The Autism studies/research thread

Post Reply New Topic

A new University Of Iowa study has found a link between suicidal thoughts and twice exceptional youth.

Twice exceptional youth are kids who have both exceptional ability and a disability.

The new UI study narrows in on children who have both an autism diagnosis and high IQ.

The study found autistic children with an IQ of 120 or higher are nearly six times more likely to have thoughts of suicide.

Researchers tell Iowa's News Now it's unexpected, because usually a high IQ is associated with better outcomes and less suicidal ideation -- if you're neurotypical.

But if you fall under the autism umbrella, the study's author says having a higher IQ can present problems other people on the spectrum may not experience.

"This is an underserved part of the autism community, and I've gotten pushback from people who are like, 'well, you know they're, they have high IQ,' and there's, from some quarters, there's a little bit less sympathy because, 'well they have that going for them," said Jacob Michaelson, PhD, UI Associate Professor of Psychiatry and senior author of the study.

Michaelson says there's a long way to go before they can apply the findings therapeutically.

Summary
Autism spectrum disorder (henceforth autism) is a neurodevelopmental condition that can be reliably diagnosed in children by age 18–24 months. Prospective longitudinal studies of infants aged 1 year and younger who are later diagnosed with autism are elucidating the early developmental course of autism and identifying ways of predicting autism before diagnosis is possible. Studies that use MRI, EEG, and near-infrared spectroscopy have identified differences in brain development in infants later diagnosed with autism compared with infants without autism. Retrospective studies of infants younger than 1 year who received a later diagnosis of autism have also showed an increased prevalence of health conditions, such as sleep disorders, gastrointestinal disorders, and vision problems. Behavioural features of infants later diagnosed with autism include differences in attention, vocalisations, gestures, affect, temperament, social engagement, sensory processing, and motor abilities. Although research findings offer insight on promising screening approaches for predicting autism in infants, individual-level predictions remain a future goal. Multiple scientific challenges and ethical questions remain to be addressed to translate research on early brain-based and behavioural predictors of autism into feasible and reliable screening tools for clinical practice.

A recent Biomedicines study hypothesized a dysfunction of the self-recognition properties of the immune system in autism.

Background
ASD is associated with several immunological defects, such as reduced complement proteins, increased number and altered functions of natural killer (NK) cells and T-cells, gastrointestinal (GI) tract inflammation, and uncharacteristic proliferative responses to mitogens. In addition, children with ASD often exhibit abnormal B-cell and monocyte levels.

Several studies have indicated that ASD enhances cytokine levels in the cerebrospinal fluid (CSF) or serum concentrations of autoantibodies to caudate nucleus, myelin basic protein, cerebellar proteins or neurofilaments, nerve growth factor, neuron-axon filament protein, and α2 adrenergic receptors. In addition, serum autoantibodies, such as cerebral folate receptor autoantibodies or anti-nucleosome specific antibodies, have also been found in other brain components of children with autism.

Elevated levels of anti-ganglioside M1 autoantibodies in serum have also been observed in autistic children. However, this finding contradicted another study that failed to find any association between autism and anti-ganglioside M1 autoantibodies.

Recently, scientists have reported on autoimmune processes associated with the central nervous system that cause mental disorders. For example, there have been several reports of children diagnosed with pediatric autoimmune neuropsychiatric disorders (PANDAS) associated with streptococcal infections. Similar conditions have been found in children with autism as well.

A crucial role of the immune system is to distinguish between “self” and “foreign.” Natural autoantibodies (NAAbs), which are antibodies present in the sera of healthy unvaccinated individuals, play an active role in protecting the host from harmful pathogens through immune response modulation, effective recognition of environmental antigens, and maintaining tissue homeostasis.

About the study
Natural anti-F(ab’)2 autoantibodies help recognize the immune self. The current study investigated the role of NAAbs, including the natural anti-F(ab’)2 autoantibodies, in changing self-recognition mechanisms in autism.

A total of 60 children with autism, which consisted of 38 males and 22 females, and 112 typically developing (TD) controls, 72 of whom were male and 40 female, were considered in this study. Both groups shared similar age, sex, and pubertal status.

All participants were Caucasian and had no history of neuroendocrinological disease or encephalopathy. The cognitive functioning of the ASD children was evaluated using the age-appropriate Wechsler intelligence scale and Kaufman K-ABC. Blood samples of the participants were collected to measure NAAbs levels.

