Posts tagged autism

ScienceDaily (July 12, 2012) — University of Kansas researchers have found larger resting pupil size and lower levels of a salivary enzyme associated with the neurotransmitter norepinephrine in children with autism spectrum disorder.

However, even though the levels of the enzyme, salivary alpha-amylase (sAA), were lower than those of typically-developing children in samples taken in the afternoon in the lab, samples taken at home throughout the day showed that sAA levels were higher in general across the day and much less variable for children with ASD.

"What this says is that the autonomic system of children with ASD is always on the same level," Christa Anderson, assistant research professor, said. "They are in overdrive."

The sAA levels of typically-developing children gradually rise and fall over the day, said Anderson, who co-directed the study with John Colombo, professor of psychology.

Norepinephrine (NE) has been found in the blood plasma levels of individuals with ASD but some researchers have questioned whether these levels were just related to the stress from blood draws.

The KU study addressed this by collecting salivary measures by simply placing a highly absorbent sponge swab under the child’s tongue and confirmed that this method of collection did not stress the children by assessing their stress levels through cortisol, another hormone.

Collecting sAA levels has the potential for physicians to screen children for ASD much earlier, noninvasively and relatively inexpensively, said Anderson.

But Anderson and Colombo also see pupil size and sAA levels as biomarkers that could be the physiological signatures of a possible dysfunction in the autonomic nervous system.

"Many theories of autism propose that the disorder is due to deficits in higher-order brain areas," said Colombo. "Our findings, however, suggest that the core deficits may lie in areas of the brain typically associated with more fundamental, vital functions."

The study, published online in the May 29, 2012 Developmental Psychobiology compared children between the ages of 20 and 72 months of age diagnosed with ASD to a group of typically developing children and a third group of children with Down Syndrome.

Both findings address the Centers for Disease Control’s urgent public health priority goals for ASD: to find biological indicators that can both help screen children earlier and lead to better understanding of how the nervous system develops and functions in the disorder.

Source: Science Daily

ScienceDaily (July 12, 2012) — Researchers at Emory University School of Medicine have identified five rare mutations in a single gene that appear to increase the chances that a boy will develop an autism spectrum disorder (ASD).

Mutations in the AFF2 gene, and other genes like it on the X chromosome, may explain why autism spectrum disorders affect four times as many boys as girls.

The mutations in AFF2 appeared in 2.5 percent (5 out of 202) boys with an ASD. Mutations in X chromosome genes only affect boys, who have one X chromosome. Girls have a second copy of the gene that can compensate.

The results were published July 5 in the journal Human Molecular Genetics.

"Our data suggest that AFF2 could be one of the major X-linked risk factors for ASD’s," says senior author Michael Zwick, PhD, assistant professor of human genetics at Emory University School of Medicine.

The finding bolsters a growing consensus among geneticists that rare variants in many different genes contribute significantly to risk for autism spectrum disorders.

The mutations in the AFF2 gene probably do not cause ASDs all by themselves, Zwick says.

"We do not think that the variants we have identified are monogenic causes of autism," he says. "Our data does support the idea that this is an autism susceptibility gene."

In some situations, mutations in a single gene are enough by themselves to lead to a neurodevelopmental disorder with autistic features, such as fragile X syndrome or tuberous sclerosis complex. But these types of mutations are thought to account for a small number of ASD cases.

Recent large-scale genetic studies of autism spectrum disorders have identified several “rare variants” that sharply increase ASD risk. Scientists believe rare variants could explain up to 15 or 20 percent of ASD cases. However, until now no single variant has been found in more than one percent of ASD cases.

Working with Zwick, postdoctoral fellow Kajari Mondal and her colleagues read the sequence of the AFF2 gene in DNA from 202 boys diagnosed with autism spectrum disorders. The patient samples came from the Autism Genetic Resource Exchange and the Simons Simplex Collection.

Tests showed that in four cases, the affected boys had inherited the risk-conferring mutations from their mothers. One boy had a “de novo” (not coming from the parents) mutation. Compared with X-linked genes in unaffected people, mutations in AFF2 were five times more abundant in the boys with ASDs.

