The immune system may be involved in the susceptibility to childhood attention deficit hyperactivity disorder (ADHD), according to Israeli scientists.Attention deficit hyperactivity disorder (ADHD) is a common childhood neurodevelopmental disorder. The causes of ADHD are unknown, but genetic factors are important. Now Israeli scientists report in Molecular Psychiatry the first findings supporting a possible involvement of a gene related to the immune system in susceptibility for ADHD.
ADHD is a common neurodevelopmental disorder characterized by inattention, hyperactivity and impulsivity. It affects 4-10% of school age children, exacting a significant clinical and public health toll.
ADHD constitutes one of the main reasons for referral to neurological/psychiatric treatment in this age group, and results in exposure of many children to prolonged courses of stimulant medication such as Ritalin.
Untreated, ADHD may lead to impairments in schooling and social adaptation in a critical period of development, eventuating in damage to the child's self esteem and personality development, with high rates of depression, conduct disorder, school dropouts and substance abuse.
The causes of ADHD are unknown. Current theories suggest altered brain activity of chemical transmitters such as dopamine and norepinepherine may play a role. This is based on pharmacological observations showing reduction in symptoms in response to stimulant drugs such as Ritalin which augment dopaminergic and noradrenergic activity in relevant brain areas. However, the current findings avoid simplistic neurochemical explanations.
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 -1 (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. Interleukin-1 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 in susceptibility for childhood ADHD.
Authors of the study include R.H. Segman, A. Meltzer, V. Gross-Tsur, A Kosov, A. Frisch, E. Inbar A. Darvasi, S. Levy, T. Goltser, A. Weizman and E. Galili-Weisstub, all at institutions in Israel, including Hadassah-Hebrew University Medical Center, Shaare Zedek Medical Center and The Hebrew University, Jerusalem and Geha Psychiatric Hospital, Tel Aviv.
(Reference: "Preferential transmission of interleukin-1 receptor antagonist alleles in attention deficit hyperactivity disorder," Molecular Psychiatry 2001 Volume 7, number 1, pages 72-74.)
Molecular Psychiatry is published by the Nature Publishing Group. Its editor is Julio Licinio, M.D.
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Molecular Psychiatry
[Contact: Dr. Ronen Segman, Julio Licinio M.D.]
09-Jan-2002
