Current Research Efforts:
1) Severe iodine deficiency during pregnancy causes endemic cretinism (deaf-mutism, mental retardation, and rigid-spastic motor disorder), considered the world's commonest preventable cause of mental retardation. We examined the effect of iodine on human brain development by systematically supplementing iodine-deficient children (newborn to 3 years) and pregnant women and following the children for five years, using neurological examination, head circumference and psychometric assessment as outcome metrics. Controls were historical (children first seen newborn-3 years); there were no untreated controls. Iodine improved all indices if given during the first or second trimester; if given during the third trimester or postnatally, only a modest effect was seen. An irreversible effect of iodine deficiency occurs in early third trimester, correlating with the rapid increase of brain weight, neuronal differentiation and synaptogenesis. This has led us to identify a critical period for thyroid hormone action during brain development, consistent with that found in experimental animals and severely premature infants.
2) In southern Xinjiang province of China, after usual methods of iodine supplementation failed, we initiated iodination of irrigation water to increase iodine in soil, crops, animals, and humans. 5% potassium iodate solution, dripped into an irrigation canal during 24-day period, increased iodine levels in soil, crops, animals, and urine iodine levels remained high over three years. Sheep production increased about 40%, a net economic benefit; and infant mortality rates decreased by half during the subsequent three years. The cost for iodine was 5 cents US/person/year. Iodination of irrigation water is a feasible and cost-effective method of supplying iodine here and in other areas dependent on irrigation. In 1997-1999, iodine dripping was extended to cover a population of >2,000,000. Follow-up studies showed that after one application of iodate to irrigation water, iodine levels in soil, crops and humans were protective for 5 to 6 years. The tests were replicated in Inner Mongolia province during 2000-2008, with similar results and expanded data on the fate of added iodine in soil. Later studiese were expanded to trials of iodinated salt blocks in Tuva, a Siberian Russian republic, with remarkable benefits for livestock health (ICCIDD Newsletter, 2008).
In another field, we made three findings in infantile autism:
1) We showed that an important subgroup of autistic spectrum disorders are related etiologically to familial major affective disorders, and may represent the early-life onset of a severe phenotype of major affective disorder. This has resulted in a major effort to link a gene or genes for this form of autism, in collaboration with the Neurogenetics laboratory. We have accumulated more than 200 informative families. With Dr. Simon Gregory of the Center for Human Genetics we are searching by family pedigrees of autistic spectrum disorders and major psychiatric disorders for genetic disorders including copy number variations, imprinting disorders, and single gene mutations. Utilizing individual pedigrees should avoid the vexing problem of genetic heterogeneity found in multifamily studies, and use of new genomic methods of genetic assessment increases the possibility of finding pertinent genetic disorders.
2) We have found that fluoxetine is a very effective agent in this form of autism, increasing cognitive processing and thus language, social skills, and programs of purposeful activity. Fluoxetine produces a remarkable improvement in cognitive processing and language acquisition in a group of young children with this form of autism who have a family history of major affective disorder. As of 2009, fluoxetine has not been generally adopted by the autism community, and no controlled studies have been completed, to my knowledge. Other psychiatric medications used in major psychiatric disorders, e.g. risperdone, are however commonly used for behavioral control in autistic individuals, and the association of a common type of autism with familial major psychiatric disorder has been increasingly accepted by the autism research community.
3) The neurological substrate of autism is disputed. We correlated clinical and neuroimaging findings in four children with isolated bilateral hippocampal sclerosis, utilizing magnetic resonance (MR) and positron emission tomography (PET) studies. These children failed to develop language, social interaction, or complex programs or purposive action. Bilateral hippocampal destruction in the young child precludes language learning, and indeed any form of higher cognitive learning. Such children have a developmental deficit equivalent to severe infantile autism. Hippocampal function appears necessary for language and related semantic learning in young children.
In collaboration with the laboratory of Dr. Teepu Siddique, Northwestern University, we studied a large New England kinship with an autosomal dominant neuromotor disorder best characterized as scapulo-peroneal atrophy, and linked the disorder to chromosome 12q21.1-12q21.3. Other families were subsequently identified at Mayo Clinic, Columbia University, and in England, and as of 2009 a specific gene mutation segregating with the clinical disorder was identified (manuscript submitted for publication).