Study findings
The serum levels of IgG anti-F(ab’)2 autoantibodies were significantly lower in children with autism as compared to the TD group and were negatively associated with autism severity. In addition, IQ scores were significantly and negatively correlated with IgG anti-F(ab’)2 levels in the autism group. Thus, autoantibody levels were more specific to autism than to intellectual disability.

The findings documented in this study are consistent with previous research revealing reduced IgG levels in children with autism as compared with the TD group.

Limitations
A key limitation is the small sample size of the autism group as compared to the control group. This is because children with mild/moderate autism typically do not go to daycare facilities on a regular basis.

Furthermore, drawing blood samples was much easier in the control group than in the ASD group. Another limitation of this study is the inability to determine the underlying mechanism associated with the observed phenomenon.

Conclusions
The current study was the first to highlight the association between abnormally low natural anti-F(ab’)2 autoantibody activity and severe autism. These findings support an autoimmune process in autism, in which a dysfunction of self-recognition mechanisms could manifest ADS. This finding opens the possibility of future therapeutic inventions for severe autism.

The complex mechanisms that underlie the onset of autism (autism spectrum disorders; ASD) are not fully understood, and researchers studying the neurodevelopmental disorder commonly use animal—especially mouse—models. A strain of mouse known as BTBR/J represents the most commonly used murine model of idiopathic autism. An international research collaboration headed by Kobe University’s Takumi Toru, PhD, and researcher Chia-wen Lin, PhD, has now made new discoveries that help to describe the onset of autism in mouse models.

The combined results of detailed imaging and behavioral experiments using the BTBR/J mouse model, and a sister murine strain, BTBR/R, suggested that endogenous retrovirus (ERV) activation increases the susceptibility of a fetus to autism. The researchers also discovered that BTBR/R mice exhibit autistic-like behaviors without reduced learning ability, which they suggest makes this strain a more accurate model of autism than the widely used BTBR/J model.

It is hoped that further research will contribute toward a better classification of autism types, as well as point to new treatment strategies for neurodevelopmental disorders. Reporting on their work in Molecular Psychiatry the scientists said their study “unravels the idiopathic etiology of the BTBR strain by suggesting it as a superimposed model of multiple genetic mechanisms and virus infection.” They further suggested that targeting enhanced ERV activity or its infection process in BTBR mice will be the next step on the road toward developing possible therapeutic strategies for ASD of immune-dysregulated subtypes.

Autism is strongly related to genetic factors and can be caused by abnormalities in DNA structure, such as copy number variations (CNVs). “… accumulating evidence suggests a prominent role of CNV, large-scale structural variations in the chromosome, contributing either directly to ASD pathology or ASD susceptibility,” the investigators added.

Animal models, especially mice, are often used in research to illuminate the pathology of autism. Among these models, BTBR/J is a commonly used mouse model of the natural onset of autism. Studies have reported various abnormalities in BTBR/J mice, including impairment of the corpus callosum (which connects the left and right hemispheres of the brain) and excessive immune system signaling. However, it is not fully understood why this particular lineage displays autistic-like behavioral abnormalities.

The aim of the newly reported study was to shed light on the onset mechanism of autistic-like behavioral abnormalities. To do this the researchers carried out comparative analyses using BTBR/J and BTBR/R animals.

The research group next used array-based comparative genomic hybridization to compare CNVs in BTBR/R and normal, B6 mouse models. The results revealed that in comparison with B6 mice, the BTBR/R animals had significantly increased levels of endogenous retroviruses (ERVs). “ERVs are remnants of ancient retrovirus infection in the germline, the team explained. “Intriguingly, by analyzing the repeat sequences in the identified CNV, we found the potential involvement of ERV in speeding up CNV formation in both BTBR strains,” they stated.

Subsequent qRT-PCR analyses showed that these retroviruses were activated in BTBR/R mice, with comparative tests in the B6 animals indicating that this retroviral activation is specific to BTBR. Single-cell RNA analysis of BTBR/R mice revealed changes in the expression of various genes (including stress response genes) that are indicative of endogenous retrovirus activation.

Single-cell RNA analyses of embryonic BTBR mouse tissues provided further evidence of ERV activation in these animals, as expression changes were observed in a group of genes downstream of ERV. “… by single-cell RNA sequencing (scRNA seq), evidence of ERV activation during embryonic development was identified,” they further noted.

