Behavioral disorders in kids with autism linked to reduced brain connectivity

Reduced Amygdala–Prefrontal Functional Connectivity in Children With Autism Spectrum Disorder and Co-occurring Disruptive Behavior

Reduced connectivity between the amygdala and ventrolateral prefrontal cortex has been identified in children on the autism spectrum who exhibit disruptive behaviors, compared to those on the spectrum who do not. Findings suggest this distinct brain network could be independent of core autism symptoms.

More than a quarter of children with autism spectrum disorder are also diagnosed with disruptive behavior disorders. For the first time, Yale researchers have identified a possible biological cause: a key mechanism that regulates emotion functions differently in the brains of the children who exhibit disruptive behavior.

Neuroscience News reports, 21/04/2019.

2019 Study Abstract

Background

Disruptive behaviors are prevalent in children with autism spectrum disorder (ASD) and often cause substantial impairments. However, the underlying neural mechanisms of disruptive behaviors remain poorly understood in ASD. In children without ASD, disruptive behavior is associated with amygdala hyperactivity and reduced connectivity with the ventrolateral prefrontal cortex (vlPFC). This study examined amygdala reactivity and connectivity in children with ASD with and without co-occurring disruptive behavior disorders. We also investigated differential contributions of externalizing behaviors and callous-unemotional traits to variance in amygdala connectivity and reactivity.

Methods

This cross-sectional study involved behavioral assessments and neuroimaging in three groups of children 8 to 16 years of age: 18 children had ASD and disruptive behavior, 20 children had ASD without disruptive behavior, and 19 children were typically developing control participants matched for age, gender, and IQ. During functional magnetic resonance imaging, participants completed an emotion perception task of fearful versus calm faces. Task-specific changes in amygdala reactivity and connectivity were examined using whole-brain, psychophysiological interaction, and multiple regression analyses.

Results

Children with ASD and disruptive behavior showed reduced amygdala–vlPFC connectivity compared with children with ASD without disruptive behavior. Externalizing behaviors and callous-unemotional traits were associated with amygdala reactivity to fearful faces in children with ASD after controlling for suppressor effects.

Conclusions

Reduced amygdala–vlPFC connectivity during fear processing may differentiate children with ASD and disruptive behavior from children with ASD without disruptive behavior. The presence of callous-unemotional traits may have implications for identifying differential patterns of amygdala activity associated with increased risk of aggression in ASD. These findings suggest a neural mechanism of emotion dysregulation associated with disruptive behavior in children with ASD.

Screening for rare epigenetic variations in autism and schizophrenia

Additional evidence that rare epivariations likely contribute to the mutational spectra underlying neurodevelopmental disorders

2019 Study Abstract

While many studies have led to the identification of rare sequence variants linked with susceptibility to autism and schizophrenia, the contribution of rare epigenetic variations (epivariations) in these disorders remains largely unexplored.

Previously we presented evidence that epivariations occur relatively frequently in the human genome, and likely contribute to a subset of congenital and neurodevelopmental disorders through the disruption of dosage-sensitive genes.

Here we extend this approach, studying methylation profiles from 297 samples with autism and 767 cases with schizophrenia, identifying 84 and 268 rare epivariations in these two cohorts, respectively, that were absent from 4,860 population controls.

We observed multiple features associated with these epivariations that support their pathogenic relevance, including

  1. a significant enrichment for epivariations in schizophrenic individuals at genes previously linked with schizophrenia,
  2. increased brain expression of genes associated with epivariations found in autism cases compared with controls,
  3. in autism families, a significant excess of epivariations found specifically in affected versus unaffected sibs,
  4. Gene Ontology terms linked with epivariations found in autism, including “D1 dopamine receptor binding.”

Our study provides additional evidence that rare epivariations likely contribute to the mutational spectra underlying neurodevelopmental disorders. Image credit Brigham and Women’s Hospital.

DES DIETHYLSTILBESTROL RESOURCES

DES Transgenerational Neurodevelopmental Deficits, 2018 Study

Collaborative on Health and the Environment Webinar, 20 March 2019

Dr. Marianthi-Anna Kioumourtzoglou, Assistant Professor in the Department of Environmental Health Sciences at Columbia University Mailman School of Public Health, describes the study Association of Exposure to Diethylstilbestrol During Pregnancy With Multigenerational Neurodevelopmental Deficits design, statistical analyses, and findings.

References

DES DIETHYLSTILBESTROL RESOURCES

Vaxxed: From Cover-Up to Catastrophe

Doctor behind film that links autism to vaccines speaks out featuring Dr. Andrew Wakefield & Polly Tommey

A 2016 American film alleging a cover-up by the Centers for Disease Control and Prevention (CDC) of a purported link between the MMR vaccine and autism.

Official site.

EU should ban brain-harming chlorpyrifos to protect health

Exposure to chlorpyrifos is linked to ADHD and autism. It should not be allowed on the European market

Today, the Health and Environment Alliance (HEAL) together with Générations Futures, Pesticide Action Network Europe and Pesticide Action Network Germany released a factsheet on the health effects of chlorpyrifos.

