The terms ‘autism’ and ‘autistic’ derive from the Greek word autos, meaning self. This is appropriate to describing the autistic behavioral phenotype in which there is a pathological impairment in socialization and verbal and nonverbal communication, in addition to behavior and interests that are often highly restricted and repetitive. The autistic individual often appears isolated, and unable to make sense of the world around them. They often reveal an inability to predict and understand the behavior of others, and perceptions of the world remain fragmented and are not embedded into a coherent pattern or structure. This book discusses the causes and risks of autism from researchers around the globe.
Chapter I - The central and peripheral serotonin (5-hydroxytryptamine, 5-HT) systems are discussed in a single conceptual framework. It is hypothesized that the abnormal development of the autistic brain and the blood hyperserotonemia of autism are caused by factors that are expressed in both 5-HT systems. The underlying biology of these processes is explored in mathematical models of blood 5-HT levels. Predictions of the models are discussed in relation to the early, unobservable development of the autistic brain.
Chapter II - Genetic heterogeneity for a multifactorial disease such as autism would imply that any two patients are unlikely to share the same susceptibility loci. Since different susceptibility loci may affect the same function and since functions may be considered at different levels of analysis, the following question arises: at what phenotypic levels is convergence attained by different genes in autism ? This is an important question to answer in order to shed light on subcellular, cellular or multicellular structures and functions possibly involved in the pathogenesis of autism. Among the various attempts made to answer this question it is worth mentioning the use of the best available genetic information to focus on the formation, structure and function of the glutamatergic synapse. How could we use this working scheme in a more efficient and hopefully fruitful way ?
Chapter III - Gastropods have an unusual genetic mechanism in which the mother's genotype determines the shell phenotype of her offspring. Experiments have shown that these unknown, maternal-effect genes determine shell chirality, the direction each snail shell coils, with dextral or right handed having a clockwise spiral, and sinistral or left handed having a counterclockwise spiral. Most snail species consist only of dextral individuals, while some species are entirely sinistral, and some species are polymorphic for shell chirality, producing both dextrals and sinistrals in the same species. This particular genetic mechanism implies a lack of homozygous-dominant (R/R) individuals in the alternative shell phenotype, while the primary phenotype can have any of the genotypes of homozygous dominant, heterozygous (R/r), or homozygous recessive (r/r) in snails. In humans, the hair-whorl rotation, the direction in which the hair spins at the back of the head, is generally either clockwise or counterclockwise and has been associated with handedness, cerebral laterality, and sexual orientation. As such, direction of hair-whorl rotation is thought to be a phenotypic marker underlying the genetics of various behavioral phenotypes in our species. Previous research has already associated handedness with sexual orientation, psychosis, and autism spectrum disorders (ASD), but to the best of my knowledge, hairwhorl rotation has not been tabulated in autistic individuals. A recent theory has proposed that maternal-effect genes are involved in determining handedness and hair-whorl rotation in humans, in addition to various behavioral phenotypes in our species. These genes (possibly RHD and RHCE) predict a lack of homozygous dominant individuals among the alternative phenotypes in humans, analogous to shell chirality in snails. If maternal-effect genes are interacting with biparentally expressed genes to cause some cases of ASD and other behavioral phenotypes in humans, then current genomic search results (i.e., linkage mapping using single nucleotide polymorphisms) for all of these genes will be obscured. To increase precision of genome searches during sibling studies, researchers should search for maternal-effect genes (i.e., never or almost never homozygous in the alternative phenotype; alleles shared less commonly than expected by chance in sets of affected siblings) in addition to biparentally-expressed genes (i.e., genes always or almost always homozygous in the alternative phenotype; alleles shared more commonly than expected by chance in siblings). If it can be shown that the snail chirality gene is homologous to the human handedness and hair-whorl genes, even if these genes turn out not to be RH genes, snails may still provide an animal model for evaluating possible environmental causes of ASD in humans. For example, aquatic snails, many of which have a short generation time and breed easily in captivity, could be treated with mercury to test the expression of the opposite chirality in their offspring. Other chemical agents or mixtures could also be tested in snails to determine possible correlates to environmental exposure in humans.
Chapter IV - The terms ‘autism’ and ‘autistic’ derive from the Greek word autos meaning self. This is appropriate to describing the autistic behavioral phenotype in which there is a pathological impairment in socialization and verbal and nonverbal communication, in addition to behavior and interests that are often highly restricted and repetitive (the triad; American Psychiatric Association, 1994). The autistic individual often appears isolated, and unable to make sense of the world around them. They often reveal an inability to predict and understand the behavior of others, and perceptions of the world remain fragmented and are not embedded into a coherent pattern or structure. Time is part of the fundamental intellectual structure in which we make sense of the events in our lives. ‘Timing and time perception allow us to unite action sequences and events occurring separately in time, to adapt to reoccurring situations, and to predicate behavior on what is expected to occur’. Timing and time perception are essential for adaptation and learning, memory and attention, cognitive development, and social synchrony and communication (see Meck, 2003). Firsthand accounts of people with autism often report a need to adhere to rituals or routines to compensate for a failure to predict events, and to their disorientation in time. They reveal a general lack of understanding about the passage of time, and appear stuck in the present.
