Kaplan + Sadock's Synopsis of Psychiatry, 11e

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Chapter 31: Child Psychiatry

spectrum disorder ranging from 5 to 16 years did not find mean values of total brain volume increased. One study followed the size of the amygdala in youth with autism spectrum disorder in the first few years of life, and similarly, found an increased size in the first few years of life, followed by a decrease in size over time. The size of the striatum has also been found in several studies to be enlarged in young children with autism spectrum disorder, with a positive correlation of striatal size with frequency of repetitive behaviors. The dynamic process of the atypical and changing total brain volume observed in children with autism spectrum disorder lends support for the overarching hypothesis that there are sensitive periods or “criti- cal periods” within the brain’s plasticity that may be disrupted in ways that may contribute to the emergence of autism spec- trum disorder. Functional MRI (fMRI) studies have focused on identify- ing biomarkers, that is, the functional brain correlates of vari- ous observed core symptoms in autism spectrum disorder. fMRI studies of children, adolescents, and adults with autism spectrum disorder have employed tasks including face percep- tion, neutral face tasks, “theory of mind” deficits, language and communication impairments, working memory and repetitive behaviors. fMRI studies have provided evidence that individu- als with autism spectrum disorder have a tendency to scan faces differently than controls, in that they focus more on the mouth region of the face rather than on the eye region and rather than scan the entire face multiple times, individuals with autism spectrum disorder focus more on individual features of the face. In response to socially relevant stimuli, researchers have come to the conclusion that individuals with autism spectrum disor- der have greater amygdala hyperarousal. In terms of “theory of mind,” that is, the ability to attribute emotional states to oth- ers, and to oneself, fMRI studies find differences in activation in brain regions such as the right temporal lobe and other areas of the brain known to become activated in controls during tasks involving theory of mind. This difference has been hypothesized by some researchers to represent dysfunction of the mirror neu- ron system (MNS). Atypical patterns of frontal lobe activation have been found in multiple studies of autism spectrum disorder during face processing tasks, suggesting that this area of the brain may be critical in social perception and emotional reason- ing. Decreased activation in individuals with autism spectrum disorder in the left frontal regions of the brain during memory and language-based tasks led researchers to hypothesize that individuals with autism spectrum disorder utilized more visual strategies during language processing than controls did. Both sMRI and fMRI research has contributed to demon- strating brain correlates of core impairments observed in indi- viduals with autism spectrum disorder. Immunological Factors Several reports have suggested that immunological incom- patibility (i.e., maternal antibodies directed at the fetus) may contribute to autistic disorder. The lymphocytes of some autistic children react with maternal antibodies, which raises the possibility that embryonic neural tissues may be damaged during gestation. These reports usually reflect single cases rather than controlled studies, and this hypothesis is still under investigation.

in autism spectrum disorder. These will be discussed further in the next section. A number of known genetically caused syndromes include autism spectrum disorder as part of a broader phenotype. The most common of these inherited disorders is fragile X syn- drome, an X-linked recessive disorder that is present in 2 to 3 percent of individuals with autism spectrum disorder. Fragile X syndrome exhibits a nucleotide repeat in the 5’ untranslated region of the FMNR1 gene, resulting in symptoms of autism spectrum disorder. Children with fragile X syndrome charac- teristically exhibit intellectual disability, gross and fine motor impairments, an unusual facies, macroorchidism, and signifi- cantly diminished expressive language ability. Tuberous sclero- sis, another genetic disorder characterized by multiple benign tumors, inherited by autosomal dominant transmission, is found with greater frequency among children with autism spectrum disorder. Up to 2 percent of children with autism spectrum dis- order also have tuberous sclerosis. Researchers who screened the DNA of more than 150 pairs of siblings with autism spectrum disorder found evidence of two regions on chromosomes 2 and 7 containing genes that may contribute to autism spectrum disorder. Additional genes hypothesized to be involved in autism spectrum disorder were found on chromosomes 16 and 17. Biomarkers in Autism Spectrum Disorder Autism spectrum disorder is associated with several biomark- ers, potentially resulting from interactions of genes and envi- ronmental factors, which then influence neuronal function, dendrite development, and contribute to altered neuronal infor- mation processing. Several biomarkers of abnormal signaling in the 5-HT system, the mTOR-linked synaptic plasticity mecha- nisms, and alterations of the γ -aminobutyric acid (GABA) inhibitory system. The first biomarker identified in autism spectrum disorder was elevated serotonin in whole blood, almost exclusively in the platelets. Platelets acquire 5-HT through the process of SERT (serotonin transporter), known to be hereditary, as they pass through the intestinal circulation. The genes that mediate SERT ( SLC64A ), and the 5-HT receptor 5-HT 2A gene ( HTR2A ) are known to be more heritable than autism spectrum disorder, and encode the same protein in the platelets and in the brain. Because 5-HT is known to be involved in brain development, it is possible that the changes in 5-HT regulation may lead to alterations in neuronal migration and growth in the brain. Both structural and functional neuroimaging studies have suggested specific biomarkers associated with autism spectrum disorder. Several studies found increased total brain volume in children younger than 4 years of age with autism spectrum dis- order, whose neonatal head circumferences were within normal limits or slightly below. By about age 5 years, however, 15 to 20 percent of children with autism spectrum disorder devel- oped macrocephaly. Additional studies found confirmatory data in samples of infants who were later diagnosed with autism spectrum disorder, who exhibited normal head circumferences at birth; by 4 years, 90 percent had larger brain volumes than controls, with 37 percent of the autism spectrum disorder group meeting criteria for macrocephaly. In contrast, structural mag- netic resonance imaging (sMRI) studies of children with autism