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IGF-I and IQ in Middle Childhood« Back to Volume 22, Issue 2, June 2006 - Table of Contents Gunnell and colleagues examined the association between circulating levels of insulin-like growth factor (IGF)-I, its main binding protein, IGFBP-3, and subsequent measures of IQ by employing data from a longitudinal cohort study. The study group for the current subanalyses consisted of 547 white singleton children, (301 boys, 246 girls) members of the Avon Longitudinal Study of Parents and Children (n=13 617), with IGF-I and IGFBP-3 measurements obtained at a mean age of 8.0 years and IQ measured with the Wechsler Intelligence Scale for Children (WISC-III) at a mean age of 8.7 years. Associations with measures of speech and language were also investigated using the Wechsler Objective Reading Dimensions (WORD; assessed at 8.7 years) test and the Wechsler Objective Language Dimensions (WOLD; assessed at 7.5 years) test. Some children (n=407) had IGF-I levels measured at approximately 5 years of age in a previous study. The mean IGF-I (ng/mL) level at age 8 years was 142.6 (± 53.9) and 154.4 (± 51.6) for boys and girls, respectively. For every 100 ng/mL increase in IGF-I, IQ increased by 3.18 points (p=.019) for boys and girls combined. This relationship achieved statistical significance only for girls. A statistically significant association was not detected between IGFBP-3 or IGF-I/IGFBP-3 ratios and IQ. WISC-III subtests are classified as Verbal or Performance: associations between IGF-I and IQ were restricted to the Verbal component. The IGF-I levels were not significantly associated with either WOLD or WORD test scores for the combined sample of boys and girls. In contrast, a positive statistically significant association between IGF-I levels and WORD scores was detected for girls, but not for boys. Associations between IGF-I levels at age 5 and WISC-III scores were similar to those for IGF-I levels measured at age 7 to 8, applied to both the boys and girls but, just as in the case of the associations reported above, were restricted to the Verbal rather than the Performance component of IQ. Follow-up analyses were performed statistically, controlling for potential confounding variables. Introducing birth weight (adjusted for gestation), breastfeeding, and BMI to the regression model strengthened the association between IGF-I and IQ; whereas controlling for maternal education and IGFBP-3 attenuated the association, as did adjustment for housing status and family socioeconomic status. The authors suggest that rather than confounding the associations of IGF-I levels with IQ, parental education and socioeconomic background of the family may themselves serve as markers of “parental IQ, and through genetic and shared environmental pathways, with their offspring’s intelligence. Similarly, offspring IGF-I levels are likely to be associated with parental IGF-I levels, through shared genetic influences.”The authors concluded, “This study provides some preliminary evidence that IGF-I is associated with brain development in childhood. Additional longitudinal research is required to clarify the role of IGF-I in neurodevelopment. Because IGF-I levels are modifiable through diet and other environmental exposures, this may be one pathway through which the childhood environment may influence neurodevelopment.” Editor’s CommentThe prospect of an association between IGF-I, brain development ,and intelligence is not new,1 but remains intriguing. The importance of the Gunnell et al study lies in the cohort design of the Avon Longitudinal Study of Parents and Children, the quality of the psychological/cognitive assessments, and detailed characterization of important contextual variables in child development (eg, diet and socioeconomic status of the family of origin). Evidence that growth factors (rather than psychosocial stress associated with short stature) may be responsible for educational and vocational outcomes suggests that stature and growth can be viewed as proxies for other biologic events rather than as a focus for its own sake. Findings from a controlled study by Kranzler and colleagues2 on the intellectual ability of children with growth hormone receptor deficiency (GHRD) (and accompanying severe IGF-I deficiency) are difficult to reconcile with the Gunnell report. Kranzler compared the intellectual ability of 18 school-age Ecuadorian GHRD probands with that of 42 relatives and 28 community controls, using a battery of intelligence tests. The intellectual ability of the patients with GHRD was not significantly different from that of their relatives, and was comparable to that of the community controls. Furthermore, homozygosity or heterozygosity for the mutation in the GHR gene common to Ecuadorian patients was unrelated to intelligence. The authors concluded that GH-induced IGF-I production is not required for normal brain growth in utero or for postnatal intellectual development. It may be overly simplistic to question, but if circulating values of IGF-I are positively related to intellectual function, then would GH-mediated increases in IGF-I result in higher performance? Indirect supportive evidence comes from a study of the effects on IQ scores of GH administered to children born small for gestational age.3 Growth hormone treatment was associated with significant increases in relative height along with improved IQ scores. Because it can be assumed that GH treatment raised IGF-I levels, then perhaps IGF-I effects on the central nervous system mediated the effects of GH on intellectual ability. Interestingly, in this report, it was only the measure of Performance IQ (and not Verbal IQ) which showed improvement with GH; the opposite pattern was observed in the Gunnell et al study. Clearly, all these findings require replication, and future investigations will hopefully be guided by a priori predictions regarding the effects of growth factors on brain development and function in order to reduce the probability of Type I errors. David E. Sandberg, PhD References - (linked to
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Volume 24 Number 1
May 2008
www.GGHjournal.com
ISSN 1932-9032
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