Consensus Paper: Pathological Role of the Cerebellum in Autism

Conclusions

The main points of consensus derived from various areas of discussion related to the role of the cerebellum in autism include the following:

1) The anatomy of the cerebellum in autism is abnormal in at least a subset of individuals; the onset of pathology is prenatal and this process continues post-natally, affecting many cerebellar functions;

2) AD is genetically heterogeneous; the analysis of syndromic disorders with co-occurring AD, including FXS, TS, JS, and Dandy-Walker malformation, points to the involvement of cerebellar genes. Additionally, three autism-associated genes, EN2, GABRB3, and MET, have roles in cerebellar development;

3) There is ongoing neuroinflammation in the brains of subjects with autism, including cerebellum, from early age to later in life;

4) Oxidative stress is present in the cerebellum of subjects with autism;

5) Abnormalities involving several neurotransmitters, amino acids and brain proteins, including GABA, glutamate, Reelin, acetylcholine, dopamine, serotonin, and oxytocin exist in brains of subjects with autism;

6) The presence of motor and cognitive deficits in autism are reflective of specific cerebellar abnormalities;

7) gene-environmental interactions can have adverse effects on developing cerebellar circuitry as seen in autism;

8) Multiple drug treatment options, such as calcium channel modulating agents, GABAB receptor agonists, and serotonin and NMDA receptor modulating drugs may be of potential use in treatment of autism;

9) Multiple relevant animal models point to the impact of the cerebellum on dopamine fluctuations in the frontal cortex, underlying executive functions;

10) Prenatal exposure to teratologic agents, such as VPA, have been shown to contribute to autism in subsets of vulnerable individuals as well as contribute to cerebellar neuropathology similar to autism in animal models.

Despite many novel findings discussed in the preceding sections, multiple issues remain undefined and require further research in order to obtain a more complete picture of cerebellar dysfunction in autism.


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