Autistic individuals

Studies with the 5-HTu agonist sumatriptan demonstrated that altered neuroendocrine response reflecting 5-HTid sensistivity significantly correlates with severity of the repetitive behavior domain (Hollander et al., 2000). In addition, there is evidence for improvement in global severity as well as improvements in both social deficits and decreased repetitive behavior in autistic individuals with serotonin reuptake inhibitor (SRI) treatment (Gordon et al., 1993, McDougle et al., 1996, Hollander et al, 1998). There is substantial evi-... 

Piven, J., Chase, G.A., Landa, R., Wzorek, M., Gayle, J., Cloud, D., and Folstein, S. (1991) Psychiatric disorders in the parents of autistic individuals. J Am Acad Child Adolesc Psychiatry 30 471— 478. 

A number of studies and case reports have suggested that mitochondrial disorders may be a causative factor in a subset of autistic individuals. In 2005, Oliveira et al. published a population-based survey among school-aged children with ASD and found that 7% of those who underwent a complete metabolic evaluation were... 

The existence of a sex bias in ASD, with a male to female sex ratio of 3 1 for autism (Lord and Schopler, 1987) and 8-9 1 for AS (Wing, 1981), as well as some characteristics of cognitive functioning and emotion perception in this condition have led some researchers to link autism to maleness . A very intriguing theory developed by Baron-Cohen et al. considers autism as an extreme form of male brain (Baron-Cohen and Hammer, 1997 Baron-Cohen, 2002, 2003). According to the Extreme Male Brain (EMB) Theory, in fact, autistic individuals show an extreme pattern of the typical male brain functions. 

All autistic children fail to show the usual relatedness normal children demonstrate to parents and other people. They show deficient attachment behavior and early failure of person-specific bonding. They do not seem to recognize or differentiate the most important people in their lives, such as parents, siblings, and teachers. In infancy, they do not show signs of separation anxiety when facing strangers. All these deficiencies in the attachment behavior of autistic individuals may be related to... 

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. 

MacLean (1985, 1990) has hypothesized that the history of the evolution of the limbic system is the history of the evolution of mammals. The deficits in the limbic structures of autistic individuals appear to ontogenetically mirror a phylogenetic deficiency in paleomammalian brain evolution. Behaviors at the basic core of autistic symptomatology - the expression of affection, social-emotional reciprocity, attachment behaviors, and the capacity to play - that are impaired in individuals with autism represent behaviors that evolved during the transition from reptiles to mammals. These abnormalities of limbic structures have profound human consequences in what is one of the most severe psychiatric disorders and undermine the essence of personality qualities we value as being human. 

Casanova et al. (2002) have compared the brains from autistic individuals with normal brains and found that in Nissl stained vertical sections taken from Brodmann s areas 9, 21, and 22, the minicolumns in the normal and autistic brains have a somewhat different structure. In the autistic brains, the minicolumns are smaller in width, and the neurons within the vertical strings are less tightly packed, leading the authors to conclude that per unit volume of cerebral cortex, the minicolumns are more numerous in the cortices of autistic individuals. Since studies by earlier authors have shown that there is no abnormality in cell density in the cortices of autistic individuals compared to controls (Coleman et al., 1985 Bailey et al., 1993), Casanova et al. (2002) suggest that autism is the consequence of a defect in migration of cells into the cortex during development. 

There are numerous reviews of the cellular neuropathology of autism (Bauman and Kemper, 1994, 2005 Kemper and Bauman, 1998 Bailey et al., 1998 Palman et al 2004 Casanova, 2007 Amaral et al., 2008). In this chapter I will discuss the relationship of the various pathologies to developmental events, a subject not covered in detail in these reviews. Emphasis will be placed on the timing and mechanisms of the known pathologies and their possible relationship to the well-documented abnormal pattern of brain growth seen in autistic individuals. 

In the cerebral cortex of autistic individuals, the pathology with the earliest time of onset is the evidence for an increased number of unusually small neuronal minicolumns in multiple cortical areas (Casanova et al., 2002 2006a 2006b Casanova, 2007 Buxhoeveden et al., 2006). These minicolumns are the fundamental building... 

Lainhart et al. (2006) pooled consistently recorded data on head circumferences from 338 well-documented individual with autism spectrum disorder, 2 9 years of age, from 10 centers in the NIH Collaborative Program of Excellence in Autism. In the entire group 17% were macrocephalic, with 12-20% macrocephalic by 3-5 years, a rate that then remained stable. They found that head circumference of the autistic individuals showed a normally distributed curve, with a shift to the right, suggesting that an increase in head circumference may be present in all autistic individuals. They noted that three other studies had not found a normally distributed head circumference (Lainhart et al., 1997 Fombonne et al., 1999 Miles et al., 2000). These three studies, however, included a smaller number of subjects, had more individuals with mental retardation, and included subjects that did not have idiopathic autism. 

Several studies that have examined the expected relationship between body length (height) and head size in autistic individuals and have failed to find evidence... 

While GABRB3 is a clear positional and functional candidate gene for autism, mutations in this gene have not been reported in autistic individuals. To explore the possibility that this protein is involved in the etiology of idiopathic autism. 

The possible model for brain growth for people with autism spectrum disorder consists of a period of overgrowth before the age of 5 years, in which several regions of the brain (and overall brain size) are enlarged. From 5 years onwards, this period of growth stops. In some autistic individuals this may be followed by a period of degeneration - a decrease in neuron numbers and volume reduction in some areas of the brain (Courchesne et al, 2007), as reported in various post-mortem studies. 

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