders including Asperger’s syndrome and antisocial personality disorder could be caused by maldevelopment due to loss of trophic influences from caudal to rostral brain centers. Growth of the human cerebral cortex continues past the second decade, but brainstem nuclei mature much earlier.7 The inferior colliculus is the earliest structure myelinated in the human brain, and the auditory system is functional by the 30^th week of gestation.8 Early maturation and intactness of the brainstem auditory system may be important for growth and development of the temporal lobes. Activity of serotonin-sensitive adenylate cyclase is especially high in the inferior and superior colliculi of immature rats and may stimulate synaptic proliferation.9

The brainstem structures damaged in Wernicke’s encephalopathy are among the brain areas of highest metabolic rate as measured by the deoxyglucose method of Sokoloff.5 The mamillary bodies, inferior olives, and cerebellar vermis are affected in Wernicke’s encephalopathy—structures all …