The Causes of Autism

Who are the marvelous authors, what is the title of the study, and what year was it published?

Authors: Barbara De Santis, Carlo Brera, Alessandra Mezzelani, Sabina Soricelli, Francesca Ciceri, Giorgio Moretti, Francesca Debegnach, Maria Clara Bonaglia, Laura Villa, Massimo Molteni & Maria Elisabetta Raggi

Title: Role of mycotoxins in the pathobiology of autism: A first evidence

Year: 2019

What is the study about?

A pilot study explores the potential link between mycotoxins in food and the development of autism spectrum disorder (ASD) in Italian children. The study analyzed the association between mycotoxins and various clinical parameters associated with ASD, such as cognitive and social behavior profiles, intestinal permeability, and oxidative stress indicators. Blood, serum, and urine samples were analyzed using chromatographic analysis, and the results were statistically analyzed. The study provides insight into possible preventive and therapeutic interventions for ASD and highlights the importance of environmental factors in neurodevelopmental disorders.

What previous research is there on this topic?

The relationship between mycotoxins and autism has been the subject of several studies, but the results have been mixed. One study by Duringer et al. (2018) found no association between mycotoxins and autism, but the sample size was small, and the study did not test for genetic risk factors.

Mycotoxins are food contaminants that can cause symptoms similar to those associated with autism, such as oxidative stress, inflammation, and intestinal permeability. Contaminated food is a significant source of mycotoxins, which can be found in various agricultural products like cereals, nuts, spices, and dried fruits. The processing, storage, and transport of food also increase the risk of mycotoxin contamination. Mycotoxins are challenging to eliminate, as they can survive high temperatures and water activity. Moreover, even when people share comparable diets, mycotoxins can still contaminate food.

What methods were used?

Participants

The pilot study exploring the association between mycotoxins and autism was conducted at IRCCS E. Medea hospital in Bosisio Parini-Lecco, Italy, and included 52 Italian children with autism and 58 healthy controls. The autistic group included 42 males and 10 females, aged 2-19 years (mean age: 8.5 years), while the control group consisted of 33 males and 25 females, aged 2-17 years (mean age: 7.2 years).

Genetic Test

To confirm that the children had autism spectrum disorder (ASD) without any chromosomal abnormalities or genetic variants that may cause similar symptoms, informed consent for a genetic test was obtained from all participants with ASD, and genetic analysis using array-based comparative genomic hybridization (array-CGH) was conducted at IRCCS E. Medea. Array-CGH is a molecular cytogenetic technique that detects chromosomal copy number variations in DNA samples. The study included only the children who tested negative for syndromic genetic variants, ensuring that the children had ASD due to non-syndromic causes.

Oxidative Stress

The study assessed oxidative stress markers like ceruloplasmin, transferrin, eosinophilic cationic protein, malondialdehyde, and free glutathione, as well as food and mold-specific IgG antibodies, and intestinal permeability. The objective was to determine the relationship between mycotoxins and autism and to identify any potential comorbidities. The study aimed to establish a reference dataset for the levels of these clinical parameters in children without autism and investigate the biological causes of autism. The authors note that the dataset of reference gathered in the study is crucial to elucidating the role of environmental risk factors in autism and clarifying biological causes.

Mycotoxins

The study collected mycotoxin levels in biologic fluids such as whole blood, serum, and urine, as well as various clinical parameters related to autism. The study compared mycotoxin levels between two groups: autistic patients and healthy controls, and statistical analyses were performed within the autistic group to explore the association between mycotoxins and clinical symptoms and parameters related to autism.

The study analyzed the presence of six mycotoxins (GLIO, OTA, ZEA, α and β-ZEL, Sa, and So) in biologic fluids of both ASD children and healthy controls.