The results from these tests demonstrated that BTBR/R mice were less anxious than BTBR/J animals and showed qualitative changes in ultrasound vocalizations, which are measured as a way to assess communicative ability in mice. BTBR/R mice also exhibited more self-grooming behaviors and buried more marbles in the marble burying test. “BTBR/R spent ~30% more time on self-grooming than BTBR/J mice. In the marble-burying test, BTBR/R showed an even stronger repetitive behavioral phenotype with more than 75% of the marbles completely or half buried.” These two tests were designed to detect repetitive behavioral abnormalities in autistic individuals. From the results, it was clear that BTBR/R mice exhibited more repetitive behaviors (i.e., they were more symptomatic) than BTBR/J animals.

Overall, the study revealed that retrovirus activation causes the copy number variants in BTBR mice to increase, leading to the differences in behavior and brain structure seen in BTBR/J and BTBR/R mice. “Intriguingly, disturbed epigenetic silencing mechanism leads to hyperactive ERV, a mobile genetic element of ancient retroviral infection, which increases de novo CNV formation in the two BTBR strains,” they stated. “This feature makes the BTBR strain a still evolving multiple-loci model toward higher ASD susceptibility … The ancient viral infection and reactivation affect host genome instability in the long term and have a continuing effect on embryonic development.”

A recent Cell Genomicsstudy hypothesized that analyzing the coexpression from pertinent tissues would provide better insights into the transcriptional effects of CRISPR perturbation. This research provides an opportunity to explore transcriptional convergence across many ASD risk genes, implicating novel shared downstream genes and pathways.

Previous research has also discovered biological pathways associated with ASD, including chromatin, synaptic function, and transcriptomic studies. Nevertheless, there is limited data on how these genes interact or whether they converge on shared downstream pathways linked to novel risk genes to
Genetic studies using CRISPR and induced pluripotent stem cells (iPSCs) provide insights into cellular and transcriptomic consequences of perturbing ASD-associated individual genes. Observations from these studies suggest several downstream genes/pathways that could contribute to ASD risk.

Using Loss of function (LoF) models, FOXP1 and CHD8 transcriptional regulators have been linked with ASD, with a possibility of more dysregulated genes potentially causing this condition. Several altered genes associated with ASD showed the absence of CHD8 and FOXP1 binding sites, thus suggesting that the manifestation of ASD is due to the perturbation of other downstream regulatory interactions.

ASD gene mutations have been classified into two groups based on changes in prefrontal cortex neurogenesis. One group inhibited, while the other improved spontaneous cortical neurogenesis.

The existence of convergent cellular and signaling phenotypes within the larger subset of ASD-associated genes was confirmed.

The current study evaluated the degree of coexpression convergence based on similar coexpression profiles among ASD risk genes using large-scale postmortem brain tissue datasets. In addition, genes that were significantly coexpressed with the ASD genes were identified.

Since in vitro experiments are costly and challenging to scale, scientists used an in silico coexpression convergence approach to implicate genes as novel ASD risk candidates. The identified genes were linked to neurodevelopmental disorder (NDD), synaptic function, and varied expressions in postmortem brains of ASD patients as compared to controls.

It was observed that coexpression could influence the regulatory consequences of CRISPR perturbation across common factors with the same correlation to replicate CRISPR experiments linked to a similar gene. A total of 993 human postmortem brains associated with the transcriptional consequences of CRISPR perturbations in human neurons were used to determine coexpression patterns.

Seventy-one ASD risk genes significantly associated with tissue-specific convergence implicating synaptic pathways were identified. The authors further used schizophrenia and atrial fibrillation risk genes to demonstrate tissue-specific convergence. The extent of ASD convergence was found to be significantly correlated with ASD association from rare dissimilarity and varied expression in ASD brains.

The convergent gene revealed intolerance to functional mutations and possessed shorter coding lengths than known risk genes, even after eliminating their association with ASD. Thus, research on convergent coexpression would likely be able to identify novel genes that would otherwise remain undetected by large-scale molecular sequencing studies.

Despite the ability of the in silico coexpression convergence approach to elucidate transcriptional consequences of disruptive mutations and functional convergence, this method is associated with certain limitations.