The AFF2 gene had already been identified as responsible for a rare inherited form of intellectual disability with autistic features. This effect is seen when the AFF2 gene is deleted or silenced completely.

AFF2 has some similarity to FMR1, the gene responsible for fragile X syndrome. Like FMR1, it can be silenced by a triplet repeat. In these cases, the presence of the triplet repeat (three genetic bases repeated dozens of times) triggers a change in chromosomal structure that prevents the gene from being turned on.

In contrast, the mutations Zwick’s team found are more subtle, slightly changing the sequence of the protein AFF2 encodes. Little is known about the precise function of the AFF2 protein. A related gene in fruit flies called lilliputian also appears to regulate the development of neurons.

Zwick says one of his laboratory’s projects is to learn more about the function of the AFF2 gene, and to probe how the mutations identified by his team affect the function. His team is also working on gauging the extent to which other genes on the X chromosome contribute to autism risk.

Source: Science Daily

July 2nd, 2012

Using a mouse model of autism, researchers at the University of Cincinnati (UC) and Cincinnati Children’s Hospital Medical Center have successfully treated an autism spectrum disorder characterized by severe cognitive impairment.

The research team, led by Joe Clark, PhD, a professor of neurology at UC, reports its findings online July 2, 2012, in the Journal of Clinical Investigation, a publication of the American Society for Clinical Investigation.

The disorder, creatine transporter deficiency (CTD) is caused by a mutation in the creatine transporter protein that results in deficient energy metabolism in the brain. Linked to the X chromosome, CTD affects boys most severely; women are carriers and pass it on to their sons.

Using cyclocreatine, researchers successfully treated an autism spectrum disorder known as creatine transporter deficiency in a mouse model of autism.

The brains of boys with CTD do not function normally, resulting in severe speech deficits, developmental delay, seizures and profound mental retardation. CTD is estimated to currently affect about 50,000 boys in the United States and is the second-most common cause of X-linked mental retardation after Fragile X syndrome.

Following CTD’s discovery at UC in 2000, researchers at UC and Cincinnati Children’s led by Clark discovered a method to treat it with cyclocreatine—also known as CincY, and pronounced cinci-why—a creatine analogue originally developed as an adjunct to cancer treatment. They then treated genetically engineered mice as an animal model of the human disease.

“CincY successfully entered the brain and reversed the mental retardation-like symptoms in the mice, with benefits seen in nine weeks of treatment,” says Clark, adding that no harmful effects to the mice were observed in the study. “Treated mice exhibited a profound improvement in cognitive abilities, including recognition of novel objects, spatial learning and memory.”

As a repurposed drug (originally developed for another therapy), CincY has already been through part of the U.S. Food and Drug Administration (FDA) approval process. It is taken orally as a pill or powder.

UC’s Office of Entrepreneurial Affairs and Technology Commercialization has reached agreement with Lumos Pharma, a privately held Austin, Texas, startup company based on UC technology, to develop and commercialize CincY. Lumos Pharma was created with technology licensed from UC’s Office of Entrepreneurial Affairs and Technology Commercialization. Its CEO is Rick Hawkins, a 30-year biotech industry veteran. Jon Saxe is its chairman.

“It has taken many years to get here and I am happy that our efforts have led to this translational effort to make a therapy available to those afflicted with CTD,” says Clark. “We look forward with commitment and hope to the day when those patients will benefit from our work.”

The collaboration gained momentum when Lumos Pharma submitted a proposal based on Clark’s technology to the National Institutes of Health and was selected as a drug development project partner by the National Center for Advancing Translational Sciences’ Therapeutics for Rare and Neglected Diseases (TRND) program. Under TRND’s collaborative operational model, project partners form joint project teams with TRND and receive in-kind support from TRND drug development scientists, laboratory and contract resources.

Lumos Pharma plans to initiate a TRND-supported preclinical development plan, with TRND support continuing through the filing of an Investigational New Drug (IND) application with the FDA prior to beginning a clinical trial. Such a trial would be about three years away, Clark says.