Chlorpyrifos is one of the most widely used pesticides in Europe and its residues are also commonly found in our food. The current authorisation for chlorpyrifos on the European market will expire on 31 January 2019. We are very concerned about the possibility of an extended authorisation due to its health harming properties. Chlorpyrifos is linked to the disruption of the hormonal system and effects on the developing human brain. Children exposed to chlorpyrifos in the womb or in early life can suffer neurodevelopmental effects later in life, like attention deficit disorders (ADHD) and autism.

This factsheet sets out the case and evidence against the use of chlorpyrifos and explains the health impacts which justify its ban.

Reference.

Can exposure to insecticide during pregnancy link to autism in children ?

Association of Maternal Insecticide Levels With Autism in Offspring From a National Birth Cohort

New research published in the American Journal of Psychiatry says that exposure to the notorious pesticide dichlorodiphenyltrichloroethane (DDT) during pregnancy could raise the risk of a child developing autism, ScienceAlert reports.

2018 Abstract

Objective
Autism is a complex neurodevelopmental disorder with a largely unknown etiology. To date, few studies have investigated prenatal exposure to toxins and risk of autism by using maternal biomarkers of exposure. Persistent organic pollutants are lipophilic halogenated organic compounds and include the insecticide dichlorodiphenyltrichloroethane (DDT), as well as its metabolite p,p′-dichlorodiphenyl dichloroethylene (p,p′-DDE), and polychlorinated biphenyls (PCBs). The objective of this study was to test whether elevated maternal levels of persistent organic pollutants are associated with autism among offspring.

Method
The investigation was derived from the Finnish Prenatal Study of Autism, a national birth cohort study based on a nested case-control design. Cases of autism among children born between 1987 and 2005 were ascertained by national registry linkages. In cases of childhood autism and matched control subjects (778 matched case-control pairs), maternal serum specimens from early pregnancy were assayed for levels of p,p′-DDE and total levels of PCBs.

Results
The odds of autism among offspring were significantly increased with maternal p,p′-DDE levels that were in the highest 75th percentile, with adjustment for maternal age, parity, and history of psychiatric disorders (odds ratio=1.32, 95% CI=1.02, 1.71). The odds of autism with intellectual disability were increased by greater than twofold with maternal p,p′-DDE levels above this threshold (odds ratio=2.21, 95% CI=1.32, 3.69). There was no association between total levels of maternal PCBs and autism.

Conclusions
These findings provide the first biomarker-based evidence that maternal exposure to insecticides is associated with autism among offspring. Although further research is necessary to replicate this finding, this study has implications for the prevention of autism and may provide a better understanding of its pathogenesis.

Too Much Medicine Helsinki Symposium 2018

Paulo Foundation International Medical Symposium, Helsinki, 15 – 17 Aug 2018

Abstracts

  • Overestimation of depression prevalence in meta-analyses via the inclusion of primary studies that assessed depression using screening tools or rating scales rather than validated diagnostic interviews
  • Clinician, patient and general public beliefs about diagnostic imaging for low back pain: A qualitative evidence synthesis
  • Overdiagnosis of low back pain
  • Defining Overdiagnosis of Mental Health Disorders: Secondary Analysis of an Overdiagnosis Scoping Review
  • Evaluating the content of Choosing Wisely recommendations and prevalence of interdisciplinary finger pointing
  • Inadequate Prescription of medicines for Parkinson’s disease in the Autonomous Community of the Basque Country. An observational study
  • Is it always necessary to treat nocturia? Natural history of nocturia among men and women during the 5-year period
  • The monocriterial source of over-testing and over-treatment: the case of bone scanning
  • Increasing prescription of opioid analgesics and neuropathic pain medicines for spinal pain in Australia
  • No benefit of additional care for ‘high-risk’ patients with acute low back pain: The PREVENT randomized, placebo-controlled trial
  • Overdiagnosis, overtreatment and low-value care in physiotherapy: a scoping review
  • Targeted information based on reimbursed drug registry
  • Journal Registration Policies and Prospective Registration in Randomized Trials of Non-Regulated Interventions: A Meta-Research Review
  • Pharmacotherapy and behavioural problems in Autism Spectrum Disorders
  • Simultaneous under and over care of eye health care in Finland
  • Decision Support and Knowledge Translation Tools to Highlight the Benefits and Downstream Harms of Screening: Resources from the Canadian Task Force for Preventive Healthcare
  • A Free Access Literature Awareness Portal That Surveilles High Quality Research and Guidelines to Inform Benefits and Downstream Harms of Screening and Prevention Strategies in Healthcare
  • From “Non‐encounters” to autonomic agency. Conceptions of patients with low back pain about their encounters in Finnish health care system
  • Does the use of CAM reflect a patients´ response to “too much medicine”?
  • Preferred Reporting Items for Overview of Systematic Reviews for abstracts (PRIO-abstracts)

Reference.

