Currently, scientists have developed different research approaches in associated areas and disciplines of the core symptom domains of autism spectrum disorder.
According to Dr. Daly, genetics in autism spectrum disorder are basically puzzles. Dr. Weiss (NEJM, 2008), in a study that involved 751 multiplex families with autism, concluded that heritability in autism seems to be idiopathic in about 90% [unknown causes] and about 10% of cases can be explained by genetic syndromes and chromosomal abnormalities. Dr. Arking and colleagues (AJHG, 2008) identified a common polymorphism in contactin-associated protein-like 2 (CNTNAP2), a member of the Neurexin super-family, that is, children with autism tended to have inherited the thymine rather than adenine variant of CNTNAP2.
Drs. Scherer and Szatmari from the Autism Genome Project (Nature Genetics, 2007) discovered a previously unidentified region of chromosome 11 the Neurexin 1 (NRXN1) gene, which is associated with the release of the neurotransmitter glutamate and plays an important role in early brain development.
The Autism Genetic Resource Exchange (AGRE), a collaborative gene bank created and managed by the Cure Autism Now Foundation, has been facilitating more rapid progress in the identification of the genetic variations of autism spectrum disorders by making this information available to the scientific community.
The M.I.N.D. institute has been a pioneer in autism research in neurodevelopment. Dr. Amaral and colleagues from the M.I.N.D. Institute are interested in a neurodevelopment genomics program with the goal of identify “biomarkers.” Dr. Amaral stated, “Our goal is to develop a diagnostic test within five years to accurately identify those newborns who are likely to develop autism. Identification of susceptible children is the first step to prevention of full-blown autism, and if we can prevent even 10 percent of the new cases of autism that will be a major accomplishment.” In a study conducted by Grether et al., (2001), researches revealed elevated levels of neuropeptides and neurotropins for children who have autism and are mentally retarded. Another area of study at the M.I.N.D Institute is the effect of the maternal immune system and environmental insults during pregnancy to understand the gene-environment interactions and their role in the development of autism.
Some patterns of neuropathologies have been examined and correlated with autism spectrum disorder such as greater brain size and weight; abnormalities in the limbic system (amygdala, thalamus, hippocampus), basal ganglia, medial temporal lobe, vestibular system, fewer Purkinje cells in the cerebellum; age-dependent cellular abnormalities in cerebellar nuclei, and cortical dysgenesis (Chugan; Kemper & Bauman, 1998). In addition, Dr. Chugani studies the role of the Serotonin in autism. According to several studies elevated blood serotonin is present in approximately 30%-50% of autistic subjects and their families, and tryptophan depletion exacerbates autism symptoms. Dr. Chugani suggests that although autism spectrum disorder shares multiple causes there is the possibility of a common neuro-chemical mechanistic feature (MP, 2002).
For example, by using
Tuberous sclerosis and epilepsy are two conditions that may relate with mutations in two genes that regulate cell growth,
Other line of neurobiological research has implicated the dopamine, serotonin and recently glutamate systems in the pathogenesis of autism (McDougle et. al. 1998). The Research Units on Pediatric Psychopharmacology (RUPP) Autism Network is testing new treatments for children and adolescents with autism and related disorders (Scahill, 2007-NYAS) Dr. Scahill quoted a line he attributed to Donald Cohen: "When there is no cure, there are 100 treatments."
Currently, drugs used for autism come from many different classes of compounds such as Clonidine, Propranolol, Depakote, D-Cycloserine, Oxytocin, Memantine, Minocycline, Riluzole and parasite treatment (Trichuris Suis Ova [
Since Autism Spectrum Disorder (
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Please let the public know that fathering babies in ones 20s and not in ones 40s 50s and beyond would prevent a substantial amount of paternal age autism and schizophrenia.
http://www.schizophreniaforum.org/for/curr/Malaspina/default.asp
Schizophrenia Risk and the Paternal Germ Line
By Dolores Malaspina
Dolores Malaspina
Paternal age at conception is a robust risk factor for schizophrenia. Possible mechanisms include de novo point mutations or defective epigenetic regulation of paternal genes. The predisposing genetic events appear to occur probabilistically (stochastically) in proportion to advancing paternal age, but might also be induced by toxic exposures, nutritional deficiencies, suboptimal DNA repair enzymes, or other factors that influence the
fidelity of genetic information in the constantly replicating male germ line. We propose that de novo genetic alterations in the paternal germ line cause an independent and common variant of schizophrenia.