For example, the majority of transcriptional data were obtained from bulk tissues that can provide obscure coexpression patterns. Second, the primary ASD convergence analysis assumed a single underlying convergent pathway, which is unlikely, as multiple pathways are more likely to be present given the heterogeneity associated with individuals diagnosed with ASD. Finally, postmortem samples used in this study failed to capture the full convergence during early development.

If I were religious I'd just shout at God for making me Aspie.

University of Iowa study links high IQ with suicidal ideation in kids with autism

That the researchers are surprised is part of the problem. Higher IQ does not automatically conflate with “mild” Autism. If you have a higher IQ you are more likely to notice 1. You can not do, or it is much harder for you to do what other people can. 2.You are being discriminated against.

We analysed breastfeeding and complementary feeding patterns in 1389 children with ASD and 1190 TD children. The Children Neuropsychological and Behavior Scale-Revision 2016 (CNBS-R2016) was used to assess neurodevelopmental levels. The Autism Behavior Checklist (ABC), Social Responsiveness Scale (SRS), Childhood Autism Rating Scale (CARS), and ASD Warning Behavior Subscale of the CNBS-R2016 were used to assess ASD symptoms.

Children with ASD had a shorter breastfeeding duration in infancy (8 (3–12) months vs. 10 (6–14) months, P < 0.001), later introduction of complementary foods (P < 0.001), and poorer acceptance of complementary foods (P < 0.001) than TD children. Total ABC and CARS scores were lower in the group of children with ASD who had been breastfed for 12 months or more than in the group who had been breastfed for less than 6 months. Children with ASD who were given complementary food after 6 months had lower general quotient (GQ), adaptive ability, fine motor and language scores than those who were given complementary food within 4–6 months. Children with ASD with poor acceptance of complementary foods had higher ABC and SRS scores and lower gross motor scores than those who had good acceptance.

The researchers analyzed BTBR/J, a widely used mouse model of autism, and its subspecies BTBR/Rusing MRI.This revealed that the corpus callosum, which connects the left and right hemispheres of the brain, was impaired in BTBR/J mice but not in BTBR/R mice.

Genome and transcription analysis showed that BTBR mice have increased levels of endogenous retrovirus genes.

Furthermore, single-cell RNA analysis of BTBR/R mice revealed changes in the expression of various genes (including stress response genes) that are indicative of endogenous retrovirus activation.

Even though BTBR/J and BTBR/R mice have the same ancestry, the results of various behavioral analysis experiments revealed differences in spatial learning ability and other behaviors between the two types of model mice.

Children with autism are less likely than their peers to receive important vision screening despite a high risk for serious eye disorders, researchers report.

Only about 36% of children with autism spectrum disorder (ASD) completed vision screenings during their health checkups, a new study found. That was far fewer than the 59% rate for children without ASD.

In addition, the screening rate for Black children with ASD was just under 28%, compared with nearly 40% for white and multiracial kids, the findings showed.

"I noticed that many of our patients with autism have never had vision screening, even though it's recommended for all young children," said senior author Dr. Brittany Perry, a pediatrician at the Nemours Swank Autism Center in Wilmington, Del.

"So, I wanted to study whether this might be a broader disparity — whether kids with autism receive vision screening less often than other kids," she added in a Nemours news release.

Early childhood is crucial for vision development, as well as for early detection and treatment of eye problems, the study authors noted.

For the study, Perry's team examined data for more than 63,800 well visits across a primary care network in Delaware, Pennsylvania and Florida. Children were 3 to 5 years of age.

In Florida, nearly 46% of kids with ASD had vision screening, compared to 28% each in Delaware and Pennsylvania.

About 80% of Florida medical practices used photoscreening, in which a specialized camera or video system captures detailed images of a child's eyes. In comparison, only 13% of medical practices in Delaware and Pennsylvania used photoscreening, the researchers noted.

The study authors explained that photoscreening is particularly helpful for children with ASD because they cannot always understand and verbally respond to instructions or questions in conventional vision tests.

The American Academy of Pediatrics recommends annual instrument-based vision screening, particularly for children with developmental delays.

Reimbursement is necessary to bring about greater use of photoscreening in primary care, the researchers said.

The report was published March 21 in the journal Pediatrics.

A study from Spain indicates that children with autism spectrum disorders (ASD) have a high rate of vision problems.

Carlota Gutiérrez and colleagues collected data on 344 children with ASD seen over a period of 8.5 years. They divided the children into four subcategories based on their diagnoses: autism, Asperger syndrome, pervasive developmental disorders not otherwise specified (PDD-NOS), and other diagnoses related to autism.