Chapter V - Language abnormalities are critical in diagnosing autism, including the absence of or severe language delay, inability to initiate or sustain a conversation and the use of stereotypic or repetitive language. Symptoms related to language may vary in intensity; however, the common denominator (i.e., an inability to establish effective communication) is ever present in these patients.
Causes and Risks for Autism | Alessia C. Giordano & Viola A. Lombardi | Nova Science Publishers | 2009
Chapter I - The central and peripheral serotonin (5-hydroxytryptamine, 5-HT) systems are discussed in a single conceptual framework. It is hypothesized that the abnormal development of the autistic brain and the blood hyperserotonemia of autism are caused by factors that are expressed in both 5-HT systems. The underlying biology of these processes is explored in mathematical models of blood 5-HT levels. Predictions of the models are discussed in relation to the early, unobservable development of the autistic brain.
Chapter II - Genetic heterogeneity for a multifactorial disease such as autism would imply that any two patients are unlikely to share the same susceptibility loci. Since different susceptibility loci may affect the same function and since functions may be considered at different levels of analysis, the following question arises: at what phenotypic levels is convergence attained by different genes in autism ? This is an important question to answer in order to shed light on subcellular, cellular or multicellular structures and functions possibly involved in the pathogenesis of autism. Among the various attempts made to answer this question it is worth mentioning the use of the best available genetic information to focus on the formation, structure and function of the glutamatergic synapse. How could we use this working scheme in a more efficient and hopefully fruitful way ?
Chapter III - Gastropods have an unusual genetic mechanism in which the mother's genotype determines the shell phenotype of her offspring. Experiments have shown that these unknown, maternal-effect genes determine shell chirality, the direction each snail shell coils, with dextral or right handed having a clockwise spiral, and sinistral or left handed having a counterclockwise spiral. Most snail species consist only of dextral individuals, while some species are entirely sinistral, and some species are polymorphic for shell chirality, producing both dextrals and sinistrals in the same species. This particular genetic mechanism implies a lack of homozygous-dominant (R/R) individuals in the alternative shell phenotype, while the primary phenotype can have any of the genotypes of homozygous dominant, heterozygous (R/r), or homozygous recessive (r/r) in snails. In humans, the hair-whorl rotation, the direction in which the hair spins at the back of the head, is generally either clockwise or counterclockwise and has been associated with handedness, cerebral laterality, and sexual orientation. As such, direction of hair-whorl rotation is thought to be a phenotypic marker underlying the genetics of various behavioral phenotypes in our species. Previous research has already associated handedness with sexual orientation, psychosis, and autism spectrum disorders (ASD), but to the best of my knowledge, hairwhorl rotation has not been tabulated in autistic individuals. A recent theory has proposed that maternal-effect genes are involved in determining handedness and hair-whorl rotation in humans, in addition to various behavioral phenotypes in our species. These genes (possibly RHD and RHCE) predict a lack of homozygous dominant individuals among the alternative phenotypes in humans, analogous to shell chirality in snails. If maternal-effect genes are interacting with biparentally expressed genes to cause some cases of ASD and other behavioral phenotypes in humans, then current genomic search results (i.e., linkage mapping using single nucleotide polymorphisms) for all of these genes will be obscured. To increase precision of genome searches during sibling studies, researchers should search for maternal-effect genes (i.e., never or almost never homozygous in the alternative phenotype; alleles shared less commonly than expected by chance in sets of affected siblings) in addition to biparentally-expressed genes (i.e., genes always or almost always homozygous in the alternative phenotype; alleles shared more commonly than expected by chance in siblings). If it can be shown that the snail chirality gene is homologous to the human handedness and hair-whorl genes, even if these genes turn out not to be RH genes, snails may still provide an animal model for evaluating possible environmental causes of ASD in humans. For example, aquatic snails, many of which have a short generation time and breed easily in captivity, could be treated with mercury to test the expression of the opposite chirality in their offspring. Other chemical agents or mixtures could also be tested in snails to determine possible correlates to environmental exposure in humans.
Chapter IV - The terms ‘autism’ and ‘autistic’ derive from the Greek word autos meaning self. This is appropriate to describing the autistic behavioral phenotype in which there is a pathological impairment in socialization and verbal and nonverbal communication, in addition to behavior and interests that are often highly restricted and repetitive (the triad; American Psychiatric Association, 1994). The autistic individual often appears isolated, and unable to make sense of the world around them. They often reveal an inability to predict and understand the behavior of others, and perceptions of the world remain fragmented and are not embedded into a coherent pattern or structure. Time is part of the fundamental intellectual structure in which we make sense of the events in our lives. ‘Timing and time perception allow us to unite action sequences and events occurring separately in time, to adapt to reoccurring situations, and to predicate behavior on what is expected to occur’. Timing and time perception are essential for adaptation and learning, memory and attention, cognitive development, and social synchrony and communication (see Meck, 2003). Firsthand accounts of people with autism often report a need to adhere to rituals or routines to compensate for a failure to predict events, and to their disorientation in time. They reveal a general lack of understanding about the passage of time, and appear stuck in the present.
Chapter V - Language abnormalities are critical in diagnosing autism, including the absence of or severe language delay, inability to initiate or sustain a conversation and the use of stereotypic or repetitive language. Symptoms related to language may vary in intensity; however, the common denominator (i.e., an inability to establish effective communication) is ever present in these patients.
Causes and Risks for Autism | Alessia C. Giordano & Viola A. Lombardi | Nova Science Publishers | 2009