The Causes of Autism

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

Authors: Kanwaljit Singh, Susan L. Connors, Eric A. Macklin, Kirby D. Smith, Jed W. Fahey, Paul Talalay, and Andrew W. Zimmerman

Title: Sulforaphane treatment of autism spectrumdisorder (ASD). Proceedings of the National Academy of Sciences of the United States of America. 2014 Oct 28; 111(43): 15550–15555

Year: 2014

What is the study about?

The study investigated the effectiveness of sulforaphane, derived from broccoli sprouts, in improving core behaviors associated with Autism Spectrum Disorder (ASD). Sulforaphane has been shown to counteract biochemical and molecular abnormalities associated with ASD, including oxidative stress, neuroinflammation, and low antioxidant capacity.

What previous research is there on this topic?

Extensive evidence shows that sulforaphane can counteract many of the biochemical and molecular abnormalities associated with ASD, including oxidative stress, reduced antioxidant capacity, mitochondrial dysfunction, and neuroinflammation. It is also observed that correcting these anomalies often improves ASD behavior. Additionally, sulforaphane activates the “stress proteome,” which regulates many of the damaging processes related to ASD. In a clinical trial, the daily oral administration of sulforaphane to 29 young men with ASD improved behavior compared with 15 placebo recipients. Sulforaphane is a dietary phytochemical that is widely consumed in cruciferous plant-rich diets and is considered to be of low toxicity.

Furthermore, anecdotal reports suggest that fever can temporarily ameliorate the disturbed behavior of many autistic patients. It is explicitly suggested that elucidation of the fever response might provide insight into the mechanisms of ASD and point to new therapeutic approaches. Fever up-regulates heat-shock proteins and related mechanisms central to multiple cellular processes in the CNS, including synaptic transmission. Sulforaphane also upregulates expression of the heat-shock response.

What methods were used in the study?

Participants

In this study, demographic data on 40 participants who completed at least part of the outcome measure evaluations was analyzed. The majority (80%) of the participants had a history of behavioral improvements with fever. All participants were male, and there were 14 who received the placebo, while 26 received sulforaphane treatment. Participants in both groups were well matched and did not differ at baseline regarding various demographic, behavioral, and clinical features, behavioral outcome score measures, abnormalities in physical examination, blood chemistries, hematology, and urinalysis.

Autism Behavior & Symptom Assessments

Various well-established assessments were used to evaluate the behavior and symptoms of the participants before and after treatment. These assessments included the Aberrant Behavior Checklist (ABC), the Social Responsiveness Scale (SRS), the Clinical Global Impression Severity and Improvement Scales (CGI-S and CGI-I), and the Ohio Autism Clinical Global Impression Severity Scale (CGI-S or OACIS-S). The ABC assesses irritability, lethargy, stereotypy, hyperactivity, noncompliance, and inappropriate speech. The SRS quantifies the core symptoms of ASD, including cognition, awareness, communication, motivation, and autistic mannerisms. The CGI-S and CGI-I are completed by study physicians to assess the severity of autistic behavior and how much it has improved during the intervention, while the OACIS-S is a clinician-rated assessment of the severity of autistic behavior. Collectively, these assessments provided a comprehensive evaluation of the different aspects of ASD symptoms, behavior, and clinical features, which enabled the researchers to measure the effectiveness of sulforaphane treatment in improving the participants’ outcomes.

Treatment & Control Groups

In the clinical trial, participants in the treatment group were given capsules of sulforaphane-rich broccoli sprout extracts, while the placebo group received capsules containing microcrystalline cellulose. The sulforaphane capsules were dosed according to the participants’ body weight, with 50 μmol given to those weighing less than 100 lb, 100 μmol for those weighing between 101-199 lb, and 150 μmol for those weighing more than 200 lb. The participants were instructed to keep the capsules in a household freezer and to take them daily for 18 weeks. Follow-up visits were scheduled at 4, 10, and 18 weeks after the first dose, and at 22 weeks after the first dose to check if any treatment changes reversed after four weeks of treatment cessation. The dispensing of capsules was handled by the MGH Research Pharmacy.

Hypothesis

In this study, the hypothesis was tested to determine whether daily treatment with sulforaphane, a small molecule from broccoli sprouts, could decrease the severity of socially impaired behavior in individuals with Autism Spectrum Disorder (ASD). The primary objective was to see if sulforaphane could improve overall behavior by addressing the biochemical abnormalities seen in ASD and reducing its core clinical features. The study’s main outcome measure was the change in scores of the Aberrant Behavior Checklist (ABC) and the Social Responsiveness Scale (SRS) between baseline and 18 weeks after starting treatment.

What were the findings?

The study observed significant differences in the primary and secondary outcome measures between the treatment and control groups at different time points.

4 Week Differences

No significant differences were found in the ABC or SRS scores between the groups.

10 Week Differences

The sulforaphane group showed significantly improved behavior compared to the placebo group in ABC and SRS scores.

18 Week Differences

The sulforaphane group showed significant improvement in ABC (p = 0.001) and SRS scores, as well as in the subscales of the CGI-I scale scores for social interaction, aberrant behavior, and verbal communication.

22 Week Differences

After the cessation of treatment, ABC scores returned to baseline for both groups, but still significantly improved in the sulforaphane group compared to the placebo group. The difference in SRS scores between the sulforaphane and placebo groups trended toward significance.

These findings suggest that sulforaphane treatment can lead to significant and clinically meaningful improvements in behavior in individuals with ASD.

What are the limitations of the study?

The study had some limitations, such as being a single-site study with a limited dose range and a small sample size of 44 male participants aged 13-27, who were predominantly Caucasian and had a history of behavioral improvements with fever. Therefore, the generalizability of the findings is limited. The study participants also continued their regular medications during the study, making it difficult to determine whether the observed effects were solely due to sulforaphane or a combination of medication and sulforaphane. Additionally, the lack of observer blinding may have led to biases in subjective assessments. Finally, while the study highlights the potential benefits of sulforaphane treatment for individuals with ASD, further research is needed to determine its potential benefits for prenatal prevention and early treatment of young children with this disorder.

What other research within the library is this study related to?

Given that evidence shows that sulforaphane can counteract many of the biochemical and molecular abnormalities associated with ASD, including oxidative stress, reduced antioxidant capacity, mitochondrial dysfunction, and neuroinflammation, the study regarding Impaired Microbial Detoxification in ASD, as well as the study on The safety of pediatric use of paracetamol (acetaminophen) are of interest in relation to this study.

Can I read the full study somewhere?

You sure can you beautiful thing. Here.