What is linked to autism?

The word "Autism" displayed child-like magnet letters on the backdrop of a jigsaw puzzle with one piece missing.

Autism represents a wide spectrum of disorders that impact how a person relates to and communicates with other people. Effects include a variety of social difficulties, “atypical” uses of language, and “restricted or repetitive behaviors.” Autism is not new; examples of individuals can be found throughout history.

In recent years, there has been controversy over the causes and antecedents of autism spectrum disorder. What does current research say that autism is linked to?

**Updated February 2021**

Quick bibliography: Articles–classic and recent–on links to autism.

*Bjørklund, G., Waly, M. I., Al-Farsi, Y., Saad, K., Dadar, M., Rahman, M. M., . . . Kałużna-Czaplińska, J. (2019). The role of vitamins in autism spectrum disorder: What do we know?Journal of Molecular Neuroscience : MN, 67(3), 373-387. [Cited by]

Vitamin or mineral supplementation is considered to be the most commonly used medical treatment for autism spectrum disorder (ASD), in addition to other interventions such as neurological and psychological interventions. There is not much evidence of therapeutic efficacy between vitamin and mineral supplementation and improvements in ASD. However, several researchers have noted that patients with ASD have various metabolic and nutritional abnormalities including issues with sulfation, methylation, glutathione redox imbalances, oxidative stress, and mitochondrial dysfunction. There is some evidence that vitamin and mineral supplementation may support these basic physiologic processes. Recently, the nutritional status of ASD patients has been gaining focus in this particular area. Pointing out the nutritional status as a potential etiological factor for attention/communication disorders, more importance has been given to this particular point. Moreover, autistic specific considerations like the feature and behavior of ASD might be increased or at least fall in the higher risk due to the sub-optimal nutritional status.”

*Bölte, S., Girdler, S., & Marschik, P. B. (2019). The contribution of environmental exposure to the etiology of autism spectrum disorder.Cellular and Molecular Life Sciences : CMLS, 76(7), 1275-1297. [PDF] [Cited by]

“Autism spectrum disorder (ASD) is a neurodevelopmental condition of heterogeneous etiology. While it is widely recognized that genetic and environmental factors and their interactions contribute to autism phenotypes, their precise causal mechanisms remain poorly understood. This article reviews our current understanding of environmental risk factors of ASD and their presumed adverse physiological mechanisms. It comprehensively maps the significance of parental age, teratogenic compounds, perinatal risks, medication, smoking and alcohol use, nutrition, vaccination, toxic exposures, as well as the role of extreme psychosocial factors. Further, we consider the role of potential protective factors such as folate and fatty acid intake. Evidence indicates an increased offspring vulnerability to ASD through advanced maternal and paternal age, valproate intake, toxic chemical exposure, maternal diabetes, enhanced steroidogenic activity, immune activation, and possibly altered zinc–copper cycles and treatment with selective serotonin reuptake inhibitors. Epidemiological studies demonstrate no evidence for vaccination posing an autism risk. It is concluded that future research needs to consider categorical autism, broader autism phenotypes, as well as autistic traits, and examine more homogenous autism variants by subgroup stratification. Our understanding of autism etiology could be advanced by research aimed at disentangling the causal and non-causal environmental effects, both founding and moderating, and gene–environment interplay using twin studies, longitudinal and experimental designs. The specificity of many environmental risks for ASD remains unknown and control of multiple confounders has been limited. Further understanding of the critical windows of neurodevelopmental vulnerability and investigating the fit of multiple hit and cumulative risk models are likely promising approaches in enhancing the understanding of role of environmental factors in the etiology of ASD.”

*Di, J., Li, J., O’Hara, B., Alberts, I., Xiong, L., Li, J., & Li, X. (2020). The role of GABAergic neural circuits in the pathogenesis of autism spectrum disorder.International Journal of Developmental Neuroscience, 80(2), 73-85. [Cited by] **New**

“Autism spectrum disorder (ASD) comprises a heterogeneous range of neurodevelopmental conditions represented by symptoms including, communication and language deficits, repetitive, and restricted patterns of behavior and inadequate social interactions. Gamma-aminobutyric acid (GABA) is known to mediate I responses in the central nervous system by interacting with GABA signaling receptors. In this context, several recent investigations suggest that imbalances in the GABAergic neurotransmission system may be implicated in the development of ASD as well as several other neurodevelopmental disorders, including Fragile X syndrome (FXS) and Rett syndrome. This review initially expounds the functional role of the GABAergic system in the mature brain and during neurodevelopment. This will be followed by discussions concerning the impact of deficiencies in the system on ASD and the other above-mentioned neurodevelopment disorders. Finally, the connections between these deficiencies and behavioral features observed in the clinic will be considered.”