Source: Neuroscience News

ScienceDaily (July 2, 2012) — Deleting a single gene in the cerebellum of mice can cause key autistic-like symptoms, researchers have found. They also discovered that rapamycin, a commonly used immunosuppressant drug, prevented these symptoms.

The deleted gene is associated with Tuberous Sclerosis Complex (TSC), a rare genetic condition. Since nearly 50 percent of all people with TSC develop autism, the researchers believe their findings will help us better understand the condition’s development.

"We are trying to find out if there are specific circuits in the brain that lead to autism-spectrum disorders in people with TSC," said Mustafa Sahin, Harvard Medical School associate professor of neurology at Boston Children’s Hospital and senior author on the paper. "And knowing that deleting the genes associated with TSC in the cerebellum leads to autistic symptoms is a vital step in figuring out that circuitry."

This is the first time researchers have identified a molecular component for the cerebellum’s role in autism. “What is so remarkable is that loss of this gene in a particular cell type in the cerebellum was sufficient to cause the autistic-like behaviors,” said Peter Tsai, HMS instructor of neurology and the first author of this particular study.

These findings were published online July 1 in Nature.

TSC is a genetic disease caused by mutations in either one of two genes, TSC1 and TSC2. Patients develop benign tumors in various organs in the body, including the brain, kidneys and heart, and often suffer from seizures, delayed development and behavioral problems.

Researchers have known that there was a link between TSC genes and autism, and have even identified the cerebellum as the key area where autism and related conditions develop.

In both cases, deleting this gene caused the three main signs of autistic-like behaviors:

• Abnormal social interactions. The mice spent less time with each other and more with inanimate objects, compared to controls.
• Repetitive behaviors. The mice spent extended amounts of time pursuing one activity or with one particular object far more than normal.
• Abnormal communication. Ultrasonic vocalizations, the communication technique among rodents, were highly distressed.

The researchers also tested learning. “These mice were able to learn new things normally,” said Tsai, “but they had trouble with ‘reversal learning,’ or re-learning what they had learned when their environment changed.”

Tsai and colleagues tested this by training the mice to swim a particular path in which a platform where they could rest was set up on one side of the pool. When the researchers moved the platform to the other side of the pool, the mice had greater difficulty than the control mice re-learning to swim to the other side.

"These changes in behavior indicate that the TSC1 gene in Purkinje cells, and by extension, the cerebellum, are a part of the circuitry for autism disorders,” emphasized Sahin.

The researchers also found that the drug rapamycin averted the effects of the deleted gene. Administering the drug to the mice during development prevented the formation of autistic-like behaviors.

Currently, Sahin is the sponsor-principal investigator for an ongoing Phase II clinical trial to test the efficacy of everolimus, a compound in the same family as rapamycin, in improving neurocognition in children with TSC. The trial will be open for enrollment until December 2013.

"Our next step will be to see how the abnormalities in Purkinje cells affect autism-like development. We don’t know how generalizable our current findings are, but understanding mechanisms beyond TSC genes might be useful to autism," said Tsai.

Source: Science Daily

ScienceDaily (June 27, 2012) — A new study shows significant differences in brain development in high-risk infants who develop autism starting as early as age 6 months. The findings published in the American Journal of Psychiatry reveal that this abnormal brain development may be detected before the appearance of autism symptoms in an infant’s first year of life. Autism is typically diagnosed around the age of 2 or 3.

The study offers new clues for early diagnosis, which is key, as research suggests that the symptoms of autism — problems with communication, social interaction and behavior — can improve with early intervention. “For the first time, we have an encouraging finding that enables the possibility of developing autism risk biomarkers prior to the appearance of symptoms, and in advance of our current ability to diagnose autism,” says co-investigator Dr. Alan Evans at the Montreal Neurological Institute and Hospital — the Neuro, McGill University, which is the Data Coordinating Centre for the study.

