More on smoking and neuropsych disorders

New research shows that using nicotine during pregnancy affects genes involved in myelination and, consequently may help explain why the children of mothers who smoke during pregnancy are more likely to develop such psychiatric disorders as attention deficit hyperactivity disorder, depression, autism, and even drug abuse. In a paper presented at Neuroscience 2010, the annual meeting of the Society for Neuroscience, Professor Ming Li, Ph.D., of the University of Virginia (Charlottesville, VA, US) reported that when rats were given nicotine during pregnancy, their offspring manifested changes in myelin genes for the limbic system, especially the prefrontal cortex, a brain region important for decision-making.

“Our research shows that gestational treatment with nicotine significantly modifies myelin gene expression in specific brain regions that are involved in behavioral processes,” according to Professor Li, leader of the study. “Myelin deficits have been observed in adults with various psychiatric disorders. Our findings suggest that abnormal myelination may contribute to the psychiatric disorders associated with maternal smoking.”

An especially interesting feature of this finding is that there appears to be a sex-specific connection to the effects. Myelin-related genes increased in the prefrontal cortex of male offspring but decreased in females, and the opposite occured in the hypothalamic paraventricular nucleus. According to Professor Li, “These findings suggest that maternal smoking may affect daughters and sons differently.”

Professor Li noted that nicotine is the active ingredient in the effects his team observed. Thus, it would not help to “go on the patch” or “chew nicotine gum” as a replacement for smoking while pregnant. Also, although I’m about to sound a note of caution about the generality of these findings, one should understand that they fit with many other findings from research using different methods. For example, Brook et al. (2000) showed that maternal smoking during pregnancy was associated with toddlers’ greater behavioral negativity. And, of course, there is the famous Milberger et al. (1996) retrospective pro-band study showing a relationship between maternal smoking and ADHD. These studies do not even touch on the physical health concerns.

As with the findings from Professor Robin Lester’s study, I recommend caution in extrapolating these findings. Not only are both based on infra-human models, but also one must understand that I am working primarily from press releases and that this research is from a discipline beyond my own.

269.2, Prenatal nicotine exposure modifies expression of myelin-related genes in the limbic system of adolescent rats in a brain region- and sex-dependent manner

J. CAO1, J. B. DWYER3, F. M. LESLIE3,4, M. D. LI2; 1Dept. of Psychiatry & Neurobehavioral Sciences, Univ. of Virginia, CHARLOTTESVILLE, VA; 2Dept. of Psychiatry & Neurobehavioral Sciences, Univ. of Virginia, Charlottesville, VA; 3Pharmacol., 4Anat. & Neurobio., Univ. of California, Irvine, Irvine, CA

Maternal smoking during pregnancy (MS) has long-lasting neurobehavioral effects on the offspring. Many MS-associated psychiatric disorders begin or change symptomology during adolescence, a period of continuous development of the central nervous system. Most of these disorders are thought to be mediated by dysfunction of the limbic system, a collection of brain nuclei that mature during adolescence. Given that deficits in central myelination are convergently observed in many psychiatric disorders, we hypothesized that myelin is impaired by gestational treatment with nicotine (GN), the major psychoactive component in tobacco, in adolescent limbic system. Pregnant Sprague Dawley rats were treated with nicotine (3 mg/kg/day) or saline via osmotic minipumps from gestational days 4 to 18. Both male and female offspring were sacrificed on postnatal day 35, and five limbic brain regions, including prefrontal cortex (PFC), hypothalamic paraventricular nucleus (PVN), caudate putamen (CPu), nucleus accumbens (NAc) and the amygdala (AMY) were dissected. Twenty-nine myelin genes, including those encoding major myelin proteins, lipid-related enzymes and transcriptional factors, were assayed with quantitative RT-PCR array. We found that GN significantly modified myelin gene expression in a brain region dependent manner. Specifically, we found that more genes were altered in the PFC compared to other brain regions, while AMY showed the least response to GN. In the striatum, more genes were changed in the CPu as compared to NAc. Further, we detected striking sex differences in each brain region. In the PFC, myelin genes were significantly upregulated by GN in males, but downregulated in females. In contrast, myelin genes in the PVN were downregulated in males but upregulated in females. In the AMY, only seven genes were significantly upregulated in females while none of them were changed in males. In the striatum, most myelin genes were upregulated in both males and females, with more genes affected in males. Taken together, we conclude that GN impaired myelination in a brain region- and sex-dependent way. Abnormal myelination may contribute to MS-linked psychiatric disorders. Furthermore, the substantial and long-lasting changes by the low dose of nicotine imply that nicotine replacement therapy during pregnancy may carry many of the same risks to the offspring as does MS.

Brook, J. S., Brook, D. W., & Whiteman, M. (2000). The influence of maternal smoking during pregnancy on the toddler’s negativity. Archives of Pediatric and Adolescent Medicine 154, 381-385.

Milberger, S., Biederman, J., Faraone, S. V., Chen, L., & Jones, J. (1996). Is maternal smoking during pregnancy a risk factor for attention deficit hyperactivity disorder in children? American Journal of Psychiatry, 153, 1138-1142. PMID: 1586058

Sources: U.Va. news release Smoking During Pregnancy Affects Genes Involved in Brain Development, UVA Researchers Find and Society for Neuroscience news release. The U.Va. Health Sciences Web page describing Professor Li’s work.

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