J. Neurosci. -- eLetters for Smith et al., 27 (40) 10695-10702

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Neurobiology of Disease:
Stephen E. P. Smith, Jennifer Li, Krassimira Garbett, Karoly Mirnics, and Paul H. Patterson
Maternal Immune Activation Alters Fetal Brain Development through Interleukin-6
J. Neurosci. 2007; 27: 10695-10702 [Abstract] [Full text] [PDF]

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Pathogenesis of Schizophrenia & Autism: The Interaction between Interleukin & Insulin Systems
Ganesan Venkatasubramanian (26 December 2007)

Pathogenesis of Schizophrenia & Autism: The Interaction between Interleukin & Insulin Systems 26 December 2007

Ganesan Venkatasubramanian,
Assistant Professor of Psychiatry, National Institute of Mental Health & Neurosciences
Bangalore-560029, India. http://venkat.nimhans.googlepages.com/home
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Re: Pathogenesis of Schizophrenia & Autism: The Interaction between Interleukin & Insulin Systems

venkat.nimhans{at}gmail.com Ganesan Venkatasubramanian

Sir:
Dr. Patterson’s group has elucidated a critical finding that supports the role of interleukin-6 (IL-6) in the pathogenesis of schizophrenia and autism in the context of maternal immune activation (Smith et al 2007). Extending the three mechanisms of action by IL-6 postulated by Smith et al (2007), I hypothesize that interaction between IL-6 and insulin systems (specifically Insulin-like Growth Factor-1 [IGF- 1]) might play a crucial role.
IGF-1 plays a significant role in fetal development (Fowden, 2003). Also, IGF-1 has neuroprotective, anti-apoptotic properties that are crucial for optimal development of the brain (Dore et al 1997). Interestingly, IL-6 inhibits the secretion of IGF-I and its biological activity (de Martino et al 2000; Lazarus et al 1993). Cerebral damage in fetal pro-inflammatory states has been associated with high IL-6 and low IGF-1 levels (Hansen-Pupp et al 2007). These studies support significant interaction between IL-6 and IGF-1.
Increased IL-6 (Potvin et al 2007) as well as deficient IGF-1 (Venkatasubramanian et al 2007) have been demonstrated in schizophrenia. Autism is also associated with higher IL-6 (Jyonouchi et al 2001) and lower IGF-1 (Riikonen et al 2006). Interestingly, maternal infection has been shown to increase the expression of fetal pro-inflammatory genes like IL-6 in the mouse (Liverman et al 2006). Hence, it is possible that maternal immune activation might result in persistent over-expression of IL-6 genes in human adolescents and adults, leading to deficient IGF-1 culminating in neurobehavioral disorders like schizophrenia and autism. In summary, this postulate of neuro-immuno-metabolic effects of IL-6 further supports the key observations reported by Smith et al (2007).
References
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Potvin S, Stip E, Sepehry AA, Gendron A, Bah R, Kouassi E (2007) Inflammatory Cytokine Alterations in Schizophrenia: A Systematic Quantitative Review. Biol Psychiatry [Epub ahead of print]
Riikonen R, Makkonen I, Vanhala R, Turpeinen U, Kuikka J, Kokki H (2006) Cere brospinal fluid insulin-like growth factors IGF-1 and IGF-2 in infantileautism.Dev Med Child Neurol 48:751-755.
Smith SE, Li J, Garbett K, Mirnics K, Patterson PH (2007) Maternal immune activation alters fetal brain development through interleukin-6. J Neurosci 27:10695-10702.
Venkatasubramanian G, Chittiprol S, Neelakantachar N, Naveen MN, Thirthall J, Gangadhar BN, Shetty KT (2007) Insulin and insulin-like growth factor-1 abnormalities in antipsychotic-naive schizophrenia. Am J Psychiatry 164:1557-1560.