"Infancy is a time when the brain is being organized and connections are developing rapidly," says Dr. Evans. "Our international research team was able to detect differences in the wiring by six months of age in those children who went on to develop autism. The difference between high-risk infants that developed autism and those that did not was specifically in white matter tract development — fibre pathways that connect brain regions." The study followed 92 infants from 6 months to age 2. All were considered at high-risk for autism, as they had older siblings with the developmental disorder. Each infant had a special type of MRI scan, known as diffusion tensor imaging, at 6 months and a behavioral assessment at 24 months. The majority also had additional scans at either or both 12 and 24 months.

At 24 months, 30% of infants in the study were diagnosed with autism. White matter tract development for 12 of the 15 tracts examined differed significantly between the infants that developed autism and those who did not. Researchers evaluated fractional anisotropy (FA), a measure of white matter organization based on the movement of water through tissue. Differences in FA values were greatest at 6 and 24 months. Early in the study, infants who developed autism showed elevated FA values along these tracts, which decreased over time, so that by 24 months autistic infants had lower FA values than infants without autism.

The study characterizes the dynamic age-related brain and behavior changes underlying autism — vital for developing tools to aid autistic children and their families. This is the latest finding from the on-going Infant Brain Imaging Study (IBIS), which is funded by the National Institutes of Health (NIH) and brings together the expertise of a network of researchers from institutes across North America. The IBIS study is headquartered at the University of North Carolina, and The Neuro is the Data Coordinating Centre where all IBIS data is centralized.

Source: Science Daily

June 25, 2012 By Rick Nauert

A new study involving children with Williams syndrome (WS) suggests that improved regulation of oxytocin and vasopressin may someday improve care for autism, anxiety, post-traumatic stress disorder and WS.

WS results when certain genes are absent because of a faulty recombination event during the development of sperm or egg cells. Virtually everyone with WS has exactly the same set of genes missing (25 to 28 genes are missing from one of two copies of chromosome 7).

“The genetic deficiencies allow researchers to examine the genetic and neuronal basis of social behavior,” said Ursula Bellugi, Ph.D., a co-author on the paper.

“This study provides us with crucial information about genes and brain regions involved in the control of oxytocin and vasopressin, hormones that may play important roles in other disorders.”

In the study, scientists at the Salk Institute for Biological Studies and the University of Utah, found that people with WS flushed with the hormones oxytocin and arginine vasopressin (AVP) when exposed to emotional triggers.

Children with WS love people, despite being challenged with numerous health problems. WS kids are extremely gregarious, irresistibly drawn to strangers, and insist on making eye contact.

They have an affinity for music. But they also experience heightened anxiety, have an average IQ of 60, experience severe spatial-visual problems, and suffer from cardiovascular and other health issues.

Yet despite their desire to befriend people, WS kids have difficulty creating and maintaining social relationships — an issue that obviously affects many people without WS.

In the new study, led by Julie R. Korenberg, M.D., 21 participants, 13 who have WS and a control group of eight people without the disorder were evaluated at the Cedars-Sinai Medical Center in Los Angeles. Because music is a known strong emotional stimulus, the researchers asked participants to listen to music.

Before the music was played, the participants’ blood was drawn to determine a baseline level for oxytocin. Remarkably, those with WS had three times as much of the hormone as those without the syndrome.

Blood also was drawn at regular intervals while the music played and was analyzed afterward to check for real-time, rapid changes in the levels of oxytocin and AVP.

While other studies have examined how oxytocin affects emotion when artificially introduced into people, such as through nasal sprays, this is one of the first significant studies to measure naturally occurring changes in oxytocin levels in rapid, real time as people undergo an emotional response.

Although the WS participants displayed little outward response to the music, an analyses of blood samples showed that the oxytocin levels, and to a lesser degree AVP, had increased sharply while they had listened to the music.

In contrast, among those without WS, both the oxytocin and AVP levels remained largely unchanged as they listened to music.

Korenberg believes the blood analyses strongly indicate that oxytocin and AVP are not regulated correctly in people with WS, and that the behavioral characteristics unique to people with WS are related to this problem. “This shows that oxytocin quite likely is very involved in emotional response,” she said.