Widespread risk from brain-harming chlorpyrifos, state scientists find

Current uses of chlorpyrifos put children at risk from unsafe levels of exposure from residues on food, contaminated water, and pesticide drift

Nerve agent chlorpyrifos is a toxic air contaminant that threatens agricultural communities and harms children’s developing brains, PAN North America reports, July 30, 2018.

Sacramento, CA – California took a step closer Monday to curbing the use of a pesticide linked to permanent brain harm, including ADHD, autism and IQ loss. Sixteen months after disgraced former EPA Administrator Scott Pruitt defied his own scientists and refused to ban the neurotoxic organophosphate chlorpyrifos, the California Department of Pesticide Regulation (DPR) has concluded their own study by largely agreeing with the EPA scientists: current uses of chlorpyrifos put children at risk from unsafe levels of exposure from residues on food, contaminated water, and pesticide drift up to half a mile. Now, children’s health advocates are pushing the department to follow the science with sound policy, and become the second state in the nation to ban it. Hawaii’s state legislature passed a statewide ban in May.

DPR’s scientific conclusions were announced at a hearing convened Monday by the state’s Scientific Review Panel (SRP), a body of independent scientists overseeing DPR’s risk assessment of chlorpyrifos. Review of the chemical had been on hold for many years pending the proposed federal ban. The SRP formally accepted the risk assessment Monday, and unanimously agreed to designate chlorpyrifos a Toxic Air Contaminant, joining a list of 46 other chemicals including a number of fumigant pesticides. DPR now has ten working days to initiate the regulatory process formalizing the Toxic Air Contaminant designation.

“We’re glad that the state has finally accepted the overwhelming consensus of federal and independent scientists who’ve studied chlorpyrifos for years and determined that it harms kids’ brains severely and irreversibly,”

said Mark Weller, co-director of the statewide coalition Californians for Pesticide Reform.

It’s what comes next that will determine for how long California’s communities will continue to be put at risk. DPR has the authority to halt exposures immediately by suspending use in California while formal assessment of control options are considered. However, DPR may also follow the timeline under the Toxic Air Contaminant regulations that allow for two years to decide how to mitigate the risk to children’s brain health. And meanwhile, almost a million pounds continues to be used on California’s food crops each year, exposing thousands of children and pregnant women to a chemical that permanently damages the developing brain.

“With everything we now know, it’s unconscionable that this toxic chemical is still being used on food crops in California,”

“The state must immediately suspend all use of chlorpyrifos to protect kids, farmworkers and agricultural communities.”

said Miriam Rotkin-Ellman, senior scientist at the Natural Resources Defense Council (NRDC).

Endocrine Disrupting Chemicals and Behavior

Special issue of Hormones and Behavior, Volume 101, Pages 1-148, May 2018

The peer-reviewed journal Hormones and Behavior, Volume 101, Pages 1-148 (May 2018), raises concern about how many of the 90,000+ chemicals in use today may disrupt our most basic endocrine systems with significant consequences for neurodevelopment, neurophysiology, healthy brain aging, and behavior.

Several articles address bisphenol A :

About PDBEs, triclosan, and other replacement chemicals :

Other studies included in this special issue address behavioral effects of voluntary taken pharmaceuticals, including birth control pills, and pain medications.

About DES and the BRAIN :

Behavioral effects of prenatal and postnatal PBDE exposures

Exposure to polybrominated diphenyl ethers (PBDEs) and child behavior: Current findings and future directions

2018 Study Highlights

  • Prenatal PBDEs are associated with executive function impairments and inattention.
  • Prenatal and postnatal PBDE exposures increase externalizing problems in children.
  • PBDEs’ association with internalizing, adaptive, and social behaviors is not clear.
  • PBDE exposure adversely affects behavioral development in children.

Abstract

Polybrominated diphenyl ethers (PBDEs) are recognized neurotoxicants, but the extent to which PBDEs influence various domains of behavior in children is not fully understood.

As such, we reviewed epidemiologic studies published to date to provide an overview of the current state of knowledge on PBDEs’ potential role in behavioral development.

We identified 19 epidemiologic studies reporting on associations of prenatal and childhood concentrations of PBDEs with behaviors assessed in children from 1 to 12 years, including executive function, attention, externalizing and internalizing behaviors, adaptive skills, and social behaviors/Autism Spectrum Disorder (ASD).

While the mechanisms of PBDE neurotoxicity in humans are still not clearly elucidated, findings from this review indicate that PBDE exposure during fetal development is associated with impairments in executive function and poorer attentional control in children. Results from large prospective cohorts demonstrate that prenatal and postnatal PBDE exposure adversely impacts externalizing behavior (e.g., hyperactivity and conduct problems). Additional studies are needed to determine whether PBDEs are associated with internalizing problems, adaptive skills, and social behaviors/ASD in children.

Future studies will help better understand the potential neurotoxic effects of PBDE exposures during adolescence, possible sex-dependent effects, and the impact of exposure to BDE-209 and alternative flame retardants. Future studies should also examine chemical mixtures to capture real-world exposures when examining PBDEs and their impact on various behavioral domains in the context of multiple chemical exposures.