Autism Assessments

The study used two standardized tests, the Autism Diagnostic Observation Schedule (ADOS) and Diagnostic Interview, Revised (ADI-R), to assess autism symptoms and behaviors such as language impairment, communication, hyperactivity, social interaction, and stereotyped behaviors. The diagnosis of ASD was made by experienced neuropsychiatric doctors and psychologists according to the DSM-V criteria, and cognitive profile was assessed with the Griffiths Mental Development Scales, Revised (GMDS 0-2) for children up to 2 years old and with the Wechsler Preschool and Primary Scale of Intelligence (WPPSI) for more competent children over 2 years old.

What were the findings?

Urine

OTA (Ochratoxin A): The levels of OTA were significantly higher in urine of autistic children compared to the levels found in controls when both siblings and unrelated healthy controls were considered together. Also, when comparing within ASD children versus their age-matched control group, significant differences were also found in the urinary concentration of OTA. GLIO: Significant differences were found in the level of GLIO in the urine of ASD children versus age-matched control group, and in GLIO levels between the ASD and the healthy control groups (siblings and unrelated subjects).

Serum

OTA (Ochratoxin A): Serum levels of OTA were found to be significantly associated with the presence of autism, as well as being the most abundant mycotoxin among all mycotoxins investigated. GLIO: Significant association was found between OTA levels in biologic fluids and GLIO (oxidative stress indicator) in serum when autistic group was compared with healthy children. The levels of GLIO did not show any significant difference between ASD and the control groups.

None of the other mycotoxins (ZEA, α and β-ZEL, Sa, and So) showed any significant difference between the ASD and control groups in both urine and serum analyses.

Oxidative Stress

The findings did not show any significant differences between ASD patients and healthy controls. However, it is worth noting that only the autistic group had subjects with oxidative stress markers out of range (below or above threshold).

The authors did not find any significant associations between mycotoxin levels and oxidative stress markers in the body fluids of ASD patients or healthy controls.

What were the limitations of the study?

The study had a relatively small sample size, lack of control over external factors, lack of consideration of confounding variables, lack of replication, and no causal inference. These limitations can increase the likelihood of having a false negative result and limit the generalizability of the findings. The study tried to minimize the influence of confounding variables, but other variables such as environmental pollutants, bacterial infections, and medications were not explored in detail. Additionally, the study was an observational pilot study, and the findings were not replicated in another study, which is essential to establish the robustness and validity of the findings. The study was not designed to establish causality between mycotoxin exposure and ASD, but rather to investigate the association between the two variables in a small sample.

What conclusions or implications can be made?

The article highlights the deleterious effects of mycotoxins on the body, which include inducing oxidative stress, altering the immune system, and causing epigenetic changes. The authors emphasize the observed correlation between OTA and GLIO levels in the autistic group and suggest that their interaction could be synergistic. They discuss the potential role of OTA in promoting DNA methylation and histone modifications, which could contribute to the onset of ASD. However, the authors note that the exact mechanisms are not fully understood, and further research is needed to investigate the relationship between mycotoxins and ASD thoroughly.

The authors also suggest that personalized diets and probiotics, particularly those containing OTA adsorbing Lactobacillus, could help alleviate symptoms in OTA-positive patients.

Finally, the potential implications of OTA’s male-specific toxicity in animal models in the context of the male predominance of ASD is also placed in the spotlight. Although this study did not examine sex differences, the authors suggested that OTA’s male-specific toxicity may be related in autism diagnosis. They stressed the need for further research aimed at exploring gender-specific mycotoxin effects in individuals with ASD to provide new insights into the pathophysiology of ASD and suggest tailored dietary and therapeutic interventions. By investigating gender-specific effects of mycotoxins, such studies may provide new insights into the cognitive gender bias and ASD pathophysiology.

What other research within the library might this study be related to?

Oxidative stress is an interesting topic, and it is a recurring theme in the genesis of ASD. Although this particular study did not exhibit findings in relation to oxidative stress, research on paracetamol (Tylenol) heavily discusses oxidative stress, and the study that found selenium supplementation could improve oxidative stress is interesting to consider.

Can I read the full study?

Of course you can. Right here.