Autism cerebellum

Fatemi SH, Folsom TD, Reutiman TJ, Thuras PD (2009a) Expression of GABA(B) receptors is altered in brains of subjects with autism. Cerebellum 8(l) 64-69 Fatemi SH, Halt A, Stary J, Kanodia R, Schulz SC, Realmuto G (2002a) Glutamic acid decarboxylase 65 and 67 kDa proteins are reduced in parietal and cerebellar cortices of autistic subjects. Biol Psychiatry 52 805-810... 

Fatemi SH, Folsom TD, Reutiman TJ, Thuras PD (2009b) GABA(A) receptor downregulation in brains of subjects with autism. Cerebellum 8 64-69. 

Recent research has indicated select abnormalities in the cholinergic system (Perry et al., 2001). Although previously unexamined neurochemically, there was an indication that the cholinergic system may be involved in autism, with abnormalities reported in neurons in the basal forebrain (Bauman Kemper, 1994). Perry et al. (2001) found extensive loss of high affinity nicotinic receptors from the neocortex (frontal and parietal), and from the cerebellum (Lee, et al., in preparation). Nicotinic receptors are implicated in attention, and also consciousness as many general anaesthetics block the receptor channel (Chapter 9). 

The following section explores the five areas most consistently found to be abnormal in postmortem studies of autistic brains - amygdala, septal nucleus, hippocampus, anterior cingulate cortex, and cerebellum - and discusses their hypothetical relationship to emotional and interpersonal psychopathology in autism. Note that other brain areas, which are inconsistently abnormal in neuropathological studies, may express inconsistent associated symptoms, variations in psychopathological subtypes, or inconsequential anomalies and are not discussed in this section. 

In another series of experiments. Heath subdurally implanted electrodes in the vermis of patients with various psychiatric disorders, who had severe emotional dyscontrol. Amelioration of aggression was obtained in a great majority of patients by electrical stimulation. Heath attributed these effects to the connection of the vermis to the limbic system (Heath, 1977). Autistic individuals have been found in some studies to have abnormalities in the cerebellar vermis (although this finding is controversial), pointing to the possibility that the modulation of anger exerted by the cerebellum in normal individuals may be impaired in some individuals with autism, and may explain, at least in part, the lack of impulse control exhibited by some autistic persons. 

DeLong GR (2005) The cerebellum in autism. In The neurology of autism (Coleman M, ed), pp. 75-90. New York Oxford University Press. 

Schmahmann JD (1994) The cerebellum in autism clinical and anatomic perspectives. In The Neurobiology of Autism (Bauman ML, Kemper TL, eds), pp. 195-226. Baltimore Johns Hopkins University Press. 

In autism, a decrease in GAD67 protein levels as measured in whole cerebellar homogenates was initially reported (Fatemi et al., 2002), suggesting a decrease in GABAergic neurotransmission in the cerebellum. More recently, anatomical studies with in situ hybridization histochemistry have shown that GAD67 mRNA levels are also markedly decreased in Purkinje cells of autistic brains (Yip et al., 2007) (Fig. 2 /t<0.0001, two tailed f-test). 

Fatemi SH, Halt AR, Realmuto GR, Earle J, Kist DA, Thuras P, Mer A (2002a) Purkinje cell size is reduced in cerebellum of patients with autism. Cell Mol Neurobiol 22 171-175. 

Walker BR, Diefenbach KS, Paiikh TN (2007) Inhibition within the nucleus tractus solitaiius (NTS) ameliorates environmental exploration deficits due to cerebellum lesions in an animal model for autism. Behav Brain Res 176 109-120. 

Eatemi SH, Stravy JM, Halt AR, et al. (2001) Dysregulation of ReeUn and Bcl-2 proteins in autistic cerebellum. 1 Autism Dev Disord 31 529-535. 

In conclusion, we think that in the years to come the challenge will be to gain a deeper understanding of the complex relationships between androgens/estrogens and development/plasticity of specific neural circuits that appear to be critical in autism, in particular reciprocal connections between the cerebral cortex and structures such as the amygdala and the cerebellum. 

This chapter correlates emotions and attachment behavior in autism with the disturbed neuroanatomy found in the brains of these individuals. Neuropathological postmortem studies have consistently found abnormalities in the limbic system and the cerebellum of autistic individuals. Abnormal limbic structures include the amygdala, hippocampus, septal nucleus, and anterior cingulate cortex. In the cerebellum, abnormalities have been found in the cerebellar hemispheres and in the fastigial, emboliform, and globose nuclei. 

They have difficulty making friends, and limited nonverbal communication. Instead of identifying people on the basis of their faces, persons with autism use only the lower face, the mouth, and other specific portions of the face to identify others. The cerebellum of some children with autism can be either hypo- or hyperplastic. There maybe evidence of dysfunction of the prefrontal cortex and its connections to the parietal lobe. 

Anomalies in the amygdala also have been found. fMRI reveals involvement of these regions in autism. Some with Asperger syndrome, a variant of autism, have abnormal interconnections between limbic and paralimbic regions, the cerebellum, and the visual cortices, revealed when they are asked to identify emotions by facial expressions. 

Patients with autism have decreased serotonin, dopamine, nicotine, and other neurotransmitters in certain regions of the brain, but no single abnormality. Chugani (2004) examined the evidence for anomalous development of the serotonin system in the brain of children with autism. Serotonin levels in the blood are often elevated in children with autism. Serotonin synthesis is decreased in the frontal region and thalamus on one side of the brain and increased in the dentate nucleus of the opposite cerebellum. 

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