In addition to listening to music, study participants already had taken three social behavior tests that evaluate willingness to approach and speak to strangers, emotional states, and various areas of adaptive and problem behavior.

Those test results suggest that increased levels of oxytocin are linked to both increased desire to seek social interaction and decreased ability to process social cues, a double-edged message that may be very useful at times, for example, during courtship, but damaging at others, as in WS.

“The association between abnormal levels of oxytocin and AVP and altered social behaviors found in people with Williams Syndrome points to surprising, entirely unsuspected deleted genes involved in regulation of these hormones and human sociability,” Korenberg said.

“It also suggests that the simple characterization of oxytocin as ‘the love hormone’ may be an overreach. The data paint a far more complicated picture.”

Overall, the researchers say, their findings paint a hopeful picture, and the study holds promise for speeding progress in treating WS, and perhaps autism and anxiety through regulation of these key players in human brain and emotion, oxytocin and vasopressin.

Source: PsychCentral

ScienceDaily (June 25, 2012) — Widely available EEG testing can distinguish children with autism from neurotypical children as early as age 2, finds a study from Boston Children’s Hospital. The study is the largest, most rigorous study to date to investigate EEGs as a potential diagnostic tool for autism, and offers hope for an earlier, more definitive test.

Widely available EEG testing can distinguish children with autism from neurotypical children as early as age 2, finds a new study. The study is the largest, most rigorous study to date to investigate EEGs as a potential diagnostic tool for autism, and offers hope for an earlier, more definitive test. (Credit: © dule964 / Fotolia)

Researchers Frank H. Duffy, MD, of the Department of Neurology, and Heidelise Als, PhD, of the Department of Psychiatry at Boston Children’s Hospital, compared raw EEG data from 430 children with autism and 554 control subjects, ages 2 to 12, and found that those with autism had consistent EEG patterns indicating altered connectivity between brain regions — generally, reduced connectivity as compared with controls.

While altered connectivity occurred throughout the brain in the children with autism, the left-hemisphere language areas stood out, showing reduced connectivity as compared with neurotypical children, consistent with neuroimaging research. Findings were published June 26 in the online open-access journal BMC Medicine.

Duffy and Als focused on children with “classic” autism who had been referred for EEGs by neurologists, psychiatrists or developmental pediatricians to rule out seizure disorders. Those with diagnosed seizure disorders were excluded, as were children with Asperger’s syndrome and “high functioning” autism, who tend to dominate (and skew) the existing literature because they are relatively easy to study. The researchers also excluded children with genetic syndromes linked to autism (such as Fragile X or Rett syndrome), children being treated for other major illnesses, those with sensory disorders like blindness and deafness and those taking medications.

"We studied the typical autistic child seeing a behavioral specialist — children who typically don’t cooperate well with EEGs and are very hard to study," says Duffy. "No one has extensively studied large samples of these children with EEGs, in part because of the difficulty of getting reliable EEG recordings from them."

The researchers used techniques developed at Boston Children’s Hospital to get clean waking EEG recordings from children with autism, such as allowing them to take breaks. They used computer algorithms to adjust for the children’s body and eye movements and muscle activity, which can throw off EEG readings.

To measure connectivity in the brain, Duffy and Als compared EEG readings from multiple electrodes placed on the children’s scalps, and quantified the degree to which any two given EEG signals — in the form of waves — are synchronized, known as coherence. If two or more waves rise and fall together over time, it indicates that those brain regions are tightly connected. (Duffy likens coherence to two people singing “Mary Had a Little Lamb” together. If they can see and hear each other, they are more likely to sing in synchrony — so their coherence is high.)

In all, using computational techniques, the researchers generated coherence readings for more than 4,000 unique combinations of electrode signals, and looked for the ones that seemed to vary the most from child to child. From these, they identified 33 coherence “factors” that consistently distinguished the children with autism from the controls, across all age groups (2 to 4, 4 to 6, and 6 to 12 years).

