Family studies suggest a major heritable contribution to ADHD, but the mode of inheritance remains obscure. To date, the search for actual genes involved focused mainly on the dopamine system, with some findings suggesting a possible involvement of dopaminergic genes in risk for ADHD.
The current study, is the first to report the possible involvement of a gene encoding a modulator of the immune system in ADHD. Recent evidence supports the involvement of immune modulators in brain processes outside the realm of their classical role in inflammatory responses. One of the major modulators, interleukin Ð1 (IL-1) is expressed in the adult brain, and plays a role in maintaining neural plasticity, neuroprotection, and response to non immune stressors. Recent theories suggest it may be involved in psychiatric disorders such as depression. In addition, IL-1 has been shown to modulate neuronal cell growth during embryonic brain development, and shown to promote the maturation of dopaminergic neurons. The authors hypothesized that genetically based differences in IL-1 activity may result in altered dopaminergic neuronal maturation during early brain development. Such alterations may bear direct relevance to altered dopaminergic reactivity implicated with the pathophysiology of ADHD. Moreover, IL-1 has been also shown to modulate the release of dopamine and norepinephrine in several brain regions. Genetic variability in central modulation of transmitter activity may similarly contribute to the expression of ADHD. InterleukinÐ1 receptor antagonist (IL-1Ra) acts as a blocker on IL-1 receptors which are distributed in the brain, serving to balance IL-1 activity. The authors found a significant association of a common genetic variation in the gene encoding IL-1Ra with ADHD. Children carrying a variant gene sequence show a significant small increase in susceptibility to express ADHD. If replicated, these results raise the novel possibility that genetically based differences in immune modulators are involved susceptibility for childhood ADHD.
ARTICLE: "Preferential transmission of interleukin-1 receptor antagonist alleles in attention deficit hyperactivity disorder"
AUTHORS: R.H. Segman, A. Meltzer, V. Gross-Tsur, A Kosov, A. Frisch, E. Inbar A. Darvasi, S. Levy, T. Goltser, A. Weizman, E. Galili-Weisstub.
Child & Adolescent Psychiatry Unit, Department of Psychiatry, Hadassah-Hebrew University Medical Center Jerusalem, Israel; Neuropediatric Unit, Shaare Zedek Medical Center, Jerusalem, Israel; Geha Psychiatric Hospital, Petah Tikva and Felsenstein Medical Research Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Life Sciences Institute, The Hebrew University, Jerusalem, Israel; Life Sciences Institute, The Hebrew University, Jerusalem, Israel
Citation source: Molecular Psychiatry 2001 Volume 7, number 1, pages 72-74.
For further information on this work, please contact Dr. Ronen Segman, Department of Psychiatry, Hadassah-Hebrew University Medical Center, Mount Scopus, Jerusalem 91240, Israel; phone: +972-2-5844317; e-mail: firstname.lastname@example.org
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