*Ho, L. K. H., Tong, V. J. W., Syn, N., Nagarajan, N., Tham, E. H., Tay, S. K., . . . Law, E. C. N. (2020). Gut microbiota changes in children with autism spectrum disorder: A systematic review.Gut Pathogens, 12, 6. [PDF]

“As more animal studies start to disentangle pathways linking the gut microbial ecosystem and neurobehavioral traits, human studies have grown rapidly. Many have since investigated the bidirectional communication between the gastrointestinal tract and the central nervous system, specifically on the effects of microbial composition on the brain and development. There was a lack of consistency in the reported gut microbiome changes across ASD studies, except for distinguishable patterns, within limits, for Prevotella, Firmicutes at the phylum level, Clostridiales clusters including Clostridium perfringens, and Bifidobacterium species. These results were inadequate to confirm a global microbiome change in children with ASD and causality could not be inferred to explain the etiology of the behaviors associated with ASD.

*Hu, Z., Xiao, X., Zhang, Z., & Li, M. (2019). Genetic insights and neurobiological implications from NRXN1 in neuropsychiatric disorders.Molecular Psychiatry, 24(10), 1400-1414. [Cited by]

Many neuropsychiatric and neurodevelopmental disorders commonly share genetic risk factors. To date, the mechanisms driving the pathogenesis of these disorders, particularly how genetic variations affect the function of risk genes and contribute to disease symptoms, remain largely unknown. Neurexins are a family of synaptic adhesion molecules, which play important roles in the formation and establishment of synaptic structure, as well as maintenance of synaptic function. Accumulating genomic findings reveal that genetic variations within genes encoding neurexins are associated with a variety of psychiatric conditions such as schizophrenia, autism spectrum disorder, and some developmental abnormalities. In this review, we focus on NRXN1, one of the most compelling psychiatric risk genes of the neurexin family. We performed a comprehensive survey and analysis of current genetic and molecular data including both common and rare alleles within NRXN1 associated with psychiatric illnesses, thus providing insights into the genetic risk conferred by NRXN1. We also summarized the neurobiological evidence, supporting the function of NRXN1 and its protein products in synaptic formation, organization, transmission and plasticity, as well as disease-relevant behaviors, and assessed the mechanistic link between the mutations of NRXN1 and synaptic and behavioral pathology in neuropsychiatric disorders.”

*Pessah, I. N., Lein, P. J., Seegal, R. F., & Sagiv, S. K. (2019). Neurotoxicity of polychlorinated biphenyls and related organohalogens.Acta Neuropathologica, 138(3), 363-387. [Cited by]

Halogenated organic compounds are pervasive in natural and built environments. Despite restrictions on the production of many of these compounds in most parts of the world through the Stockholm Convention on Persistent Organic Pollutants (POPs), many “legacy” compounds, including polychlorinated biphenyls (PCBs), are routinely detected in human tissues where they continue to pose significant health risks to highly exposed and susceptible populations. A major concern is developmental neurotoxicity, although impacts on neurodegenerative outcomes have also been noted. Here, we review human studies of prenatal and adult exposures to PCBs and describe the state of knowledge regarding outcomes across domains related to cognition (e.g., IQ, language, memory, learning), attention, behavioral regulation and executive function, and social behavior, including traits related to attention-deficit hyperactivity disorder (ADHD) and autism spectrum disorders (ASD). We also review current understanding of molecular mechanisms underpinning these associations, with a focus on dopaminergic neurotransmission, thyroid hormone disruption, calcium dyshomeostasis, and oxidative stress. Finally, we briefly consider contemporary sources of organohalogens that may pose human health risks via mechanisms of neurotoxicity common to those ascribed to PCBs.”

*Volk, H. E., Hertz-Picciotto, I., Delwiche, L., Lurmann, F., & McConnell, R. (2011). Residential proximity to freeways and autism in the CHARGE study.Environmental Health Perspectives, 119(6), 873-877. [PDF] [Cited by]

“Basic science and epidemiologic research suggest that oxidative stress and inflammation may play a role in [autism spectrum disorder] development. Traffic-related air pollution, a common exposure with established effects on these pathways, contains substances found to have adverse prenatal effects. Adjusting for sociodemographic factors and maternal smoking, maternal residence at the time of delivery was more likely be near a freeway (≤ 309 m) for [ASD] cases than for controls [odds ratio (OR) = 1.86; 95% confidence interval (CI), 1.04–3.45]. Autism was also associated with residential proximity to a freeway during the third trimester (OR = 2.22; CI, 1.16–4.42). After adjustment for socioeconomic and sociodemographic characteristics, these associations were unchanged. Living near other major roads at birth was not associated with autism. Living near a freeway was associated with autism. Examination of associations with measured air pollutants is needed.“

For additional research on the links to autism, please see the Science Primary Literature database.

Questions?  Please let me know (engelk@grinnell.edu).

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