The researchers found that 48.4 percent of the children had refractive problems, most commonly hyperopia (farsightedness) and astigmatism (distorted vision due to alterations in the shape of the cornea or lens). Myopia (nearsightedness) was more common in children with Asperger syndrome, with nearly 18 percent of them exhibiting this problem. More than 15 percent of patients with autism or autism-related disorders exhibited strabismus, a type of eye movement disorder in which the eyes do not align properly; exotropia, or an outward turning of one or both eyes, was the most common form of strabismus seen. Optic nerve abnormalities were detected in four percent of the children, while nystagmus (rapid and uncontrolled eye movement) was seen in fewer than one percent of them.

The researchers say their findings are limited by the fact that children frequently refused to cooperate with the testing. However, they note that new testing technologies have been developed since they began collecting their data, and they say, “The fact that children do not have social interaction are not able to follow objects, and present limitations in language does not mean in any way that they cannot be examined.”

They conclude, “Ophthalmologic manifestations occur more frequently in patients with ASD than in the general child population…. Therefore, we consider it necessary to perform an ophthalmological evaluation in patients with ASDs.”

“Ophthalmologic manifestations in autism spectrum disorder,” Carlota Gutiérrez, Jorge Luis Marquez Santoni, Pilar Merino, and Pilar Gómez de Liaño, Turkish Journal of Ophthalmology, August 2022 (free online).

No two people with autism have the same combination of behaviors, intellectual capabilities or connections in their brains, but these traits can be used to categorize them into four biologically relevant subgroups, according to a new study. Each subgroup correlates with a specific pattern of gene expression.

The subgroups could help researchers identify who is most likely to benefit from experimental therapeutic approaches, such as oxytocin therapy, says study investigator Amanda Buch, a postdoctoral researcher at Weill Cornell Medicine in New York City.

“A lot of the clinical trials for autism have failed,” Buch says. “That’s not that surprising if we think there are different things happening biologically in each of these subtypes.”

Buch and her colleagues took advantage of a wealth of new open-source data, including postmortem gene-expression maps, brain scans and behavioral data from people with and without autism. Although many scientists are leveraging these sophisticated tools to gain new insights into autism, outside researchers say they are impressed by the machine-learning approach Buch and her colleagues used to parse the data in multiple dimensions.

“It’s really amazing that they got four groups,” says Catherine Lord, distinguished professor of psychiatry and education at the University of California, Los Angeles, who helped establish the open-source brain scan database but was not involved in the new study. “There have been a lot of attempts to create subgroups, but it is quite hard.”

Others noted, alongside their praise, that the paper makes bold claims. “When I read it, I said, ‘Wow, these guys cracked autism somehow,’” says Alessandro Gozzi, senior researcher at the Istituto Italiano di Tecnologia in Rovereto, Italy. “Now there will be scrutiny.”

Earlier attempts to partition autism into subgroups based on behavioral traits were largely abandoned after the 2013 publication of the 5th edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5). The DSM-5 defined “autism spectrum disorder” as a broad diagnosis and eliminated subtypes, such as Asperger syndrome and the pervasive developmental disorders, that had proven to be unreliable and lacked a biological basis.

“It got so messy, and there was no reliability to the different terms people used,” Lord says. Yet the prospect of using the modern tools of genetics, neuroscience and computing to somehow partition the condition into subgroups remained a long-standing goal for many in the field.

The inspiration for the multidimensional approach initially came from Buch’s doctoral thesis adviser and a collaborator on the study, Conor Liston, associate professor of neuroscience and psychiatry at Weill Cornell Medicine. Liston had previously conducted a brain imaging study to identify depression biomarkers corresponding to four neurophysiological subtypes. Those subtypes, Liston found, could help predict who would best respond to transcranial magnetic stimulation therapy.

She and her colleagues began by obtaining data from the Autism Brain Imaging Data Exchange, which includes functional MRI data along with verbal intelligence scores and measures of social affect and repetitive behaviors. The researchers then compared resting-state brain activity patterns between 299 people with autism and 907 neurotypical controls to identify atypical patterns of functional connectivity among different brain regions.