Duffy and Als repeated their analysis 10 times, splitting their study population in half different ways and using half to identify the factors, and the other half to test and validate them. Each time, the classification scheme was validated.

"These factors allowed us to make a discriminatory rule that was highly significant and highly replicable," says Duffy. "It didn’t take anything more than an EEG — the rest was computational. Our choice of variables was completely unbiased — the data told us what to do."

The researchers believe the findings could be the basis for a future objective diagnostic test of autism, particularly at younger ages when behavior-based measures are unreliable. Their most immediate goal is to repeat their study in children with Asperger’s syndrome and see if its EEG patterns are similar to or different from autism. They also plan to evaluate children whose autism is associated with conditions such as tuberous sclerosis, fragile X syndrome and extremely premature birth.

Source: Science Daily

ScienceDaily (June 21, 2012) — A pioneering report of genome-wide gene expression in autism spectrum disorders (ASDs) finds genetic changes that help explain why one person has an ASD and another does not. The study, published by Cell Press on June 21 in The American Journal of Human Genetics, pinpoints ASD risk factors by comparing changes in gene expression with DNA mutation data in the same individuals. This innovative approach is likely to pave the way for future personalized medicine, not just for ASD but also for any disease with a genetic component.

ASDs are a heterogeneous group of developmental conditions characterized by social deficits, difficulty communicating, and repetitive behaviors. ASDs are thought to be highly heritable, meaning that they run in families. However, the genetics of autism are complex.

Researchers have found rare changes in the number of copies of defined genetic regions that associate with ASD. Although there are some hot-spot regions containing these alterations, very few genetic changes are exactly alike. Similarly, no two autistic people share the exact same symptoms. To discover how these genetic changes might affect gene transcription and, thus, the presentation of the disorder, Rui Luo, a graduate student in the Geschwind lab at UCLA, studied 244 families in which one child (the proband) was affected with an ASD and one was not.

In addition to identifying several potential new regions where copy-number variants (CNVs) are associated with ASDs, Geschwind’s team found genes within these regions to be significantly misregulated in ASD children compared with their unaffected siblings. “Strikingly, we observed a higher incidence of haploinsufficient genes in the rare CNVs in probands than in those of siblings, strongly indicating a functional impact of these CNVs on expression,” says Geschwind. Haploinsuffiency occurs when only one copy of a gene is functional; the result is that the body cannot produce a normal amount of protein. The researchers also found a significant enrichment of misexpressed genes in neural-related pathways in ASD children. Previous research has found that these pathways include other genetic variants associated with autism, which Geschwind explains further legitimizes the present findings.

Source: Science Daily

ScienceDaily (June 19, 2012) — Fish cannot display symptoms of autism, schizophrenia, or other human brain disorders. However, a team of Whitehead Institute and MIT scientists has shown that zebrafish can be a useful tool for studying the genes that contribute to such disorders.

Zebrafish with certain genes turned off during embryonic development (center and right images) showed abnormalities of brain formation (top row) and axon wiring (bottom row). At left is a normally developing zebrafish embryo. (Credit: Sive Lab)

Led by Whitehead Member Hazel Sive, the researchers set out to explore a group of about two dozen genes known to be either missing or duplicated in about 1 percent of autistic patients. Most of the genes’ functions were unknown, but a new study by Sive and Whitehead postdocs Alicia Blaker-Lee, Sunny Gupta and, Jasmine McCammon, revealed that nearly all of them produced brain abnormalities when deleted in zebrafish embryos.

The findings, published online recently in the journal Disease Models & Mechanisms, should help researchers pinpoint genes for further study in mammals, says Sive, who is also professor of biology and associate dean of MIT’s School of Science. Autism is thought to arise from a variety of genetic defects; this research is part of a broad effort to identify culprit genes and develop treatments that target them.

"That’s really the goal — to go from an animal that shares molecular pathways, but doesn’t get autistic behaviors, into humans who have the same pathways and do show these behaviors," Sive says.

