LETTER TO THE EDITOR Cerebellum and Autism S. Hossein Fatemi # Springer Science+Business Media New York 2013 The accumulation of published literature clearly indicates that the cerebellum is involved in the pathology of autism [1â3]. As to whether cerebellar pathology is primal or only part of an important brain circuitry involved in autism, the data are incomplete. What is clearly new and relevant to the etiology of autism is that cerebellar function is not limited to motor coordination but involves processing of cognition which is at the heart of autistic pathology [1, 4]. Fatemi et al. [5] recently reviewed the existing literature with respect to the pathological involvement of cerebellum in autism. The preponderance of evidence supports the involvement of this important brain area in etiology of autism. Recent supportive literature links developmental cerebellar pathol- ogy with decreased prefrontal dopamine transmission [3] and autistic behavior [6] in various animal models of autism. In a series of experiments, Rogers et al. [3] showed that despite having different cerebellar abnormalities, both the Lurcher and fragile X mental retardation 1 mutant mice exhibited abnormalities involving the cerebellarâprefrontal circuitry which resulted in abnormal dopamine transmission that underlie cognitive deficits in both mutant mouse models reminiscent of autistic phenotype. By the same token, Tsai et al. [6] showed that loss of tuberous sclerosis complex 1 protein in mouse cerebellar Purkinje cells in both heterozy- gous and homozygous mutants results in autistic behavior. Treatment with the mTOR inhibitor, rapamycin, prevented both biochemical and behavioral deficits, further supporting a cerebellar contribution to the autistic etiology [6]. Ziats and Rennert [7] question the cerebellar contribution to autistic pathology and suggest that cerebellum may sim- ply act as an anatomic beacon that reflects or exaggerates brain-wide manifestations of autistic disease but do not provide any data to support their claim. Indeed experimental evidence provided by Tsai et al. [6] and Rogers et al. [3] further support the notion that the cerebellum is partially causative for autistic behavior and pathology. Furthermore, Ziats and Rennertâs hypothesis, while plausible, clearly needs further supportive evidence and experimental and clinical verification. Finally, as Ziats and Rennert have shown in their report, cerebellar complexity is no less than in neocortex, showing that it is a site capable of modulating multiple cortical functions including cognition. Acknowledgments Dr. Fatemi is supported by the Bernstein Endowed Professorship in Adult Psychiatry. Grant support by Eunice Kennedy Shriver National Institute of Child Health and Human Development (5R01HD052074-01A2) and the National Institute of Mental Health (5R01MH086000-01A2) to SHF is gratefully acknowledged. Conflict of Interest The author declares that he has no conflicts of interest to disclose. The author does have US patents for Reelin as a diagnostic marker for autism, bipolar disorder, schizophrenia, and major depression. References 1. DâAngelo E, Casali S. Seeking a unified framework for cerebellar function and dysfunction: from circuit operations to cognition. Front Neural Circs. 2012;6:116. 2. Hoeft F, Walter E, Lightbody AA, Hazlett HC, Chang C, Piven J, et al. Neuroanatomical differences in toddler boys with S. H. Fatemi (*) Department of Psychiatry, Division of Neuroscience Research, University of Minnesota Medical School, 420 Delaware St. SE, MMC 392, Minneapolis, MN 55455, USA e-mail:
[email protected] S. H. Fatemi Department of Pharmacology, University of Minnesota Medical School, 310 Church St. SE, Minneapolis, MN 55455, USA S. H. Fatemi Department of Neuroscience, University of Minnesota Medical School, 321 Church St. SE, Minneapolis, MN 55455, USA Cerebellum DOI 10.1007/s12311-013-0484-9 fragile X syndrome and idiopathic autism. Arch Gen Psychiatry. 2011;68:295â305. 3. Rogers TD, Dickson PE, McKimm E, Heck DH, Goldowitz D, Blaha CD, et al. Reorganization of circuits underlying cerebellar modulation of prefrontal cortical dopamine in mouse models of autism spectrum disorder. Cerebellum, 2013. doi:10.1007/s12311-013-0462-2. 4. Gordon N. The cerebellum and cognition. Eur J Petiatr Neurol. 2007;11:232â4. 5. Fatemi SH, Aldinger KA, Ashwood P, Bauman ML, Blaha CD, Blatt GJ, et al. Consensus paper: pathological role of the cerebellum in autism. Cerebellum. 2012;11:777â807. 6. Tsai PT, Hull C, Chu Y, Greene-Colozzi E, Sadowski AR, Leech JM, et al. Autistic-like behaviour and cerebellar dysfunction in Purkinje cell Tsc1 mutant mice. Nature. 2012;488:647â51. 7. Ziats MN, Rennert OM. The cerebellum in autism: pathogenic or anatomical beacon? Cerebellum. 2013; in press. Cerebellum Cerebellum and Autism References