Their machine-learning technique identified three roughly orthogonal brain-connectivity scores that did the best job of predicting the mix of someone’s verbal intelligence, social affect and repetitive behaviors. The social affect dimension, for instance, ended up being closely linked to connectivity among brain regions associated with social and emotional processing. The verbal intelligence dimension, meanwhile, was associated with connectivity among brain areas related to reading and language.

The study was published on 9 March in Nature Neuroscience

By plotting an person’s score in each of these three brain-behavior dimensions, the researchers were able to identify four distinct clusters, or subgroups. Less than 5 percent of the 4,257 atypical brain connections in autism explained the majority of the differences among these four subgroups. The researchers then used the Allen Human Brain Atlas — which has measured gene-expression patterns from 3,702 brain regions from six neurotypical adults — to identify distinct molecular pathways associated with the atypical activity patterns in each of these subgroups.

In one subgroup, which was characterized by people with high levels of repetitive behaviors, brain activity patterns correlated with decreased expression of the gene HTR1A, which encodes a serotonin receptor and has been previously linked to autism. Another subgroup, which was most challenged in terms of social affect, was associated with the oxytocin receptor. The researchers say they hope to reanalyze data from a failed clinical trial of oxytocin therapy to see if there are indications that it was beneficial for this particular subgroup.

Brain scans might not even be necessary to take advantage of the approach, Buch says.

Lord is enthusiastic about that possibility and curious about how stable the subgroup assignment is over a person’s lifetime. “Are they going to be different when they are 60?” she says. “It is relevant to clinical practice.”

What a wonderful meta analysis by ASPoM!

So many of these articles suffered from "correlation is not causation" and then many other suffered from "duh". If a person is different and therefore not socially in-step with their peers, they are not likely to form the same sense of taste, sight, smell, etc as everyone else. I once had a sociology professor who explained that the reason "why" something was a tree, was because we all agree it is a tree. If you take away social agreement like that, it becomes difficult for someone to tell you if something "hurts on a scale of 1 to 10" or if taste is something separate from texture.

But it is fascinating to read what "science" is up to! Thanks!

A new study found a moderately higher risk of autism spectrum disorder in children born to pregnant people exposed to tap water with higher levels of lithium, but experts caution that this association does not show a direct link between the two.

Lithium is an alkali metal that can be found naturally in some food and ground water. It’s used in batteries, grease and air conditioners, as well as in the treatment of bipolar disorder and some blood disorders. Its levels in US drinking water are not regulated, according to the US Geological Survey.

A new study, published Monday in the journal JAMA Pediatrics, found a small association between lithium and autism diagnosis in Denmark, where the researchers say the level of lithium in drinking water is similar to that in American water systems.

The researchers checked a database of people with psychiatric disorders for children born between 2000 and 2013 to find information on 8,842 cases of ASD and 43,864 participants who did not have ASD. They then measured the concentration of lithium in 151 public waterworks that served more than half of the Danish population and mapped out where pregnant people lived in relation

As lithium levels in water increased, there was a modest increased risk of an ASD diagnosis. Specifically, compared with people at the lowest exposure level, those who had the second and third highest exposure during pregnancy had a 24% to 26% higher risk of ASD diagnosed in children. The group with the highest exposure had a 46% higher risk than those at the lowest level of exposure.

The researchers could not tell how much water the pregnant people drank, but they picked Denmark in part because residents there consume some of the lowest amounts of bottled water in Europe.

Experts say it’s important to note that the research can’t show that lithium exposure leads directly to an autism diagnosis.

Further study is required, said study co-author Dr. Beate Ritz, a professor of neurology in the David Geffen School of Medicine at UCLA, and a professor of epidemiology and environmental health at the UCLA Fielding School of Public Health.

“Any drinking water contaminants that may affect the developing human brain deserve intense scrutiny,” Ritz said in a news release. She added that the research would need to be replicated in other countries to look for a similar connection.

The implications of the findings are complex as far as public health policy is concerned, according to an editorial published alongside the study. Lithium levels in water, at concentrations that the study associated with a potential ASD risk, have also been linked with health benefits such as lower rates of hospitalization for psychiatric disorders and suicide.

“If all these of associations are valid, the wisdom of Solomon will be required to develop guidelines for lithium in drinking water that are maximally protective of the entire population,” wrote Dr. David C. Bellinger, a professor of neurology and psychology at Harvard Medical School. “Until the basic biology of ASD is better understood, it will be difficult to distinguish causal from spurious associations.”