Seminal findings
We initially examined the relationship between paternal age and the risk for schizophrenia because it is well established that paternal age is the major source of de novo mutations in the human population, and most schizophrenia cases have no family history of psychosis. In 2001, we demonstrated a monotonic increase in the risk of schizophrenia as paternal age advanced in the rich database of the Jerusalem Perinatal Cohort. Compared with the offspring of fathers aged 20-24 years, in well-controlled analyses, each decade of paternal age multiplied the risk for schizophrenia by 1.4 (95 percent confidence interval: 1.2-1.7), so that the relative risk (RR) for offspring of fathers aged 45+ was 3.0 (1.6-5.5), with 1/46 of these offspring developing schizophrenia. There were no comparable maternal age effects (Malaspina et al., 2001).
Epidemiological evidence
This finding has now been replicated in numerous cohorts from diverse populations (Sipos et al., 2004; El-Saadi et al., 2004; Zammit et al., 2003; Byrne et al., 2003; Dalman and Allenbeck, 2002; Brown et al., 2002; Tsuchiya et al., 2005). By and large, each study shows a tripling of the risk for schizophrenia for the offspring of the oldest group of fathers, in comparison to the risk in a reference group of younger fathers. There is also a "dosage effect" of increasing paternal age; risk is roughly doubled for the offspring of men in their forties and is tripled for paternal age >50 years. These studies are methodologically sound, and most of them have employed prospective exposure data and validated psychiatric diagnoses. Together they demonstrate that the paternal age effect is not explained by other factors, including family history, maternal age, parental education and social ability, family social integration, social class, birth order, birth weight, and birth complications. Furthermore, the paternal age effect is specific for schizophrenia versus other adult onset psychiatric disorders. This is not the case for any other known schizophrenia risk factor, including many of the putative susceptibility genes (Craddock et al., 2006).
There have been no failures to replicate the paternal age effect, nor its approximate magnitude, in any adequately powered study. The data support the hypothesis that paternal age increases schizophrenia risk through a de novo genetic mechanism. The remarkable uniformity of the results across different cultures lends further coherence to the conclusion that this robust relationship is likely to reflect an innate human biological phenomenon that progresses over aging in the male germ line, which is independent of regional environmental, infectious, or other routes.
Indeed, the consistency of these data is unparalleled in schizophrenia research, with the exception of the increase in risk to the relatives of schizophrenia probands (i.e., 10 percent for a sibling). Yet, while having an affected first-degree relative confers a relatively higher risk for illness than having a father >50 years (~10 percent versus ~2 percent), paternal age explains a far greater portion of the population attributable risk for schizophrenia. This is because a family history is infrequent among schizophrenia cases, whereas paternal age explained 26.6 percent of the schizophrenia cases in our Jerusalem cohort. If we had only considered the risk in the cases with paternal age >30 years, our risk would be equivalent to that reported by Sipos et al. (2004) in the Swedish study (15.5 percent). When paternal ages >25 years are considered, the calculated risk is much higher. Although the increment in risk for fathers age 26 through 30 years is small (~14 percent), this group is very large, which accounts for the magnitude of their contribution to the overall risk. The actual percentage of cases with paternal germ line-derived schizophrenia in a given population will depend on the demographics of paternal childbearing age, among other factors. With an upswing in paternal age, these cases would be expected to become more prevalent. ...
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