Sive recalls that some of her colleagues chuckled when she first proposed studying human brain disorders in fish, but it is actually a logical starting point, she says. Brain disorders are difficult to study because most of the symptoms are behavioral, and the biological mechanisms behind those behaviors are not well understood, she says.

"We thought that since we really know so little, that a good place to start would be with the genes that confer risk in humans to various mental health disorders, and to study these various genes in a system where they can readily be studied," she says.

Those genes tend to be the same across species — conserved throughout evolution, from fish to mice to humans — though they may control somewhat different outcomes in each species.

In the latest study, Sive and her colleagues focused on a genetic region known as 16p11.2, first identified by Mark Daly, a former Whitehead Fellow who discovered a type of genetic defect known as a copy number variant. A typical genome includes two copies of every gene, one from each parent; copy number variants occur when one of those copies is deleted or duplicated, and this can be associated with pathology.

The central “core” 16p11.2 region includes 25 genes. Both deletions and duplications in this region have been associated with autism, but it was unclear which of the genes might actually produce symptoms of the disease. “At the time, there was an inkling about some of them, but very few,” Sive says.

Sive and her postdocs began by identifying zebrafish genes analogous to the human genes found in this region. (In zebrafish, these genes are not clustered in a single genetic chunk, but are scattered across many chromosomes.) The researchers studied one gene at a time, silencing each with short strands of nucleic acids that target a particular gene and prevent its protein from being produced.

For 21 of the genes, silencing led to abnormal development. Most produced brain deficits, including improper development of the brain or eyes, thinning of the brain, or inflation of the brain ventricles, cavities that contain cerebrospinal fluid. The researchers also found abnormalities in the wiring of axons, the long neural projections that carry messages to other neurons, and in simple behaviors of the fish. The results show that the 16p11.2 genes are very important during brain development, helping to explain the connection between this region and brain disorders.

Furthermore, the researchers were able to restore normal development by treating the fish with the human equivalents of the genes that had been repressed. “That allows you to deduce that what you’re learning in fish corresponds to what that gene is doing in humans. The human gene and the fish gene are very similar,” Sive says.

To figure out which of these genes might have a strong effect in autism or other disorders, the researchers set out to identify genes that produce abnormal development when their activity is reduced by 50 percent, which would happen in someone who is missing one copy of the gene. (This correlation is not seen for most genes, because there are many other checks and balances that regulate how much of a particular protein is made.)

The researchers identified two such genes in the 16p11.2 region. One, called kif22, codes for a protein involved in the separation of chromosomes during cell division, and one, aldolase a, is involved in glycolysis — the process of breaking down sugar to generate energy for the cell.

In work that has just begun, Sive’s lab is working with Stanford University researchers to explore in mice predictions made from the zebrafish study. They are also conducting molecular studies in zebrafish of the pathways affected by these genes, to get a better idea of how defects in these might bring about neurological disorders.

Source: Science Daily

ScienceDaily (June 6, 2012) — Psychoactive medications in water affect the gene expression profiles of fathead minnows in a way that mimics the gene expression patterns associated with autism spectrum disorder in genetically susceptible humans, according to research published June 6 in the open access journal PLoS ONE. These results suggest a potential environmental trigger for autism spectrum disorder in this vulnerable population, the authors write.

The researchers, led by Michael A. Thomas of Idaho State University, exposed the fish to three psychoactive pharmaceuticals — fluoxetine, a selective serotonin reuptake inhibitor, or SSR1; venlafaxine, a serotonin-norepinephrine reuptake inhibitor, and carbamazepine, used to control seizures — at concentrations comparable to the highest estimated environmental levels.

They found that the only gene expression patterns affected were those associated with idiopathic autism spectrum disorders, caused by genetic susceptibility interacting with unknown environmental triggers. These results suggest that exposure to environmental psychoactive pharmaceuticals may play a role in the development of autism spectrum disorder in genetically predisposed individuals.

Lead researcher Michael A. Thomas remarks, “While others have envisioned a causal role for psychotropic drugs in idiopathic autism, we were astonished to find evidence that this might occur at very low dosages, such as those found in aquatic systems.”

Source: Science Daily